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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 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Intradiencephalon injection of histamine inhibited the recovery of locomotor function of spinal cord injured zebrafish

Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI. Immunofluorescence results showed that intradiencephalon HA administration increased the activated microglia 3 days post injury (dpi), promoted the proliferation of radial glial cells at 7 dpi and affected the morphology of radial glial cells at 11 dpi. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that intradiencephalon HA administration also reduced the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor1 (IGF-1) at the lesion site, however, had no effect on the expression of pro-inflammatory factors such as TNF-alpha and IL-1 beta. Hence, our data suggested that exogenous intradiencephalon HA retarded locomotor recovery in spinal cord injured zebrafish via modulating the repair microenvironment. - Highlights: • A novel model to study the effect of supraspinal signals on repair of SCI zebrafish. • Exogenous HA administration suppresses the locomotor function recovery after SCI. • Exogenous HA administration modulates the repair microenvironment after SCI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Zidovudine protects hyperosmolarity-stressed human corneal epithelial cells via antioxidant pathway

Highlights: • Zidovudine reduces IL-6 production in corneal cells via ROS and NFkB inhibition. • Zidovudine increases viability of corneal cells cultured in hyperosmolar conditions. • Zidovudine may serve as a novel therapeutic in the treatment of Dry Eye Disease. Dry Eye Disease (DED) is a very common disorder that can result in severe disability and vision loss. Although the pathogenesis of DED is not fully understood, hyperosmolarity, inflammation, and tear film instability are recognized as hallmarks of DED. Recently, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a class of medication used to treat HIV, have been shown to inhibit inflammation in a mouse model of retinal atrophy. In this study, we investigated whether Zidovudine (AZT) can inhibit human corneal epithelial cell (HCEC) inflammatory responses under hyperosmotic conditions. HCECs were cultured in hyperosmotic media containing AZT. Cell viability, cytokine production, and reactive oxygen species (ROS) production were measured. We found that AZT decreased nuclear factor kappa B (NF-κB) and Interleukin-6 (IL-6) levels, increased Superoxide Dismutase 1 (SOD1) production, decreased ROS production, and increased cell viability. These results support the novel use of AZT in the reduction of ocular surface inflammation and the promotion of corneal health in the context of DED.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA FIRRE/NF-kB feedback loop contributes to OGD/R injury of cerebral microglial cells

Stroke is one of the leading causes for serious long-term neurological disability. LncRNAs have been investigated to be dysregulated in ischemic stroke. However, the underlying mechanisms of some specific lncRNAs have not been clearly clarified. To determine lncRNA-mediated regulatory mechanism in ischemic stroke, we constructed OGD/R injury model of cerebral microglial cells. Microarray analysis was carried out and analyzed that lncRNA functional intergenic repeating RNA element (FIRRE) was associated with OGD/R injury. Based on the molecular biotechnology, we demonstrated that FIRRE could activate NF-kB signal pathway. Meanwhile, the activated NF-kB promoted FIRRE expression in OGD/R-treated cerebral microglial cells. Therefore, FIRRE and NF-kB formed a positive feedback loop to promote the transcription of NLRP3 inflammasome, thus contributed to the OGD/R injury of cerebral microglial cells. All findings in this study may help to explore novel and specific therapeutic target for ischemic stroke.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Autophagy induced by type III secretion system toxins enhances clearance of Pseudomonas aeruginosa from human corneal epithelial cells

Highlights: • Ocular P. aeruginosa isolates induce autophagy in human corneal epithelial cells. • T3SS mutants were defective in inducing autophagy and becn1 expression. • T3SS (−)ve strains were less sensitive to external autophagy modulators. • Pro-autophagic role of T3SS regulates intracellular survival of P. aeruginosa. Corneal ulcers caused by Pseudomonas aeruginosa may lead to severe visual disability due to impaired bacterial clearance from corneal tissues. Our purpose was to study the role of autophagy in the intracellular clearance of P. aeruginosa from human corneal epithelial cells (HCET) and its regulation by the bacterial type III secretion system (T3SS) toxins. Nine different corneal ulcer isolates of P. aeruginosa, PAO1 and T3SS mutants of PAO1 were used to infect HCET cells. Induction of autophagy (Immunofluorescence and Western blot) and pro-inflammatory gene expression (real time PCR) by P. aeruginosa and the role of autophagy in intracellular bacterial clearance were studied in the context of T3SS genotypes. The clinical isolates and PAO1 induced autophagy irrespective of the T3SS genotype, whereas the T3SS mutants were relatively defective in inducing autophagy and becn1 gene expression. External induction of autophagy significantly reduced the intracellular load of P. aeruginosa strains that were associated with worst clinical outcomes. The T3SS negative isolate and PAO1ΔexoST were less sensitive to pharmacological modulation of autophagy and had relatively higher replication potential, suggesting a possible mechanism of bacterial survival in the absence of T3SS toxins. Overall, our results highlight a selective role for autophagy in bacterial clearance from corneal epithelial cells and emphasize the pro-autophagic role of bacterial toxins in the context of corneal ulcers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Tetramethylpyrazine ameliorates experimental autoimmune encephalomyelitis by modulating the inflammatory response

Highlights: • TMP improves clinical scores in EAE mice. • TMP decreases demyelination in EAE mice. • TMP reduces inflammatory infiltration and glial activation in EAE mice. • TMP reduces NLRP3 inflammasome expression and modulates the Th1/Th17/Th2 response. Multiple sclerosis (MS) is a disabling inflammatory and demyelinating disorder of the central nervous system. Tetramethylpyrazine (TMP) has been demonstrated to ameliorate cerebral ischemic injury and spinal cord injury by inhibiting inflammatory cell activation and pro-inflammatory cytokine production. However, the effects of TMP on MS have not been studied. In this study, we evaluated the effects of TMP on the inflammatory response in experimental autoimmune encephalomyelitis (EAE), which is an animal model of MS. TMP (30 mg/kg) treatment significantly reduced the expression levels of NLR Family, Pyrin Domain-Containing 3 Protein inflammasome and caspase-1and decreased inflammatory infiltration and glial activation. Moreover, TMP (30 mg/kg) suppressed the expression of pro-inflammatory cytokines (interleukin-18 [IL-18] and IL-17) and promoted the expression of an anti-inflammatory cytokine (IL-10). The reduced inflammatory response resulted in improvement in clinical scores and decreased demyelination in EAE mice. Therefore, our results demonstrate that TMP (30 mg/kg) improved functional recovery in part by reducing inflammation in EAE mice. TMP may be a potential therapeutic agent for MS therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Deletion of JDP2 improves neurological outcomes of traumatic brain injury (TBI) in mice: Inactivation of Caspase-3

Highlights: • JDP2 deficiency attenuates cognitive performance induced by TBI in mice. • JDP2 deficiency attenuates apoptosis in cortex of TBI mice. • JDP2 increases Caspase-3 activation to promote inflammation and apoptosis in LPS-stimulated astrocytes. Traumatic brain injury (TBI) is a major cause of death and disability, also resulting in long-term serious neurological impairment in survivors. However, the pathogenesis of TBI has not been fully understood. Jun dimerization protein 2 (JDP2) is a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. JDP2 plays essential roles in various cellular processes, including differentiation, apoptosis, senescence and aging. In the study, we attempted to explore the effects of JDP2 on TBI progression both in vivo and in vitro. The wild type (WT) and JDP2 knockout (KO) mice were employed in our study and were subjected to TBI. The results showed that JDP2-deficient mice exhibited improved cognitive functions in TBI mice. The inflammatory cytokines, glial amount and apoptosis, as well as the protein of cleaved Caspase-3 were significantly increased after TBI in WT mice, and all these up-regulation were significantly mitigated by JDP2 knockout in mice. We also found that TBI induced JDP2 expression in hippocampus of mice. Lipopolysaccharide (LPS) also stimulated JDP2 expression levels in astrocytes isolated from WT mice, indicating the critical role of JDP2 in TBI. Suppressing Caspase-3 activation could reduce LPS-induced inflammation in astrocytes. Consistent with the results in vivo, LPS-induced inflammatory response and apoptosis were reversed by JDP2 deficiency in cells. Notably, we found that over-expressing JDP2 could further promoted inflammation, apoptosis and Caspase-3 activation induced by LPS. Collectively, JDP2 knockout effectively attenuate TBI in vivo and in vitro through blocking Caspase-3 activation, providing a potential therapeutic target for TBI or even other neurological disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Wucherria bancrofti glutathione S-Transferase: Insights into the 2.3 Å resolution X-ray structure and function, a therapeutic target for human lymphatic filariasis

Highlights: • Crystal structure of W. bancrofti GST with its cofactor GSH at 2.3 Å resolution was determined. • Structural comparison against human GST reveals distinct differences in substrate binding sites. • GST xenobiotic binding site is more substrate accessible and reveals non-catalytic binding sites. • Enzyme kinetic assays reveal that antifilarial drug Diethyl carbamazine binds in an uncompetitive manner. • Structural features provide insights to support future design of parasite specific inhibitors. The notoriety of parasitic nematode survival is directly related to chronic pathogenicity, which is evident in human lymphatic filariasis. It is a disease of poverty which causes severe disability affecting more than 120 million people worldwide. These nematodes down-regulate host immune system through a myriad of strategies that includes secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs). Earlier studies have shown Wuchereria bancrofti GST to be a potential therapeutic target. Parasite GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Hence, the crystal structure of WbGST along with its cofactor GSH at 2.3 Å resolution was determined. Structural comparisons against host GST reveal distinct differences in the substrate binding sites. The parasite xenobiotic binding site is more substrate/solvent accessible. The structure also suggests the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. The structure of WbGST also provides a case for the role of the π-cation interaction in stabilizing catalytic Tyr compared to stabilization interactions described for other GSTs. Hence, the obtained information regarding crucial differences in the active sites will support future design of parasite specific inhibitors. Further, the study also evaluates the inhibition of WbGST and its variants by antifilarial diethylcarbamazine through kinetic assays.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Expression profile analysis of differentially expressed genes in ruptured intracranial aneurysms: In search of biomarkers

Highlights: • Bioinformatics can identify potential biomarkers of ruptured intracranial aneurysm. • BASP1, CD74, CEBPB, ECHDC2, GZMK, HLA-DRB3, KLHL3, SLC2A3 & SOCS3 affect IA rupture. • DEGs are involved in antigen processing and presentation and immune response. • Vascular brain injury affects gene expression in IA tissue. Intracranial aneurysms (IAs) result from the bulging of arterial walls secondary to several factors such as flow, vessel morphology, and genetics. Subarachnoid hemorrhage occurs when such walls rupture, leading to high disability and mortality. Despite numerous investigations pertaining to the relationship between geometric characteristics and IA rupture, only a few have obtained consistent results. This study aimed to further identify the potential genes associated with the pathogenesis of IAs, which may provide novel molecular biomarkers. We downloaded and reanalyzed six datasets, which were divided into four groups. IA walls and blood samples were screened for differentially expressed genes (DEGs); then, functional and pathway enrichment analyses were conducted. In total, 158 common DEGs were identified from Groups 1–3 and 396 genes (187 upregulated and 209 downregulated genes) were differentially expressed in Group 4. The functional analysis revealed that the DEGs were mainly associated with the major histocompatibility complex class II protein complex and antigen processing and presentation. Finally, we identified nine key genes, both in aneurysm tissue samples and blood samples, of which three were mostly associated with the progression and rupture of IAs. Bioinformatics was used to analyze the datasets of the ruptured IAs and identify potential biomarkers, which may provide information for the early detection and treatment of IAs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium. The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via mtCOJO, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

New insights into fuel blending effects: Intermolecular chemical kinetic interactions affecting autoignition times and intermediate-temperature heat release

Fuel blending effects on chemically-dominated fuel properties, such as gasoline anti-knock quality, are influenced by fundamental chemical kinetic interactions between the blending agent and the base fuel. Historically, quantification of such interactions has focused on changes to the radical pool, including $\dot{O}$H and HO 2 , while intermolecular interactions pertaining to carbonated, non-fuel-specific intermediates are typically overlooked. In this regard, this work aims to derive new insight into intermolecular chemical kinetic interactions that are intrinsic to fuel blending effects via a case study on blends of 0–30% ethanol (by volume) into FGF-LLNL (a multi-component gasoline surrogate for FACE-F research gasoline) using a rapid compression machine at a diluted/stoichiometric fuel loading, compressed pressure of 40 bar and low- to intermediate-temperature regimes that are representative of boosted SI engine operation. Ethanol blending effects on the intermediate temperature heat release (ITHR) of FGF-LLNL are characterized using experimental measurements, where ethanol is found to promote the extent of ITHR and suppress the transition from ITHR to main ignition. Chemical kinetic modeling is undertaken using a recently updated gasoline surrogate model. Sensitivity analyses on ITHR characteristics further corroborate the ethanol blending effects, and highlight the significant dependence of ITHR on both fuel-specific and non-fuel-specific reactions. An approach allowing comprehensive characterization of the complex intermolecular chemical kinetic interactions between constitutes in a fuel blend is then proposed. Application of the approach to FGF-LLNL/E0–E30 reveals that ethanol perturbs the heat release and autoignition characteristics of FGF-LLNL not only by directly changing the $\dot{O}$H and HO 2 radical pools via fuel-specific reactions, but also through intermolecular interactions where participating intermediates can be produced and consumed by various sub-chemistries. Disabling the intermolecular interactions in carbonated species between ethanol and FGF-LLNL sub-chemistries leads to somewhat slower ITHR evolution and lower ignition reactivity. The role of the individual intermolecular interaction is also characterized using the proposed approach. Lastly, implications of intermolecular interactions for future studies that aim to improve model performance are highlighted, where it is found that further investigations on the core C0-C4 chemistry are needed for developing highly accurate chemistry models for complex fuel blends.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Probing intermediate temperature heat release in autoignition of C3-C4 iso-alcohol/gasoline blends

In this work, we report an experimental and modeling study on the blending effects of C3–C4 iso-alcohols, namely iso-propanol and iso-butanol, on the characteristics of intermediate temperature heat release (ITHR) for a research-grade gasoline (FACE-F) in a rapid compression machine operating at diluted/stoichiometric fuel loading, compressed pressure of 43 bar, and compressed temperatures from 700 to 970 K. Changes in ITHR behavior are characterized through ITHR extent and evolution at 0 to 30 vol% iso-alcohol blending levels. Experimental observations reveal the strong promoting and decelerating effects on ITHR extent and evolution, respectively, within the low-temperature regime for both iso-alcohols, with stronger effects seen for iso-propanol; within the intermediate-temperature regime, the influence of both iso-alcohols diminishes greatly. Comprehensive chemical kinetic modeling is undertaken using a recently developed gasoline surrogate/alcohol model in conjunction with a five-component gasoline surrogate (FGF-LLNL), with good agreement obtained with the experiments for all the blends. Sensitivity, rate of production and flux analyses highlight the importance of chemical kinetic interactions via both fuel-specific and non-fuel-specific reactions. Disabling all the chemical kinetic interactions between iso-alcohol and FGF-LLNL in carbonated/non-fuel-specific species leads to somewhat extended ITHR duration and reduced ignition reactivity. Direct comparison between FGF-LLNL/iso-propanol and FGF-LLNL/iso-butanol blends is also made, where iso-propanol and iso-butanol are found to influence ITHR characteristics via significantly different chemical kinetic interactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Optimization using pathwise algorithmic derivatives of electromagnetic shower simulations

Among the well-known methods to approximate derivatives of expectancies computed by Monte-Carlo simulations, averages of pathwise derivatives are often the easiest one to apply. Computing them via algorithmic differentiation typically does not require major manual analysis and rewriting of the code, even for very complex programs like simulations of particle-detector interactions in high-energy physics. However, the pathwise derivative estimator can be biased if there are discontinuities in the program, which may diminish its value for applications. This work integrates algorithmic differentiation into the electromagnetic shower simulation code HepEmShow based on G4HepEm, allowing us to study how well pathwise derivatives approximate derivatives of energy depositions in a sampling calorimeter with respect to parameters of the beam and geometry. We found that when multiple scattering is disabled in the simulation, means of pathwise derivatives converge quickly to their expected values, and these are close to the actual derivatives of the energy deposition. Additionally, we demonstrate the applicability of this novel gradient estimator for stochastic gradient-based optimization in a model example.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

The dark side of photovoltaic — 3D simulation of glare assessing risk and discomfort

Photovoltaic (PV) systems form an important force in the implementation of renewable energies, but as we all know, the force has always its dark side. Besides efficiency considerations and discussions about architectures of power distribution networks, the increasing numbers of installations of PV systems for implementing renewable energies have secondary effects. PV systems can generate glare due to optical reflections and hence might be a serious concern. On the one hand, glare could affect safety, e.g. regarding traffic. On the other hand, glare is a constant source of discomfort in vicinities of PV systems. Hence, assessment of glare is decisive for the success of renewable energies near municipalities and traffic zones for the success of solar power. Several courts decided on the change of PV systems and even on their de-installation because of glare effects. Thus, location-based assessments are required to limit potential reflections and to avoid risks for public infrastructure or discomfort of residents. The question arises on how to calculate reflections accurately according to the environment's topography. Our approach is founded in a 3D-based simulation methodology to calculate and visualize reflections based on the geometry of the environment of PV systems. This computational model is implemented by an interactive tool for simulation and visualization. Hence, project planners receive flexible assistance for adjusting the parameters of solar panels amid the planning process and in particular before the installation of a PV system. - Highlights: • Solar panels cause glare that impacts neighborhoods and traffic infrastructures. • Glare might cause disability and discomfort. • 3D environment for the calculation of glare • Interactive tool to simulate and visualize reflections • Impact assessment of solar power plant farms.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Health impact assessment of transport policies in Rotterdam: Decrease of total traffic and increase of electric car use

Background: Green house gas (GHG) mitigation policies can be evaluated by showing their co-benefits to health. Method: Health Impact Assessment (HIA) was used to quantify co-benefits of GHG mitigation policies in Rotterdam. The effects of two separate interventions (10% reduction of private vehicle kilometers and a share of 50% electric-powered private vehicle kilometers) on particulate matter (PM{sub 2.5}), elemental carbon (EC) and noise (engine noise and tyre noise) were assessed using Years of Life Lost (YLL) and Years Lived with Disability (YLD). The baseline was 2010 and the end of the assessment 2020. Results: The intervention aimed at reducing traffic is associated with a decreased exposure to noise resulting in a reduction of 21 (confidence interval (CI): 11–129) YLDs due to annoyance and 35 (CI: 20–51) YLDs due to sleep disturbance for the population per year. The effects of 50% electric-powered car use are slightly higher with a reduction of 26 (CI: 13–116) and 41 (CI: 24–60) YLDs, respectively. The two interventions have marginal effects on air pollution, because already implemented traffic policies will reduce PM{sub 2.5} and EC by around 40% and 60% respectively, from 2010 to 2020. Discussion: The evaluation of planned interventions, related to climate change policies, targeting only the transport sector can result in small co-benefits for health, if the analysis is limited to air pollution and noise. This urges to expand the analysis by including other impacts, e.g. physical activity and well-being, as a necessary step to better understanding consequences of interventions and carefully orienting resources useful to build knowledge to improve public health. - Highlights: • We estimated co-benefits of greenhouse gas reduction policies from 2010 to 2020. • The city scale health impact assessment base on real transport policy scenarios. • Effects of particulate matter, elemental carbon and noise on health are assessed. • The effects are rather small but still positive for the planned scenarios.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer

Malic enzymes (ME1, ME2, and ME3) are involved in cellular energy regulation, redox homeostasis, and biosynthetic processes, through the production of pyruvate and reducing agent NAD(P)H. Recent studies have implicated the third and least well-characterized isoform, mitochondrial NADP + -dependent malic enzyme 3 (ME3), as a therapeutic target for pancreatic cancers. Here, we utilized an integrated structure approach to determine the structures of ME3 in various ligand-binding states at near-atomic resolutions. ME3 is captured in the open form existing as a stable tetramer and its dynamic Domain C is critical for activity. Catalytic assay results reveal that ME3 is a non-allosteric enzyme and does not require modulators for activity while structural analysis suggests that the inner stability of ME3 Domain A relative to ME2 disables allostery in ME3. With structural information available for all three malic enzymes, the foundation has been laid to understand the structural and biochemical differences of these enzymes and could aid in the development of specific malic enzyme small molecule drugs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Localized energy burden, concentrated disadvantage, and the feminization of energy poverty

Energy burden directly influences households' health and safety. Amid a growing literature on energy, poverty and gender remains relatively understudied. We evaluate socioeconomic, geographic, and health factors as multidimensions of concentrated disadvantage that magnify energy burden in the United States over time. We show that the energy burden is more pronounced in disadvantaged counties with larger elderly, impoverished, disabled people, and racialized populations where people do not have health insurance. Neighborhoods with households headed by women of color (especially Black women) are more likely to face a high energy burden, which worsened during the COVID-19 pandemic. Although energy costs are often regarded as an individual responsibility, these findings illustrate the feminization of energy poverty and indicate the need for an intersectional and interdisciplinary framework in devising energy policy directed to households with the most severe energy burden.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗