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At least 1,423 records · Page 79
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage Plasmodium falciparum and Cryptosporidium parvum in cell-culture studies. Target deconvolution in P. falciparum has shown that cladosporin inhibits lysyl-tRNA synthetase (PfKRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both PfKRS1 and C. parvum KRS (CpKRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED 90 = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between PfKRS1 and CpKRS. This series of compounds inhibit CpKRS and C. parvum and Cryptosporidium hominis in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for PfKRS1 and CpKRS vs. (human) HsKRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Fine-scale damage estimates of particulate matter air pollution reveal opportunities for location-specific mitigation of emissions

Fine particulate matter (PM 2.5 ) air pollution has been recognized as a major source of mortality in the United States for at least 25 years, yet much remains unknown about which sources are the most harmful, let alone how best to target policies to mitigate them. Such efforts can be improved by employing high-resolution geographically explicit methods for quantifying human health impacts of emissions of PM 2.5 and its precursors. Here, we provide a detailed examination of the health and economic impacts of PM 2.5 pollution in the United States by linking emission sources with resulting pollution concentrations. We estimate that anthropogenic PM 2.5 was responsible for 107,000 premature deaths in 2011, at a cost to society of $886 billion. Of these deaths, 57% were associated with pollution caused by energy consumption [e.g., transportation (28%) and electricity generation (14%)]; another 15% with pollution caused by agricultural activities. A small fraction of emissions, concentrated in or near densely populated areas, plays an outsized role in damaging human health with the most damaging 10% of total emissions accounting for 40% of total damages. We find that 33% of damages occur within 8 km of emission sources, but 25% occur more than 256 km away, emphasizing the importance of tracking both local and long-range impacts. Our paper highlights the importance of a fine-scale approach as marginal damages can vary by over an order of magnitude within a single county. Information presented here can assist mitigation efforts by identifying those sources with the greatest health effects.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Land–atmosphere feedbacks exacerbate concurrent soil drought and atmospheric aridity

Compound extremes such as cooccurring soil drought (low soil moisture) and atmospheric aridity (high vapor pressure deficit) can be disastrous for natural and societal systems. Soil drought and atmospheric aridity are 2 main physiological stressors driving widespread vegetation mortality and reduced terrestrial carbon uptake. Here, we empirically demonstrate that strong negative coupling between soil moisture and vapor pressure deficit occurs globally, indicating high probability of cooccurring soil drought and atmospheric aridity. Using the Global Land Atmosphere Coupling Experiment (GLACE)-CMIP5 experiment, we further show that concurrent soil drought and atmospheric aridity are greatly exacerbated by land–atmosphere feedbacks. The feedback of soil drought on the atmosphere is largely responsible for enabling atmospheric aridity extremes. In addition, the soil moisture–precipitation feedback acts to amplify precipitation and soil moisture deficits in most regions. CMIP5 models further show that the frequency of concurrent soil drought and atmospheric aridity enhanced by land–atmosphere feedbacks is projected to increase in the 21st century. Significantly, land–atmosphere feedbacks will greatly increase the intensity of both soil drought and atmospheric aridity beyond that expected from changes in mean climate alone.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Targeted polyelectrolyte complex micelles treat vascular complications in vivo

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92a EC-TG /Apoe –/– ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe –/– mice. We tested the therapeutic effectiveness of the VCAM-1–targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1–targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti–miR-92a therapy in treating atherosclerosis and stenosis in Apoe –/– mice is markedly enhanced by the VCAM-1–targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

No evidence of canopy-scale leaf thermoregulation to cool leaves below air temperature across a range of forest ecosystems

Understanding and predicting the relationship between leaf temperature (T leaf ) and air temperature (T air ) is essential for projecting responses to a warming climate, as studies suggest that many forests are near thermal thresholds for carbon uptake. Based on leaf measurements, the limited leaf homeothermy hypothesis argues that daytime T leaf is maintained near photosynthetic temperature optima and below damaging temperature thresholds. Specifically, leaves should cool below T air at higher temperatures (i.e., > ~25–30°C) leading to slopes <1 in T leaf /T air relationships and substantial carbon uptake when leaves are cooler than air. This hypothesis implies that climate warming will be mitigated by a compensatory leaf cooling response. A key uncertainty is understanding whether such thermoregulatory behavior occurs in natural forest canopies. We present an unprecedented set of growing season canopy-level leaf temperature (T can ) data measured with thermal imaging at multiple well-instrumented forest sites in North and Central America. Our data do not support the limited homeothermy hypothesis: canopy leaves are warmer than air during most of the day and only cool below air in mid to late afternoon, leading to T can /T air slopes >1 and hysteretic behavior. We find that the majority of ecosystem photosynthesis occurs when canopy leaves are warmer than air. Using energy balance and physiological modeling, we show that key leaf traits influence leaf-air coupling and ultimately the T can /T air relationship. Canopy structure also plays an important role in T can dynamics. Future climate warming is likely to lead to even greater T can , with attendant impacts on forest carbon cycling and mortality risk.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry–based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC 50 cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets.

Science & Technology - Other Topics↗
DOE OSTI2026

Divergent trait controls on soluble sugars and starch underlie global strategies of tree carbohydrate storage

Nonstructural carbohydrate (NSC) stores buffer tree metabolism, osmotic regulation, and defense, thereby mediating tolerance and survival under climate extremes. Yet, the functional and evolutionary determinants of interspecific variation in NSC remain elusive, limiting understanding and prediction of forest carbon allocation and mortality under global change. Here, we present a cross-species synthesis of NSC concentrations across multiple organs for 281 woody species from 102 mixed forest communities worldwide, where we quantified species-specific deviations from community means to disentangle intrinsic trait effects from environmental and methodological variation. We found phylogenetic signals in NSC deviations, with coniferous gymnosperms and evergreen species consistently maintaining lower stem soluble sugars and starch concentrations than co-occurring angiosperms and deciduous species, respectively. A global pattern emerged where greater stomatal sensitivity to leaf water potential was associated with declines in the relative concentrations of both sugars and starch. In contrast, xylem hydraulic safety traits showed weak and organ-dependent relationships with NSC concentrations. Sugars increased with photosynthetic capacity and declined with wood density, whereas starch showed the reverse pattern, which aligned with the distinct functional-metabolic roles of sugars and starch. By integrating trait-based ecology with a community-centered framework, our study provides global evidence that stomatal regulation, photosynthetic capacity, specific leaf area, and wood density jointly govern interspecific NSC variation, through contrasting effects on sugars and starch. These are among the most broadly measured traits globally, thus the emergent carbohydrate–trait relationships can have broad applications toward understanding and predicting forest growth and survival under climate change.

tropic system↗
DOE OSTI2011

Efficacy of Single-Suture Incision Closures in Tagged Juvenile Chinook Salmon Exposed to Simulated Turbine Passage

Reductions in the size of acoustic transmitters implanted in migrating juvenile salmonids have resulted in the use of a shorter incision-one that may warrant only a single suture for closure. However, it is not known whether a single suture will sufficiently hold the incision closed when fish are decompressed and when outward pressure is placed on the surgical site during turbine passage through hydroelectric dams. The objective of this study was to evaluate the effectiveness of single-suture incision closures on five response variables in juvenile Chinook salmon Oncorhynchus tshawytscha that were subjected to simulated turbine passage. An acoustic transmitter (0.43 g in air) and a passive integrated transponder tag (0.10 g in air) were implanted in each fish; the 6-mm incisions were closed with either one suture or two sutures. After exposure to simulated turbine passage, none of the fish exhibited expulsion of transmitters. In addition, the percentage of fish with suture tearing, incision tearing, or mortal injury did not differ between treatments. Expulsion of viscera through the incision was higher among fish that received one suture (12%) than among fish that received two sutures (1%). The higher incidence of visceral expulsion through single-suture incisions warrants concern. Consequently, for cases in which tagged juvenile salmonidsmay be exposed to turbine passage, we do not recommend the use of one suture to close 6-mm incisions associated with acoustic transmitter implantation.

13 HYDRO ENERGY↗
DOE OSTI2014

Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na + , K + , Ca 2+ , and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na + , Ca 2+ , and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na + , Ca 2+ , K + , and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Estimating Cohort Survival through Tributaries for Salmonid Populations with Variable Ages at Migration

Abstract Survival of juvenile anadromous Pacific salmonids from their earliest age of seaward movement (“out-migration”) through the tributaries that connect their rearing grounds to larger-order rivers (“cohort survival”) is an important yet often unmonitored factor in the complex life history of these species. Populations with variable age at out-migration (e.g., steelhead Oncorhynchus mykiss) or multiple juvenile rearing strategies (e.g., Chinook Salmon O. tshawytscha) raise particular challenges in survival monitoring. A multiple-state release–recapture model is presented to estimate cohort survival for salmonid species with variable age at out-migration and demonstrated in two case studies. Annual releases of fish tagged with passive integrated transponder (PIT) tags from the same brood year (cohort) and their detections by instream PIT-tag detection arrays in tributaries and at hydroelectric dams are used to estimate survival through tributaries and the age composition of juvenile migrants reaching downstream sites. The 2010 cohort of Chinook Salmon from the Chiwawa River in Washington State had estimated survival of 0.59 to the middle Wenatchee River array in Tumwater Dam Reservoir (river distance of 30 km) and 0.12 to McNary Dam (364 km) on the Columbia River. The age composition shifted from 60.1% subyearlings at the Wenatchee River array to 100% yearlings at McNary Dam, reflecting the use of the Wenatchee River as a nonnatal rearing area, whereas McNary Dam is in the migratory corridor. The 2010 cohort of steelhead from the Twisp River in Washington State had estimated survival from the yearling stage of 0.30 to Rocky Reach Dam (146 km from the Twisp River mouth) on the Columbia River and 0.17 to McNary Dam (439 km). The low survival to the Columbia River resulted from both mortality and adoption of a resident life history and reflects the diverse population structure in the Twisp River. Received February 4, 2015; accepted June 11, 2015

Buchanan, Rebecca A.↗
DOE OSTI2017

Choosing a reliability inspection plan for interval censored data

Reliability test plans are important for producing precise and accurate assessment of reliability characteristics. This paper explores different strategies for choosing between possible inspection plans for interval censored data given a fixed testing timeframe and budget. A new general cost structure is proposed for guiding precise quantification of total cost in inspection test plan. Multiple summaries of reliability are considered and compared as the criteria for choosing the best plans using an easily adapted method. Different cost structures and representative true underlying reliability curves demonstrate how to assess different strategies given the logistical constraints and nature of the problem. Results show several general patterns exist across a wide variety of scenarios. Given the fixed total cost, plans that inspect more units with less frequency based on equally spaced time points are favored due to the ease of implementation and consistent good performance across a large number of case study scenarios. Plans with inspection times chosen based on equally spaced probabilities offer improved reliability estimates for the shape of the distribution, mean lifetime, and failure time for a small fraction of population only for applications with high infant mortality rates. The paper uses a Monte Carlo simulation based approach in addition to the common evaluation based on the asymptotic variance and offers comparison and recommendation for different applications with different objectives. Additionally, the paper outlines a variety of different reliability metrics to use as criteria for optimization, presents a general method for evaluating different alternatives, as well as provides case study results for different common scenarios.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2016

Survival Rates of Out-Migrating Yearling Chinook Salmon in the Lower Columbia River and Plume after Exposure to Gas-Supersaturated Water

Abstract In 2011, unusually high flows caused total dissolved gas (TDG) levels in the Columbia River, USA, to escalate well above the 120% regulatory limit that was imposed to prevent harmful impacts to aquatic organisms. After observing gas bubble trauma (GBT) in dead yearling Chinook Salmon Oncorhynchus tshawytscha (smolts) held in tanks, we compared estimated survival rates of acoustic-tagged in-river-migrating (IR) and transported (TR) smolts that were released below Bonneville Dam prior to and during the period of elevated TDG (>120%). The log odds of estimated daily survival in the lower river and plume was significantly lower for IR smolts that were released during elevated TDG (maximum possible exposure = 134%) than for IR smolts released when TDG was less than 120%. The TR smolts that were released 10–13 km below Bonneville Dam during elevated TDG had lower maximum possible exposure levels (126% TDG), and the log odds of estimated daily survival in the lower river and plume did not differ from that of TR smolts released when TDG was less than 120%. Direct mortality due to GBT is probably reduced in natural settings relative to laboratory experiments because smolts can move to deeper water, where pressure keeps gasses in solution, and can migrate downstream of the spillway, where TDG levels decrease as the river returns to equilibrium with the atmosphere. However, initially nonlethal GBT may reduce survival rates by increasing smolt susceptibility to predation and infection. Although our findings are limited by the observational nature of the study, our analysis is the first direct assessment of gas supersaturation's potential influence on survival of free-ranging smolts in the river and coastal ocean below a large dam. Experiments using simultaneous releases of control and gas-exposed groups are warranted and should consider the possibility that the chronic effects of TDG exposure on survival are important and persist into the early marine period. Received October 5, 2015; accepted August 18, 2016 Published online October 24, 2016

Brosnan, Ian G. (ORCID:0000000325094325)↗
DOE OSTI2021

Radium Dial Workers: Back to the Future

This report reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. The mortality experience of 3,276 radium dial painters and handlers employed between 1913-1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2024

The ICRP, MELODI, and ALLIANCE workshop on effects of ionizing radiation exposure in offspring and next generations: a summary of discussions

Task Group 121 – Effects of ionizing radiation exposure in offspring and next generations – is a task group under the Committee 1 of the International Commission on Radiological Protection (ICRP), approved by the Main Commission on 18th November 2021. The main goals of Task Group 121 are to (1) review and update the scientific literature of relevance to radiation-related effects in the offspring of parent(s) exposed to ionizing radiation in both human and non-human biota; (2) to assess preconceptional and intrauterine effects of radiation exposure and related morbidity and mortality; and, (3) to provide advice about the level of evidence and how to consider these preconceptional and postconceptional effects in the system of radiological protection for humans and non-human biota. The Task Group is reviewing relevant literature since Publication 90 ‘Biological effects after prenatal irradiation (embryo and fetus)’ (2003) and will include radiation-related effects on future generations in humans, animals, and plants. This review will be conducted to account for the health effects on offspring and subsequent generations in the current system of radiological protection. Radiation detriment calculation will also be reviewed. Finally, preliminary recommendations will be made to update the integration of health effects in offspring and next generations in the system of radiological protection. A Workshop, jointly organized by ICRP Task Group 121 and European Radiation Protection Research Platforms MELODI and ALLIANCE was held in Budapest, Hungary, from 31st May to 2nd June 2022. Participants discussed four important topics: (1) hereditary and epigenetic effects due to exposure of the germ cell line (preconceptional exposure), (2) effects arising from exposure of the embryo and fetus (intrauterine exposure), (3) transgenerational effects on biota, and (4) its potential impact on the system of radiological protection. Based on the discussions and presentations during the breakout sessions, newer publications, and gaps on the current scientific literature were identified. For instance, there are some ongoing systematic reviews and radiation epidemiology reviews of intrauterine effects. There are newer methods of Monte Carlo simulation for fetal dosimetry, and advances in radiation genetics, epigenetics, and radiobiology studies. While the current impact of hereditary effects on the global detriment was reported as small, the questions surrounding the effects of radiation exposure on offspring and the next generation are crucial, recurring, and with a major focus on exposed populations. Here, this article summarizes the workshop discussions, presentations, and conclusions of each topic and introduces the special issue of the International Journal of Radiation Biology resulting from the discussions of the meeting.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2014

A self-consistent method to assess air quality co-benefits from U.S. climate policies

Air quality co-benefits can possibly reduce the costs of greenhouse gas mitigation. However, whereas many studies of the cost of greenhouse gas mitigation model the macroeconomic welfare impacts of mitigation, most studies of air quality co-benefits do not. We enable a U.S. computable general equilibrium economic model previously linked to an air quality modeling system and enhance it to represent the economy-wide welfare impacts of fine particulate matter. We introduce a first application of this method to explore the efficiency and distributional implications of a Clean Energy Standard (CES) and a Cap and Trade (CAT) program that both reduce CO 2 emissions by 10% in 2030 relative to 2006. We find that co-benefits from fine particulate matter reduction (median $\$$6; $\$$2 to $\$$10/tCO 2 ) completely offset policy costs by 110% (40% to 190%), transforming the net welfare impact of the CAT into a gain of $\$$1 (-$\$$5 to $\$$7) billion 2005 $\$$. For the CES, the corresponding co-benefit (median $\$$8; $\$$3 to $\$$14/tCO 2 ) is a smaller fraction (median 5%; 2% to 9%) of its higher policy cost. The eastern United States garners 78% and 71% of co-benefits for the CES and CAT, respectively. By representing the effects of pollution-related morbidities and mortalities as an impact to labor and the demand for health services, we find that the welfare impact per unit of reduced pollution varies by region. These interregional differences can enhance the preference of some regions, such as Texas, for a CAT over a CES, or switch the calculation of which policy yields higher co-benefits, compared with an approach that uses one valuation for all regions. This framework could be applied to quantify consistent air quality impacts of other pricing instruments, subnational trading programs, or green tax swaps.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

A Multi-Analysis Approach for Estimating Regional Health Impacts from the 2017 Northern California Wildfires

In the evening of October 8 and early hours of October 9, 2017, high winds in Northern California downed trees and power lines, igniting some of the most devastating wildfires the state had seen, and within hours unhealthy air quality impacted millions of people. We simulated these air quality conditions using fire detection information from the MODIS, VIIRS, and GOES-16 ABI satellite instruments, and applying a set of three WRF–CMAQ simulations, one data fusion, and three machine learning methods. We investigated using the 5-min available GOES-16 fire detection data to simulate timing of fire activity to allocate emissions hourly for the WRF-CMAQ air quality modeling system. Interestingly, this approach did not necessarily improve results compared to the baseline case, which used a default time profile. However, this approach was key to simulating the initial 12-hr explosive fire activity and smoke impacts. The WRF-CMAQ simulations compared well with observational data for the October 8-15 time period and tended to overestimate concentrations October 16-20. To improve these results, we applied three machine learning algorithms. We also had a unique opportunity to evaluate results with temporary monitors deployed specifically for wildfires, and performance was markedly different. For example, at the permanent monitoring locations, the WRF-CMAQ simulations had a Pearson correlation of 0.65, and the data fusion approach improved this (Pearson correlation = 0.95), while at the temporary monitor locations across the WRF-CMAQ, data fusion, and machine learning datasets, the best Pearson correlation was 0.5. The data fusion and machine learning results were biased low and WRF-CMAQ results were biased high. Finally, we applied the optimized PM2.5 exposure estimate in a short-term exposure-response function. Total estimated mortality attributable to PM2.5 exposure during the smoke episode was 83 (95% confidence interval: 0, 196) with 47% of these deaths attributable to wildland fire smoke.

O'Neill, Susan↗
DOE OSTI2014

Initial Characterization of Embryonic Development in North American Burbot

Abstract Declining wild populations and increasing commercial interest are encouraging development of aquaculture methods for the North American Burbot Lota lota maculosa. A current focus of Burbot aquaculture research is reducing high mortality that is typically associated with culture of Burbot embryos and larvae. However, no Burbot embryonic or larval staging systems are currently available to provide a comparative baseline for studies of these life stages. To help address this gap, we examined Burbot embryonic development from egg fertilization until the onset of the larval period at first feeding. Ontogeny was characterized using diagnostic morphological features visible with stereo microscopy. Six developmental periods were characterized (cleavage, blastula, gastrula, segmentation, swim bladder inflation, and first feeding), along with 15 developmental stages. Water temperature ranged from 3°C to 5°C for the duration of this study. Cleavage cycles were approximately 8 h/division. Segmentation began at 12 d postfertilization (DPF) and continued until first hatch at 33 DPF. First feeding was observed at 45 DPF, 12 d after first hatch. Results presented here are expected to help refine Burbot culture methodology and research efforts aimed at conservation, management, and commercial production. Future research should use additional cohorts and expose embryos to a range of culture conditions to better understand the factors governing embryonic survival and variability in the timing of events during development.

Egan, Joshua P.↗
DOE OSTI2019

Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection

Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.

60 APPLIED LIFE SCIENCES↗