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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 1,333 records · Page 74
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21→I or P41→T

Amelogenesis imperfecta describes a group of inherited disorders that results in defective tooth enamel. Two disorders associated with human amelogenesis imperfecta are the point mutations T21?I or P40?T in amelogenin, the dominant protein present during the early stages of enamel biomineralization. The biophysical properties of wildtype murine amelogenin (M180) and two proteins containing the equivalent mutations in murine amelogenin, T21?I (M180-I) and P41?T (M180-T), were probed by NMR spectroscopy. At low protein concentration (0.1 mM), M180, M180-I, and M180-T are predomi- nately monomeric at pH 3.0 in 2% acetic acid and neither mutation produces a major structural change. Chemical shift perturbation studies as a function of protein (0.1–1.8 mM) or NaCl (0–400 mM) concentra- tions show that the mutations affect the self-association properties by causing self-assembly at lower protein or salt concentrations, relative to wildtype amelogenin, with the largest effect observed for M180-I. Under both conditions, the premature self-assembly is initiated near the N-terminus, providing further evidence for the importance of this region in the self-assembly process. The self-association of M180-I and M180-T at lower protein concentrations and lower ionic strengths than wildtype M180 may account for the clinical phenotypes of these mutations, defective enamel formation.

amelogenesis↗
DOE OSTI2018

Development and thermal performance verification of composite insulation boards containing foam-encapsulated vacuum insulation panels

High-performance thermal insulation is a critical need for buildings. This article presents the development and thermal characterization of composite foam insulation boards containing low-cost vacuum insulation cores. The composite foam-vacuum insulation boards were created in a semi-automatic operation in a foam insulation manufacturing plant. The low-cost vacuum insulation is a new technology called modified atmosphere insulation. The production process of modified atmosphere insulation is much simpler than traditional vacuum insulation manufacturing, and it has the potential for significant cost reduction at the same thermal performance. Prototypes of small- and full-scale composite insulation boards were created for testing and evaluation under laboratory and natural weatherization conditions. The laboratory tests showed that the overall thermal resistance of the composite insulation board is at least twice that of current rigid foam insulation used in building envelope. Lastly, ongoing test of the composite insulation in a natural exposure test facility indicates that the high thermal performance was retained through handling and installation as well as natural aging over a period of one and a half years.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2023

Film condensation with high heat fluxes and scaled experiments using pure steam for reactor containment cooling

Condensation tests were performed using a newly developed test facility for scaling the passive containment cooling system (PCCS) to a small modular reactor (SMR). The PCCS of the SMR plays a pivotal role in ensuring greater safety, reliability, and compactness than what is afforded by traditional reactors. Therefore, a well-designed PCCS is essential to SMRs. However, previous studies and test data were unsuitable for scaling, due to high variation in the test geometry and operating conditions. This study intends to close this research gap by using a novel designed scaled test facility consisting of vertical condensing test sections featuring 1-, 2-, and 4-inch-diameter condensing tubes with annular water cooling, and by applying superheated and saturated steam with different steam mass flow ranges of 5–25 g/s. Further, the primary test data, including axial temperatures, mass flow rates, and pressures, were used in conjunction with a standard data reduction method to estimate critical parameters such as heat fluxes, heat transfer coefficients, and condensation rates. These scaled test data would support improving empirical correlations and validating condensation models to identify scaling distortion for SMR PCCSs.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2021

How much information on precipitation is contained in satellite infrared imagery?

Satellite infrared (IR) brightness temperature providing information on the characteristics of cloud tops is one of the primary input data used for estimating precipitation from satellites. Thus, the natural questions to ask are: Does IR imagery contain more information about precipitation in some regions more than others? What are the factors that lead to such differences? Should we expect the amount of information provided by IR imagery to change with respect to temporal or spatial aggregation? Comprehensive analysis of the accuracy of satellite-based precipitation estimates obtained from any given algorithm may provide qualitative answers to the above questions. However, such an approach only offers conclusions within the limited context of the algorithm used to obtain precipitation estimates; that is, patterns caused by the inherent information content of IR imagery are inextricable from those induced by assumptions embedded in the precipitation estimation algorithm. Here, we address the abovementioned questions from a different perspective using an information-theoretic measure, free of structural assumptions and general to a wide range of relationships, to characterize the average and seasonal dependence between IR imagery provided by satellite sensors in the spectral range (10.7–11.5 μm) and precipitation rates in the contiguous United States (CONUS) across distinct temporal and spatial scales. We analyze a total of more than 1.3 billion pairs of IR and precipitation observations over CONUS, and we observe interesting patterns. First, we show that there is a strong inverse relationship (ρ = - 0.73) between the information content of IR data and the number of no-rain observations; however, its robustness varies regionally and seasonally with less significant correlation during the warm season. Second, we demonstrate that the intuitive relationship of increasing dependence between IR and precipitation as a result of temporal or spatial aggregation exhibits a diminishing returns behavior. For instance, temporal aggregation from 1 to 3 h increases the dependence approximately 7 times as much as temporal aggregation from 12 to 24 h. Furthermore, we quantitatively examine and re-confirm several statements previously reported in the literature such as the strong association between IR and precipitation in convective storms and the low association in orographic rainfall. Finally, we conclude by illustrating the potential of the analysis in diagnosis of operational algorithms for estimating precipitation from IR brightness temperature. The findings of this study pinpoint spatial domains and time scales at which IR is not an adequate proxy for estimating precipitation. Thus, they can potentially guide the development of operational algorithms that utilize satellite Infrared imagery for estimating, downscaling and data fusion of precipitation. Finally, the analysis presented here opens up the possibility of developing new methodologies for diagnosis of satellite-based precipitation estimation algorithms.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

A conserved serine residue regulates the stability of Drosophila Salvador and human WW domain-containing adaptor 45 through proteasomal degradation

Highlights: •Ser-17 is key for the stability of Drosophila Sav. •Ala mutation of Ser-17 promotes the proteasomal degradation of Sav. •Ser-17 residue is not the main target of Hpo-induced Sav stabilization. •Hpo-dependent and -independent mechanisms regulate Sav stability. •This mechanism is conserved in the homologue of Sav, human WW45. -- Abstract: The Hippo (Hpo) pathway is a conserved tumor suppressor pathway that controls organ size through the coordinated regulation of apoptosis and proliferation. Drosophila Salvador (Sav), which limits organ size, is a core component of the Hpo pathway. In this study, Ser-17 was shown to be important for the stability of Sav. Alanine mutation of Ser-17 promoted the proteasomal degradation of Sav. Destabilization and stabilization of the Sav protein mediated by alanine mutation of Ser-17 and by Hpo, respectively, were independent of each other. This implies that the stability of Sav is controlled by two mechanisms, one that is Ser-17-dependent and Hpo-independent, and another that is Ser-17-independent and Hpo-dependent. These dual mechanisms also regulated the human counterpart of Drosophila Sav, WW domain-containing adaptor 45 (WW45). The conservation of this regulation adds to its significance in normal physiology and tumorigenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen transmission that might arise from animal-derived materials. - Highlights: • Y-27632 promotes the proliferation of human keratinocytes. • Human keratinocytes with Y-27632 can stratify similarly to traditional method. • Y-27632 is useful for culture medium of human keratinocyte in clinical setting.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Inhibition of discoidin domain receptor 2-mediated lung cancer cells progression by gold nanoparticle-aptamer-assisted delivery of peptides containing transmembrane-juxtamembrane 1/2 domain

The delivery of biologically functional peptides into mammalian cells can be a direct and effective method for cancer therapy and treatment of other diseases. Discoidin domain receptor 2 (DDR2) is a collagen-induced receptor tyrosine kinase recently identified as a novel therapeutic target in lung cancer. In this study, we report that peptides containing the functional domain of DDR2 can be efficiently delivered into lung malignant cancer cells via a gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system. Peptide delivery resulted in the abrogation of DDR2 activation triggered by collagen. Moreover, the peptide delivered by the AuNP-Apt system inhibited cancer cell proliferation and invasion mediated by DDR2 activation. Thus, these results suggest that peptide loaded onto AuNP-Apt conjugates can be used for the development of peptide-based biomedical applications for the treatment of DDR2-positive cancer. - Highlights: • TM-JM1/2 peptides are efficiently delivered into cells by AuNP-Apt-conjugates. • TM-JM1/2 peptides loaded onto AuNP-Apt conjugates inhibit DDR2 activation. • Inhibition of DDR2 activation by TM-JM1/2 peptides decreases tumor progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Antioxidative effects of magnetized extender containing bovine serum albumin on sperm oxidative stress during long-term liquid preservation of boar semen

Magnetized water is defined as water that has passed through a magnet and shows increased permeability into cells and electron-donating characteristics. These attributes can protect against membrane damage and remove reactive oxygen species (ROS) in mammalian cells. We explored the effects of improved magnetized semen extenders containing bovine serum albumin (BSA) as antioxidants on apoptosis in boar sperm. Ejaculated semen was diluted in magnetized extender (0G and 6000G) with or without BSA (0G + BSA and 6000G + BSA), and sperm were analyzed based on viability, acrosome reaction, and H{sub 2}O{sub 2} level of live sperm using flow cytometry. Sperm were then preserved for 11 days at 18 °C. We found that viability was significantly higher in 6000G + BSA than under the other treatments (P < 0.05). The acrosome reaction was significantly lower in the 6000G + BSA group compared with the other treatments (P < 0.05). Live sperm with high intracellular H{sub 2}O{sub 2} level were significantly lower in the 6000G + BSA group than under other treatments (P < 0.05). Based on our results, magnetized extenders have antioxidative effects on the liquid preservation of boar sperm. - Highlights: • Magnetized water is water that has been passed through a magnetic field. • Magnetized extender improve viability and decrease oxidative stress of boar sperm for preservation. • Ejaculated semen diluted with magnetized extender can improve liquid preservation period.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

LY6/PLAUR domain containing 3 has a role in the maintenance of colorectal cancer stem-like cells

Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancers and the leading cause of cancer-related death for both men and women. Recent studies have revealed that a small sub-population of cancer cells, termed cancer stem-like cells (CSCs)/cancer-initiating cells (CICs), are endowed with tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs are resistant to current therapies including chemotherapy and radiotherapy. Thus, CSCs/CICs are responsible for recurrence and metastasis, and eradication of CSCs/CICs is essential to cure cancer. In this study, we isolated CR-CSCs/CICs as sphere-cultured cells and found that a product derived from LY6/PLAUR domain containing 3 (LYPD3) is preferentially expressed in CSCs/CICs. Gene overexpression and gene knockdown experiments revealed that LYPD3 has a role in the maintenance of CR-CSCs/CICs. The findings provide a novel molecular insight into CR-CSCs/CICs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Human alpha beta hydrolase domain containing protein 11 and its yeast homolog are lipid hydrolases

Mammalian alpha/beta hydrolase domain (ABHD) family of proteins have emerged as key regulators of lipid metabolism and are found to be associated with human diseases. Human α/β-hydrolase domain containing protein 11 (ABHD11) has recently been predicted as a potential biomarker for human lung adenocarcinoma. In silico analyses of the ABHD11 protein sequence revealed the presence of a conserved lipase motif GXSXG. However, the role of ABHD11 in lipid metabolism is not known. To understand the biological function of ABHD11, we heterologously expressed the human ABHD11 in budding yeast, Saccharomyces cerevisiae. In vivo [{sup 14}C]acetate labeling of cellular lipids in yeast cells overexpressing ABHD11 showed a decrease in triacylglycerol content. Overexpression of ABHD11 also alters the molecular species of triacylglycerol in yeast. Similar activity was observed in its yeast homolog, Ygr031w. The role of the conserved lipase motif in the hydrolase activity was proven by the mutation of all conserved amino acid residues of GXSXG motif. Collectively, our results demonstrate that human ABHD11 and its yeast homolog YGR031W have a pivotal role in the lipid metabolism. - Highlights: • Overexpression of ABHD11 protein and its yeast homolog Ygr031w cause a reduction in triacylglycerol levels in yeast. • The reduction in triacylglycerol is due to the presence of lipase motif GXSXG. • Overexpression of ABHD11 and Ygr031w alters the molecular species of triacylglycerol.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Cleavage of molybdopterin synthase MoaD-MoaE linear fusion by JAMM/MPN+ domain containing metalloprotease DR0402 from Deinococcus radiodurans

Highlights: • D. radiodurans encodes a fused MPT synthase, MoaD-MoaE fusion protein DR2607. • JAMM/MPN{sup +} metalloprotease DR0402 (JAMM{sub DR}) can cleave the MoaD-MoaE fusion. • JAMM{sub DR} recognizes the MoaD region in the cleavage process of MoaD-MoaE fusion. Molybdenum cofactor (Moco), molybdopterin (MPT) complexed with molybdenum, is an essential cofactor required for the catalytic center of diverse enzymes in all domains of life. Since Moco cannot be taken up as a nutrient unlike many other cofactors, Moco requires de novo biosynthesis. During the synthesis of MPT, the sulfur atom on the C-terminus of MoaD is transferred to cyclic pyranopterin monophosphate (cPMP) which is bound in the substrate pocket of MoaE. MoaD is a ubiquitin-like (Ubl) protein and has a C-terminal di-Gly motif which is a common feature of Ubl proteins. Despite the importance of free C terminal di-Gly motif of MoaD as a sulfur carrier, some bacteria encode a fused MPT synthase in which MoaD- and MoaE-like domains are located on a single peptide. Although it has recently been reported that the fused MPT synthase MoaX from Mycobacterium tuberculosis is posttranslationally cleaved into functional MoaD and MoaE in M. smegmatis, the protease responsible for the cleavage of MoaD-MoaE fusion protein has remained unknown to date. Here we report that the JAMM/MPN{sup +} domain containing metalloprotease DR0402 (JAMM{sub DR}) from Deinococcus radiodurans can cleave the MoaD-MoaE fusion protein DR2607, the sole MPT synthase in D. radiodurans, generating the MoaD having a C-terminal di-Gly motif. Furthermore, JAMM{sub DR} can also cleave off the MoaD from MoaD-eGFP fusion protein suggesting that JAMM{sub DR} recognizes the MoaD region rather than MoaE region in the cleaving process of MoaD-MoaE fusion protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Fibronectin Type III Domain Containing 4 attenuates hyperlipidemia-induced insulin resistance via suppression of inflammation and ER stress through HO-1 expression in adipocytes

Although Fibronectin Type III Domain Containing 4 (FNDC4) has been reported to be involved in the modulation of inflammation in macrophages, its effects on inflammation and insulin resistance in adipose tissue are unknown. In the current study, we investigated the effects of FNDC4 on hyperlipidemia-mediated endoplasmic reticulum (ER) stress, inflammation, and insulin resistance in adipocytes via the AMP-activated protein kinase (AMPK)/heme oxygenase-1 (HO-1)-mediated pathway. Hyperlipidemia-induced nuclear factor κB (NFκB), inhibitory κBα (IκBα) phosphorylation, and pro-inflammatory cytokines such as TNFα and MCP-1 were markedly mitigated by FNDC4. Furthermore, FNDC4 treatment attenuated impaired insulin signaling in palmitate-treated differentiated 3T3-L1 cells and in subcutaneous adipose tissue of HFD-fed mice. FNDC4 administration ameliorated glucose intolerance and reduced HFD-induced body weight gain in mice. However, FNDC4 treatment did not affect calorie intake. Additionally, treatment with FNDC4 attenuated hyperlipidemia-induced phosphorylation or expression of ER stress markers such as IRE-1, eIF2α, and CHOP in 3T3-L1 adipocytes and in subcutaneous adipose tissue of mice. FNDC4 treatment stimulated AMPK phosphorylation and HO-1 expression in 3T3-L1 adipocytes and in subcutaneous adipose tissue of mice. siRNA-mediated suppression of AMPK and HO-1 abrogated the suppressive effects of FNDC4 on palmitate-induced ER stress, inflammation, and insulin resistance. In conclusion, our results show that FNDC4 ameliorates insulin resistance via AMPK/HO-1-mediated suppression of inflammation and ER stress, indicating that FNDC4 may be a novel therapeutic agent for treating insulin resistance and type 2 diabetes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Correlation between high expression levels of jumonji domain-containing 4 and short survival in cases of colon adenocarcinoma

Highlights: • The play an important role of JMJD4 high expression in tumorgenesis of colon adenocarcinoma. • JMJD4 protein expression in colon adenocarcinoma was associated with histological grade and M-class. • The high expression of JMJD4 was significantly related with poor survival in patients with colon adenocarcinoma. • Cox proportional-hazards model analysis indicated JMJD4 could be a prognostic indicator for overall survival. In this study, we investigated the expression of jumonji domain-containing 4 (JMJD4) in colon adenocarcinoma (CA) look for evidences for future studies on clinical diagnostic and prognostic value. The immunohistochemical (IHC) reactivity of JMJD4 was assessed in human tissue microarrays using monoclonal antibodies. An initial investigation revealed that the expression of JMJD4 protein was significantly higher in tumor tissue of the colon and liver than in normal tissue. Upon further investigation, we observed significant positivity of JMJD4 between 59 paired samples from CA tissue and adjacent normal tissue. JMJD4 protein expression in CA differed significantly according to the histological grade and M-class (distant metastasis). We also determined that the mRNA or protein expression of JMJD4 was significantly associated with poor survival in patients with CA. Finally, univariate and multivariate analysis revealed that JMJD4 expression could be a prognostic indicator for patients with CA and may provide a new target for the development of novel therapies for the treatment of CA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Potent HIV‑1 protease inhibitors containing oxabicyclo octanol-derived P2-ligands: Design, synthesis, and X‑ray structural studies of inhibitor-HIV-1 protease complexes

Here, we describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands. We investigated the functional effect of these stereochemically defined fused-poly cyclic ligands on enzyme inhibition and antiviral activity in MT-2 cells. The tricyclic core of 8-oxabicyclo[3.2.1]octan-6-ol is designed to interact with the residues in the S2 subsite of HIV-1 protease. The syntheses of the ligands were carried out using the [5+2]-cycloaddition as the key step. Several inhibitors exhibited potent enzyme inhibitory activity. High resolution room-temperature X-ray structures of inhibitor-bound HIV-1 protease were determined. These structures provided important molecular insights for further design and optimization of inhibitor potency.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Solid carbon production and recovery from high temperature methane pyrolysis in bubble columns containing molten metals and molten salts

We study methane pyrolysis in a bubble column reactor consisting of a layer of molten NiBi alloy, and a molten salt layer floating on the metal layer. The molten metal is a pyrolysis catalyst; the molten salt layer is added for removing contaminants from the carbon product. Methane is introduced at the bottom of the reactor and the rising bubbles contain reactant and product gases together with metal vapor and flakes of solid carbon. When the bubbles rise through the molten salt layer the metal vapor condenses producing dense liquid metal droplets, which sink to the metal phase; the low-density carbon rises to the top of the salt layer. The carbon generated from the single-phase molten NiBi reactor has a different structure from that produced in the two-phase NiBi/salt reactor. The amount of metal in the carbon product is less than 5 wt %, in the two-phase reactor, compared to 83 wt % in the NiBi single-phase reactor. After subsequent purification steps one obtains solid carbon with less than 2 wt % salt contamination and no detectable metal contamination.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗