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At least 145 records · Page 8

Solvent friction effects propagate over the entire protein molecule through low-frequency collective modes

Protein solvation dynamics has been investigated using atom-dependent Langevin friction coefficients derived directly from molecular dynamics (MD) simulations. To determine the effect of solvation on the atomic friction coefficients, solution and vacuum MD simulations were performed for lysozyme and staphylococcal nuclease and analyzed by Langevin mode analysis. The coefficients thus derived are roughly correlated with the atomic solvent-accessible surface area (ASA), as expected from the fact that friction occurs as the result of collisions with solvent molecules. However, a considerable number of atoms with higher friction coefficients are found inside the core region. Hence, the influence of solvent friction propagates into the protein core. The internal coefficients have large contributions from the low-frequency modes, yielding a simple picture of the surface-to-core long-range damping via solvation governed by collective low-frequency modes. To make use of these findings in implicit-solvent modeling, we compare the all-atom friction results with those obtained using Langevin dynamics (LD) with two empirical representations: the constant-friction and the ASA-dependent (Pastor Karplus) friction models. The constant-friction model overestimates the core and underestimates the surface damping whereas the ASA-dependent friction model, which damps protein atoms only on the solvent-accessible surface, reproduces well the friction coefficients for both the surface and core regions observed in the explicit-solvent MD simulations. Furthermore, in LD simulation, the solvent friction coefficients should be imposed only on the protein surface.

59 BASIC BIOLOGICAL SCIENCES↗

A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline

Abstract Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 10 7 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Photon-counting 1.0 GHz-phase-modulation fluorometer

We have constructed an improved version of a photon-counting phase-modulation fluorometer (PC-PMF) with a maximum modulation frequency of 1.0 GHz, where a phase domain measurement is conducted with a time-correlated single-photon-counting electronics. While the basic concept of the PC-PMF has been reported previously by one of the authors, little attention has been paid to its significance, other than its weak fluorescence measurement capability. Recently, we have recognized the importance of the PC-PMF and its potential for fluorescence lifetime measurements. One important aspect of the PC-PMF is that it enables us to perform high-speed measurements that exceed the frequency bandwidths of the photomultiplier tubes that are commonly used as fluorescence detectors. We describe the advantages of the PC-PMF and demonstrate its usefulness based on fundamental performance tests. In our new version of the PC-PMF, we have used a laser diode (LD) as an excitation light source rather than the light-emitting diode that was used in the primary version. We have also designed a simple and stable LD driver to modulate the device. Additionally, we have obtained a sinusoidal histogram waveform that has multiple cycles within a time span to be measured, which is indispensable for precise phase measurements. With focus on the fluorescence intensity and the resolution time, we have compared the performance of the PC-PMF with that of a conventional PMF using the analogue light detection method.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Competitive behavior of photons contributing to junction voltage jump in narrow band-gap semiconductor multi-quantum-well laser diodes at lasing threshold

The junction behavior of different narrow band-gap multi-quantum-well (MQW) laser diodes (LDs) confirmed that the jump in the junction voltage in the threshold region is a general characteristic of narrow band-gap LDs. The relative change in the 1310 nm LD is the most obvious. To analyze this sudden voltage change, the threshold region is divided into three stages by I{sub th}{sup l} and I{sub th}{sup u}, as shown in Fig. 2; I{sub th}{sup l} is the conventional threshold, and as long as the current is higher than this threshold, lasing exists and the IdV/dI-I plot drops suddenly; I{sub th}{sup u} is the steady lasing point, at which the separation of the quasi-Fermi levels of electron and holes across the active region (V{sub j}) is suddenly pinned. Based on the evolutionary model of dissipative structure theory, the rate equations of the photons in a single-mode LD were deduced in detail at I{sub th}{sup l} and I{sub th}{sup u}. The results proved that the observed behavior of stimulated emission suddenly substituting for spontaneous emission, in a manner similar to biological evolution, must lead to a sudden increase in the injection carriers in the threshold region, which then causes the sudden increase in the junction voltage in this region.

36 MATERIALS SCIENCE↗

Molecular simulations and lattice dynamics determination of Stillinger-Weber GaN thermal conductivity

The bulk thermal conductivity of Stillinger-Weber (SW) wurtzite GaN in the [0001] direction at a temperature of 300 K is calculated using equilibrium molecular dynamics (EMD), non-equilibrium MD (NEMD), and lattice dynamics (LD) methods. While the NEMD method predicts a thermal conductivity of 166 ± 11 W/m·K, both the EMD and LD methods predict thermal conductivities that are an order of magnitude greater. We attribute the discrepancy to significant contributions to thermal conductivity from long-mean free path phonons. We propose that the Grüneisen parameter for low-frequency phonons is a good predictor of the severity of the size effects in NEMD thermal conductivity prediction. For weakly anharmonic crystals characterized by small Grüneisen parameters, accurate determination of thermal conductivity by NEMD is computationally impractical. The simulation results also indicate the GaN SW potential, which was originally developed for studying the atomic-level structure of dislocations, is not suitable for prediction of its thermal conductivity.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

INDETERMINATE1 -mediated expression of FT family genes is required for proper timing of flowering in Brachypodium distachyon

The transition to flowering is a major developmental switch in plants. In many temperate grasses, perception of indicators of seasonal change, such as changing day-length and temperature, leads to expression of FLOWERING LOCUS T1 ( FT1 ) and FT-Like ( FTL ) genes that are essential for promoting the transition to flowering. However, little is known about the upstream regulators of FT1 and FTL genes in temperate grasses. Here, we characterize the monocot-specific gene INDETERMINATE1 ( BdID1 ) in Brachypodium distachyon and demonstrate that BdID1 is a regulator of FT family genes. Mutations in ID1 impact the ability of the short-day (SD) vernalization, cold vernalization, and long-day (LD) photoperiod pathways to induce certain FTL genes. BdID1 is required for upregulation of FTL9 ( FT-LIKE9 ) expression by the SD vernalization pathway, and overexpression of FTL9 in an id1 background can partially restore the delayed flowering phenotype of id1 . We show that BdID1 binds in vitro to the promoter region of FTL genes suggesting that ID1 directly activates FTL expression. Transcriptome analysis shows that BdID1 is required for FT1 , FT2 , FTL12 , and FTL13 expression under inductive LD photoperiods, indicating that BdID1 is a regulator of the FT gene family. Moreover, overexpression of FT1 in the id1 background results in rapid flowering similar to overexpressing FT1 in the wild type, demonstrating that BdID1 is upstream of FT family genes. Interestingly, ID1 negatively regulates a previously uncharacterized FTL gene, FTL4, and we show that FTL4 is a repressor of flowering. Thus, BdID1 is critical for proper timing of flowering in temperate grasses.

59 BASIC BIOLOGICAL SCIENCES↗

A Fourier transform method for Vsin i estimations under nonlinear Limb-Darkening laws

Star rotation offers us a large horizon for the study of many important physical issues pertaining to stellar evolution. Currently, four methods are widely used to infer rotation velocities, namely those related to line width calibrations, on the fitting of synthetic spectra, interferometry, and on Fourier transforms (FTs) of line profiles. Almost all of the estimations of stellar projected rotation velocities using the Fourier method in the literature have been addressed with the use of linear limb-darkening (LD) approximations during the evaluation of rotation profiles and their cosine FTs, which in certain cases, lead to discrepant velocity estimates. In this work, we introduce new mathematical expressions of rotation profiles and their Fourier cosine transforms assuming three nonlinear LD laws—quadratic, square-root, and logarithmic—and study their applications with and without gravity-darkening (GD) and geometrical flattening (GF) effects. Through an analysis of He I models in the visible range accounting for both limb and GD, we find out that, for classical models without rotationally driven effects, all the Vsin i values are too close to each other. On the other hand, taking into account GD and GF, the Vsin i obtained with the linear law result in Vsin i values that are systematically smaller than those obtained with the other laws. As a rule of thumb, we apply these expressions to the FT method to evaluate the projected rotation velocity of the emission B-type star Achernar (α Eri).

79 ASTRONOMY AND ASTROPHYSICS↗

Ontobee: A linked ontology data server to support ontology term dereferencing, linkage, query and integration

Linked Data (LD) aims to achieve interconnected data by representing entities using Unified Resource Identifiers (URIs), and sharing information using Resource Description Frameworks (RDFs) and HTTP. Ontologies, which logically represent entities and relations in specific domains, are the basis of LD. Ontobee (http://www.ontobee.org/) is a linked ontology data server that stores ontology information using RDF triple store technology and supports query, visualization and linkage of ontology terms. Ontobee is also the default linked data server for publishing and browsing biomedical ontologies in the Open Biological Ontology (OBO) Foundry (http://obofoundry.org) library. Ontobee currently hosts more than 180 ontologies (including 131 OBO Foundry Library ontologies) with over four million terms. Ontobee provides a user-friendly web interface for querying and visualizing the details and hierarchy of a specific ontology term. Using the eXtensible Stylesheet Language Transformation (XSLT) technology, Ontobee is able to dereference a single ontology term URI, and then output RDF/eXtensible Markup Language (XML) for computer processing or display the HTML information on a web browser for human users. Statistics and detailed information are generated and displayed for each ontology listed in Ontobee. In addition, a SPARQL web interface is provided for custom advanced SPARQL queries of one or multiple ontologies.

97 MATHEMATICS AND COMPUTING↗

Singlets lead to photogeneration in C 60 -based organic heterojunctions

Two independent and direct measurements of exciton transport in the fullerene C 60 unambiguously indicate that singlets are responsible for energy transport and ultimately charge generation in organic photovoltaic cells. The singlet exciton diffusion length, LD was measured using fits to the external quantum efficiency of planar heterojunction photovoltaics, and via C 60 fluorescence, giving a mean value of 34 ± 3nm. Direct measurement of the C 60 singlet state transient fluorescence decay gives a lifetime of 590 ± 10ps, from which we infer a diffusivity of 0.020 ± 0.004 cm 2 /s. Furthermore, this is at least ten times that typical for organics, which we attribute to the spherical symmetry of the C 60 molecule that promotes highly efficient exciton transfer. Further, LD is used to determine that the C 60 energy gap is 18 ± 5meV larger than the analogous fullerene C 70 .

36 MATERIALS SCIENCE↗

Calibration of coronary calcium scores determined using iterative image reconstruction (AIDR 3D) at 120, 100, and 80 kVp

Purpose: Computed tomography (CT) radiation dose reduction is frequently achieved by applying lower tube voltages and using iterative reconstruction (IR). For calcium scoring, the reference protocol at 120 kVp with filtered back projection (FBP) is still used, because kVp and IR may influence the Agatston score (AS) and volume score (VS). The authors present a two-step method to optimize dose: first, to determine the lowest feasible exposure and highest noise thresholds; second, to define a calibration method that ensures that the AS and VS are similar to the reference protocol. Methods: AS and VS were measured for an anthropomorphic thoracic phantom that includes a calcium calibration module. The phantom was scanned on a 320-row CT scanner, at tube voltages of 120 kVp using FBP, and 120, 100, and 80 kVp using adaptive iterative dose reduction (AIDR 3D) reconstruction. The minimum CTDIs were determined based on three objective quality criteria. Calibration was performed to estimate adjusted CT number thresholds for the lower kVp acquisitions. Finally, the accuracies of the total and individual insert scores at dose level close to the minimum CTDI level were investigated and compared to low (FBP{sub LD} − 120) and high (FBP{sub HD} − 120) dose reference protocols (based on ten repeated acquisitions for each group). Results: IR allows the exposure to be reduced by 69% at 120 kVp, with no significant effect on the total scores when averaged over all included dose steps and compared to FBP-120 (AS: 693 vs 699, p = 0.182; VS: 588 vs 587 mm{sup 3}, p = 0.569). Also when averaged over ten repeated scans and compared to FBP{sub HD} − 120 (AS: 709 vs 704, p = 0.435; VS: 604 vs 601 mm{sup 3}, p = 0.479), there is no statistical significant effect. Reducing the peak tube voltage allows even greater dose reductions: 73% at 100 kVp and 76% at 80 kVp. The calibrated CT number thresholds for analysis at 120, 100, and 80 kVp were, respectively, 130, 133, and 160 HU for the Agatston score, and 130, 132, and 140 HU for the volume score. Following the calibration, the mean scores of the four groups with dose variation were not significantly different from the reference protocol, at 100 kVp (AS: 698 vs 699, p = 0.818; VS: 584 vs 587 mm{sup 3}, p = 0.365) or at 80 kVp (AS: 698 vs 699, p = 0.996; VS: 586 vs 587 mm{sup 3}, p = 0.827). Similarly, there was no significant score difference with FBP{sub LD} − 120 during repeated scanning: 100 kVp (AS: 690 vs 694, p = 0.394; VS: 579 vs 585 mm{sup 3}, p = 0.168) and 80 kVp (AS: 703 vs 694, p = 0.115; VS: 588 vs 585 mm{sup 3}, p = 0.613). Compared to FBP{sub HD} − 120 group, the relative score deviation for the accuracy of the 400 and 800 mg/cm{sup 3} HA inserts with 3 and 5 mm diameter is less than 7%. However, the relative deviation of the smaller 1 mm inserts is poorer (up to 41% deviations for scores <3). Conclusions: With iterative reconstruction using AIDR 3D, deviations of the total Agatston and volume scores remain within 4% of the reference protocol. The 1 mm inserts were detected as calcification, but scores less than ten tend to be underestimated. Following the calibration process, the application of IR in combination with reduced tube voltages allows up to 76% lower radiation dose.

60 APPLIED LIFE SCIENCES↗

Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here) from the protein distribution densities in the LD space defined by ln( L ) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.

59 BASIC BIOLOGICAL SCIENCES↗

Assessment of Knowledge, Attitudes, and Practices Toward Ticks and Tickborne Disease among Healthcare Professionals Working in Schools in New York and Maryland

Healthcare Professionals Working in Schools (HPWS) are responsible for providing health services to students and play a role in providing education to prevent illnesses, including tickborne diseases (TBD). Providing TBD education to children has been shown to increase prevention behaviors and knowledge of TBD symptoms, but little is known regarding the current state of TBD awareness among HPWS. In spring 2019 we conducted a cross-sectional knowledge, attitudes, and practices (KAP) survey of HPWS in two states with a high incidence of Lyme disease (LD) to inform design of TBD prevention programs. The survey queried general knowledge of TBDs, school practices regarding TBDs, and availability of TBD resources. Overall, higher confidence, experience, risk perception, prior training on TBD, and more years employed as a HPWS were independently associated with knowledge of LD transmission, symptoms, and correct tick removal practices. State and local health departments should consider prioritizing engagement with HPWS to provide educational opportunities about tickborne diseases.

Nursing↗

Structure-informed clustering for population stratification in association studies

Background: Identifying variants associated with complex traits is a challenging task in genetic association studies due to linkage disequilibrium (LD) between genetic variants and population stratification, unrelated to the disease risk. Existing methods of population structure correction use principal component analysis or linear mixed models with a random effect when modeling associations between a trait of interest and genetic markers. However, due to stringent significance thresholds and latent interactions between the markers, these methods often fail to detect genuinely associated variants. Results: To overcome this, we propose CluStrat, which corrects for complex arbitrarily structured populations while leveraging the linkage disequilibrium induced distances between genetic markers. It performs an agglomerative hierarchical clustering using the Mahalanobis distance covariance matrix of the markers. In simulation studies, we show that our method outperforms existing methods in detecting true causal variants. Applying CluStrat on WTCCC2 and UK Biobank cohorts, we found biologically relevant associations in Schizophrenia and Myocardial Infarction. CluStrat was also able to correct for population structure in polygenic adaptation of height in Europeans. Conclusions: CluStrat highlights the advantages of biologically relevant distance metrics, such as the Mahalanobis distance, which captures the cryptic interactions within populations in the presence of LD better than the Euclidean distance.

59 BASIC BIOLOGICAL SCIENCES↗

Association mapping in sunflower ( Helianthus annuus L.) reveals independent control of apical vs. basal branching

Background - Shoot branching is an important determinant of plant architecture and influences various aspects of growth and development. Selection on branching has also played an important role in the domestication of crop plants, including sunflower ( Helianthus annuus L.). Here, we describe an investigation of the genetic basis of variation in branching in sunflower via association mapping in a diverse collection of cultivated sunflower lines. Results - Detailed phenotypic analyses revealed extensive variation in the extent and type of branching within the focal population. After correcting for population structure and kinship, association analyses were performed using a genome-wide collection of SNPs to identify genomic regions that influence a variety of branching-related traits. This work resulted in the identification of multiple previously unidentified genomic regions that contribute to variation in branching. Genomic regions that were associated with apical and mid-apical branching were generally distinct from those associated with basal and mid-basal branching. Homologs of known branching genes from other study systems (i.e., Arabidopsis , rice, pea, and petunia) were also identified from the draft assembly of the sunflower genome and their map positions were compared to those of associations identified herein. Numerous candidate branching genes were found to map in close proximity to significant branching associations. Conclusions - In sunflower, variation in branching is genetically complex and overall branching patterns (i.e., apical vs. basal) were found to be influenced by distinct genomic regions. Moreover, numerous candidate branching genes mapped in close proximity to significant branching associations. Although the sunflower genome exhibits localized islands of elevated linkage disequilibrium (LD), these non-random associations are known to decay rapidly elsewhere. The subset of candidate genes that co-localized with significant associations in regions of low LD represents the most promising target for future functional analyses.

Apical dominance↗

PHYTOCHROME C regulation of photoperiodic flowering via PHOTOPERIOD1 is mediated by EARLY FLOWERING 3 in Brachypodium distachyon

Daylength sensing in many plants is critical for coordinating the timing of flowering with the appropriate season. Temperate climate-adapted grasses such as Brachypodium distachyon flower during the spring when days are becoming longer. The photoreceptor PHYTOCHROME C is essential for long-day (LD) flowering in B. distachyon. PHYC is required for the LD activation of a suite of genes in the photoperiod pathway including PHOTOPERIOD1 (PPD1) that, in turn, result in the activation of FLOWERING LOCUS T (FT1)/FLORIGEN, which causes flowering. Thus, B. distachyon phyC mutants are extremely delayed in flowering. Here we show that PHYC-mediated activation of PPD1 occurs via EARLY FLOWERING 3 (ELF3), a component of the evening complex in the circadian clock. The extreme delay of flowering of the phyC mutant disappears when combined with an elf3 loss-of-function mutation. Moreover, the dampened PPD1 expression in phyC mutant plants is elevated in phyC/elf3 mutant plants consistent with the rapid flowering of the double mutant. We show that loss of PPD1 function also results in reduced FT1 expression and extremely delayed flowering consistent with results from wheat and barley. Additionally, elf3 mutant plants have elevated expression levels of PPD1, and we show that overexpression of ELF3 results in delayed flowering associated with a reduction of PPD1 and FT1 expression, indicating that ELF3 represses PPD1 transcription consistent with previous studies showing that ELF3 binds to the PPD1 promoter. Indeed, PPD1 is the main target of ELF3-mediated flowering as elf3/ppd1 double mutant plants are delayed flowering. Our results indicate that ELF3 operates downstream from PHYC and acts as a repressor of PPD1 in the photoperiod flowering pathway of B. distachyon.

60 APPLIED LIFE SCIENCES↗

Turbulent Flame Propagation Characteristics of High Hydrogen Content Fuels

This final report describes the results of an effort to better understand turbulent flame propagation, especially at conditions relevant to gas turbines employing fuels with syngas or hydrogen mixtures. Turbulent flame speeds were measured for a variety of hydrogen/carbon monoxide (H 2 /CO) and hydrogen/methane (H 2 /CH 4 ) fuel mixtures with air as the oxidizer. The measurements include global consumption speeds (S T,GC ) acquired in a turbulent jet flame at pressures of 1-10 atm and local displacement speeds (S T,LD ) acquired in a low-swirl burner at atmospheric pressure. The results verify the importance of fuel composition in determining turbulent flame speeds. For example, different fuel-air mixtures having the same unstretched laminar flame speed (S L,0 ) but different fuel compositions resulted in significantly different ST,GC for the same turbulence levels (u'). This demonstrates the weakness of turbulent flame speed correlations based simply on u'/S L,0 . The results were analyzed using a steady-steady leading points concept to explain the sensitivity of turbulent burning rates to fuel (and oxidizer) composition. Leading point theories suggest that the premixed turbulent flame speed is controlled by the flame front characteristics at the flame brush leading edge, or, in other words, by the flamelets that advance farthest into the unburned mixture (the so-called leading points). For negative Markstein length mixtures, this is assumed to be close to the maximum stretched laminar flame speed (S L,max ) for the given fuel-oxidizer mixture. For the S T,GC measurements, the data at a given pressure were well-correlated with an SL,max scaling. However the variation with pressure was not captured, which may be due to non-quasi-steady effects that are not included in the current model. For the S T,LD data, the leading points model again faithfully captured the variation of turbulent flame speed over a wide range of fuel-compositions and turbulence intensities. These results provide evidence that the leading points model can provide useful predictions of turbulent flame speed over a wide range of operating conditions and flow geometries.

20 FOSSIL-FUELED POWER PLANTS↗

Materials 2018 Annual Progress Report

The Materials Technology Program supports the Vehicles Technologies Office’s mission to help consumers and businesses reduce their transportation energy costs while meeting or exceeding vehicle performance expectations. The propulsion materials research portfolio seeks to develop higher performance materials that can withstand increasingly extreme environments and address the future properties needs of a variety of high-efficiency powertrain types, sizes, fueling concepts, and combustion modes. Advanced lightweight materials enable improvements in fuel economy by providing properties that are equal to or better than traditional materials at a lower weight. Because it takes less energy to accelerate a lighter object, replacing cast-iron and traditional steel components with lightweight materials such as high-strength steel, magnesium (Mg), aluminum (Al), and polymer composites can directly reduce a vehicle’s fuel consumption. Materials technology activities focus on the following cost and performance targets: (1) enable a 25% weight reduction for light-duty (LD) vehicles including body, chassis, and interior as compared to a model year 2012 baseline at no more than a $\$$5/lb-saved increase in cost; and (2) validate a 25% improvement in high-temperature (300°C) development of engine exhaust catalyst materials strength relative to components made with 2010 baseline cast Al alloys (A319 or A356) for improved efficiency LD engines.

33 ADVANCED PROPULSION SYSTEMS↗