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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 199 records · Page 11

ChIP-seq Mapping of Distant-Acting Enhancers and Their In Vivo Activities

The genomic location and function of most distant-acting transcriptional enhancers in the human genome remains unknown We performed ChIP-seq for various transcriptional coactivator proteins (such as p300) directly from different embryonic mouse tissues, identifying thousands of binding sitesTransgenic mouse experiments show that p300 and other co-activator peaks are highly predictive of genomic location AND tissue-specific activity patterns of distant-acting enhancersMost enhancers are active only in one or very few tissues Genomic location of tissue-specific p300 peaks correlates with tissue-specific expression of nearby genes Most binding sites are conserved, but the global degree of conservation varies between tissues

59 BASIC BIOLOGICAL SCIENCES↗

P.L. 100-12, "National Appliance Energy Supply Act" (1987)

Amends the Energy Policy and Conservation Act to add to the list of products covered under the Act: (1) freezers which can be operated by alternating current electricity (with specified exceptions); (2) central air conditioning heat pumps; (3) direct heating equipment; and (4) pool heaters. Deletes from specific coverage: (1) humidifiers; and (2) dehumidifiers. Excludes from such coverage consumer products designed solely for use in recreational vehicles and other mobile equipment.

Energy Policy and Conservation Act, freezers, alte↗

Fast Acting Eddy Current Driven Valve for Massive Gas Injection on ITER

Tokamak plasma disruptions present a significant challenge to ITER as they can result in intense heat flux, large forces from halo and eddy currents, and potential first-wall damage from the generation of multi-MeV runaway electrons. Massive gas injection (MGI) of high Z material using fast acting valves is being explored on existing tokamaks and is planned for ITER as a method to evenly distribute the thermal load of the plasma to prevent melting, control the rate of the current decay to minimize mechanical loads, and to suppress the generation of runaway electrons. A fast acting valve and accompanying power supply have been designed and first test articles produced to meet the requirements for a disruption mitigation system on ITER. The test valve incorporates a flyer plate actuator similar to designs deployed on TEXTOR, ASDEX upgrade, and JET [1 3] of a size useful for ITER with special considerations to mitigate the high mechanical forces developed during actuation due to high background magnetic fields. The valve includes a tip design and all-metal valve stem sealing for compatibility with tritium and high neutron and gamma fluxes.

Fast Acting Eddy current↗

Designing a Successful Transportation Project: Lessons Learned from the Clean Cities American Recovery and Reinvestment Act Projects

The largest source of funding for alternative fuel vehicle and infrastructure projects in the U.S. Department of Energy's Clean Cities program's history came from the American Recovery and Reinvestment Act (Recovery Act). In 2009, the 25 cost-share projects totaled nearly $300 million in federal government investment. This effort included the involvement of 50 Clean Cities coalitions and their nearly 700 stakeholder partners who provided an additional $500 million in matching funds to support projects in their local communities. In total, those 25 projects established 1,380 alternative fueling stations and put more than 9,000 alternative fuel and advanced technology vehicles on the road. Together, these projects displaced 154 million gasoline gallon equivalents (GGE) of petroleum and averted 254,000 tons of greenhouse gas (GHG) emissions, while supporting U.S. energy independence and contributing to regional economic development. During post-project interviews, project leaders consistently cited a number of key components - ranging from technical and logistical factors, to administrative capabilities - for accomplishing an effective and impactful project. This report summarizes the high-level project design and administrative considerations for conducting a successful transportation project.

arra, doe, recovery act,clean cities, alternative ↗

Implementing the Inflation Reduction Act: What We Expect and How We Might Get There

This presentation summarizes findings from three related studies: Evaluating Impacts of the Inflation Reduction Act and Bipartisan Infrastructure Law on the U.S. Power System; The Roles and Impacts of PV-Battery Hybrids in a Decarbonized U.S. Electricity Supply; and Optimal Design and Deployment of Wind-Solar Hybrids in Low-Carbon U.S. Power System. The compilation of results from these three studies indicate that the Inflation Reduction Act could drive significant deployment of variable renewable energy technologies, but the level of deployment depends on our ability to build new transmission projects (among other factors). Hybrid systems can help, to an extent, to facilitate greater shares of wind/solar with lesser amounts of transmission expansion.

Bipartisan Infrastructure Law↗

Deactivation and Demolition (D and D) of the Toxic Substance Control Act (TSCA) Incinerator Oak Ridge, Tennessee - 19184

UCOR, an AECOM-led partnership with Jacobs, manages the cleanup of the 2,200-acre East Tennessee Technology Park for its client, the U.S. Department of Energy (DOE), in Oak Ridge, Tennessee. The site was contaminated with radioactive, hazardous and industrial wastes generated by more than 40 years of national defense and energy missions. In 1989, the U.S. Environmental Protection Agency (EPA) added the Oak Ridge Reservation to the National Priorities List of sites and facilities that pose a sufficient threat to human health or the environment to warrant cleanup. The U.S. Department of Energy is cleaning up the Oak Ridge Reservation under a Federal Facility Agreement with the EPA and the Tennessee Department of Environment and Conservation. Many types of waste have been managed and disposed as part of the multi-decade cleanup effort. One unique facility, the Toxic Substance Control Act (TSCA) Incinerator, was constructed at the Department of Energy's Est Tennessee Technology Park (ETTP) in Oak Ridge, Tennessee. The Incinerator was constructed in the mid-1980's and underwent a series of test burns and readiness reviews to obtain the necessary environmental permits and operating approvals from state and federal regulatory agencies. With these in place, the incinerator began routine operations in 1991. It was designed and permitted for receiving, sorting, storing, preparing, and thermally destroying low-level radioactive and RCRA mixed waste contaminated with PCBs. The incinerator was named after a law passed in 1976 that provides the U.S. Environmental Protection Agency with authority to require reporting, record-keeping, testing, and restrictions relating to chemical substances and/or mixtures. During its operating lifetime, the one-of-a-kind thermal treatment facility burned materials regulated under TSCA and the Resource Conservation and Recovery Act (RCRA), most notably radiologically-contaminated polychlorinated biphenyls (PCBs). The TSCA Incinerator met or exceeded environmental regulations and DOE requirements for the treatment of these types of wastes. After more than 18 years of operation and more than 35 million pounds of waste safely incinerated, the TSCA Incinerator shut down operations on December 2, 2009. The TSCA Incinerator has been called a national resource for DOE sites from coast to coast. As the only U.S. facility permitted to incinerate specialized types of wastes, it not only accepted material from the Oak Ridge Reservation but also other facilities across the nationwide DOE complex. Over the years, a dynamic team of hard working and talented people operated and maintained the facility under the most stringent environmental permits and site requirements. The facility has played a key role in the treatment of radioactive PCB and hazardous wastes (mixed wastes) from the Oak Ridge Reservation, as well as from other facilities across the DOE complex. Through its support to over 20 sites in the DOE complex, environmental waste from past and ongoing operations has been safely and permanently treated. In the years since it was shut down, deactivation workers have been preparing TSCA for demolition. This work scope included triple cleaning, rinsing of all production equipment and tanks to RCRA clean criteria, filling sumps, encapsulating PCB and radioactive contamination, removal of universal waste (asbestos. lead and mercury), draining and disposal of residual water in tanks and transfer piping, and removing and disposing of carbon vessels, which were part of the water management system. In 2018, the facility was successfully deactivated and demolished, permanently removing one of the most unique facilities in the DOE complex. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876

Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

60 APPLIED LIFE SCIENCES↗

Mitochondrial quality control pathways: PINK1 acts as a gatekeeper

Highlights: • A well-defined network of mitochondria quality control processes are required to maintain a functional and healthy pool of mitochondria within the cells. • Activation of proteins involved in mitochondrial quality control pathways, such as Parkin, Mfn2, DRP1 and Miro; is regulated by the mitochondrial kinase PINK1. • It is proposed that PINK1 acts as a gatekeeper of mitochondrial quality control mechanisms. Mitochondria have a pivotal role in the maintenance of cell homeostasis and survival. Mitochondria are involved in processes such as ATP production, reactive oxygen species production, apoptosis induction, calcium homeostasis and protein degradation. Thus, mechanisms that regulate the intrinsic quality of mitochondria have a crucial role in dictating overall cell fate. The importance of these well-regulated mechanisms is highlighted in disease scenarios such as neurodegeneration, cancer and neuromuscular atrophy. How mitochondria senses and regulates their intrinsic quality control, and consequently cell survival, is still not fully understood. In this review, we discuss the pathways that are at present considered as state-of-the-art for mitochondria quality control regulation, and highlight a mitochondrial protein–PINK1–that has revealed to act as a mitochondrial gatekeeper able to sense the presence of healthy or damaged mitochondria.

60 APPLIED LIFE SCIENCES↗

Long non-coding RNA-422 acts as a tumor suppressor in colorectal cancer

Highlights: • LncRNA-422 in CRC tissues was significantly lower than that in adjacent tissues. • The expression of lncRNA-422 was correlated with TNM stage of CRC. • LncRNA-422 inhibits the proliferation, migration and invasion of CRC cells. • LncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR pathway in CRC. Colorectal cancer (CRC) is one of the most frequent cancer in numerous of countries worldwidely. The initiation and progression of CRC is an extremely complex process, and have been suggested a correlation with Long non-coding RNAs (lncRNAs). Our results showed that lncRNA-422(ENST00000415820) significantly downregulated in the tissues and serum of CRC patients, and is closely associated with the poor prognosis. Then gain or loss of lncRNA-422 models in SW480 and SW620cells were established. The results showed that lncRNA-422 overexpression inhibited cell proliferation, migration, and invasion. Knockdown of lncRNA-422 promoted tumorigensis. Western blot and qRT-PCR were performed to examine the activity of the PI3K/AKT/mTOR pathway in CRC cells after alternation of lncRNA-422. Results showed that lncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR pathway in CRC.

60 APPLIED LIFE SCIENCES↗

The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides

The Endoplasmic Reticulum (ER) is site of production of secretory and membrane proteins in eukaryotic cells. The ER does not contain catabolic devices and misfolded proteins generated in its lumen must be dislocated across the ER membrane before clearance by cytosolic proteasomes (ER-Associated Degradation, ERAD). How misfolded proteins are dislocated across the ER membrane is a matter of controversy. For example, it remains to be established if polypeptide unfolding is always required. If unfolding is a pre-requisite for dislocation as emerging evidences seem to indicate, it is likely that the incorrect set of disulfide bonds established during unsuccessful folding-attempts that precede selection for ERAD must be reduced to eliminate tertiary and quaternary structures that could hamper dislocation. The lumen of the mammalian ER contains more than 20 members of the PDI family, a handful of which plays a role in ERAD. Here we add the atypical, membrane-bound reductase TMX1 to this list and we show that TMX1 preferentially acts on membrane-tethered folding-defective polypeptides essentially ignoring the same misfolded ectodomains, when not associated to the ER membrane. As such, TMX1 is the first example of a topology-specific client protein redox catalyst acting both in the folding and in the degradative pathways.

60 APPLIED LIFE SCIENCES↗

SpWRKY6 acts as a positive regulator during tomato resistance to Phytophthora infestans infection

Highlights: • SpWRKY6 acts as a positive regulator of tomato resistance to P. infestans infection. • Over-expressing SpWRKY6 tomato increased resistance to P. infestans by scavenging reactive oxygen species. • SpWRKY6-mediated tomato resistance to P. infestans through regulating the expression level of PR genes. WRKY transcription factors have been widely known to play key regulatory roles in plant disease resistance. In our previous study, characteristics of SpWRKY6 and its role in response to biotic and abiotic stress was studied. To further investigate the function of SpWRKY6 in tomato resistance to Phytophthora infestans (P. infestans), we studied the effects of loss and gain of function of SpWRKY6. Inhibition of SpWRKY6 mRNA accumulation in tomato leaves, using virus-induced gene silencing (VIGS), greatly reduced SpWRKY6 mRNA levels, and compromised tomato resistance to P. infestans. In contrast, overexpressing- SpWRKY6 tomato plants showed enhanced resistance to P. infestans, accompanied by decreased number of necrotic cells, lesion sizes and disease index. Furthermore, after P. infestans infection, the expression levels of pathogenesis related (PR) genes in transgenic tomato plants overexpressed SpWRKY6 were significantly higher than those in wild type plants, while the number of necrotic cells and the reactive oxygen species (ROS) accumulation were fewer and lower. Taken together, these results indicating that SpWRKY6 acts as a positive regulator of tomato resistance to P. infestans infection through regulating the ROS level and the expression level of PR genes along with alleviating cell membrane injury.

60 APPLIED LIFE SCIENCES↗

A framework for monitoring-based commissioning: Identifying variables that act as barriers and enablers to the process

The practice of monitoring-based commissioning (MBCx) using energy management and information systems (EMIS) has been shown to enable and help sustain up to 20% energy savings in buildings. Despite research that has quantified the costs, benefits, and energy savings of MBCx, the process remains under-utilized. To understand why MBCx is not more frequently adopted and how to encourage its use, this research synthesizes qualitative data from over 40 organizations, currently engaging in MBCx. The outcome of this research is a framework containing variables that emerged from the qualitative data, marked as barriers or enablers, organized by phases of the MBCx process. The framework is comprised of 51 emergent variables that fall within 13 different categories. The variables that most frequently act as barriers are data configuration, measurement & verification (M&V), developing specifications for EMIS, and data architecture. Although some variables that act as barriers for one organization were identified as enablers for another. For example, payback/ROI was considered a barrier 7 times and an enabler 3 times. One organization had difficulty making the business case for the initial investment for MBCx due to lack of cost information, while another was able to justify large investments with documented savings of previously implemented measures identified through MBCx. The framework formally validates barriers found in previous research, and can be used by practitioners to better understand common experiences with MBCx. This research also highlights the need for a similar collective data set to validate common enablers to MBCx and also the need for empirical research to determine relationships between variables.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

The thioantimonate anion SbS{sub 3}{sup 3-} acting as ligand: Syntheses, crystal structures and selected properties of [Mn(1,2-chxn){sub 2}SbS{sub 3}H] and [Cr(1,3-dap){sub 2}SbS{sub 3}]

Two new isolated thioantimonates [Mn(1,2-chxn){sub 2}SbS{sub 3}H] (1) (1,2-chxn=1,2-diaminocyclohexane) and [Cr(1,3-dap){sub 2}SbS{sub 3}] (2) (1,3-dap=1,3-diaminopropane) were synthesized under solvothermal conditions. The crystal structures of 1 and 2 consist of neutral Mn{sup 2+} or Cr{sup 3+} complexes with the transition metal cations being in a distorted octahedral environment of four nitrogen atoms of 1,2-chxn resp. 1,3-dap and two sulphur atoms of the bidentate SbS{sub 3}{sup 3-} unit. Compound 1 is remarkable because charge neutrality is achieved by the presence of Mn{sup 2+} and a SH group which was never observed before. In both compounds intermolecular S Midline-Horizontal-Ellipsis H bonding interactions connect the complexes into higher dimensionality. Compound 1 crystallizes in the monoclinic space group P2{sub 1}/c with a=21.5440(16) A, b=6.9295(3) A, c=13.9276(10) A and {beta}=102.692(8) Degree-Sign . Compound 2 crystallizes in the orthorhombic space group Pbca with a=8.5999(2), b=15.9741(4) and c=21.6770(7) A. - Graphical Abstract: The two new compounds [Mn(1,2-chxn){sub 2}SbS{sub 3}H] and [Cr(1,3-dap){sub 2}SbS{sub 3}] contain the SbS{sub 3}{sup 3-} anion acting as bidentate ligand. Highlights: Black-Right-Pointing-Pointer New isolated thioantimonates(III) with SbS{sub 3}{sup 3-} anion acting as a bidentate ligand. Black-Right-Pointing-Pointer Charge neutrality through protonated sulphur atom. Black-Right-Pointing-Pointer First neutral Mn{sup 2+} complex chelated by bidentate amines and SbS{sub 3}{sup 3-} pyramid.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

60 APPLIED LIFE SCIENCES↗

RCAN1.4 acts as a suppressor of cancer progression and sunitinib resistance in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system, and its incidence continues to increase. Regulator of calcineurin 1 (RCAN1), one of the genes on chromosome 21, is a crucial mediator of tumor inhibition. RCAN1.4 is best characterized as an endogenous inhibitor of the phosphatase calcineurin, and it has been observed to be downregulated in numerous types of cancer. However, its essential function remains unclear in ccRCC. In the present study, we found that RCAN1.4 expression was frequently downregulated in renal cell carcinoma tissues and cells and was inversely correlated with various clinicopathological parameters. Low RCAN1.4 expression was associated with poor overall survival and disease-free survival and could act as a diagnostic indicator in ccRCC patients. Furthermore, the overexpression of RCAN1.4 inhibited cell proliferation, migration and invasion, whereas RCAN1.4 knockdown promoted these functions in ccRCC cell lines. In addition, RCAN1.4 expression was downregulated in sunitinib-resistant renal cancer cell lines, and inhibition of RCAN1.4 promoted sunitinib resistance. We also found that RCAN1.4 could regulate epithelial-mesenchymal transition (EMT) and the expression of HIF2α in sunitinib-resistant cell lines. Taken together, these findings indicate that downregulation of RCAN1.4 may be crucial for the metastasis of ccRCC and may induce sunitinib resistance. RCAN1.4 may act as a prognostic indicator and potential therapeutic target for ccRCC.

60 APPLIED LIFE SCIENCES↗