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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 1,027 records · Page 57

Model Reduction for Fast Assessment of Grid Impact of High Penetration PV

A key challenge in properly analyzing the impact of solar photovoltaics (PV) during planning, interconnection and operation in the distribution grid is computational complexity. Such studies require the use of Quasi-Steady-Time-Series (QSTS) power flow to capture the complex interaction of PV with voltage regulating equipment and protection devices and a large number of scenario studies are needed to capture location specific constraints and uncertainties. In addition, a typical distribution feeder can have thousands of nodes and there can be thousands of such feeders in a given utility system. To solve this problem, a new and systematic method for distribution network reduction is proposed. The objective is to reduce the size of distribution systems by more than 80% while preserving the accuracy of power flow results. To this end, an extended Ward-equivalent method has been proposed to create an equivalent circuit. Moreover, load and PV aggregation based on the backward sweep method has been developed to further simplify the feeder. The proposed method is tested with a modified IEEE 123-node distribution test system. The simulation results demonstrate the high efficiency and accuracy of the proposed approach for distribution network reduction.

reduced order systems, load flow, load modeling, v↗

PKA and HOG signaling contribute separable roles to anaerobic xylose fermentation in yeast engineered for biofuel production

Lignocellulosic biomass offers a sustainable source for biofuel production that does not compete with food-based cropping systems. Importantly, two critical bottlenecks prevent economic adoption: many industrially relevant microorganisms cannot ferment pentose sugars prevalent in lignocellulosic medium, leaving a significant amount of carbon unutilized. Furthermore, chemical biomass pretreatment required to release fermentable sugars generates a variety of toxins, which inhibit microbial growth and metabolism, specifically limiting pentose utilization in engineered strains. Here we dissected genetic determinants of anaerobic xylose fermentation and stress tolerance in chemically pretreated corn stover biomass, called hydrolysate. We previously revealed that loss-of-function mutations in the stress-responsive MAP kinase HOG1 and negative regulator of the RAS/Protein Kinase A (PKA) pathway, IRA2, enhances anaerobic xylose fermentation. However, these mutations likely reduce cells’ ability to tolerate the toxins present in lignocellulosic hydrolysate, making the strain especially vulnerable to it. We tested the contributions of Hog1 and PKA signaling via IRA2 or PKA negative regulatory subunit BCY1 to metabolism, growth, and stress tolerance in corn stover hydrolysate and laboratory medium with mixed sugars. We found mutations causing upregulated PKA activity increase growth rate and glucose consumption in various media but do not have a specific impact on xylose fermentation. In contrast, mutation of HOG1 specifically increased xylose usage. We hypothesized improving stress tolerance would enhance the rate of xylose consumption in hydrolysate. Surprisingly, increasing stress tolerance did not augment xylose fermentation in lignocellulosic medium in this strain background, suggesting other mechanisms besides cellular stress limit this strain’s ability for anaerobic xylose fermentation in hydrolysate.

09 BIOMASS FUELS↗

Robust Decentralized State Estimation

The health of a distribution grid is maintained by a distribution management system (DMS). Before the rise of distributed energy resource (DER), the DMS primarily managed the unidirectional power flow through the distribution grid from external sources (e.g. power brought from a large generating plant to the distribution grid by a transmission grid). Now, a typical DMS will utilize distributed energy resource manage systems (DERMS) to account for DER such as rooftop solar, community solar, and wind turbines. Each DERMS is responsible for an area of the distribution grid, issuing commands to the associated real-time automation controller (RTAC) to regulate power flow and maintain health of that section of the grid.

42 ENGINEERING↗

Research in digital adaptive flight controllers

A design study of adaptive control logic suitable for implementation in modern airborne digital flight computers was conducted. Both explicit controllers which directly utilize parameter identification and implicit controllers which do not require identification were considered. Extensive analytical and simulation efforts resulted in the recommendation of two explicit digital adaptive flight controllers. Interface weighted least squares estimation procedures with control logic were developed using either optimal regulator theory or with control logic based upon single stage performance indices.

Kaufman, H.↗

Assessment of institutional barriers to the use of natural gas fuel in automotive vehicle fleets

Institutional barriers to the use of natural gas as a fuel for motor vehicle fleets were identified. Recommendations for barrier removal were developed. Eight types of institutional barriers were assessed: (1) lack of a national standard for the safe design and certification of natural gas vehicles and refueling stations; (2) excessively conservative or misapplied state and local regulations, including bridge and tunnel restrictions, restrictions on types of vehicles that may be fueled by natural gas, zoning regulations that prohibit operation of refueling stations, parking restrictions, application of LPG standards to LNG vehicles, and unintentionally unsafe vehicle or refueling station requirements; (3) need for clarification of EPA's tampering enforcement policy; (4) the U.S. hydrocarbon standard; (5) uncertainty concerning state utility commission jurisdiction; (6) sale for resale prohibitions imposed by natural gas utility companies or state utility commissions; (7) uncertainty of the effects of conversions to natural gas on vehicle manufactures warranties; and (8) need for a natural gas to gasoline equivalent units conversion factor for use in calculation of state road use taxes.

Jablonski, J.↗

Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.

Asayama, K.↗

High-frequency ac power distribution in Space Station

A utility-type 20-kHz ac power distribution system for the Space Station, employing resonant power-conversion techniques, is presented. The system converts raw dc voltage from photovoltaic cells or three-phase LF ac voltage from a solar dynamic generator into a regulated 20-kHz ac voltage for distribution among various loads. The results of EASY5 computer simulations of the local and global performance show that the system has fast response and good transient behavior. The ac bus voltage is effectively regulated using the phase-control scheme, which is demonstrated with both line and load variations. The feasibility of paralleling the driver-module outputs is illustrated with the driver modules synchronized and sharing a common feedback loop. An HF sinusoidal ac voltage is generated in the three-phase ac input case, when the driver modules are phased 120 deg away from one another and their outputs are connected in series.

Tsai, Fu-Sheng↗

Down-regulation of MAP2K1 by miR-539 inhibits hepatocarcinoma progression

Liver cancer has been considered as one of the major leading causes of cancer-related mortality. The incidence of liver cancer tends to increase in less developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs) play crucial roles in the modulation of tumor growth and progression. Whereas, the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well established. In our present study, we sought to explore biological role of miR-539 in HCC progression. qRT-PCR was utilized to evaluate the expression level of miR-539. Immunoblotting analysis, qRT-PCR and luciferase reporter assays were used for the identification of the potential target of miR-539. Proliferation, migration and invasion assays and flow cytometric were performed to assess the biological functional role of miR-539. The molecular signaling pathways related to the integration of miR-539 were also evaluated. MiR-539 was reduced in human HCC. Mitogen-activated protein kinase 1, also known as MAP2K1 was verified as the target of miR-539. Overexpression of miR-539 inhibited migration, invasion and cell proliferation, while apoptosis rate was increased. Knockdown or overexpression of MAP2K1 in HCC cell transfected with ag-miR-539 or in-miR-539 indicated that miR-539 suppresses the progression of HCC by directly targeting and regulating MAP2K1. Our results reveal that miR-539 might be a tumor suppressor in HCC, supporting a potential target for advanced therapeutic strategy for this disease.

60 APPLIED LIFE SCIENCES↗

Subtask 1.4 - Techno-Economic Assessment of Regional Carbon Utilization Scenarios and Attendant Monitoring Technology

The U.S. Department of Energy (DOE) Carbon Storage Program seeks to develop technologies to significantly improve the effectiveness of carbon capture and storage (CCS), reduce the cost of implementation, and support the readiness of widespread commercial deployment by 2035. To accomplish this goal, technical and economic barriers must be addressed and the results used to inform regulators and industry on the safety, permanence, and viability of carbon storage. To help overcome these barriers, the Energy & Environmental Research Center (EERC) conducted three activities: 1) investigate the regional techno-economic life cycle of CO2 enhanced oil recovery (EOR) in North Dakota, 2) assist DOE in determining the prospective CO2 storage resource of residual oil zones (ROZs), and 3) develop a seismic technique for monitoring geologic storage of CO2. These three activities address two strategic goals enumerated in the DOE–EERC Cooperative Agreement, namely, 1) to advance foundational science and 2) to inform data-driven policies that enhance U.S. economic growth and job creation, energy security, and environmental quality. Activity 1 In North Dakota, there is synergistic incentive to develop and implement CO2 EOR technologies. Regional industry partners are actively seeking options that can cost-effectively improve the efficiency of power production, while also coproducing CO2 for use in EOR applications. A full-value-chain techno-economic assessment that links lignite resources, power generation, and EOR is needed to determine the implications for a state or region to continue to use these resources or look elsewhere for other energy sources and revenue streams. The integration of North Dakota’s lignite power industry with the state’s oil industry has the potential to revitalize legacy oil fields and produce up to 1 billion barrels of additional oil using CO2 EOR while providing a market for a CO2 commodity captured at coal-fired power plants. Revitalization of North Dakota’s legacy oil fields will bring new industry investment to the state, resulting in the growth of oil-related jobs and revenue through oil sales, severance tax, and associated oilfield development activities (drilling, pipelines, etc.). CO2 demand for EOR and incremental oil production were calculated for 201 conventional oil fields in North Dakota. Infrastructure development in the fields was estimated using 1) a traditional vertical well arrangement of CO2 injectors and oil producers and 2) an advanced case where horizontal wells were used exclusively. Pipeline, compression, and recycling infrastructure requirements were also estimated. When viewed from the CO2 capture and CO2 EOR sectors, the advanced case showed a positive investment scenario when including potential benefits of the 45Q tax credit policy. An economic evaluation of a full implementation of CO2 EOR showed an average $60 billion potential state economic impact estimated over the 37-year construction and production time frame could be realized with an assumed oil price of $65/bbl. Oil price ranges of $35–$90/bbl cause an estimated variation of ±$5 billion over the potential effort. The total net state government revenues were estimated over the 37-year construction and production time frame. With an assumed oil price of $65/bbl, total potential fiscal impact could average $7.4 billion. This result ranges about ±$2.5 billion for a potential EOR implementation effort for oil price ranges of $35–$90/bbl. This broad-brush assessment was focused on “magnitude-of-effect” perspectives of what CO2 capture and use for EOR could mean to the state. Whether CO2 EOR ever becomes widely adopted is not the issue at this stage of evaluation. The question being answered is, How valuable could CO2 capture and CO2 EOR be for the state and local jurisdictions in western North Dakota? The results of the current economic assessment remove any ambiguity to that question. Full implementation of CO2 EOR as modeled in this study provides substantial economic benefits to the state, even at low oil prices (i.e., $35/bbl). Job creation and government revenues could be substantial, depending on the scale of implementation. With a better understanding of what CO2 EOR might mean for the state’s economy, the focus can now shift to the policies and financial mechanisms needed to make private investment in CO2 capture and use as EOR competitive with other energy-related pursuits. Activity 2 ROZs contain remnants of oil not swept away by natural waterflooding. Although nearly all of the identified ROZs are found in West Texas, there is evidence that this category of oil reservoir can be found in other major oil-producing basins of the United States. Because the formation of these oil reservoirs is distinct from other conventional reservoirs, the method to estimate the prospective CO2 storage resource in ROZs may be equally distinct from the method used for conventional fields. As such, the EERC collaborated with DOE’s National Energy Technology Laboratory (NETL) to investigate the feasibility of CO2 storage in ROZs and determine what specific modification (if any) needs to be made to the current DOE volumetric method to estimate prospective CO2 storage resource in oil reservoirs. This activity built on a previous EERC investigation to identify ROZs in the Williston and Powder River Basins and upon collaborations between the EERC and NETL to develop storage resource estimation methods for different types of geologic CO2 storage. Review of the volumetric approach raised questions about the applicability of such an approach to hydrocarbon-bearing zones without the inclusion of potential hydrocarbon production. A production-based approach was presented by the EERC to inform the working group of additional methods of increasing the CO2 storage resource potential. Because the production-based method focuses more heavily on oil recovery than CO2 storage, it was not included in the working group manuscript. Activity 3 The EERC has used sparse and irregular seismic arrays to detect CO2 injected into a reservoir. The variability of seismic noise recorded by the sensors directly impacts the seismic interpretation. However, designing noise attenuation workflows effectively can be a more challenging task using sparse and irregular arrays for data acquisition. Based on the hypothesis that noncoherent noise is stationary during weekly data acquisition, a new machine-learning algorithm was developed to automatically estimate noise conditions using passive records, noise from active records, and ancillary information. The new noise attenuation processing workflow can improve the time-lapse detection of CO2 from sparse and irregular array acquisitions. Results show spatial and temporal noise patterns can be related to the location of the sensors and the weather conditions during the data acquisition and that our attenuation processing workflow can improve the time-lapse detection of CO2 from sparse and irregular array acquisitions. This effort was funded in part through the EERC–DOE Joint Program on Research and Development for Fossil Energy-Related Resources Cooperative Agreement No. DE-FE0024233. Nonfederal funding was provided by the North Dakota Department of Commerce.

Peck, Wesly↗

A Priority-Based Control Strategy and Performance Bound for Aggregated HVAC-Based Load Shaping

Air conditioning systems have been recognized as a potential, cost-effective resource for shaping electrical load in a power system. This work presents a new priority-based control strategy that explicitly addresses three requirements for using a collection of air conditioning units in this capacity. These are 1) tracking a regulation signal, 2) maintaining the building temperature near its set point, and 3) satisfying a cycling constraint of the air conditioners. After introducing the control strategy, we derive a bound for the regulation signal within which tracking is guaranteed while also satisfying the temperature requirement. These results are illustrated with simulations.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy

Highlights: • Serum autotaxin activity is elevated in the mouse with brain edema. • LPA{sub 6} is predominantly expressed in rat brain capillary endothelial cells. • LPA–LPA{sub 6}–G{sub 12/13}–Rho pathway regulates blood brain barrier permeability. Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to the accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood-brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls. Using in vitro BBB model, LPA disrupted the structural integrity of tight junction proteins including claudin-5, occludin, and ZO-1. Furthermore, LPA decreased transendothelial electrical resistances in in vitro BBB model, and induced cell contraction in brain endothelial monolayer cultures, both being inhibited by a Rho-associated protein kinase inhibitor, Y-27632. The brain capillary endothelial cells predominantly expressed LPA{sub 6} mRNA, whose knockdown blocked the LPA-induced endothelial cell contraction. Taken together, the up-regulation of serum ATX in hepatic encephalopathy may activate the LPA–LPA{sub 6}–G{sub 12/13}–Rho pathway in brain capillary endothelial cells, leading to enhancement of BBB permeability and brain edema.

60 APPLIED LIFE SCIENCES↗

Boil-off losses along LH2 pathway

Losses along the LH 2 pathway are intrinsic to the utilization of a cryogenic fluid. They occur when the molecule is transferred between 2 vessels (liquefaction plant to trailer, trailer to station storage, station storage to pump or compressor, then fuel cell electric vehicles …) and when the fluid is warmed up due to heat transfer with the environment. Those losses can be estimated with good accuracy using thermodynamic models based on conservation of mass and energy, providing the thermodynamic states are correctly described. Indeed, the fluid undergoes various changes as it moves along the entire pathway (2 phase transition, super-heated warming, non-uniform temperature distributions across the saturation film) and accurate equations of state and 2 phase behavior implementations are essential. The balances of mass and energy during the various dynamics processes then enable to quantify the boil-off losses. In this work, a MATLAB code previously developed by NASA to simulate rocket loading is used as the basis for the LH 2 transfer model. This code implements complex physical phenomena such as the competition between condensation and evaporation and the convection vs. conduction heat transfer as a function of the relative temperatures on both sides of the saturated film. The original code was modified to consider real gas equations of state, and some semi-empirical relationships, such as between the heat of vaporization and the critical temperature, were also replaced by a REFPROP equivalent expression, assumed to be more accurate. Non-constant liquid temperature equations were added to simulate sub-cooled conditions. It is shown that although trailer depressurization and transfer losses from the receiving vessel during a LH 2 delivery may constitute the largest sources of losses, those can be greatly reduced and even eliminated if CFR/DOT regulations are properly applied and if no-vent fill methods are implemented, particularly for a stationary LH2 storage operating at reasonably low pressure (45 psia or so). As such, it is expected that the only remaining boil-off losses for a refueling station would come from the LH 2 pump (utilization and idling), pump vessel cool down/warm up, and environment heat transfer. Based on experimental data measured at LLNL on the Linde 875 bar LH 2 cryo-pump and results from the model, and extrapolating for refueling stations of various sizes, it can be shown that boil-off losses can vary from 15% of delivered LH 2 for a 100 kg/day, 5% at 400 kg/day, and down to less than 2% for stations above 1,800 kg/day (for a system similar to the one at LLNL). Less boil-off is to be expected for LH 2 pumps dispensing at 350 bar, so that less than 0.7% can be expected above 1,800 kg/day station capacities. At last, boil-off recovery solutions are briefly analyzed, including compressors, cryo-coolers and stationary fuel cell. Their economic value is strongly related to the costs of H2 and of the electricity needed to perform the recovery, on top of the initial capital expenditures. Effective boil-off could be reduced to 0.6-1% for a 2,000 kg/day station if adequate recovery solutions are used.

08 HYDROGEN↗

A study of factors related to commercial space platform services

In the past four years, the issue of the commercial development of space has come to the forefront of the U. S. national space policy. Though the Administration, Congress and NASA have all shown strong support for encouraging the private sector to become more actively involved in the commercial utilization of space, the question remains whether they must do more to foster the creation and development of a viable U. S. commercial space industry. Marketing aspects, insurance and risk loss, tax related factors, space transportation, termination liability, institutional barriers, and procurement laws and regulations are discussed.

Hosenball, S. N.↗

Simulation of Lift plus Cruise Vehicle Models to Define a Full-Scale Crash Test Campaign

A series of dynamic simulations were completed on the National Aeronautics and Space Administration(NASA) Lift plus Cruise (LPC) concept electric Vertical Take-off and Landing (eVTOL) vehicle in preparation for an anticipated future full-scale crash-test campaign. The crash test campaign is envisioned as a data gathering exercise with an intent generating full-scale test data to inform eVTOL crashworthiness regulations, evaluate the use of energy absorbing concepts within vehicle design, and validate finite element modeling techniques used in crashworthiness predictions. This report discusses the two main objectives for the simulation efforts: the development of a structural cabin section, and a series of analyses utilized to determine the sensitivities of impact variables. A structural cabin section was created based from previous research efforts involving the LPC vehicle utilized for occupant response. To refine for the structural modifications, the wing and tail sections of the vehicle were removed. The tail was replaced with a representative mass at the aft of the fuselage. The overhead wing was replaced with a beam structure sized to approximate the bending response of the wing under crash loading conditions. The beam structure was fixed to the fuselage similar to the original Wingbox design in order to properly capture effects of this overhead mass on survivable volume within the vehicle. The fidelity of the fuselage frame structure within the FEM was increased to quantify the effect of frame sizing on structural response. From this an eVTOL test article design was developed, which satisfied basic crashworthiness requirements, was reconfigurable to assess the effect of various design avenues on structural response and optimized to improve manufacturability. The impact variable sensitivity results primarily show the orientation of the impact vector played a major role in types of injuries sustained, along with their severity. The vehicle was largely insensitive to small variations in pitch attitude but highly sensitive to both impact surface at certain angles and landing gear location.

eVTOL↗

Expression of pH-sensitive green fluorescent protein in Arabidopsis thaliana

This is the first report on using green fluorescent protein (GFP) as a pH reporter in plants. Proton fluxes and pH regulation play important roles in plant cellular activity and therefore, it would be extremely helpful to have a plant gene reporter system for rapid, non-invasive visualization of intracellular pH changes. In order to develop such a system, we constructed three vectors for transient and stable transformation of plant cells with a pH-sensitive derivative of green fluorescent protein. Using these vectors, transgenic Arabidopsis thaliana and tobacco plants were produced. Here the application of pH-sensitive GFP technology in plants is described and, for the first time, the visualization of pH gradients between different developmental compartments in intact whole-root tissues of A. thaliana is reported. The utility of pH-sensitive GFP in revealing rapid, environmentally induced changes in cytoplasmic pH in roots is also demonstrated.

NASA Discipline Plant Biology↗

Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens

Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking its retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.

Environmental Molecular Sciences Laboratory↗

Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.

60 APPLIED LIFE SCIENCES↗

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↗