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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Numerical Investigation of the Effect of Rolling on the Localized Stress and Strain Induction for Wire + Arc Additive Manufactured Structures

Cold rolling can be used in-process or post-process to improve microstructure, mechanical properties and residual stress in directed-energy-deposition techniques, such as the high deposition rate wire + arc additive manufacturing (WAAM) process. Finite element simulations of the rolling process are employed to investigate the effect of rolling parameters, in particular rolling load and roller profile radius on the residual stress field as well as plastic strain distribution for the profiled roller. The results show the response to rolling of commonly used structural metals in WAAM, i.e., AA2319, S335JR steel and Ti-6Al-4V, taking into account the presence of residual stresses. The rolling load leads to changes in the location and the maximum value of the compressive residual stresses, as well as the depth of the compressive residual stresses. However, the roller profile radius only changes the maximum value of these compressive residual stresses. Changing the rolling load influences the equivalent plastic strain close to the top surface of the wall as well as in deeper areas, whereas the influence of the roller profile radius is negligible. The plastic strain distribution is virtually unaffected by the initial residual stresses prior to rolling. Finally, design curves were generated from the simulations for different materials, suggesting ideal rolling load and roller profile combinations for microstructural improvement requiring certain plastic strains at a specific depth of the additive structure.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Cell membrane dynamics induction using optogenetic tools

Highlights: • Actin-based cell membrane movements play important roles in various cellular functions. • Recently, we developed a brand-new optogenetic tool, called the Magnet system. • This tool enabled us to spatiotemporally induce the change in cell membrane dynamics. • In this review, we summarized recent advances in optogenetic tools and our Magnet system. Structures arising from actin-based cell membrane movements, including ruffles, lamellipodia, and filopodia, play important roles in a broad spectrum of cellular functions, such as cell motility, axon guidance in neurons, wound healing, and micropinocytosis. Previous studies investigating these cell membrane dynamics often relied on pharmacological inhibition, RNA interference, and constitutive active/dominant negative protein expression systems. However, such studies did not allow the modulation of protein activity at specific regions of cells, tissues, and organs in animals with high spatial and temporal precision. Recently, optogenetic tools for inducing cell membrane dynamics have been developed which address several disadvantages of previous techniques. In a recent study, we developed a powerful optogenetic tool, called the Magnet system, to change cell membrane dynamics through Tiam1 and PIP3 signal transductions with high spatial and temporal resolution. In this review, we summarize recent advances in optogenetic tools that allow us to induce actin-regulated cell membrane dynamics and unique membrane ruffles that we discovered using our Magnet system.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of immune-related gene expression by seminal exosomes in the porcine endometrium

Highlights: • Exosomes are present in sperm-rich fraction of porcine seminal plasma (SP). • Exosomes present in SP regulate immune-related genes in the porcine uterus. • Seminal exosomes may pave the way for sperm and fertilized egg transport. Seminal plasma (SP) is considered as a vehicle to carry sperm into female reproductive tract, of which functions have not been completely understood. This study aimed to identify the function of seminal exosomes on porcine endometrium. Exosomes were isolated from the sperm-rich fraction of boar semen and were confirmed by the expression of exosome marker HSP70 and size distribution using nano-sight tracking analysis. Porcine endometrial epithelial cells (EECs) were then treated with seminal exosomes, and RNA extracted were subjected to global expression analysis. Transcripts related to “immune response”, “inflammatory response” and their associated signaling pathways were up-regulated in EECs treated with seminal exosome, whereas those associated with “steroid biosynthesis”, “metabolic pathways” and “T cell differentiation” were down-regulated. The decrease in PMVK, SC5D, INSIG1, HSD17B7, NSDHL, HMGCR, SQLE and FDFT1, and increase in CCL20, TNFSF15, AMCFII, CXCL2 and CXCL8 were also found in the endometrium from the naturally mated pigs. Moreover, changes in exosome-induced CYP24A1, EBP, CCL20, AMCFII and IL1A expression were not regulated by the exosome removed SP. These observations indicated that exosomes present in SP are involved in the immune-related gene regulation in the uterus, which could pave the passage for sperm and possibly fertilized eggs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of MEK/ERK activity by AZD8055 confers acquired resistance in neuroblastoma

Highlights: • Prolonged mTOR inhibitor, AZD8055 exposure induced resistance in NB cells. • Resistance against AZD8055 correlated with over-activation of MEK/ERK signaling. • Combination of AZD8055 and U0126 overcome resistance in vitro and in vivo. Mammalian target of rapamycin (mTOR) complex (mTORC) is frequently activated in diverse cancers. Although dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. AZD8055 is a novel, potent ATP-competitive and specific inhibitor of mTOR kinase activity, which blocks both mTORC1 and mTORC2 activation. In this study, we acquired AZD8055-resistant neuroblastoma (NB) cell sublines by using prolonged stepwise escalation of AZD8055 exposure (4–12 weeks). Here we demonstrate that the AZD8055-resistant sublines (TGW-R and SMS-KAN-R) exhibited marked resistance to AZD8055 compared to the parent cells (TGW and SMS-KAN). The cell cycle G1/S transition was advanced in resistant cells. In addition, the resistance against AZD8055 correlated with over-activation of MEK/ERK signaling pathway. Furthermore, combination of AZD8055 and MEK inhibitor U0126 enhanced the growth inhibition of resistant cells significantly in vitro and in vivo. In conclusion, these data show that targeting mTOR kinase and MEK/ERK signaling simultaneously might help to overcome AZD8055 resistance in NB.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of S100A9 homodimer formation in vivo

Highlights: • Formation of pro-inflammatory S100A9 homodimers is induced in vivo under inflammatory challenge or tumor burden. • CD11b{sup +}GR1{sup +} myeloid cells are the major source of S100A9 homodimers. • S100A9 homodimers are secreted extracellularly. We show here that increased S100A8 and S100A9 protein expression is induced in spleen of animals with active inflammation or with inoculated tumors. In tumor bearing animals an increased expression was also detected in the lung. To further analyze the induced proteins, we performed chemical cross-linking followed by Western blotting. We observed in protein extracts from spleen that both S100A8/S100A9 heterodimers as well as S100A9 homodimers were formed, both after tumor and inflammatory challenge. The cellular source for S100A9 homodimers were CD11b{sup +}GR1{sup +} cells. S100A9 homodimers were also secreted into the extracellular space. Lastly, in the spleen from normal and tumor bearing animals cells expressing relatively higher levels of S100A9 compared to S100A8 could be observed by immunohistochemistry. Taken together, these data show that the biologically potent dimeric form of S100A9 is induced in vivo in situations of tumor burden or inflammatory challenge.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of inactive TGF-β1 monomer formation by hydrogen sulfide contributes to its suppressive effects on Ang II- and TGF-β1-induced EMT in renal tubular epithelial cells

Highlights: • H{sub 2}S has anti-fibrotic actions with little information available about its mechanisms. • Ang II induced EMT in renal tubular epithelial cells via TGF-β. • H{sub 2}S inhibited Ang II- and TGF-β-induced EMT. • H{sub 2}S suppressed Ang II-induced activation of TGF-β. • H{sub 2}S inactivated TGF-β via cleavage of the disulfide bonds. Hydrogen sulfide (H{sub 2}S), an endogenous gas mediator with multifaced biological functions, has been shown to be effective in the prevention and treatment of renal sclerosis in several models of chronic renal diseases. The mechanisms involved are still unclear. Given that Ang II- and TGF-β-induced renal tubular epithelial-mesenchymal transition (EMT) is a pivotal cellular event leading to renal sclerosis, we examined whether and how H{sub 2}S intervened the processes of EMT. Ang II stimulated EMT in renal tubular epithelial cells, as indicated by the increased level of α-smooth muscle actin and a decreased level of E-cadherin. This effect of Ang II was blocked by a TGF-β receptor kinase inhibitor, indicative of a mediating role of TGF-β. Consistently, Ang II stimulated TGF-β activation and addition of the exogenous TGF-β1 also induced EMT. In the presence of H{sub 2}S donor NaHS, the EMT-promoting actions of Ang II and TGF-β1 were abolished, which was associated with a reduced TGF-β activity. Further analysis using a human recombinant active TGF-β1 revealed that H{sub 2}S cleaved the disulfide bond in the dimeric active TGF-β1 and promoted the formation of inactive TGF-β1 monomer. Collectively, these results indicate that H{sub 2}S counteracted Ang II- and TGF-β1-induced EMT through mechanisms involving direct inactivation of TGF-β1. Our study thus provides novel mechanistic insight into the anti-fibrotic actions of H{sub 2}S and suggest that H{sub 2}S could be used to treat renal sclerotic diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of the mitochondrial NDUFA4L2 protein by HIF-1a regulates heart regeneration by promoting the survival of cardiac stem cell

The adult mammalian heart doesn't regenerate after cardiomyocyte injury, which was mainly caused by the severe and persistent effects of cardiomyopathy. Recently, some studies reported that the mammalian heart can regenerate under low oxygen environment. However, the mechanism that the mammalian heart can regenerate remains unknown. Here, we used cardiac stem cells (CSCs) to be planted in serum-free medium under hypoxia environment to understand the mechanism of HIF1α/NDUFA4L2 in the regulation of hypoxia-alleviated apoptosis. Our results revealed that hypoxia can alleviated CSCs apoptosis. Hypoxia inhibited the level of cleaved-caspase3 and stimulated the expression of stabilized HIF-1α. DMOG promotes the survival of CSCs and the protein expression of NDUFA4L2. 2-ME repressed the survival of CSCs and the protein expression of NDUFA4L2. CHIP assay showed that HIF-1α regulated the survival of CSCs by augmenting the combination of HIF-1α and NDUFA4L2's HRE. Knockdown of NDUFA4L2 reversed the role of hypoxia in the survival of CSCs. Taken together, hypoxia promotes the viability of CSCs in serum-free medium by HIF-1α/NDUFA4L2 signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Induction of pigmentation by a small molecule tyrosine kinase inhibitor nilotinib

Highlights: • The nilotinib induced the pigmentation of HM3KO melanoma cells. • The nilotinib decreased the phosphorylation of AKT, while increased the phosphorylation of CREB. • The inhibition of PKA signaling abrogated nilotinib-induced pigmentation. Skin color is determined by the melanin pigments that are produced in melanocytes then transferred to surrounding keratinocytes. Despite the growing number of commercial products claiming the pigmentation-regulatory effects, there is still a demand for the development of new materials that are safe and more efficacious. We tried to screen the pigmentation-regulatory materials using a commercially available drugs, and found that nilotinib could induce pigmentation in melanoma cells. When HM3KO melanoma cells were treated with nilotinib, melanin content was increased together with increase of tyrosinase activity. Nilotinib increased the expression of pigmentation-related genes such as MITF, tyrosinase and TRP1. Consistent with these results, the protein level for MITF, tyrosinase, and TRP1 was significantly increased by nilotinib. To delineate the action mechanism of nilotinib, we investigated the effects of nilotinib on intracellular signaling. As a result, nilotinib decreased the phosphorylation of AKT, while increased the phosphorylation of CREB. The pretreatment of PKA inhibitor H89 markedly blocked the nilotinib-induced phosphorylation of CREB. In accordance with, pretreatment of H89 significantly inhibited the nilotinib-induced pigmentation, indicating that nilotinib induces pigmentation via the activation of PKA signaling. Together, our data suggest that nilotinib can be developed for the treatment of hypopigmentary disorder such as vitiligo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

iRhom2 promotes atherosclerosis through macrophage inflammation and induction of oxidative stress

Highlights: • Increase of iRhom2 contributes to ox-LDL-incubated macrophages activation. • Down-regulation of iRhom2 expression attenuates inflammation in ox-LDL-incubated macrophages inflammatory infiltration. • iRhom2-knockdown alleviates oxidative stress in ox-LDL-incubated macrophages activation. • iRhom2 is expressed highly in HFD-fed ApoE{sup −/-} mouse artery. Atherosclerosis is a complex chronic inflammatory disease that is characterized by the formation of lipid-rich plaques on the inner walls of the arteries. Inactive rhomboid protein 2 (iRhom2) was recently determined as a necessary regulator for the shedding of tumor necrosis factor-alpha (TNF-α) in immune cells. In the present study, we aimed to explore the effects of iRhom2 on the inflammatory response and oxidative stress induced by low-density lipoprotein (ox-LDL) in RAW264.7 and THP-1-derived macrophages. The expression levels of iRhom2 were also investigated in apolipoprotein E knockout (ApoE{sup −/-}) mice fed a high-fat diet (HFD). iRhom2 was significantly induced by ox-LDL in macrophages, as confirmed by Western blotting and RT-qPCR analysis. Furthermore, iRhom2 knockdown showed significant suppressive effects on the activation of ox-LDL-induced RAW264.7 and THP-1-derived macrophages through reducing TACE and TNFR2 expressions, and the inactivation of the IκBα/NF-κB signaling pathway. A reduction in reactive oxygen species (ROS) generation, malondialdehyde (MDA) levels, and nitric oxide (NOX) activity and an increase in glutathione peroxidase (GSH-Px) activity were determined in the absence of iRhom2 expression. In addition, the NF-E2 related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) pathway was also upregulated in ox-LDL-treated macrophages subjected to iRhom2 inhibition. Moreover, suppression of iRhom2 expression inactivated PI3K/AKT pathway activation, contributing to ROS reduction in ox-LDL-stimulated macrophages. iRhom2 was also significantly expressed in ApoE{sup −/-} mice fed HFD. Finally, we observed increased serum levels of TNF-α, TNFR1, and TNFR2 in patients with coronary artery atherosclerosis as compared to healthy volunteers. In conclusion, our findings suggested that iRhom2 played a key role in the pathogenesis of atherosclerosis, and that iRhom2 might be a potential therapeutic target against atherosclerosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through induction of adipocyte browning

Highlights: • G.uralensis or licochalcone A reduced body weight and inguinal fat weights in obese mice. • G.uralensis or licochalcone A increased brown fat population in inguinal white adipose tissue of obese mice. • G.uralensis and LicoA reduce obesity and recover metabolic homeostasis by inducing fat browning. The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl{sub 2}) fraction was the most effective to induce expression of uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes. Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin, and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing obesity in mice by 6-week HFD, MeCl{sub 2} fraction of G. uralensis or LicoA was intraperitoneally administered for additional 19 days. MeCl{sub 2} fraction or LicoA significantly reduced body weight gain and inguinal fat pad weights. Furthermore, MeCl{sub 2} fraction or LicoA improved metabolic disorders induced by HFD as the treatments decreased serum levels of glucose and cholesterol, and blocked insulin resistance. MeCl{sub 2} fraction or LicoA enhanced expression of brown fat markers such as UCP1, PRDM16, and PGC-1α and increased brown fat phenotype population in inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA are effective to reduce obesity and to recover metabolic homeostasis by inducing the brown fat phenotype.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Low doses of multi-walled carbon nanotubes elicit hepatotoxicity in rats with markers of oxidative stress and induction of pro-inflammatory cytokines

The investigation into the potential health risks associated with the use of engineered nanoparticles is a major scientific interest in recent years. The present study elucidated the involvement of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in carboxylated multi-walled carbon nanotubes (MWCNTs)-induced hepatotoxicity. Pubertal rats were exposed to purified MWCNTs at 0, 0.25, 0.50, 0.75 and 1.0 mg/kg for 5 consecutive days. Results indicated that exposure to MWCNTs caused liver damage evidenced by significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) when compared with control. Moreover, MWCNTs significantly decreased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities as well as glutathione level whereas it significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities in liver of the treated rats. Moreover, the dose-dependent increase in hepatic hydrogen peroxide (H{sub 2}O{sub 2}) and lipid peroxidation levels were accompanied by marked increase in micronucleated polychromatic erythrocytes (MNPCE) in the MWCNTs-treated rats. Administration of MWCNTs significantly increased serum concentrations of pro-inflammatory cytokines namely interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the treated rats. Immunohistochemical analysis showed significantly increased COX-2 and iNOS protein expressions in the liver of MWCNTs-treated rats. In conclusion, carboxylated MWCNTs induces hepatic damage via disruption of antioxidant defense systems, promotion of pro-inflammatory cytokines generation and expression of COX-2 and i-NOS in rats.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mesenchymal stem cells in combination with low-dose rapamycin significantly prolong islet allograft survival through induction of regulatory T cells

Highlights: • MSCs alone are not able to promote allogeneic islet engraft and Rapamycin has detrimental effects on islet engraftment. • MSCs combined with low-dose Rapamycin significantly prolonged the survival and enhanced the function of islet allografts. • The protective effect of combination therapy is associated with induced expansion of regulatory T cells in vivo. • The combination therapy leads to profound suppression of alloreactive response to donor specific antigen. We previously demonstrated the protective effect of MSCs in an adaptive transfer mouse model. However, their therapeutic potential in an allogeneic immunocompetent setting mimicking clinical context of islet transplantation remained unknown. The aim of this study was to determine whether MSCs therapy, either by itself, or combined with Rapamycin could benefit the allograft survival of fully MHC-mismatched mouse islet transplant. Combination therapy of MSCs and low-dose Rapamycin significantly prolonged the survival of islet allografts, whereas treatment of MSCs, or Rapamycin alone, had no impact. Interestingly, this protective effect was associated with an induced expansion of regulatory T cells in islet grafts and draining lymph nodes, a skewed T-cell differentiation toward immunotolerance, and a profound suppression of alloreactivity against donor antigen. Our study suggests that a combination therapy of MSCs and low-dose Rapamycin can prolong the survival and preserve the function of islet allograft in the MHC-mismatched mouse model of islet transplantation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Retinoic acid co-treatment aggravates severity of dioxin-induced skin lesions in hairless mice via induction of inflammatory response

Highlights: • Treatment with retinoic acid (RA) is ineffective for dioxin-induced skin lesions in mice. • Co-treatment with dioxin and RA results in psoriasis-like phenotype not seen under treatment with either compound alone. • Strong inflammation is the most prominent effect induced by combined treatment with dioxin and RA. Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases. In vitro, retinoids elicit antagonistic effects on keratinocyte differentiation and proliferation, as compared to TCDD, suggesting their potential in treatment of TCDD-induced skin lesions. Nevertheless, the modulation of TCDD activity in skin by retinoids in vivo was never reported. We have used N-TERT keratinocyte cell line and hairless (hr) mice to determine if retinoic acid (RA) can lessen or reverse TCDD-induced effects in vitro and in vivo. RA co-treatment suppressed TCDD-induced changes in the expression of differentiation-associated genes and N-TERT keratinocyte viability in vitro. However, in hairless mice (in vivo), RA/TCDD co-treatment produced more severe effects, than treatment with either of the two compounds individually. RA/TCDD co-application to mouse skin strongly stimulated keratinocyte proliferation, resulting in dramatic epidermal hyperplasia. It has also led to massive immune cell infiltration into the dermis, and increased mRNA expression of inflammation markers, including IL1β, IL6 and S100A7. Thus, retinoids not only appeared ineffective in treatment of TCDD-induced skin lesions in hairless mice, but also resulted in their exaggeration. These in vivo results question previous cell culture-based claims that RA may reduce TCDD-induced skin effects and caution against the reliance on in vitro data in TCDD toxicology research.

60 APPLIED LIFE SCIENCES↗