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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

MCL1 inhibition enhances the efficacy of docetaxel against airway-derived squamous cell carcinoma cells

Highlights: • Authentic squamous cell carcinoma (SqCC) cell lines of the lung are sparse. • HARA lung SqCC cells depend highly on MCL1 for survival in vitro and in vivo. • MCL1-silenced HARA cells decline in number upon docetaxel (DTX) exposure. • High MCL1 mRNA expression is linked with shorter survival in lung SqCC patients. • MCL1 depletion + DTX is highly effective against Detroit 562 pharyngeal SqCC cells. MCL1 is an anti-apoptotic BCL2 family member that is often overexpressed in various malignant tumors. However, few reports have described the role of MCL1 in squamous cell carcinoma (SqCC) derived from airways including the lung. In this study, we examined whether MCL1 could be a novel druggable target for airway-derived SqCC, for which effective molecular targeted drugs are unavailable. We searched the Kaplan–Meier Plotter database and found that high MCL1 mRNA expression was significantly associated with shorter survival in patients with lower airway (lung) or upper airway (head and neck) derived SqCC. We also explored the Expression Atlas database and learned that authentic lung SqCC cell lines expressing both TP63 and KRT5 mRNA were extremely sparse among the publicly available “lung SqCC cell lines”, with an exception being HARA cells. HARA cells were highly dependent on MCL1 for survival, and MCL1-depleted cells were not able to grow, and even declined in number, upon docetaxel (DTX) exposure in vitro and in vivo. Similar in vitro experimental findings, including those in a 3D culture model, were also obtained using Detroit 562 pharyngeal SqCC cells. These findings suggested that combined treatment with MCL1 silencing plus DTX appears highly effective against airway-derived SqCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Development and experimental verification of an active noise cancellation (ANC) method for non-invasive sensing

Ultrasonic wave propagation may be used in non-invasive sensing to identify the properties of a fluid in a container. An ultrasonic excitation can be coupled into the liquid or the gas through the walls of the container and detected by a receiver on the other side. However, in addition to this fluid path, another signal will also propagate through the structure and is referred as noise in this study. For most materials, this structural noise will be of higher amplitude compared to the fluid signal due to the large acoustic impedance difference between the solid container and the fluid. In this paper, an active noise cancellation (ANC) method is developed and demonstrated on an experimental setup. It was shown that this method cancels more than 90% of the noise signal in a given time window of interest. A sequential version of this cancellation method is also proposed, and it was shown that its performance improves as the number of canceling excitations is increased. The performance was found to be independent of the location of canceling transducers and position of the silence window but dependent on the width of the silence window. As an example, the ANC method was applied to noise cancellation of a signal travelling through water in a stainless-steel container. The signal-to-noise ratio (SNR) of the water signal in the window of interest was increased by 148% from 13.98 dB to 34.68 dB by using the proposed ANC method.

42 ENGINEERING↗
DOE OSTI2026

An expanded registry of candidate cis -regulatory elements

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, the ENCODE consortium mapped biochemical signals across hundreds of cell types and tissues and integrated these data to develop a registry containing 0.9 million human and 300,000 mouse candidate cis-regulatory elements (cCREs) annotated with potential functions. Here we have expanded the registry to include 2.37 million human and 967,000 mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays such as STARR-seq, massively parallel reporter assay, CRISPR perturbation and transgenic mouse assays have profiled more than 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer and silencer roles in different cellular contexts. Integrating the registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by the identification of KLF1 as a novel causal gene for red blood cell traits. This expanded registry is a valuable resource for studying the regulatory genome and its impact on health and disease.

Moore, Jill E. [Univ. of Massachusetts, Worchester↗
DOE OSTI2025

UDP-glucuronic acid decarboxylase in alfalfa: a target to improve ruminal digestibility of stems

Alfalfa (Medicago sativa) has a high nutritional value, but poor digestibility of the stems limits its value as an energy source in ruminant diets. Xylan and lignin negatively affect cell wall digestibility, whereas pectins have high digestibility in the rumen. In plants, UDP-xylose synthase (UXS) catalyses the decarboxylation of UDP-glucuronic acid to form UDP-xylose in an irreversible step that is key for xylan synthesis. Here, we functionally characterized two UXS genes in alfalfa, namely MsaUXS2 and MsaUXS4, and investigated their impact on ruminal digestibility. Both genes are more highly expressed in stems than leaves, and the enzymes have UDP-glucuronic acid decarboxylase activity in vitro. Silencing of MsaUXS2 and MsaUXS4 via RNAi altered plant growth and resulted in a 40% decrease in xylose, a 115% increase in arabinose, and a 60% increase in galacturonic acid in the polysaccharide matrix as well as a 20% decrease in lignin in the cell wall. Together, our results show a major role for UXS2 and UXS4 in xylan synthesis and secondary cell wall deposition in alfalfa. Additionally, in vitro rumen digestibility assays for the silenced lines had on average 30% increased gas production at 24 h, demonstrating the potential of targeting UXS genes to increase stem digestibility.

UDP-xylose synthase↗
DOE OSTI2023

Tetratricopeptide repeat protein SlREC2 positively regulates cold tolerance in tomato

Abstract Cold stress is a key environmental constraint that dramatically affects the growth, productivity, and quality of tomato (Solanum lycopersicum); however, the underlying molecular mechanisms of cold tolerance remain poorly understood. In this study, we identified REDUCED CHLOROPLAST COVERAGE 2 (SlREC2) encoding a tetratricopeptide repeat protein that positively regulates tomato cold tolerance. Disruption of SlREC2 largely reduced abscisic acid (ABA) levels, photoprotection, and the expression of C-REPEAT BINDING FACTOR (CBF)-pathway genes in tomato plants under cold stress. ABA deficiency in the notabilis (not) mutant, which carries a mutation in 9-CIS-EPOXYCAROTENOID DIOXYGENASE 1 (SlNCED1), strongly inhibited the cold tolerance of SlREC2-silenced plants and empty vector control plants and resulted in a similar phenotype. In addition, foliar application of ABA rescued the cold tolerance of SlREC2-silenced plants, which confirms that SlNCED1-mediated ABA accumulation is required for SlREC2-regulated cold tolerance. Strikingly, SlREC2 physically interacted with β-RING CAROTENE HYDROXYLASE 1b (SlBCH1b), a key regulatory enzyme in the xanthophyll cycle. Disruption of SlBCH1b severely impaired photoprotection, ABA accumulation, and CBF-pathway gene expression in tomato plants under cold stress. Taken together, this study reveals that SlREC2 interacts with SlBCH1b to enhance cold tolerance in tomato via integration of SlNCED1-mediated ABA accumulation, photoprotection, and the CBF-pathway, thus providing further genetic knowledge for breeding cold-resistant tomato varieties.

Zhang, Ying (ORCID:0000000169841164)↗
DOE OSTI2024

Powdery mildew effectors AVR A1 and BEC1016 target the ER J‐domain protein Hv ERdj3B required for immunity in barley

Abstract The barley powdery mildew fungus, Blumeria hordei (Bh), secretes hundreds of candidate secreted effector proteins (CSEPs) to facilitate pathogen infection and colonization. One of these, CSEP0008, is directly recognized by the barley nucleotide‐binding leucine‐rich‐repeat (NLR) receptor MLA1 and therefore is designated AVR A1 . Here, we show that AVR A1 and the sequence‐unrelated Bh effector BEC1016 (CSEP0491) suppress immunity in barley. We used yeast two‐hybrid next‐generation interaction screens (Y2H‐NGIS), followed by binary Y2H and in planta protein–protein interactions studies, and identified a common barley target of AVR A1 and BEC1016, the endoplasmic reticulum (ER)‐localized J‐domain protein Hv ERdj3B. Silencing of this ER quality control (ERQC) protein increased Bh penetration. Hv ERdj3B is ER luminal, and we showed using split GFP that AVR A1 and BEC1016 translocate into the ER signal peptide‐independently. Overexpression of the two effectors impeded trafficking of a vacuolar marker through the ER; silencing of Hv ERdj3B also exhibited this same cellular phenotype, coinciding with the effectors targeting this ERQC component. Together, these results suggest that the barley innate immunity, preventing Bh entry into epidermal cells, requires ERQC. Here, the J‐domain protein Hv ERdj3B appears to be essential and can be regulated by AVR A1 and BEC1016. Plant disease resistance often occurs upon direct or indirect recognition of pathogen effectors by host NLR receptors. Previous work has shown that AVR A1 is directly recognized in the cytosol by the immune receptor MLA1. We speculate that the AVR A1 J‐domain target being inside the ER, where it is inapproachable by NLRs, has forced the plant to evolve this challenging direct recognition.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Populus MYC2 orchestrates root transcriptional reprogramming of defence pathway to impair Laccaria bicolor ectomycorrhizal development

Summary The jasmonic acid (JA) signalling pathway plays an important role in the establishment of the ectomycorrhizal symbiosis. The Laccaria bicolor effector MiSSP7 stabilizes JA corepressor JAZ6, thereby inhibiting the activity of Populus MYC2 transcription factors. Although the role of MYC2 in orchestrating plant defences against pathogens is well established, its exact contribution to ECM symbiosis remains unclear. This information is crucial for understanding the balance between plant immunity and symbiotic relationships. Transgenic poplars overexpressing or silencing for the two paralogues of MYC2 transcription factor (MYC2s) were produced, and their ability to establish ectomycorrhiza was assessed. Transcriptomics and DNA affinity purification sequencing were performed. MYC2s overexpression led to a decrease in fungal colonization, whereas its silencing increased it. The enrichment of terpene synthase genes in the MYC2‐regulated gene set suggests a complex interplay between the host monoterpenes and fungal growth. Several root monoterpenes have been identified as inhibitors of fungal growth and ECM symbiosis. Our results highlight the significance of poplar MYC2s and terpenes in mutualistic symbiosis by controlling root fungal colonization. We identified poplar genes which direct or indirect control by MYC2 is required for ECM establishment. These findings deepen our understanding of the molecular mechanisms underlying ECM symbiosis.

Marqués‐Gálvez, José Eduardo↗
DOE OSTI2022

GhBZR3 suppresses cotton fiber elongation by inhibiting very‐long‐chain fatty acid biosynthesis

SUMMARY The BRASSINAZOLE‐RESISTANT (BZR) transcription factor is a core component of brassinosteroid (BR) signaling and is involved in the development of many plant species. BR is essential for the initiation and elongation of cotton fibers. However, the mechanism of BR‐regulating fiber development and the function of BZR is poorly understood in Gossypium hirsutum L. (cotton). Here, we identified a BZR family transcription factor protein referred to as GhBZR3 in cotton. Overexpression of GhBZR3 in Arabidopsis caused shorter root hair length, hypocotyl length, and hypocotyl cell length, indicating that GhBZR3 negatively regulates cell elongation. Pathway enrichment analysis from VIGS ‐GhBZR3 cotton plants found that fatty acid metabolism and degradation might be the regulatory pathway that is primarily controlled by GhBZR3. Silencing GhBZR3 expression in cotton resulted in taller plant height as well as longer fibers. The very‐long‐chain fatty acid (VLCFA) content was also significantly increased in silenced GhBZR3 plants compared with the wild type. The GhKCS13 promoter, a key gene for VLCFA biosynthesis, contains two GhBZR3 binding sites. The results of yeast one‐hybrid, electrophoretic mobility shift, and luciferase assays revealed that GhBZR3 directly interacted with the GhKCS13 promoter to suppress gene expression. Taken together, these results indicate that GhBZR3 negatively regulates cotton fiber development by reducing VLCFA biosynthesis. This study not only deepens our understanding of GhBZR3 function in cotton fiber development, but also highlights the potential of improving cotton fiber length and plant growth using GhBZR3 and its related genes in future cotton breeding programs.

Shi, Zemin↗
DOE OSTI2025

RNAi and genome editing of sugarcane: Progress and prospects

SUMMARY Sugarcane, which provides 80% of global table sugar and 40% of biofuel, presents unique breeding challenges due to its highly polyploid, heterozygous, and frequently aneuploid genome. Significant progress has been made in developing genetic resources, including the recently completed reference genome of the sugarcane cultivar R570 and pan‐genomic resources from sorghum, a closely related diploid species. Biotechnological approaches including RNA interference (RNAi), overexpression of transgenes, and gene editing technologies offer promising avenues for accelerating sugarcane improvement. These methods have successfully targeted genes involved in important traits such as sucrose accumulation, lignin biosynthesis, biomass oil accumulation, and stress response. One of the main transformation methods—biolistic gene transfer or Agrobacterium ‐mediated transformation—coupled with efficient tissue culture protocols, is typically used for implementing these biotechnology approaches. Emerging technologies show promise for overcoming current limitations. The use of morphogenic genes can help address genotype constraints and improve transformation efficiency. Tissue culture‐free technologies, such as spray‐induced gene silencing, virus‐induced gene silencing, or virus‐induced gene editing, offer potential for accelerating functional genomics studies. Additionally, novel approaches including base and prime editing, orthogonal synthetic transcription factors, and synthetic directed evolution present opportunities for enhancing sugarcane traits. These advances collectively aim to improve sugarcane's efficiency as a crop for both sugar and biofuel production. This review aims to discuss the progress made in sugarcane methodologies, with a focus on RNAi and gene editing approaches, how RNAi can be used to inform functional gene targets, and future improvements and applications.

Brant, Eleanor [Agronomy Department, Plant Molecul↗
DOE OSTI2026

Structure-function analysis of the FCRL5–IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG

The Fc region of therapeutic IgG antibodies is often engineered to remove or “silence” Fc effector functions, but it remains unclear whether these mutations eliminate all Fc-mediated effector activity. Human Fc receptor-like 5 (FCRL5/FcRH5) is a low-affinity IgG Fc receptor expressed on B cells and is an actively pursued antibody target in multiple myeloma. Here, we show that common Fc function-silencing mutations do not impair FCRL5-mediated activity and therefore attenuate, rather than eliminate, Fc effector function. The crystal structure of the FCRL5-IgG1 Fc complex, solved at 3.4 Å resolution, revealed that FCRL5 binds IgG1 Fc in a 1:1 complex through a binding mode distinct from that of classical Fcγ receptors, explaining why mutations that attenuate Fc effector function spare FCRL5 binding. Fc-engineered antibodies that selectively engage FCRL5 inhibited B cell receptor-induced Ca 2+ flux in FCRL5-expressing B cells. These findings demonstrate that Fc-attenuated therapeutic IgG retains the ability to engage FCRL5, identifying an unappreciated pathway for B cell modulation.

Herpers, Bart M. [Department of Biomedical Enginee↗
DOE OSTI2022

Why Black Flowers? An Extreme Environment and Molecular Perspective of Black Color Accumulation in the Ornamental and Food Crops

Pollinators are attracted to vibrant flower colors. That is why flower color is the key agent to allow successful fruit set in food or ornamental crops. However, black flower color is the least attractive to pollinators, although a number of plant species produce black flowers. Cyanidin-based anthocyanins are thought to be the key agents to induce black color in the ornamental and fruit crops. R2R3-MYB transcription factors (TFs) play key roles for the tissue-specific accumulation of anthocyanin. MYB1 and MYB11 are the key TFs regulating the expression of anthocyanin biosynthesis genes for black color accumulation. Post-transcriptional silencing of flavone synthase II ( FNS ) gene is the technological method to stimulate the accumulation of cyanidin-based anthocyanins in black cultivars. Type 1 promoter of DvIVS takes the advantage of FNS silencing to produce large amounts of black anthocyanins. Exogenous ethylene application triggers anthocyanin accumulation in the fruit skin at ripening. Environment cues have been the pivotal regulators to allow differential accumulation of anthocyanins to regulate black color. Heat stress is one of the most important environmental stimulus that regulates concentration gradient of anthocyanins in various plant parts, thereby affecting the color pattern of flowers. Stability of black anthocyanins in the extreme environments can save the damage, especially in fruits, caused by abiotic stress. White flowers without anthocyanin face more damages from abiotic stress than dark color flowers. The intensity and pattern of flower color accumulation determine the overall fruit set, thereby controlling crop yield and human food needs. This review paper presents comprehensive knowledge of black flower regulation as affected by high temperature stress, and the molecular regulators of anthocyanin for black color in ornamental and food crops. It also discusses the black color-pollination interaction pattern affected by heat stress for food and ornamental crops.

Ahmad, Sagheer↗
DOE OSTI2024

Overexpression of the Mas1 gene mitigated LPS-induced inflammatory injury in mammary epithelial cells by inhibiting the NF-κB/MAPKs signaling pathways

Breast infection is the primary etiology of mastitis in dairy cows, leading to a reduction in the quality of dairy products and resulting in substantial economic losses for animal husbandry. Although antibiotic treatment can eliminate the pathogenic microorganisms that induce mastitis, it cannot repair the inflammatory damage of mammary epithelial cells and blood milk barrier. Mas1 is a G protein-coupled receptor, and its role in lipopolysaccharide (LPS) -induced inflammatory injury to mammary epithelial cells has not been studied. LPS treatment of EpH4 EV cells led to a significant downregulation of Mas1 transcript levels, which attracted our great interest, suggesting that Mas1 may be an important target for the treatment of mastitis. Therefore, this study intends to verify the role of Mas1 in the inflammatory injury of EpH4 EV cells by gene overexpression technology and gene silencing technology. The findings demonstrated that the overexpression of the Mas1 gene effectively reversed the activation of the nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathways induced by LPS, while also suppressing the upregulation of pro-inflammatory mediators. Furthermore, overexpression of the Mas1 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, and Claudin-3 caused by LPS, suggesting that Mas1 could promote to repair the blood-milk barrier. However, the silencing of the Mas1 gene using siRNA resulted in a contrasting effect. These results indicated that Mas1 alleviated the inflammatory injury of mammary epithelial cells induced by LPS.

Yan, Shuping↗
NASA NTRS1974

Reduction of diesel engine exhaust noise in the petroleum mining industry

An important noise source in a drilling plant is Diesel engine exhaust. In order to reduce this noise, a reactive silencer of the derivative resonator type was proposed, calculated from the acoustic and design point of view and applied. As a result of applying such a silencer on the exhaust conduit of a Diesel engine the noise level dropped down to 18 db.

Marinov, T.↗
NASA NTRS1985

Application of High Order Acoustic Finite Elements to Transmission Losses and Enclosure Problems

A family of acoustic finite elements was developed based on C continuity (acoustic pressure being the nodal variable) and the no-flow condition. The family include triangular, quadrilateral and hexahedral isoparametric elements with linear quadratic and cubic variation in modelling and distortion. Of greatest use in problems with irregular boundaries are the cubic isoparametric elements: the 32 node hexahedral element for three-dimensional systems; and the twelve node quadrilateral and ten node triangular elements for two-dimensional/axisymmetric applications. These elements were applied to problems involving cavity resonances, transmission loss in silencers and the study of end effects, using a Floating Point Systems 164 attached array processor accessed through an Amdahl 5860 mainframe. The elements are presently being used to study the end effects associated with duct terminations within finite enclosures. The transmission losses with various silencers and sidebranches in ducts is also being studied using the same elements.

Craggs, A.↗
NASA NTRS1989

Supersonic propeller noise in a uniform flow

The sound field produced by a supersonic propeller operating in a uniform flow is investigated. The main interest is the effect of the finite forward flight speed on the directivity of the sound field as seen by an observer on the aircraft. It is found that there are cones of silence on the axis of the propeller. The semiapex angles on these cones are equal fore and aft of the propeller plane, and depend on the tip Mach number only. The Fourier coefficients of the acoustic pressure contain the Doppler amplification factor. The sound field weakens in the upstream direction and strengthen downstream. Kinematic considerations of the emitted Mach waves not only confirm these results, but also provide physical insight into the sound generation mechanism. The predicted zone of silence and the Doppler amplification factor are compared to the theoretical prediction of shock wave formation and the flight test of the SR3 propeller.

Jou, Wen-Huei↗
NASA NTRS1995

An extension of the Lighthill theory of jet noise to encompass refraction and shielding

A formalism for jet noise prediction is derived that includes the refractive 'cone of silence' and other effects; outside the cone it approximates the simple Lighthill format. A key step is deferral of the simplifying assumption of uniform density in the dominant 'source' term. The result is conversion to a convected wave equation retaining the basic Lighthill source term. The main effect is to amend the Lighthill solution to allow for refraction by mean flow gradients, achieved via a frequency-dependent directional factor. A general formula for power spectral density emitted from unit volume is developed as the Lighthill-based value multiplied by a squared 'normalized' Green's function (the directional factor), referred to a stationary point source. The convective motion of the sources, with its powerful amplifying effect, also directional, is already accounted for in the Lighthill format: wave convection and source convection are decoupled. The normalized Green's function appears to be near unity outside the refraction dominated 'cone of silence', this validates our long term practice of using Lighthill-based approaches outside the cone, with extension inside via the Green's function. The function is obtained either experimentally (injected 'point' source) or numerically (computational aeroacoustics). Approximation by unity seems adequate except near the cone and except when there are shrouding jets: in that case the difference from unity quantifies the shielding effect. Further extension yields dipole and monopole source terms (cf. Morfey, Mani, and others) when the mean flow possesses density gradients (e.g., hot jets).

Ribner, Herbert S.↗
NASA NTRS2000

Advanced Propulsion System Studies in High Speed Research

Propulsion for acceptable supersonic passenger transport aircraft is primarily impacted by the very high jet noise characteristics of otherwise attractive engines. The mixed flow turbofan, when equipped with a special ejector nozzle seems to be the best candidate engine for this task of combining low jet noise with acceptable flight performance. Design, performance, and operation aspects of mixed flow turbofans are discussed. If the special silencing nozzle is too large, too heavy, or not as effective as expected, alternative concepts in mixed flow engines should be examined. Presented herein is a brief summary of efforts performed under cooperative agreement NCC3-193. Three alternative engine concepts, conceived during this study effort, are herein presented and their limitations and potentials are described. These three concepts intentionally avoid the use of special silencing nozzles and achieve low jet noise by airflow augmentation of the engine cycle.

Zola, Charles L.↗
NASA NTRS2002

NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons

The neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.

Hippocampus/cytology/metabolism↗