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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 1,243 records · Page 69
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Rnf112 deletion protects brain against intracerebral hemorrhage (ICH) in mice by inhibiting TLR-4/NF-κB pathway

Highlights: • Rnf112{sup −/−} mice exhibits accelerated brain injury and neuroinflammation. • Rnf112{sup −/−} promotes inflammation by enhancing TLR-4/NF-κB pathway. • Over-expressing Rnf112 attenuates brain injury after intracerebral hemorrhage. Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is modulated during brain progression and development. The study aimed to explore the role of Rnf112 in brain injury after ICH, as well as the underlying molecular mechanisms. The results indicated that ICH led to a significant decrease in Rnf112, which was confirmed in oxyhemoglobin (oxyHb)-incubated astrocytes and microglial cells. Moreover, the Rnf112 knockout (Rnf112{sup −/−}) mice and wild type (WT) mice induced by ICH were further employed. Compared to the WT/ICH group, Rnf112{sup −/−} mice exhibited accelerated brain injury, as evidenced by the increased brain water contents and neurological deficit scores (NDS). In comparison to WT/ICH group, a remarkable up-regulation in the release of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was observed in perihematoma tissues of Rnf112{sup −/−} mice on day 3 post-ICH. The process was along with promoted glial fibrillary acidic protein (GFAP) and Iba1 expression and reduced NeuN levels. Furthermore, ICH-induced increases in toll-like receptor (TLR)-4 and myeloid differentiation primary response protein (MyD88) expression were exacerbated by the loss of Rnf112. The phosphorylated expression of IKKα, inhibitor of NF-κB (IκBα) and nuclear factor-kappa B (NF-κB) induced by ICH in perihematoma tissues of mice was markedly enhanced in Rnf112{sup −/−} mice. Rnf112 repression-induced inflammatory response was verified in lipopolysaccharide (LPS)-incubated glial cells. In contrast, over-expressing Rnf112 markedly attenuated ICH-induced brain injury by restraining inflammation via inactivating TLR-4/NF-κB pathway. In summary, our findings suggested that Rnf112 expression was highly involved in the progression of ICH, and targeting Rnf112 signaling might be a promising therapeutic strategy against ICH development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

SAR optimization studies on modified salicylamides as a potential treatment for acute myeloid leukemia through inhibition of the CREB pathway

Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. In this paper, we describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Review of thermal comfort infused with the latest big data and modeling progresses in public health

Thermal environment is important for both occupants’ comfort and health. Previously, the impacts of thermal environment were explored in the areas of thermal comfort and public health separately. This paper aims to bridge both disciplines by examining the correlation between comfort temperature and Minimum Mortality Temperature (MMT), which is a key index quantifying the association of health and weather temperature, through literature review and data-driven approach. It was found that the MMT data obtained from the public health area are generally in good agreement with the thermal neutral temperatures from the comfort perspective. The MMT data range from 17.2 °C to 30 °C, which are similar to the thermal neutral temperatures ranging from 19.5 °C to 30 °C based on the global field tests. Moreover, the MMT data demonstrate the potential to capture some complex distribution patterns of the field comfort data. The introduction of the health-temperature data could assist the intensive field experiments and modeling efforts and complement the thermal comfort dataset, which suffers from the problems of limited sample size. Some discrepancies between the two datasets were identified as well. The contextual factors other than the climate factor which may cause such discrepancies, such as socio-economics, population densities, etc. should be analyzed to enable the potential application of the health-temperature data and modeling to thermal comfort and health studies.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2024

Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis

Seaweeds represent a rich source of sulfated polysaccharides with similarity to heparan sulfate, a facilitator of myriad virus host cell attachment. For this reason, attention has been drawn to their antiviral activity, including the potential for anti-SARS-CoV-2 activity. We have identified and structurally characterized several fucoidan extracts, including those from different species of brown macroalga, and a rhamnan sulfate from a green macroalga species. A high molecular weight fucoidan extracted from Saccharina japonica (FSjRPI-27), and a rhamnan sulfate extracted from Monostroma nitidum (RSMn), showed potent competitive inhibition of spike glycoprotein receptor binding to a heparin-coated SPR chip. This inhibition was also observed in cell-based assays using hACE2 HEK-293 T cells infected by pseudotyped SARS-CoV-2 virus with IC50 values <1 μg/mL. Effectiveness was demonstrated in vivo using hACE2–transgenic mice. Intranasal administration of FSjRPI-27 showed protection when dosed 6 h prior to and at infection, and then every 2 days post-infection, with 100 % survival and no toxicity at 104 plaque-forming units per mouse vs. buffer control. At 5-fold higher virus dose, FSjRPI-27 reduced mortality and yielded reduced viral titers in bronchioalveolar fluid and lung homogenates vs. buffer control. Furthermore, these findings suggest the potential application of seaweed-based sulfated polysaccharides as promising anti-SARS-CoV-2 prophylactics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Exercise provides a robust physiological stimulus that evokes cross-talk between a wide range of tissues via hormonal, cellular and molecular signals that when repeated regularly over time (i.e., training) improves physiological capacity, benefits numerous organ systems and decreases the risk for premature mortality. In spite of its fundamental importance, a gap remains in identifying the detailed molecular signals and responses to exercise and its benefits for health and disease prevention. To further knowledge in this emerging area, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to generate a molecular map of the effects of acute and chronic exercise. MoTrPAC investigators are conducting preclinical and clinical studies to better understand the systemic effects of exercise across multiple tissues. The preclinical studies were performed on more than 700 rats with the analysis of twenty or more organs per rat. The clinical study involves a large cohort of ~2600 individuals with a range of ages and fitness levels (untrained, trained, highly trained) who will be evaluated physiologically and by molecular probing of blood, muscle and adipose tissues before and after acute and chronic endurance or resistance exercise. Multi-omic analyses (genomics, epigenomics, transcriptomics, proteomics and metabolomics/lipidomics) will be performed followed by state-of-the-art bioinformatics to create a molecular map of exercise. This mapping project will provide a public database that is expected to enhance our understanding of the health benefits of physical activity in many organ systems and potentially provide insight into mitigating diseases through activity.

Sanford, James A.↗
DOE OSTI2019

Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Validation of spatiodemographic estimates produced through data fusion of small area census records and household microdata

Techniques such as Iterative Proportional Fitting have been previously suggested as a means to generate new data with the demographic granularity of individual surveys and the spatial granularity of small area tabulations of censuses and surveys. This article explores internal and external validation approaches for synthetic, small area, household- and individual-level microdata using a case study for Bangladesh. Using data from the Bangladesh Census 2011 and the Demographic and Health Survey, we produce estimates of infant mortality rate and other household attributes for small areas using a variation of an iterative proportional fitting method called P-MEDM. We conduct an internal validation to determine: whether the model accurately recreates the spatial variation of the input data, how each of the variables performed overall, and how the estimates compare to the published population totals. We conduct an external validation by comparing the estimates with indicators from the 2009 Multiple Indicator Cluster Survey (MICS) for Bangladesh to benchmark how well the estimates compared to a known dataset which was not used in the original model. The results indicate that the estimation process is viable for regions that are better represented in the microdata sample, but also revealed the possibility of strong overfitting in sparsely sampled sub-populations.

42 ENGINEERING↗
DOE OSTI2018

Time-dependent behavioral data from zebrafish reveals novel signatures of chemical toxicity using point of departure analysis

High-content imaging of embryonic zebrafish behavior can be used as a screening approach to rapidly evaluate the relative potential for chemicals to cause toxicity. However, most statistical methods applied to these data so far transform movement values to incidence-based “hits” and calculate lowest effect levels (LELs), which loses individual fish resolution of behavior and defies hazard ranking due to reliance on applied dose levels. Here, we have developed and parallelized a workflow to calculate benchmark dose (BMD) values from dynamic, high-content zebrafish behavior data that scales for high-throughput chemical screening. To appropriately capture the dynamics of zebrafish response from light to dark stimulus, we summarized time-dependent data using both area under the curve and immediate change at the transition point into two novel metrics that characterized abnormal behavior as a function of chemical concentration. The BMD workflow was applied to calculate BMD 10 values of 1,060 ToxCast chemicals for 24 zebrafish endpoints, including behavior, mortality and morphology. The BMD 10 values provided better precision and separation than LELs for clustering chemicals since they were derived from models that best-fit their concentration-response curves. Clustering analysis revealed behavioral signatures as the most sensitive endpoints. High concordance in chemical activity was observed between ToxCast assays and zebrafish behavioral endpoints, however ToxPi analysis indicated that rankings based on in vitro data was not a reliable predictor of in vivo rankings for lower potency chemicals. The methods developed in this work will enable the use of high-content zebrafish behavioral screening data for BMD analysis in toxicological hazard assessment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Effects of PFOS on the behavior, growth, emergence, and predation susceptibility of larval mosquitoes ( Culex quinquefasciatus )

Per-/polyfluoroalkyl substances (PFAS) have been commonly used over several decades for a variety of products and are very persistent in the environment. However, not much is known about their direct effects on aquatic invertebrates and their ecosystems. We examined the survival, behavior, development, and predation susceptibility of mosquito larvae Culex quinquefasciatus exposed to concentrations of perfluorooctanesulfonic acid (PFOS) ranging from 0.02 to 453.7 µg/L. PFOS exposure resulted in reduced larval survival, with a 48 hour LC50 (concentration with 50 % mortality) of 255.99 µg/L. PFOS exposure also resulted in reduced developmental success and slower maturation to adulthood (and thus slower emergence from the water) compared to control larvae. PFOS also resulted in delays in reaction to prodding stimuli, which were meant to simulate a predator attack, and longer reactions to prodding. Larvae exposed to PFOS also spent more time at the bottom of the water column, rather than at the surface where respiration takes place. Effects of larval mosquito PFOS exposure on predation by unexposed damselfly naiads (genus Ischnura) were not detected. Overall, this research suggests that PFOS impacts mosquito larvae survival, behavior, development, and adult emergence, which could have important implications for food webs or public health given the role of mosquitos as disease vectors.

Food web dynamics↗
DOE OSTI2021

Transcriptional and translational landscape of Candida auris in response to caspofungin

Candida auris has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against C. auris. In this work, we treated two distinct strains of C. auris for 24h with caspofungin, and the cellular responses were evaluated at the morphological, translational and transcriptional levels. We first observed that the echinocandin caused morphological alterations, aggregation of yeast cells, and modifications in the cell wall composition of C. auris. Transcriptomic analysis revealed an upregulation of genes related to the synthesis of the cell wall, ribosome, and cell cycle after exposure to caspofungin. Supporting these findings, the integrated proteomic analysis showed that caspofungin-treated cells were enriched in ribosome-related proteins and cell wall, especially mannoproteins. Altogether, these results provide further insights into the biology of C. auris and expands our understanding regarding the antifungal activity of caspofungin and reveal cellular targets, as the mannose metabolism, that can be further explored for the development of novel antifungals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

In Situ Characterization of Turbine Hydraulic Environment to Support Development of Fish-Friendly Hydropower Guidelines in the Lower Mekong River Region

The Mekong River is one of the most biodiverse rivers on the planet. As a result, many communities located near the river and its tributaries rely on fisheries for sustenance as well as economic viability. Along the Mekong River mainstem, there are plans for 11 new hydropower projects with potentially several hundred smaller hydropower projects along the tributaries. Currently, there is little information to guide construction of fish-friendly hydropower systems. Preliminary guidelines for construction on the mainstem Mekong call for safe upstream and downstream fish passage for 95% of target species. To understand the hydraulic conditions at existing dams in the region, Sensor Fish, a small neutrally buoyant autonomous sensor package capable of measuring and collecting in situ motion and force data, were deployed at Nam Ngum Dam in Lao PDR. The Sensor Fish were released through two turbine units—Unit 1, which contains an older 17.5-MW Francis turbine, and Unit 4, which contains a slightly newer 40-MW Francis turbine. Comparisons were made between the results from the two turbine units at Nam Ngum Dam to results for four hydroelectric dams in the U.S. Pacific Northwest for which live fish survival studies had been conducted. Three of the U.S. dams have Francis-turbine units and the other has a fish-friendly Kaplan turbine. Based on the occurrence of severe acceleration events, the survival rate of juvenile salmonids at a dam like Nam Ngum Dam would be expected to between the 11.1% to 54.1% survival rates experienced at the U.S. with Francis turbines and the 97.0% survival rate at the U.S. dam equipped with fish-friendly Kaplan turbines. Between the newer and older turbine units tested at Nam Ngum Dam, the newer Unit 4 had a higher median nadir pressure of 126 kPaA compared to 99 kPaA for Unit 1. Based on a dose-response relationship for juvenile Chinook salmon, these nadir pressures predict probabilities of mortal injury of 5% for Unit 4 and 12% for Unit 1. With respect to both pressure and acceleration, the older 17.5-MW Francis turbine had more severe hydraulic conditions than the newer 40-MW Francis turbine. Francis turbines, like the ones involved in this study, are the most common type of hydropower turbines in the throughout the world. The results from this study can be used to guide the construction of new hydropower structures and make design and operational changes to existing hydropower structures that will improve fish passage conditions.

Francis turbine, Mekong River, sustainable hydropo↗
DOE OSTI2022

Stochastic agent-based model for predicting turbine-scale raptor movements during updraft-subsidized directional flights

Rapid expansion of wind energy development across the world has highlighted the need to better understand turbine-caused avian mortality. The risk to golden eagles (Aquila chrysaetos) is of particular concern due to their small population size and conservation status. Golden eagles subsidize their flight in part by soaring in orographic updrafts, which can place them in conflict with wind turbines utilizing the same low-altitude wind resource. Understanding the behavior of soaring raptors in varying atmospheric conditions can therefore be relevant to predicting and mitigating their risk of collision. We present a predictive movement model that simulates individual paths of golden eagles during directional flight (such as migration) that is subsidized by orographic updraft. We modeled eagles in a 50 km by 50 km study area in Wyoming containing three wind power plants with documented golden eagle collisions with turbines. The movement model is applicable to any region where ground elevation is known at turbine scale (50 m) and wind conditions are known at facility scale (3 km). For a given set of atmospheric conditions, the model simulates movements of thousands of orographic soaring eagles to produce a density map quantifying the relative probability of eagle presence. We validated the simulated tracks with GPS telemetry data showing four directional tracks made by golden eagles transiting through the area in 2019 and 2020. For each eagle track, validation was performed using the ratio of the model-simulated eagle presence likelihood with uniform eagle presence and the presence computed using directed random-walk movements. We found that the predictive performance of the model was significantly better (likelihood ratio 1) for low-altitude movements than high-altitude movements that can involve thermal-soaring. We employed the model to produce seasonal presence maps for migrating golden eagles. We found significant turbine-level variations in eagle presence between northerly and southerly migration routes through the study area. Overall, the proposed model offers a generalizable, probabilistic, and predictive tool to assist wind energy developers, ecologists, wildlife managers, and industry consultants in estimating the potential for conflict between soaring birds and wind turbines, thereby reducing the need for site-specific data on golden eagle movements.

17 WIND ENERGY↗
DOE OSTI2025

Enhancing carbon storage through proactively managing fire-prone coniferous mountain forests

Mountain ecosystems typically serve as carbon (C) sinks. However, studies also suggest that they could be C sources due to climate warming, drought and insect-related mortality, wildfires, and management actions. We applied the Lund-Potsdam-Jena General Ecosystem Simulator (LPJ-GUESS), a process-based dynamic vegetation-ecosystem model, to investigate the role of ecosystem management in C storage under Mediterranean climate over the 21 st century. We modified LPJ-GUESS to include implementing mechanical thinning by vegetation size classes, components, and types along with a new mechanistic fire-occurrence model that accounts for wind speed and lightning ignition. Simulations show that mechanical thinning or prescribed fire performed 5-20 years in advance of a high-severity wildfire reduced direct wildfire C emissions by 38-66 %. Our results also show that long-term management actions repeated every 5-20 years, including thinning relatively small trees (diameters up to 7 inches or ∼178 mm), can maintain stable C levels in the forest and lower dead-fuel amounts. We found that, although prescribed fire mitigated wildfire severity, ecosystem C storage from reduced wildfire emissions can be outweighed by the added emissions from the prescribed fire themselves. Thinning plus removing and sequestering the thinned biomass can ensure that forests act as net C sinks through the end of the 21 st century. However, addition of prescribed fire is needed to reduce understory and lower the projected extent of high-severity wildfire. Achieving the competing goals of reducing wildfire and making the Sierra Nevada long-term C sink can be advanced through carefully coordinated thinning, sequestration of thinned biomass, and prescribed fire.

Climate solutions↗
DOE OSTI2024

Health and air pollutant emission impacts of net zero CO2 by 2050 scenarios from the energy modeling forum 37 study

Carbon dioxide and non-greenhouse gas air pollutants are emitted from many of the same sources. Decarbonization actions thus typically yield air pollutant emission reductions, resulting in significant air quality benefits. Although several studies have highlighted this connection, including in the context of net zero carbon emission targets, substantial uncertainty remains regarding how alternative technological pathways to this goal will affect the spatial distribution and magnitude of air pollutants. Comprehensive multi-model and multi-scenario analyzes are needed to explore the relative impacts of alternative pathways. Here, our study begins to address this gap by leveraging the results from the recent Energy Modeling Forum 37 inter-model comparison exercise on U.S. decarbonization pathways. Comparing the results of the six teams who submitted air pollutant emissions suggests that strategies that target net zero U.S. carbon emissions would yield significant reductions in many air pollutants, and that this finding is generally robust across pathways. However, some energy sources, such as biomass and fossil fuels with carbon capture, will emit air pollutants and can potentially influence the magnitude, spatial distribution, and even sign of localized air pollutant emission changes. In the second part of this analysis, a simplified air quality and health impacts screening model is used to evaluate the air quality impacts in 2035 of sectoral emission changes from the three models that provided sectoral detail. Relative to a reference scenario, a net zero pathway is estimated to reduce fine particulate matter concentrations across the contiguous U.S., with health benefits from reduced mortality ranging from $\$$65 billion to $\$$250 billion in 2035 alone (2023$\$$s). These benefits would be expected to grow over time as the net zero trajectory becomes more stringent. Both the magnitude of potential benefits and the substantial variation of the projections across models underscore the need for an EMF-like inter-model comparison exercise focused on air quality.

Air pollutants↗
DOE OSTI2012

Health impact assessment of air pollution using a dynamic exposure profile: Implications for exposure and health impact estimates

In both ambient air pollution epidemiology and health impact assessment an accurate assessment of the population exposure is crucial. Although considerable advances have been made in assessing human exposure outdoors, the assessments often do not consider the impact of individual travel behavior on such exposures. Population-based exposures to NO{sub 2} and O{sub 3} using only home addresses were compared with models that integrate all time-activity patterns-including time in commute-for Flanders and Brussels. The exposure estimates were used to estimate the air pollution impact on years of life lost due to respiratory mortality. Health impact of NO{sub 2} using an exposure that integrates time-activity information was on average 1.2% higher than when assuming that people are always at their home address. For ozone the overall estimated health impact was 0.8% lower. Local differences could be much larger, with estimates that differ up to 12% from the exposure using residential addresses only. Depending on age and gender, deviations from the population average were seen. Our results showed modest differences on a regional level. At the local level, however, time-activity patterns indicated larger differences in exposure and health impact estimates, mainly for people living in more rural areas. These results suggest that for local analyses the dynamic approach can contribute to an improved assessment of the health impact of various types of pollution and to the understanding of exposure differences between population groups. - Highlights: Black-Right-Pointing-Pointer Exposure to ambient air pollution was assessed integrating population mobility. Black-Right-Pointing-Pointer This dynamic exposure was integrated into a health impact assessment. Black-Right-Pointing-Pointer Differences between the dynamic and residential exposure were quantified. Black-Right-Pointing-Pointer Modest differences in health impact were found at a regional level. Black-Right-Pointing-Pointer At municipal level larger differences were found, influenced by gender and age.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV)

The high morbidity and mortality associated with SARS-CoV-2 infection, the etiological agent of COVID-19, has had a major impact on global public health. Significant progress has been made in the development of an array of vaccines and biologics, however, the emergence of SARS-CoV-2 variants and breakthrough infections are an ongoing major concern. Furthermore, there is an existing paucity of small-molecule host and virus-directed therapeutics and prophylactics that can be used to counter the spread of SARS-CoV-2, and any emerging and re-emerging coronaviruses. Here, we describe herein our efforts to address this urgent need by focusing on the structure-guided design of potent broad-spectrum inhibitors of SARS-CoV-2 3C-like protease (3CL pro or Main protease), an enzyme essential for viral replication. The inhibitors exploit the directional effects associated with the presence of a gem-dimethyl group that allow the inhibitors to optimally interact with the S4 subsite of the enzyme. Several compounds were found to potently inhibit SARS-CoV-2 and MERS-CoV 3CL proteases in biochemical and cell-based assays. Specifically, the EC50 values of aldehyde 1c and its corresponding bisulfite adduct 1d against SARS-CoV-2 were found to be 12 and 10 nM, respectively, and their CC50 values were >50 μM. Furthermore, deuteration of these compounds yielded compounds 2c/2d with EC50 values 11 and 12 nM, respectively. Replacement of the aldehyde warhead with a nitrile (CN) or an α-ketoamide warhead or its corresponding bisulfite adduct yielded compounds 1g, 1e and 1f with EC50 values 60, 50 and 70 nM, respectively. High-resolution cocrystal structures have identified the structural determinants associated with the binding of the inhibitors to the active site of the enzyme and, furthermore, have illuminated the mechanism of action of the inhibitors. Overall, the high Safety Index (SI) (SI=CC50/EC50) displayed by these compounds suggests that they are well-suited to conducting further preclinical studies.

3-Chymotrypsin-like protease (3CLpro)↗
DOE OSTI2017

Shifts in historical streamflow extremes in the Colorado River Basin

The global phenomenon of climate change-induced shifts in precipitation leading to "wet regions getting wetter" and "dry regions getting drier" has been widely studied. However, the propagation of these changes in atmospheric moisture within stream channels is not a direct relationship due to differences in the timing of how changing precipitation patterns interact with various land surfaces. Streamflow is of particular interest in the Colorado River Basin (CRB) due to the region’s rapidly growing population, projected temperature increases that are expected to be higher than elsewhere in the contiguous United States, and subsequent climate-driven disturbances including drought, vegetation mortality, and wildfire, which makes the region more vulnerable to changes in hydrologic extremes. Here in this study, we determine how streamflow extremes have shifted in the CRB using two statistical methods—the Mann-Kendall trend detection analysis and Generalized Extreme Value (GEV) theorem. We evaluate these changes in the context of key flow metrics that include high and low flow percentiles, maximum and minimum 7-day flows, and the center timing of streamflow using historical gage records representative of natural flows. Monthly results indicate declines of up to 41% for high and low flows during the June to July peak runoff season, while increases of up to 24% were observed earlier from March to April. Finally, our results highlight a key threshold elevation and latitude of 2300 m and 39° North, respectively, where there is a distinct shift in the trend. The spatiotemporal patterns observed are indicative of changing snowmelt patterns as a primary cause of the shifts. Identification of how this change varies spatially has consequences for improved land management strategies, as specific regions most vulnerable to threats can be prioritized for mitigation or adaptation as the climate warms.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

High-performance windows improve thermal survivability of occupants during cold snaps

Exposure to low indoor air temperature is a major contributor to temperature-related mortality during extreme cold events, especially when power outages disrupt operation of space heating systems. This study explores the impact of high-performance windows on the thermal resilience of residential buildings during extreme cold weather and grid power outages, as well as their long-term benefits through energy efficiency and reduced risk of property damage. Building performance simulations were conducted for reference residential buildings in three construction vintages and two major U.S. cities located in cold climate zones, considering two types of extreme cold events: short and severe, and long and milder. Our research found that even houses compliant with current energy codes struggle to maintain safe indoor temperatures for more than a few hours during power outages, necessitating rapid evacuations. High-performance windows can extend the thermal survivability time by up to 3.8 days within a 7-day cold snap and significantly reduce risk of bursting frozen water pipes, depending on the building’s insulation and infiltration level, cold event severity, and occupant vulnerability. This extended thermal safety time is crucial in scenarios where reduced mobility complicates emergency responses in senior housing. In addition to boosting thermal resilience, upgrading older homes with high-performance windows can reduce heating energy consumption by over 18% and cooling energy by 15%. Our findings highlight the need to incorporate thermal resilience assessments into new designs or major retrofits, including the use of typical and extreme weather scenarios and advanced technologies like high-performance windows.

Krelling, Amanda F↗