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At least 739 records · Page 41

Basin-scale study of CO 2 storage in stacked sequence of geological formations

Commercial scale decarbonization through carbon capture and storage may likely involve many CO 2 storage projects located in close proximity. The close proximity could raise concerns over caprock integrity associated with reservoir pressure buildup and interference among adjacent projects. Commercial-scale injection will also require large prospective CO 2 storage resource and high injectivity in the targeted storage formations. To accommodate the need for both large resource and high injectivity, project operators could consider injecting CO 2 into a stacked sequence of formations. This analysis investigates the benefits of injecting CO 2 into a vertically stacked sequence of saline formations, over injecting the same amount of CO 2 into a single saline formation, in addressing these challenges. Our analysis shows that injecting into the stacked sequence mitigates the extent of pressure buildup among the stacked formations, while still achieving the same or greater target CO 2 storage volumes. Among cases modeled, the resulting pressure buildup front is most reduced when each storage site distributes injection volumes over several wells, each of which injects a portion of the total CO 2 mass across the stacked sequence. This favorable case not only results in the smallest CO 2 aerial footprint, but also shows the largest reduction in the pressure buildup at the top of perforation at the injection wells (upwards of approximately 46% compared to the single-formation storage), the result of which is crucial to maintain caprock integrity. This analysis provides insights into required decision-making when considering multi-project deployment in a shared basin.

42 ENGINEERING↗

Novel Anti-LY6G6D/CD3 T-Cell–Dependent Bispecific Antibody for the Treatment of Colorectal Cancer

Abstract New therapeutics and combination regimens have led to marked clinical improvements for the treatment of a subset of colorectal cancer. Immune checkpoint inhibitors have shown clinical efficacy in patients with mismatch-repair–deficient or microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC). However, patients with microsatellite-stable (MSS) or low levels of microsatellite instable (MSI-L) colorectal cancer have not benefited from these immune modulators, and the survival outcome remains poor for the majority of patients diagnosed with mCRC. In this article, we describe the discovery of a novel T-cell–dependent bispecific antibody (TDB) targeting tumor-associated antigen LY6G6D, LY6G6D-TDB, for the treatment of colorectal cancer. RNAseq analysis showed that LY6G6D was differentially expressed in colorectal cancer with high prevalence in MSS and MSI-L subsets, whereas LY6G6D expression in normal tissues was limited. IHC confirmed the elevated expression of LY6G6D in primary and metastatic colorectal tumors, whereas minimal or no expression was observed in most normal tissue samples. The optimized LY6G6D-TDB, which targets a membrane-proximal epitope of LY6G6D and binds to CD3 with high affinity, exhibits potent antitumor activity both in vitro and in vivo. In vitro functional assays show that LY6G6D-TDB–mediated T-cell activation and cytotoxicity are conditional and target dependent. In mouse xenograft tumor models, LY6G6D-TDB demonstrates antitumor efficacy as a single agent against established colorectal tumors, and enhanced efficacy can be achieved when LY6G6D-TDB is combined with PD-1 blockade. Our studies provide evidence for the therapeutic potential of LY6G6D-TDB as an effective treatment option for patients with colorectal cancer.

60 APPLIED LIFE SCIENCES↗

Systems integration of lunar Campsite vehicles

This paper describes the configuration design and subsystems integration resolution for lunar Campsite vehicles and the crew vehicles (CVs) which support them. This concept allows early return to the moon while minimizing hardware development. Once in place, the Campsite can be revisited for extended periods. Configuration and operations issues are addressed, and explanations of the parametric subsystem analysis, as well as descriptions of the hardware concept and performance data, are provided. Within an assumed set of launch and mission constraints, a common vehicle stage design for both the Campsite and the CV landers was the chief design driver. Accommodation of a heat-shielded, ballistic crew transportation/return vehicle, scars for later system growth and upgrades, landing the crew in close proximity to the Campsite, and appropriate kinds of robotic systems were all secondary design drivers. Physical integration of the crew module and airlock, structural system, thermal radiators, power production and storage systems, external life support consumables, and payloads are covered. The vehicle performance data were derived using a Boeing lunar transportation sizing code to optimize vehicle stage sizes and commonality. Configuration trades were conducted and detailed sketches were produced.

Capps, Stephen↗

Rigorous analysis of a circular patch antenna excited by a microstrip transmission line

Boundary conditions are enforced on a portion of the microstrip feed line as well as the patch antenna. The integral equation for the unknown currents on the antenna and feed is solved by applying the Galerkin method of moments in the Fourier transform domain. The validity of the solution is tested by comparison of computed results with experimental data. The theoretical treatment proves to be applicable to the most common feeding arrangements, namely, the direct edge-feed and proximity coupling excitation. In the latter case, two-layer substrates having distinct dielectric constants are studied. The purpose of the study is to deduce, for a given overall substrate thickness, the smallest line-ground plane separation for which a match of the radiator to the feed line is still possible. The advantages of such a configuration are discussed.

Davidovitz, Marat↗

Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of CisPt-triggered DDR leads to cytoprotection. • Lovastatin attenuates CisPt-induced kidney DNA damage and apoptosis in vivo.

60 APPLIED LIFE SCIENCES↗

Size-Dependent Onset of Nitric Acid Dissociation in Cs + ·(HNO 3 )(H 2 O) n =0–11 Clusters at 20 K

We report the water-mediated charge separation of nitric acid upon incorporation into size-selected Cs + ∙(HNO 3 )(H 2 O) n=0-11 clusters at 20 K. Dramatic spectral changes are observed in the range n=7-9 that are traced to the formation of many isomeric structures associated with intermediate transfer of the acidic proton to the water network. This transfer is complete by n=10, which exhibits much simpler vibrational band patterns consistent with those expected for a tri-coordinated hydronium ion (the Eigen motif) along with the NO stretching bands predicted for a hydrated NO 3 – anion that is directly complexed to the Cs + cation. Theoretical analysis of the n=10 spectrum indicates that the dissociated ions adopt a solvent-separated ion-pair configuration such that the Cs + and H 3 O + cations flank the NO 3 – anion in a microhydrated salt bridge. In conclusion, this charge separation motif is evidently assisted by the electrostatic stabilization of the product NO 3 – /H 3 O + ion pair by the proximal metal ion.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Field-Coupled Water Splitting with Metal-Free Donor–Acceptor Covalent Organic-Framework Junctions

Advancing metal-free electrocatalysts for hydrogen and oxygen evolution reactions (HER/OER) across acidic and alkaline media requires coordinated control of intermediate binding thermodynamics, interfacial charge delivery, and near-electrode transport dynamics. Here, we design amide-linked benzene–triazine covalent organic frameworks (BTA/TzTA-Hz COFs) and integrate them with carbon nanotubes (CNTs) to form COF–CNT junctions that establish a built-in interfacial electric field. Density functional theory (DFT) and electrostatic potential maps indicate complementary active motifs, with benzene-proximal fragments associated with HER and triazine-proximal motifs associated with OER. CNT integration shifts the contact-potential difference by ≈0.20 V, while operando electrochemical impedance spectroscopy suggests partially separable high-frequency junction-charging and lower-frequency Faradaic/transport responses. A 300 mT static magnetic field lowers the HER and OER overpotentials by tens of millivolts. Under anodic bias, the effective interfacial charging capacitance increases, and Mott–Schottky analysis shows an apparent ∼0.15 V flat-band shift with an essentially unchanged slope. Together, these observations are consistent with field-perturbed interfacial charging and altered bias partitioning. Field-dependent impedance and bubble imaging are consistent with magnetohydrodynamic convection that promotes bubble detachment and near-electrode mass transport for both half-reactions, and they reveal an OER-specific high-frequency perturbation under anodic bias. Under field, the heterostructure reaches an OER onset overpotential of ∼261 mV and requires an overpotential of 366 mV at 10 mA cm –2 in alkaline electrolyte. These results illustrate how reticular-framework chemistry, junction engineering, and both built-in and applied fields can program reactivity through interfacial electrostatics and near-electrode transport in organic-framework electrocatalysts.

Garcia-Enriquez, Lissette [Univ. of Texas at El Pa↗

Crystal structure of Pistol, a class of self-cleaving ribozyme

Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation. Comparative genomic analysis has led to the discovery of a new class of small self-cleaving ribozymes named Pistol. We report herein the crystal structure of Pistol at 2.97-Å resolution. Our results suggest that the Pistol ribozyme self-cleavage mechanism likely uses a guanine base in the active site pocket to carry out the phosphoester transfer reaction. The guanine G40 is in close proximity to serve as the general base for activating the nucleophile by deprotonating the 2'-hydroxyl to initiate the reaction (phosphoester transfer). Furthermore, G40 can also establish hydrogen bonding interactions with the nonbridging oxygen of the scissile phosphate. The proximity of G32 to the O5' leaving group suggests that G32 may putatively serve as the general acid. The RNA structure of Pistol also contains A-minor interactions, which seem to be important to maintain its tertiary structure and compact fold. Our findings expand the repertoire of ribozyme structures and highlight the conserved evolutionary mechanism used by ribozymes for catalysis.

59 BASIC BIOLOGICAL SCIENCES↗

Discovering the Whole by the Coarse: A topological paradigm for data analysis

The increasing interest in big data applications is ushering in a large effort in seeking new, efficient, and adapted data models to reduce complexity, while preserving maximal intrinsic information. Graph-based models have recently been getting a lot of attention on account of their intuitive and direct connection to the data. The cost of these models, however, is to some extent giving up geometric insight as well as algebraic flexibility. Topology, as an intermediate analysis medium, focuses on coarse structures of an object/signal in general. It affords a formalism of transitioning from a local to a global description of an object, while providing significant information, which respects the local structure of measurements. It may also support a global visualization (e.g., data variation trends) and enhances the understanding of the underlying phenomenon. Throughout this article, measurements may be considered proximal in various ways, depending on the specific application, and the selected proximity metrics are subsequently used in the construction of a graph structure, thus highlighting various groups of neighboring data. As described later, these groups, often based on proximity criteria, are represented by n-simplices, where n + 1 corresponds to the number of points in an associated group. Collectively, they form what is (and will be throughout) referred to as a simplicial complex, a special representation of a topological space. We find the key advantage of computational topology is its inherently algebraic structure on the basic elements of the resulting graph-like structure.

97 MATHEMATICS AND COMPUTING↗

The LandScan Global Population Distribution Project: Current State of the Art and Prospective Innovation

Advances in remote sensing, dasymetric mapping techniques, and the ever-increasing availability of spatial datasets have enhanced global human population distribution databases. These datasets demonstrate an enormous improvement over the conventional use of choropleth maps to represent population distribution and are vital for analysis and planning purposes including humanitarian response, disease mapping, risk analysis, and evacuation modeling. Dasymetric mapping techniques have been employed to address spatial mismatch, but also to develop finer resolution population distributions in areas of the world where subnational census data are coarse or non-existent. One such implementation is the LandScan Global model which provides a 30 arc-second global population distribution based on ancillary datasets such as land cover, slope, proximity to roads, and settlement locations. This work will review the current state of the LandScan model, future innovations aimed at increasing spatial and demographic resolution, and situate LandScan within the landscape of other global population distribution datasets.

Rose, Amy N↗

Case History : Using time-lapse vertical seismic profiling data to constrain velocity-saturation relations: the Frio brine pilot CO 2 injection: Time-lapse VSP to constrain VSRs

CO 2 sequestration projects benefit from quantitative assessment of saturation distribution and plume extent for field development and leakage prevention. In this work, we carry out quantitative analysis of time-lapse seismic by using rock physics and seismic modelling tools. We investigate the suitability of Gassmann's equation for a CO 2 sequestration project with 1600 tons of CO 2 injected into high-porosity, brine-saturated sandstone. We analyze the observed time delays and amplitude changes in a time-lapse vertical seismic profile dataset. Both reflected and transmitted waves are analyzed qualitatively and quantitatively. To interpret the changes obtained from the vertical seismic profile, we perform a 2.5D elastic, finite-difference modelling study. The results show a P-wave velocity reduction of 750 m/s in the proximity of the injection well evident by the first arrivals (travel-time delays and amplitude change) and reflected wave amplitude changes. These results do not match with our rock physics model using Gassmann's equation predictions even when taking uncertainty in CO 2 saturation and grain properties into account. We find that time-lapse vertical seismic profile data integrated with other information (e.g., core and well log) can be used to constrain the velocity–saturation relation and verify the applicability of theoretical models such as Gassmann's equation with considerable certainty. The study shows that possible nonelastic factors are in play after CO 2 injection (e.g., CO 2 –brine–rock interaction and pressure effect) as Gassmann's equation underestimated the velocity reduction in comparison with field data for all three sets of time-lapse vertical seismic profile attributes. Here, our work shows the importance of data integration to validate the applicability of theoretical models such as Gassmann's equation for quantitative analysis of time-lapse seismic data.

58 GEOSCIENCES↗

Simulating wind power forecast error distributions for spatially aggregated wind power plants

Dispersion and aggregation of wind power plants lower the uncertainty of wind power by reducing wind power forecasting errors. Using quantitative methods, this paper studies the dispersion's impact on the uncertainty of the aggregated wind power production. A method to simulate day-ahead forecast error distributions at different dispersion and forecasting skill scenarios is presented. The proposed method models the uncertainty of wind power forecasting on an annual basis and at different levels of production. As a result, the uncertainty in the forecasting of spatially dispersed wind power plants is modelled using two continuous distributions: Laplace and beta distribution. The analysis shows that even the production level uncertainty can be modelled in various dispersion and forecasting skill scenarios. The model for aggregated forecast error distributions requires only four variables: capacity-weighted distance of the total wind power plant fleet, mean of the site-specific mean absolute errors (MAEs), number of aggregated wind power plants, and the mean variability of the elevations from the proximities of the aggregated wind power plants. Here, the results are especially promising when the number of aggregated wind power plants exceeds five, the terrain complexity is low or moderate, and the aggregation region is large. This is demonstrated through a case study for Texas, United States.

17 WIND ENERGY↗

Identification and quantification of multinuclear Cu active sites derived from monomeric Cu moieties for dry NO oxidation over Cu-SSZ-13

The identification and quantification of multinuclear Cu-oxo cations in Cu-zeolites is a challenge amidst the dynamic nature of Cu ions in Cu-zeolites. Herein, we synthesized Cu-SSZ-13 zeolites containing varying densities of monomeric Cu cations (Z 2 Cu and ZCuOH, where Z represents an anionic site on the zeolite framework). The number of Cu-oxo cations, quantified using carbon monoxide temperature programmed reduction (CO-TPR), quadratically increased with increasing ZCuOH density, evidencing that proximal ZCuOH sites are precursors to Cu-oxo dimers. We also find that dehydrated proximal ZCuOH with overlapping diffusion radii of at most 0.5 nm can form Cu-oxo dimers. CO-TPR also revealed the presence of three distinct pools (i.e types) of Cu-oxo dimers; these pools catalyze dry NO oxidation at different turnover rates, with the fastest pool 2 to 30 times faster than the slowest pool. Finally, from reaction kinetics and rate law analysis, we also proposed a cohesive dry NO oxidation mechanism and demonstrated that nitrates detected by in situ FTIR are a spectator species.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis

During development, multipotent progenitor cells establish tissue-specific programs of gene expression. In this paper, we show that p63 transcription factor, a master regulator of epidermal morphogenesis, executes its function in part by directly regulating expression of the genome organizer Satb1 in progenitor cells. p63 binds to a proximal regulatory region of the Satb1 gene, and p63 ablation results in marked reduction in the Satb1 expression levels in the epidermis. Satb1 -/- mice show impaired epidermal morphology. In Satb1-null epidermis, chromatin architecture of the epidermal differentiation complex locus containing genes associated with epidermal differentiation is altered primarily at its central domain, where Satb1 binding was confirmed by chromatin immunoprecipitation–on-chip analysis. Furthermore, genes within this domain fail to be properly activated upon terminal differentiation. Satb1 expression in p63 +/- skin explants treated with p63 small interfering ribonucleic acid partially restored the epidermal phenotype of p63-deficient mice. These data provide a novel mechanism by which Satb1, a direct downstream target of p63, contributes in epidermal morphogenesis via establishing tissue-specific chromatin organization and gene expression in epidermal progenitor cells.

59 BASIC BIOLOGICAL SCIENCES↗

MULTI-WAVELENGTH STUDY OF A DELTA-SPOT. I. A REGION OF VERY STRONG, HORIZONTAL MAGNETIC FIELD

Active region NOAA 11035 appeared in 2009 December, early in the new solar activity cycle. This region achieved a delta sunspot (δ spot) configuration when parasitic flux emerged near the rotationally leading magnetic polarity and traveled through the penumbra of the largest sunspot in the group. Both visible and infrared imaging spectropolarimetry of the magnetically sensitive Fe i line pairs at 6302 and 15650 Å show large Zeeman splitting in the penumbra between the parasitic umbra and the main sunspot umbra. The polarized Stokes spectra in the strongest field region display anomalous profiles, and strong blueshifts are seen in an adjacent region. Analysis of the profiles is carried out using a Milne–Eddington inversion code capable of fitting either a single magnetic component with stray light or two independent magnetic components to verify the field strength. The inversion results show that the anomalous profiles cannot be produced by the combination of two profiles with moderate magnetic fields. The largest field strengths are 3500–3800 G in close proximity to blueshifts as strong as 3.8 km s{sup −1}. The strong, nearly horizontal magnetic field seen near the polarity inversion line in this region is difficult to understand in the context of a standard model of sunspot magnetohydrostatic equilibrium.

79 ASTRONOMY AND ASTROPHYSICS↗

Guidance logic for spiral approaches

A spiral approach concept is proposed as a standard procedure for independent, commercial VTOL operations conducted in close proximity to CTOL operations. A guidance logic is developed for this VTOL application, although the results may be applicable to curved approaches by STOL or CTOL aircraft as well. The guidance concept attempts to maintain constant airspeed along a fixed radius nominal spiral. The presence of wind requires a continuous variation in bank angle and heading rate to remain on the desired path. Linear perturbation analysis is used to select satisfactory feedback gains for commanded bank angle, longitudinal acceleration and vertical speed. A wind estimator detects differences between the predicted and observed wind and uses the result to modify the nominal control. For 4-D guidance the nominal time must be computed as a function of turn angle, which requires the solution of an elliptic integral. Time-varying longitudinal accelerations are necessary for 4-D guidance when the observed wind differs from the predicted wind, or when wind shear is present. The logic and the linear feedback gains have been tested in a nonlinear simulation. Results have generally verified the performance predicted by linear analysis.

Hollister, W. M.↗

Tower Mesonetwork Climatology and Interactive Display Tool

Forecasters at the 45th Weather Squadron and Spaceflight Meteorology Group use data from the tower network over the Kennedy Space Center (KSC) and Cape Canaveral Air Force Station (CCAFS) to evaluate Launch Commit Criteria, and issue and verify forecasts for ground operations. Systematic biases in these parameters could adversely affect an analysis, forecast, or verification. Also, substantial geographical variations in temperature and wind speed can occur under specific wind directions. To address these concerns, the Applied Meteorology Unit (AMU) developed a climatology of temperatures and winds from the tower network, and identified the geographical variation and significant tower biases. The mesoclimate is largely driven by the complex land-water interfaces across KSC/CCAFS. Towers with close proximity to water typically had much warmer nocturnal temperatures and higher wind speeds throughout the year. The strongest nocturnal wind speeds occurred from October to March whereas the strongest mean daytime wind speeds occurred from February to May. These results of this project can be viewed by forecasters through an interactive graphical user interface developed by the AMU. The web-based interface includes graphical and map displays of mean, standard deviation, bias, and data availability for any combination of towers, variables, months, hours, and wind directions.

Case, Jonathan L.↗

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.

61 RADIATION PROTECTION AND DOSIMETRY↗