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At least 415 records · Page 23

Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor

The 14-3-3 family of phosphoserine/threonine-recognition proteins engage multiple nodes in signaling networks that control diverse physiological and pathophysiological functions and have emerged as promising therapeutic targets for such diseases as cancer and neurodegenerative disorders. Thus, small molecule modulators of 14-3-3 are much needed agents for chemical biology investigations and therapeutic development. To analyze 14-3-3 function and modulate its activity, we conducted a chemical screen and identified 4-[(2Z)-2-[4-formyl-6-methyl-5-oxo-3-(phosphonatooxymethyl)pyridin-2-ylidene]hydrazinyl]benzoate as a 14-3-3 inhibitor, which we termed FOBISIN (FOurteen-three-three BInding Small molecule INhibitor) 101. FOBISIN101 effectively blocked the binding of 14-3-3 with Raf-1 and proline-rich AKT substrate, 40 kD{sub a} and neutralized the ability of 14-3-3 to activate exoenzyme S ADP-ribosyltransferase. To provide a mechanistic basis for 14-3-3 inhibition, the crystal structure of 14-3-3{zeta} in complex with FOBISIN101 was solved. Unexpectedly, the double bond linking the pyridoxal-phosphate and benzoate moieties was reduced by X-rays to create a covalent linkage of the pyridoxal-phosphate moiety to lysine 120 in the binding groove of 14-3-3, leading to persistent 14-3-3 inactivation. We suggest that FOBISIN101-like molecules could be developed as an entirely unique class of 14-3-3 inhibitors, which may serve as radiation-triggered therapeutic agents for the treatment of 14-3-3-mediated diseases, such as cancer.

59 BASIC BIOLOGICAL SCIENCES↗

Assessment of global and regional tectonic models for faulting in the ancient terrains of Mars

The structural mapping of tectonic landforms on Mars has provided a great deal of information regarding the planet's tectonic history. The present paper has the objective to test models of regional and global fracturing by evaluating the spatial distribution and orientation of the ancient heavily cratered terrain (HCT) structural landforms. Attention is given to background information concerning earlier studies, landform selection and analysis, rose diagrams, tests for Tharsis generation, and a calculation of thermal stress in the early Martian lithosphere. The contribution of classical Tharsis-centered tectonism to the production of HCT structural landforms was found to be very small. Few structural landforms investigated are either perpendicular to calculated principal stress trajectories or radial to Tharsis.

Schultz, R. A.↗

Temperatures and Composition in the Saturn System from Cassini CIRS

We summarize recent observations by the Composite Infrared Spectrometer of Saturn, its rings, Titan, and the icy satellites. Limb observations of Saturn show vertical oscillations of temperatures and zonal-wind shears in the equatorial region that may be related to a temporal oscillation similar to the terrestrial QBO and Jupiter's QQO. There is also evidence of subsidence at mid-northern latitudes driven by the equatorial activity. Nadir-viewing observations show compact warm spots in the troposphere and stratosphere at both (summer and winter) poles, likely associated with subsidence. Observations of Titan have defined better the characteristics of the northern winter polar vortex, with 190 m/s winds surrounding a cold atmosphere at 1 microbar. The very warm polar stratopause at 10 microbar and the enhanced abundances of organic compounds suggest subsidence within the vortex. Analysis of the zonal structure in temperature indicates that the stratospheric zonal winds rotate about an axis that is displaced approximately 4.1 deg from the IAU pole. Additional flybys, including a close one in March 2008, continue to characterize the endogenic activity in Enceladus s south polar region. Temperature maps of bright and dark terrains on Iapetus indicate that its ice is approximately stable to sublimation in the bright regions and highly unstable in the dark regions. Thermal mapping of Saturn s rings continues to constrain their composition, and observations at different solar phase angles, spacecraft elevations, solar elevations, and local hour angles have elucidated the effects of ring-particle shadowing and vertical motions on the thermal structure, and revealed the presence of small-scale structure associated with self-gravity wakes.

Flasar, F. Michael↗

Small and arbitrary shock structures in spin 1/2 magnetohydrodynamic quantum plasma

The shock structures in spin-1/2 quantum plasma, in the presence of magnetic diffusivity, are studied in the framework of the quantum magnetohydrodynamic model. Linear dispersion relation for the system is carried out analytically, and the results are plotted numerically for several values of the plasma parameters. Numerical analysis for arbitrary amplitude waves is carried out, whereas for waves of small amplitude, the reductive perturbation technique is applied to obtain the Korteweg-de Vries-Burgers equation. Both the analyses are observed to give the same qualitative picture. Most importantly, the different plasma parameters are found to play significant roles in determining the nature of the shock waves. The parametric ranges for which monotonic shock and oscillatory shock solutions are observed, are found analytically.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

The completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: measurement of the growth rate of structure from the small-scale clustering of the luminous red galaxy sample

ABSTRACT We measure the small-scale clustering of the Data Release 16 extended Baryon Oscillation Spectroscopic Survey Luminous Red Galaxy sample, corrected for fibre-collisions using Pairwise Inverse Probability weights, which give unbiased clustering measurements on all scales. We fit to the monopole and quadrupole moments and to the projected correlation function over the separation range $7-60\, h^{-1}{\rm Mpc}$ with a model based on the aemulus cosmological emulator to measure the growth rate of cosmic structure, parametrized by fσ8. We obtain a measurement of fσ8(z = 0.737) = 0.408 ± 0.038, which is 1.4σ lower than the value expected from 2018 Planck data for a flat ΛCDM model, and is more consistent with recent weak-lensing measurements. The level of precision achieved is 1.7 times better than more standard measurements made using only the large-scale modes of the same sample. We also fit to the data using the full range of scales $0.1\text{--}60\, h^{-1}{\rm Mpc}$ modelled by the aemulus cosmological emulator and find a 4.5σ tension in the amplitude of the halo velocity field with the Planck + ΛCDM model, driven by a mismatch on the non-linear scales. This may not be cosmological in origin, and could be due to a breakdown in the Halo Occupation Distribution model used in the emulator. Finally, we perform a robust analysis of possible sources of systematics, including the effects of redshift uncertainty and incompleteness due to target selection that were not included in previous analyses fitting to clustering measurements on small scales.

79 ASTRONOMY AND ASTROPHYSICS↗

REIONIZATION IN THE WARM DARK MATTER MODEL

Compared with the cold dark matter (CDM) model, the formation of the small-scale structure of the universe is suppressed in the warm dark matter (WDM) model. It is often thought that this would delay the reionization of the intergalactic medium (IGM) because the star formation rate during the epoch of reionization (EOR) would be lowered. However, during the later stage of the EOR, a large portion of the ionizing photons is consumed by recombination inside the minihalos, which is where the gas has higher density and recombination rates than that in the IGM. The suppression of the small-scale structure would therefore reduce the recombination rate and could potentially shorten the reionization process. This effect is investigated here by using the analytical 'bubble model' of reionization. We find that, in some cases, although the initiation of the EOR is delayed in the WDM model, its completion could be even earlier than the CDM case, but the effect is generally small. We obtain limits on the mass of WDM particles for different reionization redshifts.

79 ASTRONOMY AND ASTROPHYSICS↗

A Machine Learning–Based Approach to Time-series Wave Identification in the Solar Wind

The Wind spacecraft has yielded several decades of high-resolution magnetic field data, a large fraction of which displays small-scale structures. In particular, the solar wind is full of wavelike fluctuations that appear in both the field magnitude and its components. The nature of these fluctuations can be tied to the properties of other structures in the solar wind, such as shocks, that have implications for the time evolution of the solar wind. As such, having a large collection of wave events would facilitate further study of the effects that these fluctuations have on solar wind evolution. Given the large volume of magnetic field data available, machine learning is the most practical approach to classifying the myriad small-scale structures observed. To this end, a subset of Wind data is labeled and used as a training set for a multibranch 1D convolutional neural network aimed at classifying circularly polarized wave modes. Using this algorithm, a preliminary statistical study of 1 yr of data is performed, yielding about 300,000 wave intervals out of about 5,000,000 solar wind intervals. The wave intervals come about more often in the fast solar wind and at higher temperatures, and the number of waves per day is highly periodic. This machine learning–based approach to wave detection has the potential to be a powerful, inexpensive way to catalog waves throughout decades of spacecraft data.

79 ASTRONOMY AND ASTROPHYSICS↗

Coronal Heating Observed with Hi-C

The recent launch of the High‐Resolution Coronal Imager (Hi‐C) as a sounding rocket has offered a new, different view of the Sun. With approx 0.3" resolution and 5 second cadence, Hi‐C reveals dynamic, small‐scale structure within a complicated active region, including coronal braiding, reconnection regions, Alfven waves, and flows along active region fans. By combining the Hi‐C data with other available data, we have compiled a rich data set that can be used to address many outstanding questions in solar physics. Though the Hi‐C rocket flight was short (only 5 minutes), the added insight of the small‐scale structure gained from the Hi‐C data allows us to look at this active region and other active regions with new understanding. In this talk, I will review the first results from the Hi‐C sounding rocket and discuss the impact of these results on the coronal heating problem.

Winebarger, Amy R.↗

A Machine Learning-Based Approach to Time-Series Wave Identification in the Solar Wind

The Wind spacecraft has yielded several decades of high-resolution magnetic field data, a large fraction of which displays small-scale structures. In particular, the solar wind is full of wavelike fluctuations that appear in both the field magnitude and its components. The nature of these fluctuations can be tied to the properties of other structures in the solar wind, such as shocks, that have implications for the time evolution of the solar wind. As such, having a large collection of wave events would facilitate further study of the effects that these fluctuations have on solar wind evolution. Given the large volume of magnetic field data available, machine learning is the most practical approach to classifying the myriad small-scale structures observed. To this end, a subset of Wind data is labeled and used as a training set for a multi-branch 1D convolutional neural network aimed at classifying circularly polarized wave modes. Using this algorithm, a preliminary statistical study of one year of data is performed, yielding about 300,000 wave intervals out of about 5,000,000 solar wind intervals. The wave intervals come about more often in the fast solar wind and at higher temperatures, and the number of waves per day is highly periodic. This machine learning-based approach to wave detection has the potential to be a powerful, inexpensive way to catalog waves throughout decades of spacecraft data.

Samuel Fordin↗

Sensitivity of optimized control systems to minor structural modifications

A procedure for checking whether small changes in a structure have the potential for significant enhancements of its optimized vibration control system is described. The first step in the procedure consists of the calculation of the sensitivity of the parameters of the optimized control system to small changes in the structural parameters. Theh second step consists of the optimization of the structural parameters to produce maximal increase in the performance of the control system with minimal change in the structure. The procedure has been demonstrated for a flexible laboratory structure controlled by several rate-feedback colocated force-actuator velocity-sensor pairs. Significant improvements in the performance of the control system were obtained with small structural modifications. Analytical predictions of such effects have also been validated experimentally.

Haftka, R. T.↗

Comparison of Cellulose Ib Simulations with Three Carbohydrate Force Fields

Molecular dynamics simulations of cellulose have recently become more prevalent due to increased interest in renewable energy applications, and many atomistic and coarse-grained force fields exist that can be applied to cellulose. However, to date no systematic comparison between carbohydrate force fields has been conducted for this important system. To that end, we present a molecular dynamics simulation study of hydrated, 36-chain cellulose I{beta} microfibrils at room temperature with three carbohydrate force fields (CHARMM35, GLYCAM06, and Gromos 45a4) up to the near-microsecond time scale. Our results indicate that each of these simulated microfibrils diverge from the cellulose I{beta} crystal structure to varying degrees under the conditions tested. The CHARMM35 and GLYCAM06 force fields eventually result in structures similar to those observed at 500 K with the same force fields, which are consistent with the experimentally observed high-temperature behavior of cellulose I. The third force field, Gromos 45a4, produces behavior significantly different from experiment, from the other two force fields, and from previously reported simulations with this force field using shorter simulation times and constrained periodic boundary conditions. For the GLYCAM06 force field, initial hydrogen-bond conformations and choice of electrostatic scaling factors significantly affect the rate of structural divergence. Our results suggest dramatically different time scales for convergence of properties of interest, which is important in the design of computational studies and comparisons to experimental data. This study highlights that further experimental and theoretical work is required to understand the structure of small diameter cellulose microfibrils typical of plant cellulose.

09 BIOMASS FUELS↗

Evaluating the influence of life‐history characteristics on genetic structure: a comparison of small mammals inhabiting complex agricultural landscapes

Abstract Conversion of formerly continuous native habitats into highly fragmented landscapes can lead to numerous negative demographic and genetic impacts on native taxa that ultimately reduce population viability. In response to concerns over biodiversity loss, numerous investigators have proposed that traits such as body size and ecological specialization influence the sensitivity of species to habitat fragmentation. In this study, we examined how differences in body size and ecological specialization of two rodents (eastern chipmunk; Tamias striatus and white‐footed mouse; Peromyscus leucopus ) impact their genetic connectivity within the highly fragmented landscape of the Upper Wabash River Basin ( UWB ), Indiana, and evaluated whether landscape configuration and complexity influenced patterns of genetic structure similarly between these two species. The more specialized chipmunk exhibited dramatically more genetic structure across the UWB than white‐footed mice, with genetic differentiation being correlated with geographic distance, configuration of intervening habitats, and complexity of forested habitats within sampling sites. In contrast, the generalist white‐footed mouse resembled a panmictic population across the UWB , and no landscape factors were found to influence gene flow. Despite the extensive previous work in abundance and occupancy within the UWB , no landscape factor that influenced occupancy or abundance was correlated with genetic differentiation in either species. The difference in predictors of occupancy, abundance, and gene flow suggests that species‐specific responses to fragmentation are scale dependent.

59 BASIC BIOLOGICAL SCIENCES↗

Variable EUV emission in the quiet sun and coronal heating

We review the characteristics of the variable emission from the small scale structure in the quiet sun, in view of the recent theoretical proposals that microflares are responsible for the heating of the corona and the solar wind. We consider the observational properties of the variable emission in quiet regions and coronal holes. Our results are based primarily on simultaneous multiwavelength EUV observations, supplemented by combinations of simultaneous cm radio, He I 10830 A, X-ray and line of sight photospheric magnetic field measurements. We show that the variable emission from the small-scale structure has surprisingly well-defined properties. Yet, within the limit of the temporal and spatial resolution of data currently available, the radiative losses, from this component of the emission, are a factor of ten smaller than that in the quiet sun. Hence, the theory of microflare heating cannot rely on these observations for support.

Habbal, S. R.↗

Imprints of the early Universe on axion dark matter substructure

Despite considerable experimental progress large parts of the axionlike particle (ALP) parameter space remain difficult to probe in terrestrial experiments. In some cases, however, small-scale structure of the ALP dark matter (DM) distribution is strongly enhanced, offering opportunities for astrophysical tests. Such an enhancement can be produced by a period of prenucleosynthesis early matter domination (EMD). This cosmology arises in many ultraviolet completions and generates the correct relic abundance for weak coupling f a ~ 10 16 GeV , ALP masses in the range 10 - 13 eV < m a < 1 eV , and without fine-tuning of the initial misalignment angle. This range includes the QCD axion around 10 - 9 - 10 - 8 eV . EMD enhances the growth of ALP small-scale structure, leading to the formation of dense ALP miniclusters which can contain nearly all of DM (depending on ALP mass and reheating temperature). We study the interplay between the initial ALP oscillation, reheating temperature, and effective pressure to provide analytic estimates of the minicluster abundance and properties. ALP miniclusters in the EMD cosmology are denser and more abundant than in Λ CDM . While enhanced substructure generically reduces the prospects of direct detection experiments, we show that pulsar timing and lensing observations can discover these minihalos over a large range of ALP masses and reheating temperatures.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Aeroacoustics of Turbulent High-Speed Jets

Aeroacoustic noise generation in a supersonic round jet is studied to understand in particular the effect of turbulence structure on the noise without numerically compromising the turbulence itself. This means that direct numerical simulations (DNS's) are needed. In order to use DNS at high enough Reynolds numbers to get sufficient turbulence structure we have decided to solve the temporal jet problem, using periodicity in the direction of the jet axis. Physically this means that turbulent structures in the jet are repeated in successive downstream cells instead of being gradually modified downstream into a jet plume. Therefore in order to answer some questions about the turbulence we will partially compromise the overall structure of the jet. The first section of chapter 1 describes some work on the linear stability of a supersonic round jet and the implications of this for the jet noise problem. In the second section we present preliminary work done using a TVD numerical scheme on a CM5. This work is only two-dimensional (plane) but shows very interesting results, including weak shock waves. However this is a nonviscous computation and the method resolves the shocks by adding extra numerical dissipation where the gradients are large. One wonders whether the extra dissipation would influence small turbulent structures like small intense vortices. The second chapter is an extensive discussion of preliminary numerical work using the spectral method to solve the compressible Navier-Stokes equations to study turbulent jet flows. The method uses Fourier expansions in the azimuthal and streamwise direction and a 1-D B-spline basis representation in the radial direction. The B-spline basis is locally supported and this ensures block diagonal matrix equations which are solved in O(N) steps. A very accurate highly resolved DNS of a turbulent jet flow is expected.

Rao, Ram Mohan↗

ℤ{sub 2} SIMP dark matter

Dark matter with strong self-interactions provides a compelling solution to several small-scale structure puzzles. Under the assumption that the coupling between dark matter and the Standard Model particles is suppressed, such strongly interacting massive particles (SIMPs) allow for a successful thermal freeze-out through N-to-N{sup ′} processes, where N dark matter particles annihilate to N{sup ′} of them. In the most common scenarios, where dark matter stability is guaranteed by a ℤ{sub 2} symmetry, the seemingly leading annihilating channel, i.e. 3-to-2 process, is forbidden, so the 4-to-2 one dominate the production of the dark matter relic density. Moreover, cosmological observations require that the dark matter sector is colder than the thermal bath of Standard Model particles, a condition that can be dynamically generated via a small portal between dark matter and Standard Model particles, à la freeze-in. This scenario is exemplified in the context of the Singlet Scalar dark matter model.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The evolution of small payload carrier systems

The design of a bridge-like structure to span the Space Shuttle cargo bay but occupy only 3 feet of its length is discussed. The new structure was named the Missions Peculiar Equipment Support Structure (MPESS). The basic design requirements were as follows: to serve as support structure for small number of experiments; to occupy the minimal length of cargo bay; to have a standard interface hole pattern; to provide support at an elevated position; to employ standard Spacelab pallet trunnion; and to ensure natural frequency between the STS liftoff and landing frequency. The bridge-like structure is a riveted and bolted truss with machind end fittings which interface with the Spacelab trunnions. The structure is fabricated from aluminum alloy and assembled with stainless steel fasteners.

Breaux, C. G.↗