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Evans, Charles R.

Publications and source records attributed to Evans, Charles R..

9 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Temporal dynamics of the multi-omic response to endurance exercise training

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

metabCombiner 2.0: Disparate Multi-Dataset Feature Alignment for LC-MS Metabolomics

Liquid chromatography–high-resolution mass spectrometry (LC-HRMS), as applied to untargeted metabolomics, enables the simultaneous detection of thousands of small molecules, generating complex datasets. Alignment is a crucial step in data processing pipelines, whereby LC-MS features derived from common ions are assembled into a unified matrix amenable to further analysis. Variability in the analytical factors that influence liquid chromatography separations complicates data alignment. This is prominent when aligning data acquired in different laboratories, generated using non-identical instruments, or between batches from large-scale studies. Previously, we developed metabCombiner for aligning disparately acquired LC-MS metabolomics datasets. Here, we report significant upgrades to metabCombiner that enable the stepwise alignment of multiple untargeted LC-MS metabolomics datasets, facilitating inter-laboratory reproducibility studies. To accomplish this, a “primary” feature list is used as a template for matching compounds in “target” feature lists. We demonstrate this workflow by aligning four lipidomics datasets from core laboratories generated using each institution’s in-house LC-MS instrumentation and methods. We also introduce batchCombine, an application of the metabCombiner framework for aligning experiments composed of multiple batches. metabCombiner is available as an R package on Github and Bioconductor, along with a new online version implemented as an R Shiny App.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2020

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Exercise provides a robust physiological stimulus that evokes cross-talk between a wide range of tissues via hormonal, cellular and molecular signals that when repeated regularly over time (i.e., training) improves physiological capacity, benefits numerous organ systems and decreases the risk for premature mortality. In spite of its fundamental importance, a gap remains in identifying the detailed molecular signals and responses to exercise and its benefits for health and disease prevention. To further knowledge in this emerging area, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to generate a molecular map of the effects of acute and chronic exercise. MoTrPAC investigators are conducting preclinical and clinical studies to better understand the systemic effects of exercise across multiple tissues. The preclinical studies were performed on more than 700 rats with the analysis of twenty or more organs per rat. The clinical study involves a large cohort of ~2600 individuals with a range of ages and fitness levels (untrained, trained, highly trained) who will be evaluated physiologically and by molecular probing of blood, muscle and adipose tissues before and after acute and chronic endurance or resistance exercise. Multi-omic analyses (genomics, epigenomics, transcriptomics, proteomics and metabolomics/lipidomics) will be performed followed by state-of-the-art bioinformatics to create a molecular map of exercise. This mapping project will provide a public database that is expected to enhance our understanding of the health benefits of physical activity in many organ systems and potentially provide insight into mitigating diseases through activity.

Sanford, James A.↗
NASA NTRS1994

Physical processes in eclipsing pulsars: Eclipse mechanisms and diagnostics

We investigate how the radio emission of a pulsar interacts with plasma derived from a stellar companion. Various physical mechanisms that can cause radio pulse eclipse are discussed, and predictions are made for the polarization properties of the emergent radio wave. We consider eclipses by a wind from the stellar companion, by a stellar magnetosphere, or by material entrained in the pulsar wind. Eclipses due to refraction require either a relatively high plasma density or a sharp edge to the plasma distribution. The conditions that must prevail for free-free absorption to be effective in eclipsing a radio beam are also outlined. Pulse smearing may be important at higher frequencies; related eclipse mechanisms include pulse spreading due to a rapidly changing electron column, and scattering by Langmuir turbulence. The high brightness temperature radio beam can generate its own plasma turbulence via a number of nonlinear parametric instabilities, such as the instability associated with stimulated Raman scattering. When the plasma turbulence is heavily damped, the radio bean can still undergo induced Compton scattering. Stimulated scattering effects such as these are very sensitive to the presence of narrow-band substructure in the pulsar radio emission. Finally, we consider the possibility that plasma derived from a stellar companion may mix with the relativistic pulsar wind and cause cyclotron absorption at low radio frequencies. Even if the cyclotron optical depth is small, fluctuations in the emergent polarization of the radio beam on the timescale of a few seconds are a very sensitive probe of the spatial structure of the magnetic field in the pulsar wind. The current observational properties of two known eclipsing pulsar systems, PSR 1957+20 and PSR 1744-24A, are used to construct tentative eclipse models. The favored model for PSR 1957+20 is cyclotron or synchrotron absorption by plasma embedded in the pulsar wind combined with pulse smearing at high frequency, and the favored model for PSR 1744-24A is backscattering off plasma turbulence generated by the stimulated Raman scattering parametric instability. Pulsar eclipses promise to provide a good diagnostic of pulsar winds and possible of the pulse emission mechanism.

Thompson, C.↗
NASA NTRS1992

A test suite for magnetohydrodynamical simulations

A collection is presented of MHD problems that will provide researchers who have interests in modeling MHD phenomena with a battery of tests (a 'test suite') for calibrating their numerical algorithms. Use of these tests will provide a common reference for comparison of different numerical MHD algorithms. The test suite includes both 1D and 2D problems. Taken together, these problems test the abilities of a numerical method to propagate accurately all of the MHD wave families in moving and stationary media, to capture MHD shocks and contact discontinuities, and to model accurately Lorentz force terms in multiple dimensions. An example solution of each test problem is presented. Diagnostic convergence-testing procedures that provide a quantitative evaluation of MHD algorithms are demonstrated.

Stone, James M.↗
NASA NTRS1990

Determining gravitational radiation from Newtonian self-gravitating systems

Quadrupole gravitational radiation formulas are tested and compared in a calculation of rotating stellar core collapse. While the standard quadrupole formula (SQF) allows an economical calculation of the waveform in postlinear gravity, it has several shortcomings that become apparent in a finite difference (FD) calculation. These shortcomings are related to the large-moment arm of the quadrupole moment and the two (numerical) time derivatives that separate it from the waveform. These shortcomings lead to high-frequency noise in the SQF waveform. Several alternatives to the SQF are developed. Each is mathematically equivalent to the SQF and applicable to self-gravitating sources. For FD calculations, the new quadrupole formulas are all superior to the SQF and capable of producing waveforms free of the high-frequency noise characteristics of its use.

Finn, Lee Samuel↗
NASA NTRS1989

The tidal disruption of a star by a massive black hole

Results are reported from a three-dimensional numerical calculation of the tidal disruption of a low-mass main-sequence star on a parabolic orbit around a massive black hole (Mh = 10 to the 6th stellar mass). The postdisruption evolution is followed until hydrodynamic forces becomes negligible and the liberated gas becomes ballistic. Also given is the rate at which bound mass returns to pericenter after orbiting the hole once. The processes that determine the time scale to circularize the debris orbits and allow an accretion torus to form are discussed. This time scale and the time scales for radiative cooling and accretion inflow determine the onset and duration of the subsequent flare in the AGN luminosity.

Evans, Charles R.↗