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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 1,135 records · Page 63

Freezing of the Lattice in the Kagome Lattice Heisenberg Antiferromagnet Zn-Barlowite ZnCu 3 (OD) 6 FBr

Here, we use 79 Br nuclear quadrupole resonance (NQR) to demonstrate that ultraslow lattice dynamics set in below the temperature scale set by the Cu-Cu superexchange interaction J (≃160 K) in the kagome lattice Heisenberg antiferromagnet Zn-barlowite. The lattice completely freezes below 50 K, and 79 Br NQR line shapes become twice broader due to increased lattice distortions. Moreover, the frozen lattice exhibits an oscillatory component in the transverse spin echo decay, a typical signature of pairing of nuclear spins by indirect nuclear spin-spin interaction. This indicates that some Br sites form structural dimers via a pair of kagome Cu sites prior to the gradual emergence of spin singlets below ~30 K. Our findings underscore the significant roles played by subtle structural distortions in determining the nature of the disordered magnetic ground state of the kagome lattice.

36 MATERIALS SCIENCE↗

Inference and analysis of population-specific fine-scale recombination maps across 26 diverse human populations

Fine-scale rates of meiotic recombination vary by orders of magnitude across the genome and differ between species and even populations. Studying cross-population differences has been stymied by the confounding effects of demographic history. To address this problem, we developed a demography-aware method to infer fine-scale recombination rates and applied it to 26 diverse human populations, inferring population-specific recombination maps. These maps recapitulate many aspects of the history of these populations including signatures of the trans-Atlantic slave trade and the Iberian colonization of the Americas. We also investigated modulators of the local recombination rate, finding further evidence that Polycomb group proteins and the trimethylation of H3K27 elevate recombination rates. Further differences in the recombination landscape across the genome and between populations are driven by variation in the gene that encodes the DNA binding protein PRDM9, and we quantify the weak effect of meiotic drive acting to remove its binding sites.

Science & Technology - Other Topics↗

Distinct Pools of Non-Glycolytic Substrates Differentiate Brain Regions and Prime Region-Specific Responses of Mitochondria

Many hereditary diseases are characterized by region-specific toxicity, despite the fact that disease-linked proteins are generally ubiquitously expressed. The underlying basis of the region-specific vulnerability remains enigmatic. Here, we evaluate the fundamental features of mitochondrial and glucose metabolism in synaptosomes from four brain regions in basal and stressed states. Although the brain has an absolute need for glucose in vivo, we find that synaptosomes prefer to respire on non-glycolytic substrates, even when glucose is present. Moreover, glucose is metabolized differently in each brain region, resulting in region-specific ‘‘signature’’ pools of non-glycolytic substrates. The use of non-glycolytic resources increases and dominates during energy crisis, and triggers a marked region-specific metabolic response. We envision that disease-linked proteins confer stress on all relevant brain cells, but region-specific susceptibility stems from metabolism of non-glycolytic substrates, which limits how and to what extent neurons respond to the stress.

59 BASIC BIOLOGICAL SCIENCES↗

Estimation of Radiation Doses to U.S. Military Test Participants from Nuclear Testing: A Comparison of Historical Film-Badge Measurements, Dose Reconstruction and Retrospective Biodosimetry

Retrospective radiation dose estimations, whether based on physical or biological measurements, or on theoretical dose reconstruction, are limited in their precision and reliability, particularly for exposures that occurred many decades ago. Here, we studied living U.S. military test participants, believed to have received high-dose radiation exposures during nuclear testing-related activities approximately six decades ago, with two primary goals in mind. The first was to compare three different approaches of assessing past radiation exposures: 1. Historical personnel monitoring data alone; 2. Dose reconstruction based on varying levels of completeness of individual information, which can include film badge data; and 3. Retrospective biodosimetry using chromosome aberrations in peripheral blood lymphocytes. The second goal was to use the collected data to make the best possible estimates of bone marrow dose received by a group with the highest military recorded radiation doses of any currently living military test participants. Six nuclear test participants studied had been on Rongerik Atoll during the 1954 CASTLE Bravo nuclear test. Another six were present at the Nevada Test Site (NTS) and/or Pacific Proving Ground (PPG) and were believed to have received relatively high-dose exposures at those locations. All were interviewed, and all provided a blood sample for cytogenetic analysis. Military dose records for each test participant, as recorded in the Defense Threat Reduction Agency's Nuclear Test Review and Information System, were used as the basis for historical film badge records and provided exposure scenario information to estimate dose via dose reconstruction. Dose to bone marrow was also estimated utilizing directional genomic hybridization (dGH) for high-resolution detection of radiation-induced chromosomal translocations and inversions, the latter being demonstrated for the first time for the purpose of retrospective biodosimetry. As the true dose for each test participant is not known these many decades after exposure, this study gauged the congruence of different methods by assessing the degree of correlation and degree of systematic differences. Overall, the best agreement between methods, defined by statistically significant correlations and small systematic differences, was between doses estimated by a dose reconstruction methodology that exploited all the available individual detail and the biodosimetry methodology derived from a weighted average dose determined from chromosomal translocation and inversion rates. Employing such a strategy, we found that the Rongerik veterans who participated in this study appear to have received, on average, bone marrow equivalent doses on the order of 300–400 mSv, while the NTS/ PPG participants appear to have received approximately 250–300 mSv. The results show that even for nuclear events that occurred six decades in the past, biological signatures of exposure are still present, and when taken together, chromosomal translocations and inversions can serve as reliable retrospective biodosimeters, particularly on a group-average basis, when doses received are greater than statistically-determined detection limits for the biological assays used.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Measurements and Analyses to Enable Science for the Eastern Pacific Cloud Aerosol Precipitation Experiment (EPCAPE)

Coastal cities provide the opportunity to characterize the substantial effects of manmade particles on marine cloud properties and processes. La Jolla lies to the north of San Diego, California, but it is often about a day directly downwind of the major pollution sources located in the ports of Los Angeles and Long Beach. The large dynamic range of aerosol particle concentrations combined with the multi-hour to multi-day persistence of stratocumulus cloud layers makes the site ideal for investigating the seasonal changes in cloud and aerosol properties as well as the quantitative relationships between cloud and aerosol properties. The Eastern Pacific Cloud Aerosol Precipitation Experiment (EPCAPE) characterized the extent, radiative properties, aerosol interactions, and precipitation characteristics of stratocumulus clouds in the Eastern Pacific across all four seasons at two coastal sites in La Jolla. This project was designed to enhance and expand the scientific uses of the ARM AMF1 measurements from EPCAPE. The goal was to ensure meaningful observations were collected that would enable science. The project included the following objectives: (1) Reviewing the ARM AMF1 measurements [ARM, 2021a; b] and circulating a summary of the measurements each week, (2) Comparing AMF1 measurements to those provided by collaborators (including filter measurements at the pier), (3) Collecting and analyzing filter samples from Scripps Pier by Fourier Transform Infrared spectroscopy (FTIR) and X-ray Fluorescence (XRF), (4) Assisting in operations of instruments provided by Guest PIs when possible, and (5) Providing an initial compilation of EPCAPE aerosol and cloud seasonal differences. The expected outcomes of these objectives were enhanced proposals and publications using EPCAPE measurements by helping to identify instrument issues, expanded data access and awareness by distributing weekly plots and related summaries, improved source-related attribution of aerosols with elemental tracers, additional observations provided by Guest PIs, and accelerated ACI studies enabled by the compiled seasonal summaries of aerosol and cloud properties. Three examples of the science enabled by this project are findings that (i) aerosol and cloud aqueous production contributes more than half of sulfate particle mass concentration, (ii) upwind sources make chemical composition very similar at nearby sites despite local differences in meteorology, and (iii) most of the large mass concentration of semi-volatile organic components is co-emitted and co-evaporated with nitrate. Together these findings illustrate how ARM extended field campaigns in coastal regions can be used to constrain ACI processes with direct observations. By using the unique ARM suite of cloud radiative products in addition to the measured aerosol properties at a coastal location, we were able to address the more specific question of which aerosol particles cause how much of the effects on clouds. Identifying this signature in coastal areas provides an opportunity to test the representation of aerosol sources by global models in a range of clean and urban-influenced conditions.

Russell, Lynn [Univ. of California, San Diego, CA ↗

Versatile soil gas concentration and isotope monitoring: optimization and integration of novel soil gas probes with online trace gas detection

Abstract. Gas concentrations and isotopic signatures can unveil microbial metabolisms and their responses to environmental changes in soil. Currently, few methods measure in situ soil trace gases such as the products of nitrogen and carbon cycling or volatile organic compounds (VOCs) that constrain microbial biochemical processes like nitrification, methanogenesis, respiration, and microbial communication. Versatile trace gas sampling systems that integrate soil probes with sensitive trace gas analyzers could fill this gap with in situ soil gas measurements that resolve spatial (centimeters) and temporal (minutes) patterns. We developed a system that integrates new porous and hydrophobic sintered polytetrafluoroethylene (sPTFE) diffusive soil gas probes that non-disruptively collect soil gas samples with a transfer system to direct gas from multiple probes to one or more central gas analyzer(s) such as laser and mass spectrometers. Here, we demonstrate the feasibility and versatility of this automated multiprobe system for soil gas measurements of isotopic ratios of nitrous oxide (δ18O, δ15N, and the 15N site preference of N2O), methane, carbon dioxide (δ13C), and VOCs. First, we used an inert silica matrix to challenge probe measurements under controlled gas conditions. By changing and controlling system flow parameters, including the probe flow rate, we optimized recovery of representative soil gas samples while reducing sampling artifacts on subsurface concentrations. Second, we used this system to provide a real-time window into the impact of environmental manipulation of irrigation and soil redox conditions on in situ N2O and VOC concentrations. Moreover, to reveal the dynamics in the stable isotope ratios of N2O (i.e., 14N14N16O, 14N15N16O, 15N14N16O, and 14N14N18O), we developed a new high-precision laser spectrometer with a reduced sample volume demand. Our integrated system – a tunable infrared laser direct absorption spectrometry (TILDAS) in parallel with Vocus proton transfer reaction mass spectrometry (PTR-MS), in line with sPTFE soil gas probes – successfully quantified isotopic signatures for N2O, CO2, and VOCs in real time as responses to changes in the dry–wetting cycle and redox conditions. Broadening the collection of trace gases that can be monitored in the subsurface is critical for monitoring biogeochemical cycles, ecosystem health, and management practices at scales relevant to the soil system.

54 ENVIRONMENTAL SCIENCES↗

A First Look at the Mineralogy and Geochemistry of the MER-B Landing Site in Meridiani Planum

The second MER rover (Opportunity) landed on Meridiani Planum on January 24, 2004 inside a shallow crater. The science rational for the selection of the landing site centered on detection of the mineral hematite from martian orbit by the Mars Global Surveyor Thermal Emission Spectrometer (MGS-TES) [1,2]. Other smaller occurrences of hematite are in Aram Chaos and several isolated spots in Valles Marineris. Proposed formation pathways for martian hematite include both aqueous (e.g., low temperature precipitation of Fe oxides/oxyhydroxides in a lacustrine environment, laterite-style weathering, and precipitation from fluids having a hydrothermal origin) and dry (e.g., oxidation of magnetite rich ash) processes [e.g., 1,2,3]. The crystallographic c-face of martian hematite must be exaggerated to account for the thermal emissions spectra and it must be gray in color so as to account for the absence of the characteristic spectral signature of red hematite at visible wavelengths

Morris, Richard V.↗

Overview of Mars Science Laboratory (MSL) Environmental Program

This viewgraph presentation is an overview of the Mars Science Laboratory (MSL) program. The engineering objectives of the program are to create a Mobile Science Laboratory capable of one Mars Year surface operational lifetime (670 Martian sols = 687 Earth days). It will be able to land and operation over wide range of latitudes, altitudes and seasons It must have controlled propulsive landing and demonstrate improved landing precision via guided entry The general science objectives are to perform science that will focus on Mars habitability, perform next generation analytical laboratory science investigations, perform remote sensing/contact investigations and carry a suite of environmental monitoring instruments. Specific scientific objectives of the MSL are: (1) Characterization of geological features, contributing to deciphering geological history and the processes that have modified rocks and regolith, including the role of water. (2) Determination of the mineralogy and chemical composition (including an inventory of elements such as C, H, N, O, P, S, etc. known to be building blocks for life) of surface and near-surface materials. (3) Determination of energy sources that could be used to sustain biological processes. (4) Characterization of organic compounds and potential biomarkers in representative regolith, rocks, and ices. (5) Determination the stable isotopic and noble gas composition of the present-day bulk atmosphere. (6) Identification potential bio-signatures (chemical, textural, isotopic) in rocks and regolith. (7) Characterization of the broad spectrum of surface radiation, including galactic cosmic radiation, solar proton events, and secondary neutrons. (8) Characterization of the local environment, including basic meteorology, the state and cycling of water and C02, and the near-surface distribution of hydrogen. Several views of the planned MSL and the rover are shown. The MSL environmental program is to: (1) Ensure the flight hardware design is capable of surviving all the environments throughout its mission life time, including ground, transportation, launch, cruise, entry decent and landing (EDL) and surface operation environments. (2) Verify environmental testing and analysis have adequately validated the flight hardware's ability to withstand all natural, self-induced, and mission-activity-induced environments. The planned tests to ascertain the capability of the MSL to perform as desired are reviewed.

spacecraft↗

Water chemistry in flume channel and hyporheic zone (i.e., porewater) associated with: “Rethinking Aerobic Respiration in the Hyporheic Zone Under Variation in Carbon and Nitrogen Stoichiometry”

Dissolved oxygen (DO), total organic carbon (TOC), total nitrogen (TN), molecular data for organic matter, and biochemical reactions for surface water and porewater (i.e., hyporheic zone) collected from a water recirculating flume located at the University of Texas, Austin. The flume contained real river water from Lower Colorado River(Austin, TX) and clean sand. Hyporheic exchange in the flume was induced through The study aims to understand relationships between aerobic metabolism of organic matter and molecular characteristics of organic matter, such as thermodynamic signature and nitrogen content, through the extent of the hyporheic zone at 10 cm- resolution, and through time. During the experiment, organic matter (dry leaves) was added to the flume and removed after 24 hours. The water samples were collected before the addition of leaves, at the time of removal of leaves, and at hour 72. The water samples were analyzed using ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and total organic carbon (TOC) and total nitrogen (TN) analysis. Dissolved oxygen content throughout the surface water and the hyporheic zone of the flume was measured with a large planar optode. This data package is associated with the publication ’ Rethinking Aerobic Respiration in the Hyporheic Zone Under Variation in Carbon and Nitrogen Stoichiometry’ published in Environmental Science and Technology (Turețcaia et al., 2023 https://doi.org/10.1021/acs.est.3c04765). The dataset is comprised of five folders (1) Diss_O2_pic, (2) input_files (3) output_files; (4) python_code; and (5) R_code . Diss_O2_pic contains siximages of dissolved oxygen distribution in a bedform at hours 0, 24, and 72 of the experiment conducted in a large recirculation flume. Images are in separate R and G channels (i.e., RGB). The input_files contains (1) a csv file with FTICR peaks identified within each sample, (2) a csv file with molecular information pertinent to FTICR data with Gibbs free energy calculations adjusted for environmental temperature, (3) a csv file containing concentrations of non-purgeable organic carbon measured throughout the experiment , (4) a csv file containing concentrations of total nitrogen measured throughout the experiment, (5) a csv file containing total biochemical reactions (i.e., transformations) identified in the dataset, (6) a csv containing transformation profiles, and (7) a csv file containing transformations with formulas, and (8) a jpg file with schematic representation of locations for sample collection. The output_files contains (1) and xlsx file containing percent biochemical reactions containing nitrogen identified across all 39 sample, (2) a csv file of merged FTICR data and molecular information files, (3) a csv files containing average Gibbs free energy within sampling domains and at each sampling location, (4) a csv file with average concentrations of dissolved oxygen across sampling locations at hour 0, (5) a csv file with average concentrations of dissolved oxygen across sampling locations at hour 24, (6) a csv file with average concentrations of dissolved oxygen across sampling locations at hour 72, (7) a csv file with percent chemical classes identified across sampling locations at hour 0, (8) a csv file with percent chemical classes identified across sampling locations at hour 24, (9) a csv file with percent chemical classes identified across sampling locations at hour 72, and (10) a csv file containing percent nitrogen containing biochemical reactions identified across sampling locations at hours 0, 24, and 72. The python_code contains seven ipynb files which are Jupyter Notebooks used for data analysis and figures generation. The R_code contains 3 R files with R code used for data analysis and figures generation. This data package contains the processed data used in the associated manuscript. This data has not been previously published.

54 ENVIRONMENTAL SCIENCES↗

Photophysics of nanographenes: from polycyclic aromatic hydrocarbons to graphene nanoribbons

Graphene quantum dots (GQDs) and nanoribbons (GNRs) are classes of nanographene molecules that exhibit highly tunable photophysical properties. There have been great strides in recent years to advance our understanding of nanographene photophysics and develop their use in light-harvesting systems, such as artificial photosynthesis. Here, we review the latest studies of GQDs and GNRs which have shed new light onto their photophysical underpinnings through computational and advanced spectroscopic techniques. We discuss how the size, symmetry, and shape of nanographenes influence their molecular orbital structures and, consequentially, their spectroscopic signatures. The scope of this review is to comprehensively lay out the general photophysics of nanographenes starting with benzene and building up to larger polycyclic aromatic hydrocarbons, GQDs, and GNRs. We also explore a collection of publications from recent years that build upon the current understanding of nanographene photophysics and their potential application in light-driven processes from display, lasing, and sensing technology to photocatalytic water splitting.

59 BASIC BIOLOGICAL SCIENCES↗

Pushing the limits: Resolving paleoseawater signatures in nanoscale fluid inclusions by atom probe tomography

New insight into the geochemistry of ancient environments can be gained through structural and chemical analyses of nanometer-scale features within minerals. Here, we present recent developments using atom probe tomography (APT) enabling direct visualization of nanoscale fluid inclusions trapped within pyrite (FeS 2 ) and thereby chemical characterization of remnant seawater. Pyrite framboids (spherical clusters of nanocrystals) were sampled from the Middle Devonian Leicester Pyrite Member (New York). Scanning transmission electron microscopy shows low density regions distributed within the pyrite consistent with nanoscale pores (<4 nm in size). APT 3D visualization and compositional mapping reveals that the nanopores are filled with water. The inclusions appear to preserve the elemental signature of the water column in which the framboids formed, specifically seawater components including Na, K, Mg, and Ca. Mg/Ca ratios within the pyrite were generally measured to be within 0.6±0.2 – consistent with calcite-dominated seawater conditions existing in the Middle Devonian. Furthermore, this study demonstrates the potential for a novel approach to reconstruct paleoenvironmental conditions from coupled elemental and structural analyses of nanoscale fluid inclusions.

54 ENVIRONMENTAL SCIENCES↗

Ground-state oxygen holes and the metal–insulator transition in the negative charge-transfer rare-earth nickelates

The metal-insulator transitions and the intriguing physical properties of rare-earth perovskite nickelates have attracted considerable attention in recent years. However, a complete understanding of these materials remains elusive. Here, taking a NdNiO 3 thin film as a representative example, we utilize a combination of x-ray absorption (XAS) and resonant inelastic x-ray scattering (RIXS) spectroscopies to resolve important aspects of the complex electronic structure of the rare-earth nickelates. The unusual coexistence of bound and continuum excitations observed in the RIXS spectra provides strong evidence for the abundance of oxygen 2p holes in the ground state of these materials. Using cluster calculations and Anderson impurity model interpretation, we show that these distinct spectral signatures arise from a Ni 3d 8 configuration along with holes in the oxygen 2p valence band, confirming suggestions that these materials do not obey a “conventional” positive charge-transfer picture, but instead exhibit a negative charge-transfer energy, in line with recent models interpreting the metal to insulator transition in terms of bond disproportionation.

36 MATERIALS SCIENCE↗

Weyl nodes and magnetostructural instability in antiperovskite Mn 3 ZnC

The room temperature ferromagnetic phase of the cubic antiperovskite Mn 3 ZnC is suggested from first-principles calculation to be a nodal line Weyl semimetal. Features in the electronic structure that are the hallmark of a nodal line Weyl state—a large density of linear band crossings near the Fermi level—can also be interpreted as signatures of a structural and/or magnetic instability. Indeed, it is known that Mn 3 ZnC undergoes transitions upon cooling from a paramagnetic to a cubic ferromagnetic state under ambient conditions and then further into a noncollinear ferrimagnetic tetragonal phase at a temperature between 250 K and 200 K. The existence of Weyl nodes and their destruction via structural and magnetic ordering are likely to be relevant to a range of magnetostructurally coupled materials.

36 MATERIALS SCIENCE↗

Comparative Genomics of Saccharomyces cerevisiae Natural Isolates for Bioenergy Production

Lignocellulosic plant material is a viable source of biomass to produce alternative energy including ethanol and other biofuels. However, several factors—including toxic by products from biomass pretreatment and poor fermentation of xylose and other pentose sugars—currently limit the efficiency of microbial biofuel production. To begin to understand the genetic basis of desirable traits, we characterized three strains of Saccharomyces cerevisiae with robust growth in a pretreated lignocellulosic hydrolysate or tolerance to stress conditions relevant to industrial biofuel production, through genome and transcriptome sequencing analysis. All stress resistant strains were highly mosaic, suggesting that genetic admixture may contribute to novel allele combinations underlying these phenotypes. Strain-specific gene sets not found in the lab strain were functionally linked to the tolerances of particular strains. Furthermore, genes with signatures of evolutionary selection were enriched for functional categories important for stress resistance and included stress-responsive signaling factors. Comparison of the strains’ transcriptomic responses to heat and ethanol treatment—two stresses relevant to industrial bioethanol production—pointed to physiological processes that were related to particular stress resistance profiles. Many of the genotype-by-environment expression responses occurred at targets of transcription factors with signatures of positive selection, suggesting that these strains have undergone positive selection for stress tolerance. Our results generate new insights into potential mechanisms of tolerance to stresses relevant to biofuel production, including ethanol and heat, present a backdrop for further engineering, and provide glimpses into the natural variation of stress tolerance in wild yeast strains.

59 BASIC BIOLOGICAL SCIENCES↗

Second dome of superconductivity in YBa 2 Cu 3 O 7 at high pressure

Evidence is growing that a second dome of high-T c superconductivity can be accessed in the cuprates by increasing the doping beyond the first dome. Here, in this study, we use ab initio methods without invoking any free parameters, such as the Hubbard U, to reveal that pressure could turn YBa 2 ⁢Cu 3 ⁢O 7 into an ideal candidate for second dome superconductivity, displaying the predicted signature of strongly hybridized d x 2 -y 2 and d z 2 orbitals. Notably, pressure is found to induce a phase transition replacing the antiferromagnetic phases with an orbitally degenerate d-d phase. Our study suggests that the origin of the second dome is correlated with the oxygen-hole fraction in the CuO 2 planes and the collapse of the pseudogap phase.

36 MATERIALS SCIENCE↗

Isotopic insights into methane production, oxidation, and emissions in Arctic polygon tundra

Arctic wetlands are currently net sources of atmospheric CH 4 . Due to their complex biogeochemical controls and high spatial and temporal variability, current net CH 4 emissions and gross CH 4 processes have been difficult to quantify, and their predicted responses to climate change remain uncertain. Here, we investigated CH 4 production, oxidation, and surface emissions in Arctic polygon tundra, across a wet-to-dry permafrost degradation gradient from low-centered (intact) to flat- and high-centered (degraded) polygons. From 3 microtopographic positions (polygon centers, rims, and troughs) along the permafrost degradation gradient, we measured surface CH 4 and CO 2 fluxes, concentrations and stable isotope compositions of CH 4 and DIC at three depths in the soil, and soil moisture and temperature. More degraded sites had lower CH 4 emissions, a different primary methanogenic pathway, and greater CH 4 oxidation than did intact permafrost sites, to a greater degree than soil moisture or temperature could explain. Surface CH 4 flux decreased from 64 nmol m -2 s -1 in intact polygons to 7 nmol m -2 s -1 in degraded polygons, and stable isotope signatures of CH 4 and DIC showed that acetate cleavage dominated CH 4 production in low-centered polygons, while CO 2 reduction was the primary pathway in degraded polygons. We see evidence that differences in water flow and vegetation between intact and degraded polygons contributed to these observations. In contrast to many previous studies, these findings document a mechanism whereby permafrost degradation can lead to local decreases in tundra CH 4 emissions.

54 ENVIRONMENTAL SCIENCES↗

An African-Specific Variant of TP5 3 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression

TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors.

60 APPLIED LIFE SCIENCES↗

IC Post-Doctoral Fellowship Abstract and Bio.

Whole cell biosensors (WCBs) utilize an organism’s natural ability to sense and respond to the environment. Through implementation of two different protein engineering methods, I seek to develop a WCB for the detection of important chemical signatures in the environment. I will reengineer the ligand binding profile of proteins known to alter transcription of genes, and I will engineer signal transduction in proteins already known to bind relevant compounds. In both cases, detection of compounds of interest will lead to the production of a measurable fluorescent signal within the organism. These approaches will provide the groundwork for the development of novel chemical sensing technologies that provide a cheap and efficient alternative to traditional methods for detection of compounds.

60 APPLIED LIFE SCIENCES↗