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At least 955 records · Page 53

Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence

Cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to age-related arterial dysfunction, in part, by promoting oxidative stress and inflammation, which reduce the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice. We found that fisetin decreased cellular senescence in human endothelial cell culture. In old mice, vascular cell senescence and SASP-related inflammation were lower 1 week after the final dose of oral intermittent (1 week on—2 weeks off—1 weeks on dosing) fisetin supplementation. Old fisetin-supplemented mice had higher endothelial function. Leveraging old p16-3MR mice, a transgenic model allowing genetic clearance of p16 INK4A -positive senescent cells, we found that ex vivo removal of senescent cells from arteries isolated from vehicle- but not fisetin-treated mice increased endothelium-dependent dilation, demonstrating that fisetin improved endothelial function through senolysis. Enhanced endothelial function with fisetin was mediated by increased NO bioavailability and reduced cellular- and mitochondrial-related oxidative stress. Arterial stiffness was lower in fisetin-treated mice. Ex vivo genetic senolysis in aorta rings from p16-3MR mice did not further reduce mechanical wall stiffness in fisetin-treated mice, demonstrating lower arterial stiffness after fisetin was due to senolysis. Lower arterial stiffness with fisetin was accompanied by favorable arterial wall remodeling. The findings from this study identify fisetin as promising therapy for clinical translation to target excess cell senescence to treat age-related arterial dysfunction.

59 BASIC BIOLOGICAL SCIENCES↗

Opposite Response of DNA and RNA Viruses to Soil Warming and Implications for Microbial Functions

Soil viruses control the dynamics and metabolism of their hosts, strongly modifying carbon and nutrient cycling as well as soil biochemistry. Warming specifically affects viruses and their hosts, but the consequences of climate warming on the virus–host interactions, and for soil functions, remain unknown. Here, we investigated the viral communities and the virus–host interactions under warming in situ based on a forest soil column translocation experiment. The abundance of the Petitvirales (DNA viruses) decreased by 25%, but that of the Durnavirales and Martellivirales (RNA viruses) strongly increased. The DNA viral lysogenic signals and RNA viral lytic proteins increased in soil, indicating the opposite lifestyles of DNA and RNA viruses. Correspondingly, the DNA abundance of viral hosts increased, whereas RNA viral hosts remained stable. The high DNA viruses/host ratios reflect very intensive interactions between the virus and host, leading to the drop in the host functions (such as carbon metabolism processes and nitrogen and phosphorus cycles) up to 43%. In contrast, the functions of the hosts for RNA viruses increased by up to 48%. The fundamental difference in behaviour of DNA and RNA viruses is that the former use mainly lysogenic, whereas the latter lytic, lifestyles and thus control the responses of host communities to warming. Conclusively, the opposite response of DNA and RNA viruses to warming in abundance, lifestyle, and interactions with hosts leads to divergent changes in nutrient fluxes in soil. These new perspectives on viral regulations of microbial communities and their function under soil warming reveal the undeniable role of viruses in microbial ecology.

forest soil↗

From remotely sensed solar-induced chlorophyll fluorescence to ecosystem structure, function, and service: Part I—Harnessing theory

Solar-induced chlorophyll fluorescence (SIF) is a remotely sensed optical signal emitted during the light reactions of photosynthesis. The past two decades have witnessed an explosion in availability of SIF data at increasingly higher spatial and temporal resolutions, sparking applications in diverse research sectors (e.g., ecology, agriculture, hydrology, climate, and socioeconomics). These applications must deal with complexities caused by tremendous variations in scale and the impacts of interacting and superimposing plant physiology and three-dimensional vegetation structure on the emission and scattering of SIF. At present, these complexities have not been overcome. To advance future research, the two companion reviews aim to (1) develop an analytical framework for inferring terrestrial vegetation structures and function that are tied to SIF emission, (2) synthesize progress and identify challenges in SIF research via the lens of multi-sector applications, and (3) map out actionable solutions to tackle these challenges and offer our vision for research priorities over the next 5-10 years based on the proposed analytical framework. This paper is the first of the two companion reviews, and theory oriented. It introduces a theoretically rigorous yet practically applicable analytical framework. Guided by this framework, we offer theoretical perspectives on three overarching questions: (1) The forward (mechanism) question—How are the dynamics of SIF affected by terrestrial ecosystem structure and function? (2) The inference question: What aspects of terrestrial ecosystem structure, function, and service can be reliably inferred from remotely sensed SIF and how? (3) The innovation question: What innovations are needed to realize the full potential of SIF remote sensing for real-world applications under climate change? In conclusion, the analytical framework elucidates that process complexity must be appreciated in inferring ecosystem structure and function from the observed SIF; this framework can serve as a diagnosis and inference tool for versatile applications across diverse spatial and temporal scales.

59 BASIC BIOLOGICAL SCIENCES↗

Putting error bars on density functional theory dataset

This dataset contains submission files and raw output files from high-throughput DFT simulations to analyze the systemic errors in lattice constant, bulk moduli and formation energy predictions for a range of binary and ternary oxides using four exchange correlation functionals (LDA, PBE, PBEsol and vdW-DF-C09). This data was then used as the basis for employing materials informatics methods to predict the expected errors in the lattice constants of the studied compounds. Predicted errors were also used to better the DFT-predicted lattice parameters. Our results emphasize the link between the computed errors and the electron density and hybridization errors of a functional. In essence, these results provide “error bars” for choosing a functional for the creation of high-accuracy, high-throughput datasets as well as avenues for the development of XC functionals with enhanced performance, thereby enabling the accelerated discovery and design of new materials.

36 MATERIALS SCIENCE↗

Rotational symmetry relation for efficient response function generation in the coarse mesh transport method COMET

The coarse mesh transport code COMET is a continuous energy hybrid stochastic-deterministic neutronics solver with high fidelity and formidable computation speed in solving reactor core problems. Its method is based on the incident flux expansion theory. In this work, we take advantage of the local geometric symmetry in many reactor cores lattices (e.g., fuel lattices and reflector blocks) to develop relations among the flux response expansion coefficients for symmetric surfaces to further improve the computational efficiency of the COMET response function generation tool (method). This is done by a rigorous derivation of the transformation matrices for the angular and spatial expansion moments resulting from a rotation of a coarse mesh by an arbitrary angle. The relations for the response coefficients for the symmetric surfaces can be then written as the Kronecker product of those transformation matrices. The method is implemented into COMET and tested on two advanced high temperature reactor (AHTR) full-length single assembly benchmark problems. The COMET results using the response function library based on the symmetry relations were compared to those using the library directly generated by continuous energy Monte Carlo for all surfaces. It was found that the eigenvalues and stripe-wise fission densities using the two libraries are in statistical agreement as expected. This indicates that the new method maintains the high fidelity of the original COMET method while improving the computational efficiency in the response function generation by 270% to 400%, depending on the local geometric symmetry. This method also reduces the size of the response function library by the same magnitude (270% to 400%). (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

A Functional All-Hazard Approach to Critical Infrastructure Dependency Analysis

The critical infrastructures protection landscape is a vast and varied pattern of independent, but interconnected infrastructure systems that are essential to the function of our modern society. The U.S. policy on critical infrastructure protection has been continually evolving since the “President’s Commission on Critical Infrastructure Protection” was published in 1997. In response to these policies, federal, state, and local governments, along with research institutions, have invested a substantial amount of time and effort into identifying and analyzing critical infrastructure, their functions, and dependencies/interdependencies to better understand their vulnerabilities. To date, the ability to assess vulnerabilities, resiliency, and priorities for protecting interdependent critical infrastructure systems from an all-hazards perspective remains a difficult problem. In this paper we introduce the All-Hazards Analysis (AHA) methodology, which provides an integrated functional basis across infrastructure systems, through the implementation of a common language and a scalable level of decomposition to effectively evaluate the resilience of interconnected infrastructure systems. AHA models infrastructure systems as directed multidimensional graphs, which enable the evaluation of cross-sector interdependencies prior to, during, and after disruptive events. Finally, and by design, AHA enables the cross linking of data taxonomies to enable more effective data sharing, such as the National Critical Functions (NCF) and Infrastructure Data Taxonomy (IDT).

02 PETROLEUM↗

Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up – baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

60 APPLIED LIFE SCIENCES↗

Stability Functions in the Stable Surface Layer Derived from the Mellor–Yamada–Nakanishi–Niino (MYNN) Scheme

It is desirable that a surface layer scheme in an atmospheric numerical model is consistent with an atmospheric boundary layer scheme incorporated in the same model. In this study, stability functions based on Monin–Obukhov similarity theory for momentum and heat, φ m and φ h , in the stable surface layer are derived from the Mellor–Yamada–Nakanishi–Niino (MYNN) scheme. The resulting stability functions are approximated by φ m = 1 + 4.8z/L and φ h = 0.74 + 6.0z/L, which can be analytically integrated with respect to height z to obtain momentum and heat fluxes, where L is the Obukhov length. The fluxes thus, obtained are compared with those acquired from stability functions in four previous studies: they are nearly the same as those from two of them, and show better agreement with observational data of the Surface Heat Budget of the Arctic Ocean experiment (SHEBA) over sea ice than those from the other two studies. Detailed comparisons of the results of the MYNN scheme with the SHEBA data suggest that significant variations of the fluxes observed during “winter” when the ice was covered with dry snow may have been caused by those of the surface roughness around the observational site. The stability functions obtained from the MYNN scheme predict that the bulk and flux Richardson numbers approach critical values of 0.26 and 0.21, respectively, in the limit of z/L → ∞. These critical values result from the Kolmogorov hypothesis applied to the turbulent dissipation in the MYNN scheme and are considered to correspond to a transition from Kolmogorov to non-Kolmogorov turbulence.

54 ENVIRONMENTAL SCIENCES↗

Fragility Functions Resource Report: Documented Sources for Electricity and Water Resilience Valuation

Fragility curves provide the vulnerability between hazard intensity and an asset. Federal installations may include many different electricity and water infrastructure types (or assets) such as generators, wind turbines, solar PV, switch yards, substations and power lines as well as water distribution systems that could be affected by different hazards. The vulnerability of each asset is a function of its age, type of materials and maintenance. In addition, the vulnerability changes with the hazards intensity and has a probability distribution function associated with it. The fragility functions are used in conjunction with hazard probability and consequence valuations to determine the values at risk for examination of investment grade analyses of alternative mitigation strategies. This document provides examples of fragility functions and links to their sources for different electricity and water infrastructure assets by hazard type.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Feasibility of a Novel Density Functional Method Outside the Kohn-Sham Framework for Modeling Global Potential Energy Surfaces of Molecular Chemical Reactions (Final Technical Report)

The project aimed towards the construction of computational methods capable of modeling the global potential energy surface (PES) of small molecules, molecular ions, and radicals — including the parts of the PES which correspond to chemical reactions, and the reaction paths connecting reactants, intermediates, and reaction products. This goal may seem humble at first glance, but for chemical systems with more than about six atoms in total, at the time the project was proposed, there were no established theoretical methods capable of simulating such systems reliably, not even for small molecules in the gas phase which are electronically benign. This restriction severely hampers our ability to model and control chemical processes under harsh conditions. With the goal of constructing a method capable of modeling such chemical systems, we proposed to pursue a novel approach towards a Multi-Configuration (MC) DFT outside the traditional frameworks of Kohn-Sham theory and other methods of coupling wave function theory with DFT. Rather than being a complete active space (CAS) method, the proposed DOCI-DFT would employ a special restricted form of the active space wave function, called Doubly-Occupied CI (DOCI)—this wave function form is sufficient to describe not only heterolytic, but also homolytic bond dissociation processes at the zeroth order (i.e., as active space wave function). There are no other standard mean field methods which can do so. In the original proposal, we also outlined strong formal and practical arguments speaking for this method. The project proposal was accepted by the Department of Energy and provided two years of seed funding for one graduate student, as well as two years of two weeks PI summer-salary for the PI. However, ultimately the project could not be effectively pursued due to severe interferences outside the context scientific problems and was cancelled. Apart from two weeks of PI salary (and associated fringe & overhead costs issues by the performing institution), no costs were charged against the award, with the entire rest of funding returned to the Department of Energy. This report reiterates the primary background information regarding the project, its original goals, and outlines the preliminary work performed during the two weeks of DOE funding charged.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

On the light-front wave functions of quarkonia

The light-front wave functions of hadrons allow us to calculate a wide range of physical observables; however, the wave functions themselves cannot be measured. We discuss recent results for quarkonia obtained in basis light-front quantization using an effective Hamiltonian with a confining model in both the transverse and longitudinal directions and with explicit one-gluon exchange. In particular, we focus on the numerical convergence of the basis expansion, as well as the asymptotic behavior of the light-front wave functions. Finally, we also illustrate that, for mesons with unequal quark masses, the maxima of the light-front wave functions depend in a non-trivial way on the valence quark-mass difference.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

From microbial diversity to functional potential using dimensionality reduction

The high dimensionality of microbial diversity data from ‘omics observations can be reduced using Machine Learning, with many recent studies showcasing ML utility for exploratory ecological feature finding and process prediction. Here, we compare the Self Organizing Map (SOM) dimensionality reduction method to the well-documented sample-based Principal Coordinate Analysis (PCoA) and taxa-based Weighted Gene Correlation Network Analysis (WGCNA) using near daily 16S rRNA gene amplicon sequencing data from the 2019 to 2020 MOSAiC International Arctic Drift Expedition. We then map k-means clustering outputs from each method to available metagenomes, extracting functionally distinct seasonal microbial ecotypes in the surface Arctic Ocean. Our results indicate the SOM method better represented expected seasonal transitions and identified a greater number of metabolically distinct functional groups than the more traditional PCoA ordination. Ultimately, we identified four community ecotypes with distinct taxonomic and functional cut-offs driven by seasonality, water mass, and substrate turnover, highlighting the importance of succession in functional diversity for the central Arctic Ocean. These results reinforce ML dimensionality reduction as a meaningful translator in the mining of historical amplicon datasets to address modern mechanistic questions and potentially provide ’omics informed ecotype diversity to leverage in mechanistic biogeochemical models.

Arctic Ocean↗

Recent Advances in the Application of Functionalized Lignin in Value-Added Polymeric Materials

The quest for converting lignin into high-value products has been continuously pursued in the past few decades. In its native form, lignin is a group of heterogeneous polymers comprised of phenylpropanoids. The major commercial lignin streams, including Kraft lignin, lignosulfonates, soda lignin and organosolv lignin, are produced from industrial processes including the paper and pulping industry and emerging lignocellulosic biorefineries. Although lignin has been viewed as a low-cost and renewable feedstock to replace petroleum-based materials, its utilization in polymeric materials has been suppressed due to the low reactivity and inherent physicochemical properties of lignin. Hence, various lignin modification strategies have been developed to overcome these problems. Herein, we review recent progress made in the utilization of functionalized lignins in commodity polymers including thermoset resins, blends/composites, grafted functionalized copolymers and carbon fiber precursors. In the synthesis of thermoset resins such as polyurethane, phenol-formaldehyde and epoxy, they are covalently incorporated into the polymer matrix, and the discussion is focused on chemical modifications improving the reactivity of technical lignins. In blends/composites, functionalization of technical lignins is based upon tuning the intermolecular forces between polymer components. In addition, grafted functional polymers have expanded the utilization of lignin-based copolymers to biomedical materials and value-added additives. Different modification approaches have also been applied to facilitate the application of lignin as carbon fiber precursors, heavy metal adsorbents and nanoparticles. These emerging fields will create new opportunities in cost-effectively integrating the lignin valorization into lignocellulosic biorefineries.

36 MATERIALS SCIENCE↗

Coordination Chemistry in the Structural and Functional Exploration of Actinide-Based Metal-Organic Frameworks

The coordination chemistry between inorganic and organic species can be optimally exemplified by metal–organic frameworks (MOFs), whose structures and functionalities can be rationally designed from these highly tunable building blocks. The high porosity, stability, and versatile functionalities of MOFs have attracted wide-spread attention from energy-related research and pollution remediation to biomedical applications. A unique and underexplored subset of these materials are MOFs based on actinide nodes; these MOFs have distinguished themselves as a unique platform for investigating the versatile oxidation states, reactivity, and coordination chemistry of actinides. Herein, we will focus on the rational design and synthesis of actinide-based MOFs under the general guidelines of coordination chemistry for their structural and functional explorations. The dimensionality, topology, and structures of actinide-based MOFs can be controlled by selecting pre-designed building blocks of actinide-based nodes and organic linkers with certain desired coordination geometries and functionalities. Furthermore, these unique actinide-based MOFs have shown promise for applications in nuclear waste mitigation, pollution control, and catalysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Comparison of left ventricular diastolic function in obstructive hypertrophic cardiomyopathy in patients undergoing percutaneous septal alcohol ablation versus surgical myotomy/myectomy

Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.

Non-NASA Center↗

Effect of 6 degrees head-down tilt on cardiopulmonary function: comparison with microgravity

BACKGROUND: Head-down tilt (HDT) of 6 degrees is a commonly used model of weightlessness, but there are few comparisons with actual microgravity. HYPOTHESIS: Our study was designed to prove that the changes in cardiopulmonary function seen in HDT would be similar to those seen in microgravity. METHODS: We compared measurements of cardiovascular and pulmonary function from three separate spaceflights of 14 to 17 d duration, with data collected during a 17-d period of HDT. RESULTS: HDT proved a good model of the cardiovascular response to microgravity, resulting in increases in cardiac output and stroke volume of a similar magnitude to those seen in microgravity, with a concomitant reduction in heart rate. By contrast, HDT was a poor model of the effects of microgravity on pulmonary ventilation and gas exchange. CONCLUSION: Pulmonary function in HDT approximated the changes seen in the 1-G supine posture, while in microgravity this was much closer to that seen in the 1-G upright position. The differences probably reflect the fact that changes in cardiovascular function result primarily from fluid shifts within the entire body, whereas changes in pulmonary ventilation are primarily a result of mechanical influences on the lung and chest and abdominal wall.

NASA Discipline Cardiopulmonary↗

Formal Verification of the Interaction Between Semi-Algebraic Sets and Real Analytic Functions

Semi-algebraic sets and real analytic functions are fundamental concepts in Real Algebraic Geometry and Real Analysis, respectively. These concepts interact in the study of Differential Equations, where the real analytic solution to a differential equation is known to enter or exit a semi-algebraic set in a predicable way. Motivated to enhance the capability to reason about differential equations in the Prototype Verification System (PVS), a formalization of multivariate polynomials, semi-algebraic sets, and real analytic functions is developed. The favorable way that a real analytic function enters and exits a semi-algebraic set is proven. It is further shown that if the function is assumed to be smooth, a slightly weaker assumption than real analytic, these favorable interactions with semi-algebraic sets may fail.

Real analytic functions↗

NESC GN&C TDT Workshop on 2D Image Motion Optical Transfer Functions, Pointing Performance Analysis, and Requirements

What You Will Learn: The focus is on payload imaging performance due to pointing motion. Some historical background on pointing performance analysis is given. The Optical Transfer Function (OTF) and Modulation Transfer Function (MTF) are defined. The imaging performance due to pointing motion is measured by image motion optical transfer functions (IM OTF). IM OTFs are defined for displacement, smear, and jitter motions, which are all rigorously defined. Deterministic and Statistical IM OTFs are briefly derived and graphically illustrated and compared. The IM OTFs are parameterized by pointing error metrics(PEM), which are means and covariances of displacement, smear, and jitter. Emphasis is on procedures and algorithms to evaluate the image motion optical transfer functions and pointing error metrics. Three procedures are covered, which depend on whether the pointing error data is from time-domain simulation, frequency-domain analysis, or stochastic modeling. A method to evaluate the relative contribution of disturbance sources and to identify the most significant contributors is presented. The presentation includes pertinent discussion of flexible structures and control-structure interaction. No single book can adequately cover this subject, so a book is not required for the course. A list of selected articles, reports, documents, and books is provided for reference and further study. Mathis kept to the minimum necessary to convey principles; lengthy derivations are left to the reference material. Graphics are used to illustrate concepts. As with any such learning endeavor, the knowledge gained will be retained and strengthened through actual practice.c©2019–2021 Mark E. Pittelkau— 5

NASA Engineering and Safety Center (NESC)↗