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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
DOE OSTI2018

Developments of Highly Multiplexed, Multi-chroic Pixels for Balloon-Borne Platforms

We present our work to develop and characterize low thermal conductance bolometers that are part of sinuous antenna multi-chroic pixels (SAMP). We use longer, thinner and meandered bolometer legs to achieve 9 pW/K thermal conductance bolometers. We also discuss the development of inductor–capacitor chips operated at 4 K to extend the multiplexing factor of the frequency domain multiplexing to 105, an increase of 60% compared to the factor currently demonstrated for this readout system. This technology development is motivated by EBEX-IDS, a balloon-borne polarimeter designed to characterize the polarization of foregrounds and to detect the primordial gravity waves through their B-mode signature on the polarization of the cosmic microwave background. EBEX-IDS will operate 20,562 transition edge sensor bolometers spread over 7 frequency bands between 150 and 360 GHz. Balloon and satellite platforms enable observations at frequencies inaccessible from the ground and with higher instantaneous sensitivity. This development improves the readiness of the SAMP and frequency domain readout technologies for future satellite applications.

42 ENGINEERING↗
DOE OSTI2019

Investigation of Stress Field and Fracture Development During Shale Maturation Using Analog Rock Systems

The emergence of hydrocarbons within shale as a major recoverable resource has sparked interest in fluid transport through these tight mudstones. Recent studies suggest the importance to recovery of microfracture networks that connect localized zones with large organic content to the inorganic matrix. This paper presents a joint modeling and experimental study to examine the onset, formation, and evolution of microfracture networks as shale matures. Both the stress field and fractures are simulated and imaged. A novel laboratory-scale, phase-field fracture propagation model was developed to characterize the material failure mechanisms that play a significant role during the shale maturation process. The numerical model developed consists of coupled solid deformation, pore pressure, and fracture propagation mechanisms. Benchmark tests were conducted to validate model accuracy. Laboratory-grade gelatins with varying Young’s modulus were used as scaled-rock analogs in two dimensional Hele-Shaw cell apparatus. Yeast within the gelatin generates gas in a fashion analogous to hydrocarbon formation as shale matures. These setups allow study and visualization of host rock elastic-brittle fracture and fracture network propagation mechanisms. The experimental setup was fitted to utilize photoelasticity principles coupled with birefringence properties of gelatin to explore visually the stress field of the gelatin as the fracture network developed. Stress optics image analysis and Linear Elastic Fracture Mechanics (LEFM) principles for crack propagation were used to monitor fracture growth for each gelatin type. Observed and simulated responses suggest gas diffusion within and deformation of the gelatin matrix as predominant mechanisms for energy dissipation depending on gelatin strength. LEFM, an experimental estimation of principal stress development with fracture growth, at different stages was determined for each gelatin rheology. Here, the interplay of gas diffusion and material deformation determines the resulting frequency and pattern of fractures. Results correlate with Young’s modulus. Experimental and computed stress fields reveal that fractures resulting from internal gas generation are similar to, but not identical to, type 1 opening mode.

58 GEOSCIENCES↗
DOE OSTI2019

Origin of the {111}〈112〉 Cold Rolling Texture Development in a Soft Magnetic Fe-27%Co Alloy

Plastic deformation of Fe-27%Co alloy at room temperature was investigated. The present alloy, usually delivered with a low-texture component for the magnetic core in rotating machines, develops a rather high intensity of Goss texture after recrystallization, when a suitable manufacturing process is applied. Thanks to this texture and its magnetic properties, this material can replace the grain-oriented Fe-3%Si alloy in electric transformer application. The intensity of the recrystallization Goss component depends directly on the sharpness of the {111}〈112〉 orientation developed during cold rolling. Thus, the origin of this {111}〈112〉 deformation texture has been studied using visco-plastic self-consistent (VPSC) simulations. This model showed that only the {110}〈111〉 slip systems allow developing the {111}〈112〉 texture. The predominance of this slip system has been effectively identified from slip markings on the deformed sample by EBSD. More, this simulation has shown that a Goss texture at the hot-rolled state favors the {111}〈112〉 development during cold rolling, as observed experimentally.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Development of NiO-Nanocarbon and MnO{sub 2}-Nanocarbon Energetic Catalytic Electrode Materials to Synthesize Electrical Energy through Electrochemical Oxidation of Glucose

Automobile and transportation on land and in air are the major causes of global environment pollution through the chemical combustion of petroleum fuels. The need of the hour is to run the transportation units by fuel cells which convert fuels to energy through electrochemical oxidation, straight to pure electrical energy with no polluting substances. Development of fuel cell lies on exhaustive research on development of high energetic electrocatalytic electrodes over which the fuels break to produce free electron and ions, delivering electrical energy. The present work aims at developing two electrocatalytic materials: NiO-nanocarbon and MnO{sub 2}-nanocarbon by electrosynthesis method. The performance of the materials was investigated by electrochemical characterization: cyclic voltammetry, chronoammetry, polarization tests and impedance spectroscopy. The materials were found to deliver a high current on electro-oxidation of glucose. The effect of nanocarbon on NiO and MnO{sub 2} has enhanced the current to a level of over 100 mA/cm{sup 2}. XRD study showed the presence of metal oxides and carbon. The electron microscopy images revealed fine grain oxides with entrapped nanocarbon. The carbon seems to be in the form of graphene, produced during electrochemical exfoliation at anode. The SEM morphology of enhanced 3D surface area with high energetic nanocarbon phase entrapped with fine structure metal oxides accounts for the high current obtained by electro-oxidation of the fuel. The materials developed are found to be very good energetic electrodes for future fuel cell in automotive industry.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Investigation into the Development and Testing of a Simplex Capacitance Sensor for Rotor Tip Clearance Measurement in Turbo Machinery

The rotor tip clearance is a vital parameter to characterize turbomachinery performance. It is an essential measurement during engine development and testing. The efficiency of the major modules like fan, compressor and turbine depends on the optimum running clearances. The capacitive sensor is preferred for tip clearance measurements because of various inherent advantages. They are fabricated through complex processes for turbomachinery application and are expensive. These sensors are exposed to harsh engine environments and are likely to exhibit degraded performance. Insulation failure at sensing head, connector contamination and micro-cracks in the MI (Mineral Insulated) cable leads to noise in the signal output. Frequent mechanical failures are also seen due to work hardening of MI cables, lead connector detachments and failure of micro fins at interconnects. Fault fixing of these is tedious and very expensive. This paper presents the concerted effort in developing a simple capacitance sensor addressing potential sensor failure issues. The design features include simple construction, ease of sensor assembly, component realization and troubleshooting. The design also addresses all safety requirements. The sensor has a large sensing area (7.6 mm diameter) producing very stable, high-level signal. The developed sensor produces output that varies from 1 V{sub P-P} to 11 V{sub P-P} for blade-tip gaps between 3 mm to 0.4 mm respectively. Blade pass simulation studies across the sensor, display almost flat response at minimum clearance. This feature results in very minimal data acquisition errors. The sensor along with RC (Resistance-Capacitance) conditioning electronics was successfully used for clearance measurement on fan stage of gas turbine engine. Test results are in line with the predictions. Extensive tip clearance measurements on the engine validate the design. The current work provides an insight into the development of a simplex capacitance sensor for tip clearance measurement.

42 ENGINEERING↗
DOE OSTI2022

Phase transformation dynamics guided alloy development for additive manufacturing

Fusion-based additive manufacturing technologies enable the fabrication of geometrically and compositionally complex parts unachievable by conventional manufacturing methods. However, the non-uniform and far-from-equilibrium heating/cooling conditions pose a significant challenge to consistently obtaining desirable phases in the as-printed parts. Here, in this study, we report a martensite stainless steel development guided by phase transformation dynamics revealed by in-situ high-speed, high-energy, high-resolution X-ray diffraction. This developed stainless steel consistently forms desired fully martensitic structure across a wide range of cooling rates (10 2 –10 7 °C/s), which enables direct printing of parts with fully martensitic structure. The as-printed material exhibits a yield strength of 1157 ± 23 MPa, comparable to its wrought counterpart after precipitation-hardening heat-treatment. The as-printed property is attributed to the fully martensitic structure and the fine precipitates formed during the intrinsic heat treatment in additive manufacturing. The phase transformation dynamics guided alloy development strategy demonstrated here opens the path for developing reliable, high-performance alloys specific for additive manufacturing.

17–4 PH stainless steel↗
DOE OSTI2023

Development of a Benchmark Eddy Flux Evapotranspiration Dataset for Evaluation of Satellite-Driven Evapotranspiration Models Over the CONUS

A large sample of ground-based evapotranspiration (ET) measurements made in the United States, primarily from eddy covariance systems, were post-processed to produce a benchmark ET dataset. The dataset was produced primarily to support the intercomparison and evaluation of the OpenET satellite-based remote sensing ET (RSET) models and could also be used to evaluate ET data from other models and approaches. OpenET is a web-based service that makes field-delineated and pixel-level ET estimates from well-established RSET models readily available to water managers, agricultural producers, and the public. The benchmark dataset is composed of flux and meteorological data from a variety of providers covering native vegetation and agricultural settings. Flux footprint predictions were developed for each station and included static flux footprints developed based on average wind direction and speed, as well as dynamic hourly footprints that were generated with a physically based model of upwind source area. The two footprint prediction methods were rigorously compared to evaluate their relative spatial coverage. Data from all sources were post-processed in a consistent and reproducible manner including data handling, gap-filling, temporal aggregation, and energy balance closure correction. The resulting dataset included 243,048 daily and 5,284 monthly ET values from 194 stations, with all data falling between 1995 and 2021. We assessed average daily energy imbalance using 172 flux sites with a total of 193,021 days of data, finding that overall turbulent fluxes were understated by about 12% on average relative to available energy. Multiple linear regression analyses indicated that daily average latent energy flux may be typically understated slightly more than sensible heat flux. This dataset was developed to provide a consistent reference to support evaluation of RSET data being developed for a wide range of applications related to water accounting and water resources management at field to watershed scales.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Development of a novel minigenome and recombinant VSV expressing Seoul hantavirus glycoprotein-based assays to identify anti-hantavirus therapeutics

Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ~2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system to identify potential antiviral compounds for SEOV and generated additional assays to characterize the mode of action of any promising antivirals. Here, to test if candidate antivirals targeted SEOV glycoprotein-mediated entry, we developed a recombinant reporter vesicular stomatitis virus expressing SEOV glycoproteins. To facilitate the identification of candidate antiviral compounds targeting viral transcription/replication, we successfully generated the first reported minigenome system for SEOV. This SEOV minigenome (SEOV-MG) screening assay will also serve as a prototype assay for discovery of small molecules inhibiting replication of other hantaviruses, including Andes and Sin Nombre viruses. Ours is a proof-of-concept study in which we tested several compounds previously reported to have activity against other negative-strand RNA viruses using our newly developed hantavirus antiviral screening systems. These systems can be used under lower biocontainment conditions than those needed for infectious viruses, and identified several compounds with robust anti-SEOV activity. Our findings have important implications for the development of anti-hantavirus therapeutics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Aerosols consistently suppress the convective boundary layer development

Aerosols with different vertical distribution and various optical properties induce diverse heating rates and thereby affecting convective boundary layer (CBL) development. Our results showed consistent CBL-suppression of aerosols during daytime with numerical experiments, in which aerosols were specified at different heights with synthesized single scattering albedo from 64 studies and asymmetry factor from 20 studies globally. Absorbing aerosols concentrated below but close to the CBL top had the strongest suppression effect on CBL development relative to that concentrated near surface or above CBL. Aerosol cooling effect by attenuating incident solar radiation and surface heat flux exceeded its warming effect by reheating the atmosphere layer with absorbed shortwave radiation, and eventually declined net heating rate, which inhibited CBL development, lowered mixed-layer potential temperature and stabilized atmospheric stratification. Stove effect of absorbing aerosols (CBL enhancement) under a zero background aerosol extinction coefficient is negligible for dominant dome effect (CBL suppression) which consistently suppresses CBL development regardless of aerosol vertical height and background aerosol extinction coefficient. Our study also highlighted the importance of specifying background aerosol extinction coefficient in numerical experiments for accurate assessment of aerosol radiative forcing and CBL-aerosol interactions.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Involvement of mouse and porcine PLCζ-induced calcium oscillations in preimplantation development of mouse embryos

In mammals, phospholipase Cζ (PLCζ) has the ability to trigger calcium (Ca{sup 2+}) oscillations in oocytes, leading to oocyte activation. Although there is a species-specific difference in the PLCζ-induced Ca{sup 2+} oscillatory pattern, whether PLCζ-induced Ca{sup 2+} oscillations affect preimplantation embryonic development remains unclear. Here, we show that Ca{sup 2+} oscillations in mouse PLCζ cRNA-injected oocytes stopped just before pronuclear formation, while that in porcine PLCζ cRNA-injected oocytes continued for several hours after pronuclei had been formed. This difference of Ca{sup 2+} oscillations in oocytes after pronuclear formation was dependent on the difference in the nuclear localization signal (NLS) sequence of PLCζ between the mouse and pig. However, mouse and porcine PLCζ cRNA-injected oocytes parthenogenetically developed to blastocysts regardless of the absence or presence of Ca{sup 2+} oscillations after pronuclear formation. Furthermore, the developmental rate of mouse or porcine PLCζ-activated oocytes injected with round spermatids to the blastocyst stage was not significantly different from that of strontium-activated oocytes injected with round spermatids. These results suggest that the PLCζ-induced Ca{sup 2+} oscillatory pattern in mouse oocytes is dependent on the NLS sequence of PLCζ and injection of PLCζ may be a useful method for activation of round spermatid-injected and somatic nuclear transferred oocytes. - Highlights: • Porcine PLCζ-induced Ca{sup 2+} oscillations continued after pronuclear formation. • The Ca{sup 2+} oscillatory pattern was dependent on the difference in the NLS sequence of PLCζ. • PLCζ-activated oocytes parthenogenetically developed to blastocysts. • PLCζ-activated oocytes injected with round spermatids developed to blastocysts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Vitamin D receptor deficiency impairs inner ear development in zebrafish

The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development. - Highlights: • VDR signaling is involved in ear development. • Knockdown of vdrb causes inner ear malformations during embryogenesis. • Knockdown of vdrb affects otic placode induction. • Knockdown of vdrb reduces the number of sensory hair cells in the inner ear. • Knockdown of vdrb disrupts balance and motor coordination.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Near-infrared laser irradiation improves the development of mouse pre-implantation embryos

The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing of blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. - Highlights: • Irradiation of blastocysts with a near-infrared laser improves embryo development. • Irradiation of blastocysts increases the live birth rate after embryo transfer. • Irradiation of blastocysts did not affect the normality of the pups. • Near-infrared laser irradiation may be useful to enhance the quality of embryos. • This study may contribute to improvements in reproductive technologies in mammals.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Newly developed selective immunoinactivation assay revealed reduction in adipose triglyceride lipase activity in peripheral leucocytes from patients with idiopathic triglyceride deposit cardiomyovasculopathy

Highlights: • Development of selective immunoinactivation assay for ATGL activity in leucocytes. • ATGL activity was markedly reduced in idiopathic TGCV without ATGL mutations. • ATGL in leucocytes may be an important biomarker for the diagnosis of TGCV. • Selective immunoinactivation assay provides insights into pathogenesis for TGCV. Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare and newly identified disease among patients requiring cardiac transplantation. TGCV is characterized by cardiomyocyte steatosis and triglyceride (TG)-deposit atherosclerosis, resulting from the abnormal intracellular metabolism of TG. TGCV is classified into primary and idiopathic types. Primary TGCV carries ultra-rare genetic mutations in the adipose triglyceride lipase (ATGL), a rate-liming enzyme that hydrolyzes intracellular TG in adipose and non-adipose tissues. Idiopathic TGCV, first identified among autopsied individuals with diabetes mellitus (DM) with severe heart diseases, shows no ATGL mutations and its causes and underlying mechanisms are still unknown. TGCV is difficult to diagnose in daily clinics, thereby demanding feasible diagnostic procedures. We aimed to develop an assay to measure ATGL activity using peripheral leucocytes. Human his6-ATGL was expressed in COS1 cells, purified to homogeneity, and used to raise a polyclonal antibody neutralizing TG-hydrolyzing activity of ATGL. We developed a selective immunoinactivation assay (SIIA) for the quantitation of ATGL activity in cell lysates of leucocytes by the antibody neutralizing ATGL activities. ATGL activity was measured in 13 idiopathic TGCV patients, with two patients with primary TGCV as the negative control. Healthy (non-DM) and DM controls without heart diseases were also subjected. The developed SIIA assay revealed significant reduction in ATGL activity in leucocytes from patients with idiopathic TGCV who did not carry ATGL mutations as compared with non-DM and DM controls. Thus, ATGL in leucocytes may be an important biomarker for the diagnosis of TGCV and our assay may provide insights into pathophysiology and elucidate the underlying mechanism of TGCV and related disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction

Highlights: • Flk1 is expressed in ECs with an epicardial-to-endocardial transmural gradient. • Flt1 is homogeneously expressed in ECs in neonatal and adult mouse hearts. • Flk1 is transiently induced but Flt1 is maintained in coronary vessels after MI. • The kinetics of Flk1 and Flt1 after MI recapitulates that in cardiac development. The coronary vascular system is critical for myocardial growth and cardiomyocyte survival. However, the molecular mechanism regulating coronary angiogenesis remains elusive. Vascular endothelial growth factor (VEGF) regulates angiogenesis by binding to the specific receptors Flk1 and Flt1, which results in different functions. Despite the importance of Flk1 and Flt1, their expression in the coronary vasculature remains largely unknown due to the lack of appropriate antibodies for immunostaining. Here, we analyzed multiple reporter mice including Flk1-GFP BAC transgenic (Tg), Flk1-LacZ knock-in, Flt1-DsRed BAC Tg, and Flk1-GFP/Flt1-DsRed double Tg animals to determine expression patterns in mouse hearts during cardiac growth and after myocardial infarction (MI). We found that Flk1 was expressed in endothelial cells (ECs) with a pattern of epicardial-to-endocardial transmural gradients in the neonatal mouse ventricle, which was downregulated in adult coronary vessels with development. In contrast, Flt1 was homogeneously expressed in the ECs of neonatal mouse hearts and expression was maintained until adulthood. After MI, expression of both Flk1 and Flt1 was induced in the regenerating coronary vessels at day 7. Intriguingly, Flk1 expression was downregulated thereafter, whereas Flt1 expression was maintained in the newly formed coronary vessels until 30 days post-MI, recapitulating their expression kinetics during development. This is the first report demonstrating the spatiotemporal expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after MI; thus, this study suggests that these factors have distinct and important functions in coronary angiogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Harmine promotes molar root development via SMAD1/5/8 phosphorylation

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo. Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mice overexpressing latent matrix metalloproteinase-2 develop lung emphysema after short-term exposure to cigarette smoke extract

Highlights: • Protease/anti-protease imbalance is an important event in the pathogenesis of lung emphysema. • Long time exposure to cigarette smoke is generally required to induce mouse model of lung emphysema. • Mice overexpressing matrix metalloproteinase-2 develop lung emphysema after short exposure to cigarette smoke extract. Chronic obstructive pulmonary disease is the major growing cause of mortality and morbidity worldwide, and it is going to become the third most common cause of death by 2020. Chronic obstructive pulmonary disease is pathologically characterized by lung emphysema and small airway inflammation. Animal models are very important to get insights into the disease pathogenesis but current models of chronic obstructive pulmonary disease take a long time to develop. The need of a new model is compelling. In the present study we focus on the role of matrix metalloproteinases in the pathogenesis of chronic obstructive pulmonary disease and hypothesized that lung overexpression of latent matrix metalloproteinases-2 would allow the development of emphysema after short-term exposure to cigarette smoke extract inhalation. Human latent matrix metalloproteinases-2 transgenic mouse expressing high level of the protein in the lungs and wild type mouse were exposed to aerosolized cigarette smoke extract for two weeks. Transgenic mice showed significant lung emphysematous changes, increased infiltration of inflammatory cells and enhanced lung concentrations of inflammatory cytokines in the lungs compared to their wild type counterparts after inhalation of cigarette smoke extract. This novel mouse model will be a very useful tool for evaluating the mechanistic pathways and for development of novel therapies in cigarette smoke-associated lung emphysema.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Loss of RapC causes defects in cytokinesis, cell migration, and multicellular development of Dictyostelium

Highlights: • We characterized the functions of RapC, an isoform of Rap1 small GTPase. • Loss of RapC causes defects in cytokinesis, cell migration, and development. • RapC plays a negative role in cell spreading and cell adhesion. • RapC is involved in tip formation from mounds during multicellular development. • This contributes to the understanding of Ras-mediated cellular processes. The small GTPase Ras proteins are involved in diverse cellular processes. We investigated the functions of RapC, one of 15 Ras subfamily GTPases in Dictyostelium. Loss of RapC resulted in a spread shape of cells; severe defects in cytokinesis leading to multinucleation; decrease of migration speed in chemoattractant-mediated cell migration, likely through increased cell adhesion; and aberrations in multicellular development producing abnormal multiple tips from one mound and multi-branched developmental structures. Defects in cells lacking RapC were rescued by expressing GFP-RapC in rapC null cells. Our results demonstrate that RapC, despite its high sequence homology with Rap1, plays a negative role in cell spreading and cell adhesion, in contrast to Rap1, which is a key regulator of cell adhesion and cytoskeleton rearrangement. In addition, RapC appears to have a unique function in multicellular development and is involved in tip formation from mounds. This study contributes to the understanding of Ras-mediated cellular processes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RBM14 is indispensable for pluripotency maintenance and mesoderm development of mouse embryonic stem cells

Highlights: • RBM14 knockout mouse embryonic stem cells were successfully generated. • RBM14 depletion altered gene expression profiles in mouse embryonic stem cells. • RBM14 depletion impeded mesoderm development in vitro. • RBM14 depletion impeded mesoderm development in vivo. The pluripotency of embryonic stem cells (ESCs) is maintained by core pluripotency transcription factors, cofactors and several signaling pathways. RBM14 is a component of the para-speckle complex, which has been implicated in multiple important biological processes. The role of RBM14 in ESCs and lineage differentiation remains to be elucidated. In the present study, we provided evidence that RBM14 plays important roles in maintaining pluripotency and in the early differentiation of ESCs. RBM14 was demonstrated to be expressed in mouse embryonic stem cells (mESCs) and localized in the nucleus. RBM14 expression was depleted in mESCs using clustered regularly interspaced short palindromic repeats (CRISPR) technology. Our results also showed that RBM14 depletion altered the gene expression profiles of mESCs. In particular, pluripotency-associated genes and genes involved in the Wnt and TGF-β signaling pathways were downregulated in RBM14 knockout mESCs. Furthermore, RBM14 was found to be essential for mesoderm development in vitro and in vivo. The specific effects of RBM14 depletion were verified by conducting a rescue experiment. Our findings demonstrated that RBM14 not only plays an important role in maintaining the pluripotency of mESCs but is also indispensable for mesoderm development.

60 APPLIED LIFE SCIENCES↗