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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 775 records · Page 43
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

FTO regulates myoblast proliferation by controlling CCND1 expression in an m6A-YTHDF2-dependent manner

Highlights: • Silencing FTO delays cell cycle and inhibits cell proliferation. • FTO regulates cell proliferation depending on its m{sup 6}A demethylation activity. • Silencing FTO suppresses CCND1 expression via YTHDF2-mediated mRNA degradation. • Knockdown YTHDF2 eliminates the cell cycle arrest in FTO-deficient cells. N6-Methyladenosine (m{sup 6}A) modification is the most abundant chemical modification in mRNA, and it participates in various biological processes, such as cell differentiation and proliferation. However, little is known about the function of m{sup 6}A demethylase fat mass and obesity-associated (FTO) in myoblast proliferation. Here, we demonstrated that knockdown of FTO can significantly inhibit myoblast proliferation and promote apoptosis. RNA sequencing analysis revealed that a lot of downregulated genes in FTO knockdown cells are associated with cell cycle and apoptosis. Furthermore, silencing FTO drastically decreased cyclin D1 (CCND1) expression through YTHDF2-mediated mRNA degradation, thereby delaying the progression of G1 phase, and leading to impaired myoblast proliferation. These findings unraveled that FTO regulates myoblast proliferation by controlling CCND1 expression in an m{sup 6}A-YTHDF2-dependent manner, which highlights the critical roles of m{sup 6}A modification in myoblast proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Knockdown of NLE1 inhibits development of malignant melanoma in vitro and in vivo NLE1 promotes development of malignant melanoma

Melanoma, which originates from neural crest derived melanocytes, causes severe pain and even death to numerous patients. Previous studies reported that Notchless Homolog 1 (NLE1) plays an important role in cell proliferation, transcription and signal transduction. However, the clinical significance and biological behavior of NLE1 in melanoma remain a mystery. Thus, the role of NLE1 in melanoma was investigated in vitro and in vivo. The expression of NLE1 in melanoma was elevated and the expression level was positively correlated with lymphatic metastasis and tumor stage. In addition, NLE1 knockdown by shRNA specifically inhibited proliferation, enhanced the apoptotic sensitivity and hindered migration of melanoma cells in vitro. Mice xenograft model further showed that NLE1 knockdown could inhibit the tumor formation of melanoma in vivo. Additionally, the induction of apoptosis of melanoma cells by NLE1 knockdown required the participation of a series of apoptosis-related proteins. Besides, NLE1 can activate the PI3K/AKT signaling pathway. In summary, NLE1 was involved in the development and progression of melanoma, which may be a novel potential target for molecular therapy of melanoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Single-cell RNA-seq revealed diverse cell types in the mouse placenta at mid-gestation

The mammalian placenta consists of a set of cells to ensure normal placental functions throughout gestation. Dysfunctional placentae are considered as the origin of a series of pregnancy complications. Therefore, it is urgent for detailed information about the molecular recipes of the cell types within the normal placenta. In the past years, gene expression analysis via single-cell RNA-seq (scRNA-seq) offers opportunities to identify new cell types in a variety of organs and tissues. In this study, scRNA-seq was used to explore the cell heterogeneity within the E10.5 mouse placenta and unravel their discrepancies in cell composition and communications. We identified sixteen cell clusters, including some cell clusters that originated from the maternal tissue. Moreover, we traced the developmental trajectories of trophoblasts and Hofbauer-like cells. Further analysis revealed cell connections between the endothelial cells and pericytes, syncytiotrophoblasts, as well as decidual cells. Besides, we highlighted several signaling pathways, such as the EGF, FGF, canonical, and non-canonical WNT signaling pathways, which mediated the potential crosstalk between different cell types within placenta. Our research provides an in-depth understanding of placental development, cellular composition, and communications at the maternal-fetal interface.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Interleukin-35 inhibits lipopolysaccharide-induced endothelial cell activation by downregulating inflammation and apoptosis

Inflammation is an essential factor contributing to sepsis-induced endothelial cell (EC) activation. Interleukin-35 (IL-35) is an anti-inflammatory/immunosuppressive cytokine that exerts protective effects on many inflammatory diseases. In this study, we investigated the effects of IL-35 on lipopolysaccharide (LPS)-induced EC activation and the potential underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (1 μg/ml) for 24 h and then cocultured with different concentrations (0, 1, 10, or 100 ng/ml) of recombinant human IL-35 (rhIL-35) for 12 h. Flow cytometry analysis revealed that IL-35 inhibited LPS-induced HUVEC apoptosis in a dose-dependent manner. RT-qPCR and Western blot analyses showed significantly higher mRNA and protein levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the inflammatory factors IL-6 and IL-8 in the LPS group than in the control group. These changes were alleviated by IL-35 treatment, suggesting that IL-35 protects ECs by downregulating inflammation. Furthermore, IL-35 induced signal transducer and activator of transcription 1 (STAT1) and STAT4 activation and promoted their interaction. Blocking STAT1 or STAT4 expression by fludarabine (STAT1 inhibitor) treatment or siRNA-STAT4-interfering fragment transfection inhibited the protective effect of IL-35 on ECs. Moreover, we observed a similar protective effect of IL-35 treatment on ECs in a mouse sepsis model induced by intraperitoneal LPS injection. This study indicated that IL-35 exerts anti-inflammatory and antiapoptotic effects on LPS-induced EC activation by activating the STAT1 and STAT4 signaling pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

AGTR1 blocker attenuates activation of Tenon's capsule fibroblasts after glaucoma filtration surgery via the NF-κB signaling pathway

Activation of Tenon's capsule fibroblasts limits the success rate of glaucoma filtration surgery (GFS), the most efficacious therapy for patients with glaucoma. Angiotensin type 1 receptor (AGTR1) is involved in tissues remodeling and fibrogenesis. However, whether AGTR1 is involved in the progress of fibrogenesis after GFS is not fully elucidated. The aim of this study was to investigate the role of an AGTR1 in scar formation after GFS and the potential anti-fibrosis effect of AGTR1 blocker. AGTR1 expression level was increased in subconjunctival tissues in a rat model of GFS and transforming growth factor-beta 2 (TGF-β2)-induced human Tenon's capsule fibroblasts (HTFs). AGTR1 blocker treatment suppressed TGF-β2-induced HTF migration and α-smooth muscle actin (α-SMA) and fibronectin (FN) expression. AGTR1 blocker treatment also attenuated collagen deposition and α-SMA and FN expression in subconjunctival tissues of the rat model after GFS. Moreover, AGTR1 blocker decreased TGF-β2-induced P65 phosphorylation, P65 nuclear translocation, and nuclear factor kappa B (NF-κB) luciferase activity. Additionally, BAY 11–7082 (an NF-κB inhibitor) significantly suppressed HTF fibrosis. In conclusion, our results indicate that AGTR1 is involved in scar formation after GFS. The AGTR1 blocker attenuates subconjunctival fibrosis after GFS by inhibiting the NF-κB signaling pathway. These findings indicate that targeting AGTR1 is a potential approach to attenuate fibrosis after GFS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Triggering the stringent response enhances synthetic methanol utilization in Escherichia coli

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, i.e. the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here in this paper, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. By activating the stringent/stress response via ppGpp overproduction, or DksA and RpoS overexpression, we demonstrate improved biosynthesis of proteinogenic amino acids via endogenous upregulation of amino acid synthesis pathway genes. Thus, we were able to achieve biosynthesis of several limiting amino acids from methanol-derived carbon, in contrast to the control methylotrophic E. coli strain. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via stringent/stress response activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

The distributional impact of FEMA’s community rating system

Community Rating System (CRS) incentivizes investments in risk reduction above NFIP standards using discounts on insurance premiums. These discounts are cross-subsidized by increasing premiums in non-CRS communities. We examine the distribution of these subsidies and find that redistribution does occur, but the gains and losses are not economically large with 95% of households gaining or losing no more than 0.3% of household income. We also examine their relationship with other community characteristics and find that the strongest predictor of premium reductions is the underlying flood risk level within the community. Thus, CRS appears to reduce the cost of living in the riskier communities.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2026

Revisiting the validity of eddy viscosity models for predicting airflow over water waves

In this study, we revisit the validity of eddy viscosity models for predicting wave-induced airflow disturbances over ocean surface waves. We first derive a turbulence curvilinear model for the phase-averaged Navier–Stokes equations, extending the work of Cao, Deng & Shen (2020 J. Fluid Mech. 901, A27), by incorporating turbulence stress terms previously neglected in the linearised viscous curvilinear model. To verify our formulation, we perform a priori tests by numerically solving the model using mean wind and turbulence stress profiles from large-eddy simulations (LES) of airflow over waves across various wave ages. Results show that including turbulence stress terms improves wave-induced airflow predictions compared with the previous viscous curvilinear model. We further show that using a standard mixing-length eddy viscosity yields inaccurate predictions at certain wave ages, as it fails to capture wave-induced turbulence, which fundamentally differs from mean shear-driven turbulence. The LES data show that accurate representations of wave-induced stresses require a complex-valued eddy viscosity. The maximum magnitude of this eddy viscosity scales as ∼𝑢 𝜏 ⁢𝜁 𝑖𝑛𝑛𝑒𝑟 , where 𝑢 𝜏 is the friction velocity and 𝜁 𝑖𝑛𝑛𝑒𝑟 is the inner-layer thickness, the height at which the eddy-turnover time matches the wave advection time scale. This scaling aligns with the prediction by Belcher & Hunt (1993 J. Fluid Mech. 251, 109–148). Overall, the findings demonstrate that traditional eddy viscosity models are inadequate for capturing wave-induced turbulence. More sophisticated turbulence models are essential for the accurate prediction of airflow disturbances and form drag in wind–wave interaction models.

16 TIDAL AND WAVE POWER↗
DOE OSTI2025

Anisotropic Heating and Parallel Heat Flux in Electron-only Magnetic Reconnection with Intense Guide Fields

Electron-only reconnection (E-REC) is a process recently observed in the Earth’s magnetosheath, where magnetic reconnection occurs at electron kinetic scales, and ions do not couple to the reconnection process. Electron-only reconnection is likely to have a significant impact on the energy conversion and dissipation of turbulence cascades at kinetic scales in some settings. This paper investigates E-REC under different intensities of strong guide fields (the ratio between the guide field and the in-plane asymptotic field strength is 5, 10 and 20, respectively) via two-dimensional fully kinetic particle-in-cell simulations, focusing on electron heating. The simulations are initialized with a force-free current sheet equilibrium under various intensities of strong guide fields. Similarly to previous experimental studies, electron temperature anisotropy along separatrices is observed, which is found to be mainly caused by the variations of parallel temperature. Both regions of anisotropy and parallel temperature increase/decrease along separatrices become thinner with increasing guide fields. Besides, we find a transition from a quadrupolar to a hexapolar (six-polar) to an octopolar (eight-polar) structure in temperature anisotropy and parallel temperature as the guide field intensifies. Non-Maxwellian electron velocity distribution functions (EVDFs) at different locations in the three simulations are observed. Our results show that parallel electron velocity varies notably with different guide field intensities and finite parallel electron heat flux density is observed. The three simulations exhibit features of the Chew–Goldberger–Low theory, with the level of consistency increasing as the guide field strength increases. This explains the electron parallel temperature variations and the shape of the EVDFs observed along the separatrices. This work may provide insights into the understanding of electron heating and parallel heat flux density in E-REC observed in the turbulent magnetosheath.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

A Novel Solid Form of Erlotinib: Synthesis by Heterogeneous Complexation and Characterization by NMR Crystallography

We describe the synthesis of a novel complex of the anticancer "active pharmaceutical ingredient erlotinib (ERL) via heterogeneous nucleation on polished zinc tiles. The resulting product, ERL 2 ·ZnCl 2 , is characterized by single-crystal X-ray diffraction, multinuclear solid-state NMR (ssNMR) spectroscopy, and density functional theory (DFT) calculations. Also characterized are the hydrochloride salt (ERL·HCl) and monohydrate free base (ERL·H 2 O) forms of erlotinib. 13 C ssNMR spectroscopy is useful for site-by-site assignment and rapid fingerprinting, while also providing preliminary structural interpretations, such as the number of molecules in the asymmetric unit. 35 Cl ssNMR can readily differentiate between the chloride ions in ERL·HCl and the covalently bonded chlorine in ERL 2 ·ZnCl 2 . 15 N ssNMR proves to be critical here because of the large isotropic chemical shift differences between ERL·H 2 O, ERL·HCl, and ERL 2 ·ZnCl 2 . The 15 N chemical shift tensors are linked directly to differences in structure and bonding with the aid of DFT calculations. Together, these results demonstrate the utility of multinuclear NMR crystallography for the characterization of solid forms of APIs, especially when other analytical techniques face significant challenges.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Crystal Structure and Atomic Vacancy Optimized Thermoelectric Properties in Gadolinium Selenides

Thermoelectric materials enable the energy conversion of waste heat into electricity, helpful to relieve global energy crisis. Here, we report a systematic investigation on high-temperature thermoelectric gadolinium selenides, cubic Gd 3-x Se 4 (x = 0.16, 0.21 and 0.25) and orthorhombic Gd 2 Se 3-y (y = 0.02, 0.06 and 0.08). High energy synchrotron x-ray diffraction and total scattering have been used to investigate the crystallographic and local structures. Atomic-scale clusters of Gd vacancy in the cubic phase are observed by employing the reverse Monte Carlo simulation. For cubic Gd 3-x Se 4 , adjusting Gd vacancy triggers the effect of multiple conduction bands, confirmed by the increase in effective masses and theoretical calculations. A reasonable peak zT value of 0.27 is achieved at 850 K for Gd 3-x Se 4 (x = 0.16). On the other hand, tuning Se vacancy enables the optimization of electron concentration for the orthorhombic Gd 2 Se 3-y . More significantly, its low deformation potential (Ξ = 12eV) gives rise to enhanced electron mobility and higher peak zT value of 0.54 at 850 K for Gd 2 Se 3-y (y = 0.02). Intriguingly, a higher zT of 1.2 at 1200 K is reasonably predicted by quality factor analysis. Finally, this work extends the scope of high-temperature thermoelectric materials and facilitates the exploration of novel high-temperature thermoelectric materials

36 MATERIALS SCIENCE↗
DOE OSTI2021

Nanoscale Phase Separation and Large Refrigerant Capacity in Magnetocaloric Material LaFe 11.5 Si 1.5

Here, ferromagnetic transitions, the magnetocaloric effect, and the atomic-scale microstructure in an annealed bulk material of LaFe 11.5 Si 1.5 were investigated using magnetic measurements, Mössbauer spectroscopy, high-resolution X-ray diffraction analysis, and high-resolution transmission electron microscopy. The results provide evidence of the coexistence of two ferromagnetic phases with different Curie temperatures. The phase with a Curie temperature of 216 K corresponds to a Si-rich phase of a NaZn 13 -type structure with a small lattice volume, whereas the phase with a Curie temperature of 185 K corresponds to a Si-poor phase of a NaZn 13 -type structure with a large lattice volume. This phase coexistence is observed on a nanometer scale and it can account for inverse thermal hysteresis of the ferromagnetic transition in the Si-rich phase during warming. Furthermore, the phase coexistence helps the bulk material achieve a refrigeration capacity of 170 J kg -1 due to a combination of the magnetocaloric effect in each phase. It is determined that the magnetocaloric effect in the Si-rich and the Si-poor phase brings about a maximum of the total entropy change of -3.55 and -6.80 and J kg -1 K -1 at respective Curie temperatures, respectively. Fundamentally, the phase coexistence indicates coloring of Si atoms in the lattice of a NaZn 13 -type structure and can be attributed to nanoscale phase separation of a disordered precursor during annealing of the bulk material. The nanoscale phase separation may occur in other magnetocaloric materials, thus allowing for improvement of their refrigeration capacity.

36 MATERIALS SCIENCE↗