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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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136 records · Page 8

Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET

A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with non–small cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and cross-phosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After the final step, we selected the EGFR and MET arms for the lead BsAb and added low fucose Fc engineering to generate amivantamab (JNJ-61186372). The crystal structure of the anti-MET Fab of amivantamab bound to MET was solved, and the interaction between the two molecules in atomic details was elucidated. Amivantamab antagonized the hepatocyte growth factor (HGF)-induced signaling by binding to MET Sema domain and thereby blocking HGF β-chain—Sema engagement. The amivantamab EGFR epitope was mapped to EGFR domain III and residues K443, K465, I467, and S468. Furthermore, amivantamab showed superior antitumor activity over small molecule EGFR and MET inhibitors in the HCC827-HGF in vivo model. Based on its unique mode of action, amivantamab may provide benefit to patients with malignancies associated with aberrant EGFR and MET signaling.

59 BASIC BIOLOGICAL SCIENCES↗

Magnifying the Early Episodes of Star Formation: Super Star Clusters at Cosmological Distances

We study the spectrophotometric properties of a highly magnified (μ≃40--70) pair of stellar systems identified at z = 3.2222 behind the Hubble Frontier Field galaxy cluster MACS J0416. Five multiple images (out of six) have been spectroscopically confirmed by means of VLT/MUSE and VLT/X-Shooter observations. Each image includes two faint (m{sub UV}≃30.6), young (≲100 Myr), low-mass (<10{sup 7} M{sub ⊙}), low-metallicity (12 + Log(O/H) ≃ 7.7, or 1/10 solar), and compact (30 pc effective radius) stellar systems separated by ≃300 pc after correcting for lensing amplification. We measured several rest-frame ultraviolet and optical narrow (σ{sub v}≲25 km s{sup −1}) high-ionization lines. These features may be the signature of very hot (T>50,000 K) stars within dense stellar clusters, whose dynamical mass is likely dominated by the stellar component. Remarkably, the ultraviolet metal lines are not accompanied by Lyα emission (e.g., C iv/Lyα > 15), despite the fact that the Lyα line flux is expected to be 150 times brighter (inferred from the Hβ flux). A spatially offset, strongly magnified (μ>50) Lyα emission with a spatial extent ≲7.6 kpc{sup 2} is instead identified 2 kpc away from the system. The origin of such a faint emission could be the result of fluorescent Lyα induced by a transverse leakage of ionizing radiation emerging from the stellar systems and/or may be associated with an underlying and barely detected object (with m{sub UV}>34 de-lensed). This is the first confirmed metal-line emitter at such low-luminosity and redshift without Lyα emission—suggesting that, at least in some cases, a non-uniform covering factor of the neutral gas might hamper the Lyα detection.

79 ASTRONOMY AND ASTROPHYSICS↗

Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their stemness in culture

The neural stem cell (NSC) niche in subventricular zone (SVZ) of adult mammalian brain contains dense vascular plexus, where endothelial cells (ECs) regulate NSCs by releasing plenty of angiocrine factors. However, the role of ECs-derived exosomes, a novel type of mediators of intercellular communications, in the regulation of NSCs remains unclear. In the current study, primary NSCs isolated from embryonic mouse brains form more neurospheres when cultured in the presence of human umbilical vein endothelial cells (HUVECs). The supportive role of ECs in the coculture was significantly attenuated when GW4869, a blocker of exosome formation, was included, suggesting that HUVECs-derived exosomes played a significant role in supporting NSCs. In order to investigate the role of ECs-derived exosomes on NSCs, we collected exosomes from HUVECs. We found that HUVECs-derived exosomes could significantly promote the formation of neurospheres by primary murine NSCs. EdU incorporation and TUNEL assays indicated that the proliferation of NSCs increased while apoptosis decreased when cultured in the presence of HUVECs-derived exosomes. NSCs incubated with the HUVECs-derived exosomes maintained their potential of multi-lineage differentiation potentials. The expression of stemness-related genes was up-regulated. These data suggested that ECs-derived exosomes could play an importantly role in NSC niche, and they might be used as a reagent for ex vivo NSC amplification for medical application.

60 APPLIED LIFE SCIENCES↗

Intensive and extensive margins of the peak load: Measuring adaptation with mixed frequency panel data

In this work we investigate the response of daily electricity peak load to daily maximum temperatures across states in Europe and India. We propose a method that decomposes short- from medium/long-run effects, retains the high frequency nature of the load-weather covariation and treats economic growth as a modulating factor. By simultaneously exploiting variation in unexpected daily weather anomalies and decade-long climatic changes in each location we decompose transitory - intensive margin - adjustments from permanent - extensive margin - adjustments. We find that the shocks over the long-run differ substantially from the short-run dynamics. Furthermore, we find evidence that per capita income modulates the adjustments over the short- and long-run. We project that in response to climate change around 2050 the peak load may increase by up to 20%-30% in Southern Europe and in several states in India, depending on the degree of warming and the evolution of socio-economic conditions. Even with a limited scope to two world regions, we identify that the structure of the economy and differences in future income growth matter in shaping the adaptation to climate change. Our decomposition allows to identify how future weather anomalies can further amplify the relative increase associated to the shift in the climate norm. Assuming that the interannual variability of maximum temperatures follows the distribution observed in the past, we find a doubling of the impacts of climate change during the summer in Europe. Uncertainty around the distribution of future weather anomalies may lead to further unexpected peak load amplifications. Our results have important policy implications for power systems’ generation capacity, transmission and storage, as we show that the challenges to accommodate the peak load in days with extreme temperatures may substantially increase already around mid-century.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Reaching a burning plasma and ignition using smaller capsules/ Hohlraums , higher radiation temperatures, and thicker ablator/ice on the national ignition facility

In indirect-drive implosions, the final core hot spot energy and pressure and, hence, neutron yield attainable in 1D increase with increasing laser peak power and, hence, radiation drive temperature at the fixed capsule and Hohlraum size. Here we present simple analytic scalings validated by 1D simulations that quantify the improvement in performance and use this to explain existing data and simulation trends. Extrapolating to the 500 TW National Ignition Facility peak power limit in a low gas-fill 5.4 mm diameter Hohlraum based on existing high adiabat implosion data at 400 TW, 1.3 MJ and 1 × 10 16 yield, we find that a 2–3 × 10 17 yield (0.5–0.7 MJ) is plausible using only 1.8 MJ of laser energy. Based on existing data varying deuterium–tritium (DT) fuel thickness and dopant areal density, further improvements should be possible by increasing DT fuel areal density, and hence confinement time and yield amplification.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Toward a more realistic representation of surface albedo in NASA CERES-derived surface radiative fluxes

Accurate multidecadal radiative flux records are vital to understand Arctic amplification and constrain climate model uncertainties. Uncertainty in the NASA Clouds and the Earth’s Radiant Energy System (CERES)-derived irradiances is larger over sea ice than any other surface type and comes from several sources. The year-long Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in the central Arctic provides a rare opportunity to explore uncertainty in CERES-derived radiative fluxes. First, a systematic and statistically robust assessment of surface shortwave and longwave fluxes was conducted using in situ measurements from MOSAiC flux stations. The CERES Synoptic 1degree (SYN1deg) product overestimates the downwelling shortwave flux by +11.40 Wm –2 and underestimates the upwelling shortwave flux by –15.70 Wm –2 and downwelling longwave fluxes by –12.58 Wm –2 at the surface during summer. In addition, large differences are found in the upwelling longwave flux when the surface approaches the melting point (approximately 0°C). The biases in downwelling shortwave and longwave fluxes suggest that the atmosphere represented in CERES is too optically thin. The large negative bias in upwelling shortwave flux can be attributed in large part to lower surface albedo (–0.15) in satellite footprint relative to surface sensors. Additionally, the results show that the spectral surface albedo used in SYN1deg overestimates albedo in visible and mid-infrared bands. A series of radiative transfer model perturbation experiments are performed to quantify the factors contributing to the differences. The CERES-MOSAiC broadband albedo differences (approximately 20 Wm –2 ) explain a larger portion of the upwelling shortwave flux difference than the spectral albedo shape differences (approximately 3 Wm –2 ). In addition, the differences between perturbation experiments using hourly and monthly MOSAiC surface albedo suggest that approximately 25% of the sea ice surface albedo variability is explained by factors not correlated with daily sea ice concentration variability. Biases in net shortwave and longwave flux can be reduced to less than half by adjusting both albedo and cloud inputs toward observed values. The results indicate that improvements in the surface albedo and cloud data would substantially reduce the uncertainty in the Arctic surface radiation budget derived from CERES data products.

54 ENVIRONMENTAL SCIENCES↗

Laser damage of crazed electron-beam high-reflectors following infrared and ultraviolet irradiation in the nanosecond pulse regime

Laser damage of optical components can be a limiting factor in scaling the energetics of high-peak and average power laser systems. Specifically for optical coatings, damage under nanosecond pulsed irradiation is initiated by pre-existing defects in the coating layers, including those that cause discontinuities in the structure, like craze lines. Crazing or cracking in a multilayer dielectric optical coating is induced when the overall coating stress is sufficiently tensile, and is an occasionally observed issue when employing more porous deposition techniques like electron-beam evaporation. Here, in this study, electron-beam high-reflectors were fabricated utilizing process parameters that are known to induce crazing based on prior processing history to systematically evaluate the impact of crazing on reflector damage performance for 1064 and 355 nm lasers. The crazing that was observed was apparently nucleated at nodular defects. When the cross-section of these nodules was investigated, it was observed that there were cracks into the fused silica substrate of approximately 5 µm in depth. The craze lines were irradiated with 1064 and 355 nm light at fluences slightly above the onset of damage initiation fluence of the coating. The 1064 nm irradiated sub-apertures exhibit laser damage but with no spatial correlation with the craze line, whereas the 355 nm irradiated area exhibited many damage sites along the craze line. Finite-difference time-domain electric-field simulations were conducted, and ∼2× field amplification in hafnia was observed for the 355 nm wavelength case. The laser damage can be attributed to a slight electric-field intensification coincidental with an area where UV damage-prone precursors are known to occur. The 355 nm laser damage in uncoated fused silica substrates has been previously correlated to initiate through localized UV absorption at the broken silica bonds in the tips of fractures.

Harthcock, Colin [Lawrence Livermore National Labo↗

On the potential impact of a half-degree warming on cold and warm temperature extremes in mid-latitude North America

This study focuses on potential impacts of climate change on the early spring (March-April) temperature and its extremes in the mid-latitudes of North America, discriminated between the 1.5 °C and 2 °C levels of global warming, as projected by a suit of numerical experiments. The results suggest relatively mild seasonal average warming (0.25 °C-1.5 °C), but also an intensification of both warm and cold temperature extremes. Furthermore, the derived changes feature much stronger warming over the West of the United States and weak to no warming to the East, which is congruent with the ventilating effect of the intensified northerly wind over central Canada and the East of the United States. The intensified northerly component of the mid-latitude jet is likely a contributing factor to the derived increased seasonal variability of March-April temperatures over parts of Manitoba and Ontario in Canada, and the Midwest of the United States. The projected changes in temperature extremes agree to some extent with the previous studies: Warm extremes intensify especially over southern mid-latitudes, while cold extremes are weakening over the north mid-to high-latitudes. However, high-resolution simulations with the Community Atmospheric Model 5 (CAM5) indicate much sharper spatial gradients, which translate into higher magnitudes and also more complex patterns of changes. Particularly, cold extremes feature not only reductions north of ~45°N latitudes, but also a very strong intensification of cold extremes (by-4 °C for 20 year return values) in the band 25°-45°N, centered in the Midwest of the United States. While general warming and intensification of the warm extremes may accelerate the arrival of early spring, the intensifying cold extremes may increase the risk of early spring frost damage, and hence may yield a profound impact on the regional agriculture of North America. Combined with reliable information on expected temperature variability at interannual-to-decadal timescales, the background longer-term projections can help inform decision makers in the food security sector.

54 ENVIRONMENTAL SCIENCES↗

Collaborative Research: Quantifying Climate Feedbacks of the Terrestrial Biosphere under Thawing Permafrost Conditions in the Arctic

Our overall goal in this research was to quantify the potential for threshold changes in natural emission rates of trace gases, particularly methane and carbon dioxide, from pan-arctic terrestrial systems under the spectrum of anthropogenically-forced climate warming, and the conditions under which these emissions provide a strong feedback mechanism to global climate warming. This goal was motivated under the premise that polar amplification of global climate warming will induce widespread thaw and degradation of the permafrost, and would thus cause substantial changes to the landscape of wetlands and lakes, especially thermokarst (thaw) lakes, across the Arctic. Through a suite of numerical experiments that encapsulate the fundamental processes governing methane emissions and carbon exchanges – as well as their coupling to the global climate system - we tested the following hypothesis in the proposed research: There exists a climate warming threshold beyond which permafrost degradation becomes widespread and stimulates large increases in methane emissions (via thermokarst lakes and poorly-drained wetland areas upon thawing permafrost along with microbial metabolic responses to higher temperatures) and increases in carbon dioxide emissions from well-drained areas. Besides changes in biogeochemistry, this threshold will also influence global energy dynamics through effects on surface albedo, evapotranspiration and water vapor. These changes would outweigh any increased uptake of carbon (e.g. from peatlands and higher plant photosynthesis) and would result in a strong, positive feedback to global climate warming. In collaboration with our Purdue and MIT colleagues, we have attempted to quantify global climate warming effects on land-atmosphere interactions, land-river network interactions, permafrost degradation, vegetation shifts, and land use influence water, carbon, and nitrogen fluxes to and from terrestrial ecosystems in the pan-arctic along with their uncertainties. Based on our study results along with a review of observed and projected climate changes in Northern Eurasia by others, we have also outlined a more integrated modelling approach that may be developed and applied in future studies to better capture the influence of earth system feedbacks and human activities on the evolution of climate change effects over time. Specifically, we have examined: 1) how evapotranspiration and water availability have been changing in Northern Eurasia and may change in the future including the impact of forcing uncertainties (Liu et al., 2013, 2014, 2015); 2) how soil consumption of atmospheric methane across the globe have been influenced and may be influenced by climate change and nitrogen deposition during the 20th and 21st centuries (Zhuang et al., 2013); 3) how wetland inundation extent influences net CO2 and CH4 fluxes from northern high latitudes (Zhuang et al., 2015); 4) the relative effects of various environmental factors (including permafrost degradation) on terrestrial dissolved organic carbon (DOC) loading of river networks across the pan-Arctic and how they have changed over the 20th century (Kicklighter et al., 2013); 5) the impacts of recent and future permafrost thaw on land-atmosphere greenhouse gas exchange across the pan-Arctic (Gao et al., 2012, 2013; Hayes et al., 2014; Kicklighter et al. 2015a, 2018); 6) how climate-induced vegetation shifts may affect carbon fluxes and future land use in Northern Eurasia (Jiang et al., 2012, 2016; Kicklighter et al., 2014a) and the globe (Zhuang et al. 2015b); 7) the relative importance of legacies from past land use, future land-use change and climate change on projections of terrestrial carbon fluxes (Monier et al., 2015; Kicklighter et al., 2016); and 8) how the effects of earth system feedbacks and human activities can be better incorporated in assessments of climate change impacts (Monier et al., 2017; Groisman et al., 2018).

54 ENVIRONMENTAL SCIENCES↗

Uncertain role of clouds in shaping summertime atmosphere-sea ice connections in reanalyses and CMIP6 models

Downwelling longwave radiation (DLR) driven by the atmospheric and cloud conditions in the troposphere is suggested to be a dominant factor to determine the summertime net surface energy budget over the Arctic Ocean and thus plays a key role to shape the September sea ice. We use reanalyses and the self-organizing map (SOM) method to distinguish CMIP6 model performance in replicating the observed strong atmosphere-DLR connection. We find all models can reasonably simulate the linkage between key atmosphere variables and the clear sky DLR but behave differently in replicating the atmosphere-DLR connection due to cloud forcing. In ERA5 and strongly coupled models, tropospheric high pressure is associated with decreased clouds in the mid- and high-levels and increased clouds near the surface. This out-of-phase structure indicates that DLR cloud forcing is nearly neutral, making the clear sky DLR more important to bridge JJA circulation to late-summer sea ice. In MERRA-2 and weakly coupled models, tropospheric clouds display a vertically homogeneous reduction; the cloud DLR is thus strongly reduced due to the cooling effect, which partially cancels out the clear sky DLR and makes the total DLR less efficient to translate circulation forcing to sea ice. The differences of cloud vertical distribution in CMIP6 appear to be differentiated by circulation related relative humidity. Therefore, a better understanding of the discrepancy of different reanalyses and remote sensing products is critical to comprehensively evaluate simulated interactions among circulation, clouds, sea ice and energy budget at the surface in summer.

54 ENVIRONMENTAL SCIENCES↗