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At least 19 records

Function Based Risk Assessment: Mapping Function to Likelihood

The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by presenting a mathematical mapping from product function to risk likelihood. This risk information is composed of design parameters, failure modes, and likelihood values. A spacecraft orientation subsystem, subsystem used to guide science instruments, and a Bell 206 rotorcraft are used to test the mapping which continues research on these products relating function to failure. Finally, a case study is presented in which the risk element likelihood is calculated for a fuel cell which is in the conceptual design phase at NASA JPL.

Tumer, Irem Y.↗

Evaluation of current tropospheric mapping functions by Deep Space Network very long baseline interferometry

To compare the validity of current algorithms that map zenith tropospheric delay to arbitrary elevation angles, 10 different tropospheric mapping functions are used to analyze the current data base of Deep Space Network Mark 3 intercontinental very long baseline interferometric (VLBI) data. This analysis serves as a stringent test because of the high proportion of low-elevation observations necessitated by the extremely long baselines. Postfit delay and delay-rate residuals are examined, as well as the scatter of baseline lengths about the time-linear model that characterizes tectonic motion. Among the functions that utilize surface meteorological data as input parameters, the Lanyi 1984 mapping shows the best performance both for residuals and baselines, through the 1985 Davis function is statistically nearly identical. The next best performance is shown by the recent function of Niell, which is based on an examination of global atmospheric characteristics as a function of season and uses no weather data at the time of the measurements. The Niell function shows a slight improvement in residuals relative to Lanyi, but also an increase in baseline scatter that is significant for the California-Spain baseline. Two variants of the Chao mapping function, as well as the Chao tables used with the interpolation algorithm employed in the Orbit Determination Program software, show substandard behavior for both VLBI residuals and baseline scatter. The length of the California-Australia baseline (10,600 km) in the VLBI solution can vary by as much as 5 to 10 cm for the 10 mapping functions.

Sovers, O. J.↗

HHL algorithm with mapping function and enhanced sampling for model predictive control in microgrids

Here, this paper presents a refined quantum Harrow Hassidim Lloyd (HHL) algorithm for microgrid control. The first novelty of the developed method is that a mapping shift function enables the original HHL algorithm to handle general linear equations with non-singular and indefinite matrix. Second, a method of Matrix Extension for Amplifying Sampling Probabilities of Intended Solution (ME-ASPI) is proposed to design the reformulated linear algebraic equations, allowing for improved sampling efficiency of the quantum tomography in the refined HHL algorithm. Then, we applied the method to solve the model predictive control (MPC) problem in nonlinear dynamical microgrids. Specifically, with the ME-ASPI method, the refined HHL algorithm can effectively obtain the intended partial optimal control inputs for MPC. The optimization of quadratic programming problem in each time step of MPC is transformed into a linear system problem, which is addressed by the proposed quantum solver through using only partial information, with the time complexity improved from $\mathscr{O}(\mathscr{N}^{2.37286})$ classically to $\mathscr{O}(\mathscr{N}^{2} log \mathscr{N}$ x $p$ log $p)$ in quantum. Numerical examples have validated the effectiveness of the refined HHL algorithm with the proposed mapping function and the ME-ASPI method. By leveraging quantum properties, the proposed method provides a hybrid quantum–classical framework for microgrid control. This generic method can also potentially tackle many other challenges in analyzing and controlling general complex engineered systems.

24 POWER TRANSMISSION AND DISTRIBUTION↗

A functional map of HIV-host interactions in primary human T cells

Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary cells. Here, we target 426 genes previously implicated in the HIV lifecycle through protein interaction studies for CRISPR-Cas9-mediated knock-out in primary human CD4+ T cells in order to systematically assess their functional roles in HIV replication. We achieve efficient knockout (>50% of alleles) in 364 of the targeted genes and identify 86 candidate host factors that alter HIV infection. 47 of these factors validate by multiplex gene editing in independent donors, including 23 factors with restrictive activity. Both gene editing efficiencies and HIV-1 phenotypes are highly concordant among independent donors. Importantly, over half of these factors have not been previously described to play a functional role in HIV replication, providing numerous novel avenues for understanding HIV biology. These data further suggest that host-pathogen protein-protein interaction datasets offer an enriched source of candidates for functional host factor discovery and provide an improved understanding of the mechanics of HIV replication in primary T cells.

60 APPLIED LIFE SCIENCES↗

Mapping Functional Substrate–Enzyme Interactions in the pol β Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs

We report high-resolution crystal structures of DNA polymerase (pol) β in ternary complex with a panel of incoming dNTPs carrying acidity-modified 5'-triphosphate groups. These novel dNTP analogues have a variety of halomethylene substitutions replacing the bridging oxygen between Pβ and Pγ of the incoming dNTP, whereas other analogues have alkaline substitutions at the bridging oxygen. Use of these analogues allows the first systematic comparison of effects of 5'-triphosphate acidity modification on active site structures and the rate constant of DNA synthesis. These ternary complex structures with incoming dATP, dTTP, and dCTP analogues reveal the enzyme’s active site is not grossly altered by the acidity modifications of the triphosphate group, yet with analogues of all three incoming dNTP bases, subtle structural differences are apparent in interactions around the nascent base pair and at the guanidinium groups of active site arginine residues. Lastly, these results are important for understanding how acidity modification of the incoming dNTP’s 5'-triphosphate can influence DNA polymerase activity and the significance of interactions at arginines 183 and 149 in the active site.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Functional mapping reveals mechanistic clusters for OER catalysis across (Cu–Mn–Ta–Co–Sn–Fe)O x composition and pH space

Identification of stable electrocatalysts for the oxygen evolution reaction (OER) remains a primary challenge in materials for energy. The pH-dependent activity is known for very few catalysts, prompting our exploration of a broad range of catalysts using high throughput experiments and data science. This approach enables the largest screening of OER activity and operational stability to date, as illustrated through investigation of the (Cu-Mn-Ta-Co-Sn-Fe)O x composition space as 15 unique quaternary composition spaces. In total 2121 compositions are tested between pH 3 and 13, creating an extensive dataset whose interpretation requires development and application of data science to provide insights that are both beyond the standard composition-activity relationships and beyond human interpretation due to the dimensionality of the dataset. In this work, three distinct classes of OER catalysts are identified with respect to pH-dependent activity and stability. The large-scale screening reveals a new class of Co-rich OER catalysts that can be compositionally tailored to a specified pH and perform on par with state-of-the-art acid OER catalysts.

36 MATERIALS SCIENCE↗

Integrative Structure–Function Mapping of the Nucleoporin Nup133 Suggests a Conserved Mechanism for Membrane Anchoring of the Nuclear Pore Complex

The nuclear pore complex (NPC) is the sole passageway for the transport of macromolecules across the nuclear envelope. Nup133, a major component in the essential Y-shaped Nup84 complex, is a large scaffold protein of the NPC's outer ring structure. Here, we describe an integrative modeling approach that produces atomic models for multiple states of Saccharomyces cerevisiae (Sc) Nup133, based on the crystal structures of the sequence segments and their homologs, including the related Vanderwaltozyma polyspora (Vp) Nup133 residues 55 to 502 (VpNup133 55–502 ) determined in this study, small angle X-ray scattering profiles for 18 constructs of ScNup133 and one construct of VpNup133, and 23 negative-stain electron microscopy class averages of ScNup1332–1157. Using our integrative approach, we then computed a multi-state structural model of the full-length ScNup133 and validated it with mutational studies and 45 chemical cross-links determined via mass spectrometry. Finally, the model of ScNup133 allowed us to annotate a potential ArfGAP1 lipid packing sensor (ALPS) motif in Sc and VpNup133 and discuss its potential significance in the context of the whole NPC; we suggest that ALPS motifs are scattered throughout the NPC's scaffold in all eukaryotes and play a major role in the assembly and membrane anchoring of the NPC in the nuclear envelope. Our results are consistent with a common evolutionary origin of Nup133 with membrane coating complexes (the protocoatomer hypothesis); the presence of the ALPS motifs in coatomer-like nucleoporins suggests an ancestral mechanism for membrane recognition present in early membrane coating complexes.

59 BASIC BIOLOGICAL SCIENCES↗

MAPS of Cancer

Our goal was to produce an interactive visualization from a mathematical model that successfully predicts metastases from head and neck cancer. We met this goal early in the project. The visualization is available for the public to view. Our work appears to fill a need for more information about this deadly disease. The idea of this project was to make an easily interpretable visualization based on what we call "functional maps" of disease. A functional map is a graphic summary of medical data, where distances between parts of the body are determined by the probability of disease, not by anatomical distances. Functional maps often beat little resemblance to anatomical maps, but they can be used to predict the spread of disease. The idea of modeling the spread of disease in an abstract multidimensional space is difficult for many people. Our goal was to make the important predictions easy to see. NASA must face this problem frequently: how to help laypersons and professionals see important trends in abstract, complex data. We took advantage of concepts perfected in NASA's graphics libraries. As an analogy, consider a functional map of early America. Suppose we choose travel times, rather than miles, as our measures of inter-city distances. For Abraham Lincoln, travel times would have been the more meaningful measure of separation between cities. In such a map New Orleans would be close to Memphis because of the Mississippi River. St. Louis would be close to Portland because of the Oregon Trail. Oklahoma City would be far from Little Rock because of the Cheyenne. Such a map would look puzzling to those of us who have always seen physical maps, but the functional map would be more useful in predicting the probabilities of inter-site transit. Continuing the analogy, we could predict the spread of social diseases such as gambling along the rivers and cattle rustling along the trails. We could simply print the functional map of America, but it would be more interesting to show meaningful patterns of dispersal. We had previously published the functional map of the head and neck, but it was difficult to explain to either patients or surgeons because that view of our body did not resemble anatomy. This discrepancy between functional and physical maps is just a mathematical restatement of the well-known fact that some diseases, such as head and neck cancer, spread in complex patterns, not always to the next nearest site. We had discovered that a computer could re-arrange anatomy so that this particular disease spreads to the next nearest site. The functional map explains over 95% of the metastases in 1400 patients. In a sense, we had graphed what our body "looks like" to a tumor. The tumor readily travels between adjacent areas in the functional map. The functional map is a succinct visual display of trends that are not easily appreciated in tables of probabilities.

Gray, Lincoln↗

Tropospheric Delay Effects in Radio Interferometry

A new tropospheric mapping function is derived which is more accurate than previous mapping functions above elevations of 4 degrees. The error due to the given analytic approximation is estimated to be less than 0.02% for elevation angles larger than 6 degrees, (less than 0.4 cm at 6 degrees, and approximately 0.004% or 0.03 cm at 20 degrees). The mathematical expansion used in the derivation is valid for any laterally homogeneous atmospheric model of refractivity. The new mapping function, computer generated ray tracing tables and other mapping functions are compared. The results can be used in correcting for tropospheric delays of radio signals.

Lanyi, G.↗