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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
All sourcesNASA NTRSDOE OSTI
DOE OSTI2010

Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer

Accumulating evidence suggests that both levels and activity of the estrogen receptor (ER) and the progesterone receptor (PR) are dramatically influenced by growth-factor receptor (GFR) signaling pathways, and that this crosstalk is a major determinant of both breast cancer progression and response to therapy. The phosphatidylinositol 3-kinase (PI3K) pathway, a key mediator of GFR signaling, is one of the most altered pathways in breast cancer. We thus examined whether deregulated PI3K signaling in luminal ER + breast tumors is associated with ER level and activity and intrinsic molecular subtype. We defined two independent molecular signatures of the PI3K pathway: a proteomic (reverse-phase proteomic array) PI3K signature, based on protein measurement for PI3K signaling intermediates, and a PI3K transcriptional (mRNA) signature based on the set of genes either induced or repressed by PI3K inhibitors. By using these signatures, we scored each ER + breast tumor represented in multiple independent expression-profiling datasets (four mRNA, n = 915; one protein, n = 429) for activation of the PI3K pathway. Effects of PI3K inhibitor BEZ-235 on ER expression and activity levels and cell growth were tested by quantitative real-time PCR and cell proliferation assays. Within ER + tumors, ER levels were negatively correlated with the PI3K activation scores, both at the proteomic and transcriptional levels, in all datasets examined. PI3K signature scores were also higher in ER + tumors and cell lines of the more aggressive luminal B molecular subtype versus those of the less aggressive luminal A subtype. Notably, BEZ235 treatment in four different ER + cell lines increased expression of ER and ER target genes including PR, and treatment with IGF-I (which signals via PI3K) decreased expression of ER and target genes, thus further establishing an inverse functional relation between ER and PI3K. BEZ-235 had an additional effect on tamoxifen in inhibiting the growth of a number of ER + cell lines. Our data suggest that luminal B tumors have hyperactive GFR/PI3K signaling associated with lower ER levels, which has been correlated with resistance to endocrine therapy. Targeting PI3K in these tumors might reverse loss of ER expression and signaling and restore hormonal sensitivity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

CRISPR-mediated multigene integration enables Shikimate pathway refactoring for enhanced 2-phenylethanol biosynthesis in Kluyveromyces marxianus

Background: 2-phenylethanol (2-PE) is a rose-scented flavor and fragrance compound that is used in food, beverages, and personal care products. Compatibility with gasoline also makes it a potential biofuel or fuel additive. A biochemical process converting glucose or other fermentable sugars to 2-PE can potentially provide a more sustainable and economical production route than current methods that use chemical synthesis and/or isolation from plant material. Results: We work toward this goal by engineering the Shikimate and Ehrlich pathways in the stress-tolerant yeast Kluyveromyces marxianus. First, we develop a multigene integration tool that uses CRISPR-Cas9 induced breaks on the genome as a selection for the one-step integration of an insert that encodes one, two, or three gene expression cassettes. Integration of a 5-kbp insert containing three overexpression cassettes successfully occurs with an efficiency of 51 ± 9% at the ABZ1 locus and was used to create a library of K. marxianus CBS 6556 strains with refactored Shikimate pathway genes. The 3 3 -factorial library includes all combinations of KmARO4, KmARO7, and KmPHA2, each driven by three different promoters that span a wide expression range. Analysis of the refactored pathway library reveals that high expression of the tyrosine-deregulated KmARO4 K221L and native KmPHA2, with the medium expression of feedback insensitive KmARO7 G141S , results in the highest increase in 2-PE biosynthesis, producing 684 ± 73 mg/L. Ehrlich pathway engineering by overexpression of KmARO10 and disruption of KmEAT1 further increases 2-PE production to 766 ± 6 mg/L. The best strain achieves 1943 ± 63 mg/L 2-PE after 120 h fed-batch operation in shake flask cultures. Conclusions: The CRISPR-mediated multigene integration system expands the genome-editing toolset for K. marxianus, a promising multi-stress tolerant host for the biosynthesis of 2-PE and other aromatic compounds derived from the Shikimate pathway.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Brg1 modulates enhancer activation in mesoderm lineage commitment

The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also required to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM-associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit gene Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunopurification with mass spectrometry, we have determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocyte (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60c and BAF170 modulate chromatin accessibility, to promote accessibility at activated genes while closing chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific sites. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

A Model Integration Pipeline for the Improvement of Human Genome-Scale Metabolic Reconstructions

Abstract Metabolism has been a major field of study in the last years, mainly due to its importance in understanding cell physiology and certain disease phenotypes due to its deregulation. Genome-scale metabolic models (GSMMs) have been established as important tools to help achieve a better understanding of human metabolism. Towards this aim, advances in systems biology and bioinformatics have allowed the reconstruction of several human GSMMs, although some limitations and challenges remain, such as the lack of external identifiers for both metabolites and reactions. A pipeline was developed to integrate multiple GSMMs, starting by retrieving information from the main human GSMMs and evaluating the presence of external database identifiers and annotations for both metabolites and reactions. Information from metabolites was included into a graph database with omics data repositories, allowing clustering of metabolites through their similarity regarding database cross-referencing. Metabolite annotation of several older GSMMs was enriched, allowing the identification and integration of common entities. Using this information, as well as other metrics, we successfully integrated reactions from these models. These methods can be leveraged towards the creation of a unified consensus model of human metabolism.

Vieira, Vítor↗
DOE OSTI2017

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations and changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Genome-wide screen identifies a novel prognostic signature for breast cancer survival

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion, cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

A robust gene expression-based prognostic risk score predicts overall survival of lung adenocarcinoma patients

Identification of reliable predictive biomarkers and new therapeutic targets is a critical step for significant improvement in patient outcomes. Here, we developed a multi-step bioinformatics analytic strategy to mine large omics and clinical data to build a prognostic scoring system for predicting the overall survival (OS) of lung adenocarcinoma (LuADC) patients. In latter we first identified 1327 significantly and robustly deregulated genes, 600 of which were significantly associated with the OS of LuADC patients. Gene co-expression network analysis revealed the biological functions of these 600 genes in normal lung and LuADCs, which were found to be enriched for cell cycle-related processes, blood vessel development, cell-matrix adhesion and metabolic processes. Finally, we implemented a multiple resampling method combined with Cox regression analysis to identify a 27-gene signature associated with OS, and then created a prognostic scoring system based on this signature. This scoring system robustly predicted OS of LuADC patients in 100 sampling test sets and was further validated in four independent LuADC cohorts. In addition, in comparison to other existing prognostic gene signatures published in the literature, our signature was significantly superior in predicting OS of LuADC patients. In summary, our multiomics and clinical data integration study created a 27-gene prognostic risk score that can predict OS of LuADC patients independent of age, gender and clinical stage. This score could guide therapeutic selection and allow stratification in clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas

The tumor suppressor gene FBXW7 is deleted and mutated in many different types of human cancers. FBXW7 primarily exerts its tumor suppressor activity by ubiquitinating different oncoproteins including mTOR. Here we used gene transcript profiling to gain a deeper understanding of the role of FBXW7 in tumor development and to determine the influence of mTOR inhibition by rapamycin on tumor transcriptome and biological functions. In comparison to tumors from p53 single heterozygous (p53+/-) mice, we find that radiation-induced thymic lymphomas from Fbxw7/p53 double heterozygous (Fbxw7+/-p53+/-) mice show significant deregulation of cholesterol metabolic processes independent of rapamycin treatment, while cell cycle related genes were upregulated in tumors from placebo treated Fbxw7+/-p53+/- mice, but not in tumors from rapamycin treated Fbxw7+/-p53+/- mice. On the other hand, tumors from rapamycin treated Fbxw7+/-p53+/- mice were enriched for genes involved in the integrated stress response, an adaptive mechanism to survive in stressful environments. Finally, we demonstrated that the Fbxw7 gene signatures identified in mouse tumors significantly overlap with FBXW7 co-expressed genes in human cancers. Importantly these common FBXW7 gene signatures between mouse and human are predictive for disease-free survival in human colon, breast and lung adenocarcinoma cancer patients. These results provide novel insights into the role of FBXW7 in tumor development and have identified a number of potential targets for therapeutic intervention.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

Trends in U.S. Venture Capital Investments Related to Energy: 1980 through the Third Quarter of 2010

This report documents trends in U.S. venture capital investments over the period 1980 through the third quarter of calendar year 2010 (2010 Q1+Q2+Q3). Particular attention is given to U.S. venture capital investments in the energy/industrial sector over the period 1980-2010 Q1+Q2+Q3 as well as in the more recently created cross-cutting category of CleanTech over the period 1995-2010 Q1+Q2+Q3. During the early 1980s, U.S. venture capital investments in the energy/industrial sector accounted for more than 20% of all venture capital investments. However subsequent periods of low energy prices, the deregulation of large aspects of the energy industry, and the emergence of fast growing new industries like computers (both hardware and software), biotechnology and the Internet quickly reduced the priority accorded to energy/industrial investments. To wit, venture capital investments related to the energy/industrial sector accounted for only 1% of the $132 billion (in real 2010 US$) invested in 2000 by the U.S. venture capital community. The significant increase in the real price of oil that began in 2003-2004 correlates with renewed interest and increased investment by the venture capital community in energy/industrial investment opportunities. Venture capital investments for 2009 for the energy/industrial sector accounted for $2.4 billion or slightly more than 13% of all venture capital invested that year. The total venture capital invested in energy/industrial during the first three quarters of 2010 is close to $2.4 billion accounting for slightly less than 15% of all venture capital investments during the first three quarters of 2010. In 2009, the aggregate amount invested in CleanTech was $2.1 billion (11% of the total US venture capital invested in that lean year) and for the first three quarters of 2010 US venture capital investments in CleanTech have already exceeded $2.8 billion (18% of all US venture capital investments made during the first three quarters of 2010). Between 2004 and 2009, U.S. venture capital investments in energy/industrial as well as CleanTech have more than quadrupled in real terms.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2014

Lancaster Landfill Solar Facility

The Town of Lancaster constructed a 500KWH Solar Array on our landfill parcel, that using other financial mechanisms in the deregulated Massachusetts Electric Market would allow the Town to obtain free electricity.

14 SOLAR ENERGY↗
DOE OSTI2014

Advanced Small Modular Reactor Economics Status Report

This report describes the data collection work performed for an advanced small modular reactor (AdvSMR) economics analysis activity at the Oak Ridge National Laboratory. The methodology development and analytical results are described in separate, stand-alone documents as listed in the references. The economics analysis effort for the AdvSMR program combines the technical and fuel cycle aspects of advanced (non-light water reactor [LWR]) reactors with the market and production aspects of SMRs. This requires the collection, analysis, and synthesis of multiple unrelated and potentially high-uncertainty data sets from a wide range of data sources. Further, the nature of both economic and nuclear technology analysis requires at least a minor attempt at prediction and prognostication, and the far-term horizon for deployment of advanced nuclear systems introduces more uncertainty. Energy market uncertainty, especially the electricity market, is the result of the integration of commodity prices, demand fluctuation, and generation competition, as easily seen in deregulated markets. Depending on current or projected values for any of these factors, the economic attractiveness of any power plant construction project can change yearly or quarterly. For long-lead construction projects such as nuclear power plants, this uncertainty generates an implied and inherent risk for potential nuclear power plant owners and operators. The uncertainty in nuclear reactor and fuel cycle costs is in some respects better understood and quantified than the energy market uncertainty. The LWR-based fuel cycle has a long commercial history to use as its basis for cost estimation, and the current activities in LWR construction provide a reliable baseline for estimates for similar efforts. However, for advanced systems, the estimates and their associated uncertainties are based on forward-looking assumptions for performance after the system has been built and has achieved commercial operation. Advanced fuel materials and fabrication costs have large uncertainties based on complexities of operation, such as contact-handled fuel fabrication versus remote handling, or commodity availability. Thus, this analytical work makes a good faith effort to quantify uncertainties and provide qualifiers, caveats, and explanations for the sources of these uncertainties. The overall result is that this work assembles the necessary information and establishes the foundation for future analyses using more precise data as nuclear technology advances.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2014

Economic Conditions and Factors Affecting New Nuclear Power Deployment

This report documents work performed in support of the US Department of Energy Office of Nuclear Energy’s Advanced Small Modular Reactor (AdvSMR) program. The report presents information and results from economic analyses to describe current electricity market conditions and those key factors that may impact the deployment of AdvSMRs or any other new nuclear power plants. Thus, this report serves as a reference document for DOE as it moves forward with its plans to develop advanced reactors, including AdvSMRs. For the purpose of this analysis, information on electricity markets and nuclear power plant operating costs will be combined to examine the current state of the nuclear industry and the process required to successfully move forward with new nuclear power in general and AdvSMRs in particular. The current electricity market is generally unfavorable to new nuclear construction, especially in deregulated markets with heavy competition from natural gas and subsidized renewables. The successful and profitable operation of a nuclear power plant (or any power plant) requires the rate at which the electricity is sold to be sufficiently greater than the cost to operate. The wholesale rates in most US markets have settled into values that provide profits for most operating nuclear power plants but are too low to support the added cost of capital recovery for new nuclear construction. There is a strong geographic dependence on the wholesale rate, with some markets currently able to support new nuclear construction. However, there is also a strong geographic dependence on pronuclear public opinion; the areas where power prices are high tend to have unfavorable views on the construction of new nuclear power plants. The use of government-backed incentives, such as subsidies, can help provide a margin to help justify construction projects that otherwise may not seem viable. Similarly, low interest rates for the project will also add a positive margin to the economic analysis. In both cases, the profitable price point is decreased, making more markets open to profitable entry. Overall, the economic attractiveness of a nuclear power construction project is not only a function of its own costs, but a function of the market into which it is deployed. Many of the market characteristics are out of the control of the potential nuclear power plant operators. The decision-making process for the power industry in general is complicated by the short-term market volatility in both the wholesale electricity market and the commodity (natural gas) market. Decisions based on market conditions today may be rendered null and void in six months. With a multiple-year lead time, nuclear power plants are acutely vulnerable to market corrections.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2015

Epigenomic Adaptation to Low Dose Radiation

The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Foundational Report Series: Advanced Distribution Management Systems for Grid Modernization, DMS Integration of Distributed Energy Resources and Microgrids

Deregulation of the electric utility industry, environmental concerns associated with traditional fossil fuel-based power plants, volatility of electric energy costs, Federal and State regulatory support of “green” energy, and rapid technological developments all support the growth of Distributed Energy Resources (DERs) in electric utility systems and ensure an important role for DERs in the smart grid and other aspects of modern utilities. DERs include distributed generation (DG) systems, such as renewables; controllable loads (also known as demand response); and energy storage systems. This report describes the role of aggregators of DERs in providing optimal services to distribution networks, through DER monitoring and control systems—collectively referred to as a Distributed Energy Resource Management System (DERMS)—and microgrids in various configurations.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2019

Innovative Utility Offerings at the Distribution Edge: Case Studies from Around the Globe

The global evolution of the electricity sector - from deregulation, to higher penetrations of DERs, to digitization and changing consumer preferences - has delivered the utility industry to an inflection point. The vertically integrated, regulated model that persisted over most of the 20th century is undergoing a transformation, and utilities worldwide are responding with new approaches to the provision of products and services. This report catalogs several of these innovative approaches to incorporate new technologies such as electric vehicles, meet societal goals for a cleaner, more efficient electricity system, and empower consumers to make smarter energy choices and provide system benefits. The report comprises a series of 10 case studies across six continents, and features solutions touching on energy supply, energy efficiency, lighting, transport, data, heating and cooling, and rural/off-grid solutions. The diversity of products, programs, and markets documented illustrates the extent of the shift underway. Ultimately, the report demonstrates that utilities will continue to serve as critical partners in a global energy transition, and have been actively engaged in securing their position as such.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2021

Business Models for Coal Plant Decommissioning

Aging coal-fired power plants are retiring across the United States. Researchers at Pacific Northwest National Laboratory studied coal-fired power plant decommissioning business models to support program development for the Department of Energy’s Office of Energy Efficiency & Renewable Energy (EERE) to engage with communities affected by power plant retirement processes. Evaluating and reducing the impact on coal-dependent communities from phasing out coal production is a crucial piece of nationwide economic development and community-directed engagement in the clean energy future. This report describes the steps in the typical coal-fired power plant decommissioning process, including analysis of the following key factors: Drivers including policy and regulations, competition with other fuels, and corporate responsibility goals; Types of coal plant decommissioning including plant retirement without full decommissioning, repurposing with fuel switch, redeveloping to utilize existing transmission, and decommissioning and repurposing with other commercial activities; and, Costs of coal plant decommissioning, including variations across regulated and deregulated markets and the funding resources to support decommissioning activities. The details described in this report relied heavily on the availability of local news reports and communications regarding plant retirements, as the researchers identified a lack of formal literature surrounding business models for coal plant decommissioning and a need for a more robust source material collection. In addition, a lack of oversight entities responsible for decommissioning processes may have led to this shortfall of information. Future research regarding coal plant decommissioning can include quantitative studies on power plant retirement drivers, procedures, and costs, qualitative assessments on affects decommissioning has on surrounding communities, investors, and other stakeholders, and identifying best practices to engage community stakeholders in the decommissioning process.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2021

Understanding Your Utility Bills: Natural Gas

As a fossil fuel NG is a colorless and odorless gas in its natural state and is one of the cleanest burning hydrocarbons. The factors that contribute to the popularity of natural gas in the US manufacturing sector include ease of availability, clean burning properties, market deregulation, and increased domestic production. Analyzing natural gas (NG) bills can sometimes pose unique problems. Learning to read your utility bills and understand why your utility charges different fees is critical in maximizing your cost savings through energy efficiency. A key to creating a baseline is collecting and analyzing natural gas utility data. Historical data from NG bills can identify trends and help to find the baseline usage for a manufacturing operation. This guide intends to help Better Plant Program partners in understanding natural gas bills and analyzing usage to reduce costs. The guide focuses on natural gas production and transportation, understanding key charges on bills, different rate structures, and saving opportunities. A fictitious worked out example in the final section demonstrates how readers could go about analyzing natural gas bills.

03 NATURAL GAS↗