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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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All sourcesNASA NTRSDOE OSTI
NASA NTRS2013

Materials Combustion Testing and Combustion Product Sensor Evaluations in FY12

NASA Centers continue to collaborate to characterize the chemical species and smoke particles generated by the combustion of current space-rated non-metallic materials including fluoropolymers. This paper describes the results of tests conducted February through September 2012 to identify optimal chemical markers both for augmenting particle-based fire detection methods and for monitoring the post-fire cleanup phase in human spacecraft. These studies follow up on testing conducted in August 2010 and reported at ICES 2011. The tests were conducted at the NASA White Sands Test Facility in a custom glove box designed for burning fractional gram quantities of materials under varying heating profiles. The 623 L chamber was heavily instrumented to quantify organics (gas chromatography/mass spectrometry), inorganics by water extraction followed by ion chromatography, and select species by various individual commercially-available sensors. Evaluating new technologies for measuring carbon monoxide, hydrogen cyanide, hydrogen fluoride, hydrogen chloride and other species of interest was a key objective of the test. Some of these sensors were located inside the glovebox near the fire source to avoid losses through the sampling lines; the rest were located just outside the glovebox. Instruments for smoke particle characterization included a Tapered Element Oscillating Microbalance Personal Dust Monitor (TEOM PDM) and a TSI Dust Trak DRX to measure particle mass concentration, a TSI PTrak for number concentration and a thermal precipitator for collection of particles for microscopic analysis. Materials studied included Nomex®, M22759 wire insulation, granulated circuit board, polyvinyl chloride (PVC), Polytetrafluoroethylene (PTFE), Kapton®, and mixtures of PTFE and Kapton®. Furnace temperatures ranged from 340o to 640o C, focusing on the smoldering regime. Of particular interest in these tests was confirming burn repeatability and production of acid gases with different fuel mixture compositions, as well as the dependence of aerosol concentrations on temperature.

Smoke↗
NASA NTRS2013

Materials Combustion Testing and Combustion Product Sensor Evaluations in FY12

NASA Centers continue to collaborate to characterize the chemical species and smoke particles generated by the combustion of current space-rated non-metallic materials including fluoropolymers. This paper describes the results of tests conducted February through September 2012 to identify optimal chemical markers both for augmenting particle-based fire detection methods and for monitoring the post-fire cleanup phase in human spacecraft. These studies follow up on testing conducted in August 2010 and reported at ICES 2011. The tests were conducted at the NASA White Sands Test Facility in a custom glove box designed for burning fractional gram quantities of materials under varying heating profiles. The 623 L chamber was heavily instrumented to quantify organics (gas chromatography/mass spectrometry), inorganics by water extraction followed by ion chromatography, and select species by various individual commercially-available sensors. Evaluating new technologies for measuring carbon monoxide, hydrogen cyanide, hydrogen fluoride, hydrogen chloride and other species of interest was a key objective of the test. Some of these sensors were located inside the glovebox near the fire source to avoid losses through the sampling lines; the rest were located just outside the glovebox. Instruments for smoke particle characterization included a Tapered Element Oscillating Microbalance Personal Dust Monitor (TEOM PDM) and a TSI Dust Trak DRX to measure particle mass concentration, a TSI PTrak for number concentration and a thermal precipitator for collection of particles for microscopic analysis. Materials studied included Nomex(R), M22759 wire insulation, granulated circuit board, polyvinyl chloride (PVC), Polytetrafluoroethylene (PTFE), Kapton(R), and mixtures of PTFE and Kapton(R). Furnace temperatures ranged from 340 to 640 C, focusing on the smoldering regime. Of particular interest in these tests was confirming burn repeatability and production of acid gases with different fuel mixture compositions, as well as the dependence of aerosol concentrations on temperature.

Combustion↗
DOE OSTI2018

DNA polymerase β deficiency in the p53 null cerebellum leads to medulloblastoma formation

Highlights: • DNA polymerase β inactivation leads to medulloblastoma formation in the p53 null cerebellum. • The DNA polymerase β null medulloblastoma is histopathologically similar to human medulloblastoma. • DNA polymerase β and Xrcc1 null medulloblastomas show the characteristics of the SHHα subtype. Defects in DNA damage response or repair mechanisms during neurogenesis result in genomic instability, which is causative for several neural defects. These include brain tumors, particularly medulloblastoma, which occurs in the cerebellum with a high incidence in children. We generated an animal model with defective base excision repair during brain development through selective inactivation of DNA polymerase β (Polb) in neuroprogenitor cells. All of Polb conditional knockout mice developed medulloblastoma in a p53 null background, similar to the Xrcc1 and p53 double deficient animal model. XRCC1 is a scaffolding protein which is involved in DNA damage repair and binds to POLB. In both animal models, the histopathological characteristics of the medulloblastoma were similar to those of human classic medulloblastoma. Brain tumor development was slower in the Polb and p53 double null animals than in the Xrcc1 and p53 double knockout animals. Molecular marker analysis suggested that Polb- and Xrcc1-deficient medulloblastomas belonged to the SHHα subtype, underscoring the important role of genomic stability in preventing this devastating pediatric cerebellar tumor.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Development of genetic tools for the thermophilic filamentous fungus Thermoascus aurantiacus

Abstract Background Fungal enzymes are vital for industrial biotechnology, including the conversion of plant biomass to biofuels and bio-based chemicals. In recent years, there is increasing interest in using enzymes from thermophilic fungi, which often have higher reaction rates and thermal tolerance compared to currently used fungal enzymes. The thermophilic filamentous fungus Thermoascus aurantiacus produces large amounts of highly thermostable plant cell wall-degrading enzymes. However, no genetic tools have yet been developed for this fungus, which prevents strain engineering efforts. The goal of this study was to develop strain engineering tools such as a transformation system, a CRISPR/Cas9 gene editing system and a sexual crossing protocol to improve the enzyme production. Results Here, we report Agrobacterium tumefaciens -mediated transformation (ATMT) of T. aurantiacus using the hph marker gene, conferring resistance to hygromycin B. The newly developed transformation protocol was optimized and used to integrate an expression cassette of the transcriptional xylanase regulator xlnR , which led to up to 500% increased xylanase activity. Furthermore, a CRISPR/Cas9 gene editing system was established in this fungus, and two different gRNAs were tested to delete the pyrG orthologue with 10% and 35% deletion efficiency, respectively. Lastly, a sexual crossing protocol was established using a hygromycin B- and a 5-fluoroorotic acid-resistant parent strain. Crossing and isolation of progeny on selective media were completed in a week. Conclusion The genetic tools developed for T. aurantiacus can now be used individually or in combination to further improve thermostable enzyme production by this fungus.

09 BIOMASS FUELS↗
DOE OSTI2016

Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

MetaPop: a pipeline for macro- and microdiversity analyses and visualization of microbial and viral metagenome-derived populations

Abstract Background Microbes and their viruses are hidden engines driving Earth’s ecosystems from the oceans and soils to humans and bioreactors. Though gene marker approaches can now be complemented by genome-resolved studies of inter-(macrodiversity) and intra-(microdiversity) population variation, analytical tools to do so remain scattered or under-developed. Results Here, we introduce MetaPop, an open-source bioinformatic pipeline that provides a single interface to analyze and visualize microbial and viral community metagenomes at both the macro - and microdiversity levels. Macrodiversity estimates include population abundances and α- and β-diversity. Microdiversity calculations include identification of single nucleotide polymorphisms, novel codon-constrained linkage of SNPs, nucleotide diversity ( π and θ ), and selective pressures (pN/pS and Tajima’s D ) within and fixation indices ( F ST ) between populations. MetaPop will also identify genes with distinct codon usage. Following rigorous validation, we applied MetaPop to the gut viromes of autistic children that underwent fecal microbiota transfers and their neurotypical peers. The macrodiversity results confirmed our prior findings for viral populations (microbial shotgun metagenomes were not available) that diversity did not significantly differ between autistic and neurotypical children. However, by also quantifying microdiversity, MetaPop revealed lower average viral nucleotide diversity ( π ) in autistic children. Analysis of the percentage of genomes detected under positive selection was also lower among autistic children, suggesting that higher viral π in neurotypical children may be beneficial because it allows populations to better “bet hedge” in changing environments. Further, comparisons of microdiversity pre- and post-FMT in autistic children revealed that the delivery FMT method (oral versus rectal) may influence viral activity and engraftment of microdiverse viral populations, with children who received their FMT rectally having higher microdiversity post-FMT. Overall, these results show that analyses at the macro level alone can miss important biological differences. Conclusions These findings suggest that standardized population and genetic variation analyses will be invaluable for maximizing biological inference, and MetaPop provides a convenient tool package to explore the dual impact of macro - and microdiversity across microbial communities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Advanced urothelial cancer: a radiology update

The recent genomic characterization of urothelial carcinoma by the Cancer Genome Atlas Project, made possible by the introduction of high throughput, reduced cost, and sequence analysis, has shed new insights on the biology of advanced disease. In addition, studies on imaging of advanced urothelial carcinoma have widened the knowledge on disease presentation and on pattern of metastatic spread and their correlation with the underlying biology of urothelial carcinoma. The wide range of treatments for advanced urothelial cancer, including combined chemotherapy regimens and immune checkpoint inhibitors, each result in treatment class-specific patterns of response and adverse events. Results of studies point to the need for a reliable biomarker, perhaps with imaging, that predicts prognosis and treatment response to systemic treatment, and can be used to select the most effective treatment while minimizing toxicity. This review of advanced urothelial cancer introduces the latest advances in genetic profiling, the current role of imaging, the radiographic appearance of treatment response and their toxicities, and details potential future areas of imaging research.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

FeGenie: a comprehensive tool for the identification of iron genes and iron gene neighborhoods in genomes and metagenome assemblies

Iron is a micronutrient for nearly all life on Earth. It can be used as an electron donor and electron acceptor by iron-oxidizing and iron-reducing microorganisms and is used in a variety of biological processes, including photosynthesis and respiration. While it is the fourth most abundant metal in the Earth’s crust, iron is often limiting for growth in oxic environments because it is readily oxidized and precipitated. Much of our understanding of how microorganisms compete for and utilize iron is based on laboratory experiments. However, the advent of next-generation sequencing and surge in publicly available sequence data has made it possible to probe the structure and function of microbial communities in the environment. To bridge the gap between our understanding of iron acquisition, iron redox cycling, iron storage, and magnetosome formation in model microorganisms and the plethora of sequence data available from environmental studies, we have created a comprehensive database of hidden Markov models (HMMs) based on genes related to iron acquisition, storage, and reduction/oxidation in Bacteria and Archaea. Along with this database, we present FeGenie, a bioinformatics tool that accepts genome and metagenome assemblies as input and uses our comprehensive HMM database to annotate provided datasets with respect to iron-related genes and gene neighborhood. An important contribution of this tool is the efficient identification of genes involved in iron oxidation and dissimilatory iron reduction, which have been largely overlooked by standard annotation pipelines. We validated FeGenie against a selected set of 28 isolate genomes and showcase its utility in exploring iron genes present in 27 metagenomes, 4 isolate genomes from human oral biofilms, and 17 genomes from candidate organisms, including members of the candidate phyla radiation. We show that FeGenie accurately identifies iron genes in isolates. Furthermore, analysis of metagenomes using FeGenie demonstrates that the iron gene repertoire and abundance of each environment is correlated with iron richness. While this tool will not replace the reliability of culture-dependent analyses of microbial physiology, it provides reliable predictions derived from the most up-to-date genetic markers. FeGenie’s database will be maintained and continually updated as new genes are discovered.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2012

Pulmonary Toxicity Studies of Lunar Dust in Rodents

NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological changes, a similar study was conducted to microscopically examine rat lung tissue and the associated lymph nodes for lesions, including fibrosis, 1 or 3 months after the instillation. The results from this ITI study led us to select two concentrations (20 and 60 mg/cu m) for an inhalation study, in which rats were exposed to lunar dust 6 h daily for 4 weeks (5d/wk). Similar biochemical and histopathological assessments were carried out in these rats 1 day or 1, 4, or 13 weeks after the dust exposure. Rats exposed to lunar dust by ITI or inhalation showed effects indicating that the dust is moderately toxic. The data will be useful to establish safe exposure limits for astronauts working in a lunar habitat and also help engineers designing dust mitigation systems for lunar vehicles and habitats.

Lam, Chiu-Wing↗
NASA NTRS2021

Analysis of Exercise Loads to Inform Vibration Isolation System Design

BACKGROUND: This study was conducted with the primary interest of providing data that would inform Vibration Isolation and Stabilization (VIS) system design and performance for the European Enhanced Exploration Exercise Device (E4D). In preparation for the International Space Station (ISS) in-flight demonstration, a list of critical Human Health Countermeasures (HHC) exercises was compiled [1]. The goal of this study was to assess the ground reaction forces and moments imposed by an exercising subject in each of the six VIS Degrees of Freedom (DOFs) during a comprehensive set of these critical exercises performed on the E4D. METHODS AND RESULTS: The ISS in-flight demonstration list of critical exercises included seated aerobic rowing, bent-over rowing, cycling, front squats, back squats, conventional deadlifts, Romanian deadlifts, heel raises, overhead presses, reverse chops, and power clean presses. At the NASA Johnson Space Center (JSC) Prototype Immersive Technology (PIT) laboratory, motion capture data were collected on critical E4D exercises for six subjects. At the NASA JSC Active Response Gravity Offload System (ARGOS) facility, additional motion capture and load cell data were collected on offloaded trials for four subjects. Select data were extrapolated to represent a 5th percentile female subject and a 95th percentile male subject. A previous investigation comparing the forces obtained from the load cell and from motion capture based data found a satisfactory level of agreement between the two measurements [2]. The motion capture based data were analyzed for this study since it is driven by the subject’s trajectory alone, automatically excluding any forces exerted on the subject by the ARGOS offloading harness. The OpenSim [3, 4] biomechanical simulation inverse kinematics tool was used to calculate the joint angles based on the locations of motion capture markers placed at key positions on the subject’s body. An OpenSim plugin was then used to obtain the forces and moments generated by the subject during each trial, with the moments computed relative to the equilibrium location of the subject’s feet [5]. The force of gravity was also removed to simulate the loads generated by the exercise when performed in microgravity. The load plots for each trial were generated and visually analyzed to obtain the magnitudes of the peak loads for each exercise in each DOF. The typical period of exercise for each trial was also estimated and used to calculate the frequency for each trial. The exercise loads data was then organized in multiple ways to capture different aspects of the data. As a result of this study, we present a summary of the load magnitudes observed during these critical exercises utilizing the E4D.

C A Bell↗
DOE OSTI2016

Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease

Recently, hydropersulfide (RSSH) was found to exist in mammalian tissues and fluids. Cysteine hydropersulfide can be found in free cysteine residues as well as in proteins, and it has potent antioxidative activity. Human serum albumin (HSA) is the most abundant protein in mammalian serum. HSA possesses a free thiol group in Cys-34 that could be a site for hydropersulfide formation. HSA hydropersulfide of high purity as a positive control was prepared by treatment of HSA with Na{sub 2}S. The presence of HSA hydropersulfide was confirmed by spectroscopy and ESI-TOFMS analysis where molecular weights of HSA hydropersulfide by increments of approximately 32 Da (Sulfur atom) were detected. The fluorescent probe results showed that Alexa Fluor 680 conjugated maleimide (Red-Mal) was a suitable assay and bromotrimethylammoniumbimane bromide appeared to be a selective reagent for hydropersulfide. The effect of oxidative stress related disease on the existence of albumin hydropersulfides was examined in rat 5/6 nephrectomy model of chronic kidney disease (CKD). Interestingly, the level of hydropersulfides in rat 5/6 nephrectomy model serum was decreased by a uremic toxin that increases oxidative stress in rat 5/6 nephrectomy model. Furthermore, we demonstrated that the levels of HSA hydropersulfide in human subjects were reduced in CKD but restored by hemodialysis using Red-Mal assay. We conclude that HSA hydropersulfide could potentially play an important role in biological anti-oxidative defense, and it is a promising diagnostic and therapeutic marker of oxidative diseases. - Highlights: • Hydropersulfide can behave as potent antioxidants. • We firstly detected human serum albumin hydropersulfide in healthy subjects. • Human serum albumin hydropersulfide in human subjects were reduced in chronic kidney disease but restored by hemodialysis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Cellular response to high pulse repetition rate nanosecond pulses varies with fluorescent marker identity

Nanosecond electric pulses (nsEP's) are a well-studied phenomena in biophysics that cause substantial alterations to cellular membrane dynamics, internal biochemistry, and cytoskeletal structure, and induce apoptotic and necrotic cell death. While several studies have attempted to measure the effects of multiple nanosecond pulses, the effect of pulse repetition rate (PRR) has received little attention, especially at frequencies greater than 100 Hz. In this study, uptake of Propidium Iodide, FM 1–43, and YO-PRO-1 fluorescent dyes in CHO-K1 cells was monitored across a wide range of PRRs (5 Hz–500 KHz) using a laser-scanning confocal microscope in order to better understand how high frequency repetition rates impact induced biophysical changes. We show that frequency trends depend on the identity of the dye under study, which could implicate transmembrane protein channels in the uptake response due to their chemical selectivity. Finally, YO-PRO-1 fluorescence was monitored in the presence of Gadolinium (Gd{sup 3+}), Ruthenium Red, and in calcium-free solution to elucidate a mechanism for its unique frequency trend. - Highlights: • Pulse repetition rate (PRR) is understudied in nanosecond electric pulsing. • 200 V pulses were applied to CHO-K1 cells from 5 Hz to 500 KHz. • Pulsing was repeated using a variety of fluorophores and imaging conditions. • The response is highly dependent on the fluorophore and the imaging conditions. • This may implicate protein channels in the nanoporation response.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Extending Classification Algorithms to Case-Control Studies

Classification is a common technique applied to ’omics data to build predictive models and identify potential markers of biomedical outcomes. Despite the prevalence of case-control studies, the number of classification methods available to analyze data generated by such studies is extremely limited. Conditional logistic regression is the most commonly used technique, but the associated modeling assumptions limit its ability to identify a large class of sufficiently complicated ’omic signatures. We propose a data preprocessing step which generalizes and makes any linear or nonlinear classification algorithm, even those typically not appropriate for matched design data, available to be used to model case-control data and identify relevant biomarkers in these study designs. We demonstrate on simulated case-control data that both the classification and variable selection accuracy of each method is improved after applying this processing step and that the proposed methods are comparable to or outperform existing variable selection methods. Finally, we demonstrate the impact of conditional classification algorithms on a large cohort study of children with islet autoimmunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Karyopherinβ1 regulates proliferation of human glioma cells via Wnt/β-catenin pathway

Karyopherinβ1 (KPNB1), one of the cytosolic factors involved in the selective protein transport across nucleus, docked at nuclear pore complex and transported through nuclear envelope in an ATP-dependent style, assisting proteins to be recognized as import substrates. It has been reported to be bound up with the origination and progress of lung cancer, cervical cancer, head and neck cancer and hepatocellular carcinoma. In current study, we demonstrated for the first time that the role of KPNB1 in human glioma. KPNB1 was over-expressed as the well-known trend of Ki-67(p < 0.01) and tightly closed to poor prognosis, as an independent prognostic factor. In vitro, up-regulation of KPNB1 was accompanied by certain rising levels of proliferation markers, employing U251 and U87MG cells as serum-starve models. Silencing KPNB1 in U251 and U87MG led to G1 phase arrested directly via flow cytometry analysis. In the nucleus of KPNB1-depletion cell models, the decreasing expression of KPNB1 and β-catenin was detected respectively, which indicated that KPNB1 functioned via β-catenin signal. Besides, the interaction between KPNB1 and β-catenin was proved clearly by immunoprecipitation. Taken together, it showed that KPNB1 might enhance human glioma proliferation via Wnt/β-Catenin Pathway. - Highlights: • KPNB1 accelerated the progress of human glioma via Wnt/β-catenin pathway. • The decreased β-catenin expression in nucleus of KPNB1-depletion cells. • We identified the interaction between β-catenin and KPNB1 for the first time. • The close positive relationship between KPNB1 expression and glioma proliferation. • Two kinds of glioma cell lines were applied to this study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Necrostatin-7 suppresses RANK-NFATc1 signaling and attenuates macrophage to osteoclast differentiation

Highlights: • Nec-7, but not Nec-1, inhibited osteoclast formation and function. • Nec-7 did not affect the M-CSF-supported survival of osteoclast precursor cells. • Nec-7 selectively attenuated RANK-NFATc1 axis and osteoclastic gene expression. • Forced overexpression of RANK restored osteoclastogenesis and NFATc1 amplification. Osteoclasts play a crucial role in osteolytic bone diseases, such as osteoporosis, rheumatoid arthritis, periodontitis, Paget's disease of bone and bone metastatic tumors. Therefore, controlling osteoclast differentiation and function has been considered a promising therapeutic strategy. Here, we show that necrostatin (Nec)-7, an inhibitor of programmed necrosis, strongly suppressed receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption, without compromising macrophage colony-stimulating factor (M-CSF)-supported survival and growth of osteoclast precursor cells. Accordingly, Nec-7 significantly decreased the levels of RANKL-induced osteoclastogenic marker genes, such as cathepsin K. Mechanistically, Nec-7 neither affected MAPK nor NF-κB activation; however, it strongly inhibited the RANKL receptor (RANK) to nuclear factor of activated T cells c1 (NFATc1) signaling. Lentiviral expression of RANK in bone marrow-derived macrophages significantly restored osteoclastogenesis and NFATc1 amplification in Nec-7-treated cells. In this study, we revealed that Nec-7-sensitive pathways are crucially involved in osteoclast formation and function. Investigation of the molecular mechanism(s) through which Nec-7 inhibits RANK-NFATc1 signaling axis may lead to the development of new therapeutic strategies for bone disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Selective reflection of laser radiation from submicron layers of Rb and Cs atomic vapors: Applications in atomic spectroscopy

We studied selective reflection (SR) of laser radiation from a window of a nanocell with thickness L ~ λ{sub 1,2}/2 filled with Rb and Cs atoms, where λ{sub 1} = 780 nm and λ{sub 2} = 852 nm are the wavelengths resonant with the D{sub 2} laser lines for Rb and Cs, respectively. It is demonstrated that the negative derivative of the SR signal profile for L > λ/2 changes to the positive one for L < λ/2. It is shown that the real-time formation of the SR signal profile derivative (SRD) with the spectral width 30–40 MHz and located at the atomic transition is, in particular, a convenient frequency marker of D{sub 2} transitions in Rb and Cs. The amplitudes of SRD signals are proportional to the atomic transition probabilities. A comparison with the known saturated absorption (SA) method demonstrated a number of advantages, such as the absence of cross-over resonances in the SRD spectrum, the simplicity of realization, a low required power, etc. An SRD frequency marker also operates in the presence of the Ne buffer gas at a pressure of 6 Torr, which allowed us to determine the Ne–Rb collisional broadening, whereas the SA method is already inapplicable at buffer gas pressures above 0.1 Torr. The realization simplicity makes the SRD method a convenient tool for atomic spectroscopy. Our theoretical model well describes the SRD signal.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2016

Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014.

62 RADIOLOGY AND NUCLEAR MEDICINE↗