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At least 1,099 records · Page 61

Continuous in vitro evolution of bacteriophage RNA polymerase promoters

Rapid in vitro evolution of bacteriophage T7, T3, and SP6 RNA polymerase promoters was achieved by a method that allows continuous enrichment of DNAs that contain functional promoter elements. This method exploits the ability of a special class of nucleic acid molecules to replicate continuously in the presence of both a reverse transcriptase and a DNA-dependent RNA polymerase. Replication involves the synthesis of both RNA and cDNA intermediates. The cDNA strand contains an embedded promoter sequence, which becomes converted to a functional double-stranded promoter element, leading to the production of RNA transcripts. Synthetic cDNAs, including those that contain randomized promoter sequences, can be used to initiate the amplification cycle. However, only those cDNAs that contain functional promoter sequences are able to produce RNA transcripts. Furthermore, each RNA transcript encodes the RNA polymerase promoter sequence that was responsible for initiation of its own transcription. Thus, the population of amplifying molecules quickly becomes enriched for those templates that encode functional promoters. Optimal promoter sequences for phage T7, T3, and SP6 RNA polymerase were identified after a 2-h amplification reaction, initiated in each case with a pool of synthetic cDNAs encoding greater than 10(10) promoter sequence variants.

Non-NASA Center↗

Reliability-Based Design Optimization of a Composite Airframe Component

A stochastic optimization methodology (SDO) has been developed to design airframe structural components made of metallic and composite materials. The design method accommodates uncertainties in load, strength, and material properties that are defined by distribution functions with mean values and standard deviations. A response parameter, like a failure mode, has become a function of reliability. The primitive variables like thermomechanical loads, material properties, and failure theories, as well as variables like depth of beam or thickness of a membrane, are considered random parameters with specified distribution functions defined by mean values and standard deviations.

Pai, Shantaram S.↗

A pilot study: Auditory steady-state responses (ASSR) can be measured in human fetuses using fetal magnetoencephalography (fMEG)

Auditory steady-state responses (ASSRs) are ongoing evoked brain responses to continuous auditory stimuli that play a role for auditory processing of complex sounds and speech perception. Transient auditory event-related responses (AERRs) have previously been recorded using fetal magnetoencephalography (fMEG) but involve different neurological pathways. Previous studies in children and adults demonstrated that the cortical components of the ASSR are significantly affected by state of consciousness and by maturational changes in neonates and young infants. To our knowledge, this is the first study to investigate ASSRs in human fetuses. 47 fMEG sessions were conducted with 24 healthy pregnant women in three gestational age groups (30–32 weeks, 33–35 weeks and 36–39 weeks). The stimulation consisted of amplitude-modulated (AM) tones with a duration of one second, a carrier frequency (CF) of 500 Hz and a modulation frequency (MF) of 27 Hz or 42 Hz. Both tones were presented in a random order with equal probability adding up to 80–100 repetitions per tone. The ASSR across trials was quantified by assessing phase synchrony in the cortical signals at the stimulation frequency. Ten out of 47 recordings were excluded due to technical problems or maternal movements. Analysis of the included 37 fetal recordings revealed a statistically significant response for the phase coherence between trials for the MF of 27 Hz but not for 42 Hz. An exploratory subgroup analysis moreover suggested an advantage in detectability for fetal behavioral state 2F (active asleep) compared to 1F (quiet asleep) detected using fetal heart rate. In conclusion, this pilot study is the first description of a method to detect human ASSRs in fetuses. The findings warrant further investigations of the developing fetal brain.

59 BASIC BIOLOGICAL SCIENCES↗

Nuclear Data Uncertainty Quantification for Adjoint-Weighted Quantities via XGPT in Monte Carlo Codes

The Total Monte Carlo method (TMC) is an innovative approach to nuclear data uncertainty propagation. In TMC, a large number of independent ENDF files are randomly generated starting from nuclear models parameters and their uncertainties. These files are then processed with NJOY or similar codes to produce a set of formatted continuous-energy cross sections (i.e., ACE files), and independent Monte Carlo neutron transport simulations are run with these different ACE files as input. Finally the distributions of the considered response functions are obtained directly from the results of the Monte Carlo runs. Despite several improvements of the TMC method, this approach is often considered an inefficient way of propagating nuclear data uncertainties, as it requires several computationally expensive Monte Carlo runs. Covariance-based methods present important advantages for several applications, especially when different sources of uncertainties are to be investigated. For this reason, sensitivity analysis and uncertainty quantification capabilities are being implemented in several Monte Carlo neutron transport codes. On the other hand, the fact that no artificial multi-group covariance matrices are required and that higher moments of the responses distributions can be easily obtained, are definite advantages of the TMC method. In an effort to overcome the limitations of both approaches, a new method, called eXtended Generalized Perturbation Theory (XGPT) is under development. When performing nuclear data uncertainty propagation, such XGPT approach does not require generating discretized (i.e., multigroup) covariance matrices, and allows to estimate higher moments of the response probability distributions, via linear perturbation theory. One of the promising applications of the XGPT method involves its adoption in conjunction with the Proper Orthogonal Decomposition (POD) of nuclear data, to build a Reduced Order Model (ROM) for the approximation of thousands of independent TMC results in a single criticality source simulation. In the present work, this approach is employed for the first time to evaluate the impact of uncertainty in nuclear data on adjoint-weighted quantities. The method has been implemented in an extended version of the Serpent-2.1.24 Monte Carlo code and is demonstrated on two fast spectrum benchmarks, focusing on {sup 208}Pb nuclear data. A new method for propagating nuclear data uncertainties in criticality source Monte Carlo simulations has been developed. This eXtended Generalized Perturbation Theory (XGPT) approach allows to accurately reproduce reference Total Monte Carlo (TMC) uncertainty estimates in a single criticality source simulation. The present work aims to demonstrate that the proposed method can quantify nuclear data uncertainty based on adjoint-weighted quantities. The XGPT approach was applied to evaluate the impact of {sup 208}Pb nuclear data uncertainties on the effective prompt neutron lifetime (l{sub eff}) in two fast spectrum systems. The obtained XGPT results show a good agreement with the reference TMC results, obtained from independent Monte Carlo runs with {sup 208}Pb nuclear data from random TENDL-2013 evaluations. The XGPT method, implemented in a extended version of the Serpent Monte Carlo code and adopted along with the Proper Orthogonal Decomposition (POD) of the nuclear data, is able to provide an accurate reduced order model to approximate thousands TMC results within a single run, ensuring a large saving in computational requirements. The effect of {sup 208}Pb nuclear data uncertainties appears to be rather large. This is consistent with previous studies that adopted the same input random evaluations data from TENDL. (authors)

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

On a framework for generating PoD curves assisted by numerical simulations

The Probability of Detection (PoD) curve method has emerged as an important tool for the assessment of the performance of NDE techniques, a topic of particular interest to the nuclear industry where inspection qualification is very important. The conventional experimental means of generating PoD curves though, can be expensive, requiring large data sets (covering defects and test conditions), and equipment and operator time. Several methods of achieving faster estimates for PoD curves using physics-based modelling have been developed to address this problem. Numerical modelling techniques are also attractive, especially given the ever-increasing computational power available to scientists today. Here we develop procedures for obtaining PoD curves, assisted by numerical simulation and based on Bayesian statistics. Numerical simulations are performed using Finite Element analysis for factors that are assumed to be independent, random and normally distributed. PoD curves so generated are compared with experiments on austenitic stainless steel (SS) plates with artificially created notches. We examine issues affecting the PoD curve generation process including codes, standards, distribution of defect parameters and the choice of the noise threshold. We also study the assumption of normal distribution for signal response parameters and consider strategies for dealing with data that may be more complex or sparse to justify this. These topics are addressed and illustrated through the example case of generation of PoD curves for pulse-echo ultrasonic inspection of vertical surface-breaking cracks in SS plates.

36 MATERIALS SCIENCE↗

Influence of metal nanocomposite morphology on Helium implantation response

This work reports on Helium (He) accumulation in novel metal nanocomposites fabricated by phase separation in three-dimensions. These nanocomposites are dense with semi-coherent interfaces that ultimately influence He implantation response. The effect of film morphology on three aspects of He response is investigated: size and distribution of He precipitates, He retention, and He-induced changes in mechanical properties. Here, transmission electron microscopy analysis showed that He bubbles agglomerated along the vertical phase boundaries in morphologies with lateral and random domains of Cu and Mo. Nuclear Reaction Analysis (NRA) and nanoindentation results show He retention and hardness is morphology dependent.

36 MATERIALS SCIENCE↗

Propagation of priors for more accurate and efficient spectroscopic functional fits and their application to ferroelectric hysteresis

Multi-dimensional spectral-imaging is a mainstay of the scanning probe and electron microscopies, micro-Raman, and various forms of chemical imaging. In many cases, individual spectra can be fit to a specific functional form, with the model parameter maps, providing direct insight into material properties. Since spectra are often acquired across a spatial grid of points, spatially adjacent spectra are likely to be similar to one another; yet, this fact is almost never used when considering parameter estimation for functional fits. On datasets tried here, we show that by utilizing proximal information, whether it be in the spatial or spectral domains, it is possible to improve the reliability and increase the speed of such functional fits by ~2-3x, as compared to random priors. We explore and compare three distinct new methods: (1) spatially averaging neighborhood spectra, and propagating priors based on functional fits to the averaged case, (2) hierarchical clustering-based methods where spectra are grouped hierarchically based on response, with the priors propagated progressively down the hierarchy, and (3) regular clustering without hierarchical methods with priors propagated from fits to cluster means. Our results highlight that utilizing spatial and spectral neighborhood information is often critical for accurate parameter estimation in noisy environments, which we show for ferroelectric hysteresis loops acquired on a prototypical PbTiO3 thin film with piezoresponse spectroscopy. This method is general and applicable to any spatially measured spectra where functional forms are available. Examples include exploring the superconducting gap with tunneling spectroscopy, using the Dynes formula, or current-voltage curve fits in conductive atomic force microscopy mapping. Here we explore the problem for ferroelectric hysteresis, which, given its large parameter space, constitutes a more difficult task than, for example, fitting current-voltage curves with a Schottky emission formula.

42 ENGINEERING↗

Complex-energy approach to sum rules within nuclear density functional theory

The linear response of the nucleus to an external field contains unique information about the effective interaction, correlations governing the behavior of the many-body system, and properties of its excited states. To characterize the response, it is useful to use its energy-weighted moments, or sum rules. By comparing computed sum rules with experimental values, the information content of the response can be utilized in the optimization process of the nuclear Hamiltonian or nuclear energy density functional (EDF). But the additional information comes at a price: compared to the ground state, computation of excited states is more demanding. To establish an efficient framework to compute energy-weighted sum rules of the response that is adaptable to the optimization of the nuclear EDF and large-scale surveys of collective strength, we have developed a new technique within the complex-energy finite-amplitude method (FAM) based on the quasiparticle random- phase approximation. The proposed sum-rule technique based on the complex-energy FAM is a tool of choice when optimizing effective interactions or energy functionals. The method is very efficient and well-adaptable to parallel computing. As a result, the FAM formulation is especially useful when standard theorems based on commutation relations involving the nuclear Hamiltonian and external field cannot be used.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Reducing motion sickness - A comparison of autogenic-feedback training and an alternative cognitive task

Eighteen men were randomly assigned to three groups matched for susceptibility to Coriolis motion sickness. All subjects were given six Coriolis Sickness Susceptibility Index (CSSI) tests separated by 5-d intervals. Treatment Group I subjects were taught to control their own autonomic responses before the third, fourth, and fifth CSSI tests (6 h total training). Group II subjects were given 'sham' training in an alternative cognitive task under conditions otherwise identical to those of Group I. Group III subjects received no treatment. Results showed that Group I subjects could withstand the stress of Coriolis acceleration significantly longer after training. Neither of the other two groups changed significantly.

Toscano, W. B.↗

System identification of the Large-Angle Magnetic Suspension Test Facility (LAMSTF)

The Large-Angle Magnetic Suspension Test Facility (LAMSTF), a laboratory-scale research project to demonstrate the magnetic suspension of objects over wide ranges of attitudes, has been developed. This system represents a scaled model of a planned Large-Gap Magnetic Suspension System (LGMSS). The LAMSTF system consists of a planar array of five copper electromagnets which actively suspend a small cylindrical permanent magnet. The cylinder is a rigid body and can be controlled to move in five independent degrees of freedom. Five position variables are sensed indirectly by using infra-red light-emitting diodes and light-receiving phototransistors. The motion of the suspended cylinder is in general nonlinear and hence only the linear, time-invariant perturbed motion about an equilibrium state is considered. One of the main challenges in this project is the control of the suspended element over a wide range of orientations. An accurate dynamic model plans an essential role in controller design. The analytical model of the LAMSTF system includes highly unstable real poles (about 10 Hz) and low-frequency flexible modes (about 0.16 Hz). Projection filters are proposed to identify the state space model from closed-loop test data in time domain. A canonical transformation matrix is also derived to transform the identified state space model into the physical coordinate. The LAMSTF system is stabilized by using a linear quadratic regulator (LQR) feedback controller. The rate information is obtained by calculating the back difference of the sensed position signals. The reference inputs contain five uncorrelated random signals. This control input and the system reponse are recorded as input/output data to identify the system directly from the projection filters. The sampling time is 4 ms and the model is fairly accurate in predicting the step responses for different controllers while the analytical model has a deficiency in the pitch axis.

Huang, Jen-Kuang↗

Micromechanics-based Modeling of Laminated SiC/SiC Ceramic Matrix Composites

The behavior and response of ceramic matrix composites (CMCs), in particular silicon carbide fiber reinforced silicon carbide matrix (SiC/SiC), is affected by many factors such as variation of fiber volume fraction, residual stresses resulting from processing of the composites at high temperature, random microstructures, and the presence of matrix flaws (e.g., voids, pores, cracks etc.) as well as general material nonlinearity and heterogeneity that occurs randomly in a composite. Residual stresses arising from the phase change of constituents are evaluated in this paper and it is shown that they do influence composite strength and need to be properly accounted for. Additionally, the microstructures (location of fiber centers, coating thickness etc.) of advanced CMCs are usually disordered (or random) and fiber diameter and strength typically have a distribution. They rarely resemble the ordered fiber packing (square, rectangular, or hexagonal) that is generally assumed in micromechanics-based models with periodic boundary conditions for computational expediency. These issues raise the question of how should one model such systems effectively? Can an ordered hexagonal packed repeating unit cell (RUC) accurately represent the random microstructure behavior? How many fibers need to be included to enable accurate representation? Clearly, the number of fibers within an RUC must be limited to insure a balance between accuracy and efficiency. NASA’s in-house micromechanics-based code MAC/GMC provides a framework to analyze such RUCs for the overall composite behavior and the FEAMAC computer code provides linkage of MAC/GMC to the commercial FEA code, ABAQUS. The appropriate level of discretization of the RUC as well as the analysis method employed, i.e., Generalized Method of Cells (GMC) or High Fidelity Generalized Method of Cells (HFGMC), is investigated in this paper in the context of a unidirectional as well as a cross-ply laminated CMC. Results including effective composite properties, proportional limit stress (an important design parameter) and fatigue are shown utilizing both GMC as well as HFGMC. Finally, a few multiscale analyses are performed on smooth bar test coupons as well as test coupons with features such as open-hole and double notches using FEAMAC. Best practices and guidance are provided to take these phenomena into account and keep a proper balance between fidelity (accuracy) and efficiency. Following these guidelines can account for important physics of the problem and provide significant advantages when performing large multiscale composite structural analyses.

Ceramic Matrix Composites↗

Sparse Bayesian Regression with Integrated Feature Selection for Nuclear Reactor Analysis

High-dimensional, nonlinear function estimation using large datasets is a current area of interest in the machine learning community, and applications may be found throughout the analytical sciences, where ever-growing datasets are making more information available to the analyst. In this paper, we leverage the existing relevance vector machine, a sparse Bayesian version of the well-studied support vector machine, and expand the method to include integrated feature selection and automatic function shaping. These innovations produce an algorithm that is able to distinguish variables that are useful for making predictions of a response from variables that are unrelated or confusing. We test the technology using synthetic data, conduct initial performance studies, and develop a model capable of making position-independent predictions of the coreaveraged burnup using a single specimen drawn randomly from a nuclear reactor core.

Dayman, Ken J↗

3D printable feedstock inks for signal control or computation

A 3D printable feedstock ink is disclosed for use in a 3D printing process where the ink is flowed through a printing nozzle. The ink may be made up of a non-conductive flowable material and a plurality of chiplets contained in the non-conductive flowable material in random orientations. The chiplets may form a plurality of percolating chiplet networks within the non-conductive flowable material as ones of the chiplets contact one another. Each one of the chiplets has a predetermined circuit characteristic which is responsive to a predetermined electrical signal, and which becomes electrically conductive when the predetermined electrical signal is applied to the ink, to thus form at least one conductive signal path through the ink.

Murialdo, Maxwell↗

Active Control of the Forced and Transient Response of a Finite Beam

When studying structural vibrations resulting from a concentrated source, many structures may be modelled as a finite beam excited by a point source. The theoretical limit on cancelling the resulting beam vibrations by utilizing another point source as an active controller is explored. Three different types of excitation are considered, harmonic, random, and transient. In each case, a cost function is defined and minimized for numerous parameter variations. For the case of harmonic excitation, the cost function is obtained by integrating the mean squared displacement over a region of the beam in which control is desired. A controller is then found to minimize this cost function in the control interval. The control interval and controller location are continuously varied for several frequencies of excitation. The results show that control over the entire beam length is possible only when the excitation frequency is near a resonant frequency of the beam, but control over a subregion may be obtained even between resonant frequencies at the cost of increasing the vibration outside of the control region. For random excitation, the cost function is realized by integrating the expected value of the displacement squared over the interval of the beam in which control is desired. This is shown to yield the identical cost function as obtained by integrating the cost function for harmonic excitation over all excitation frequencies. As a result, it is always possible to reduce the cost function for random excitation whether controlling the entire beam or just a subregion, without ever increasing the vibration outside the region in which control is desired. The last type of excitation considered is a single, transient pulse. A cost function representative of the beam vibration is obtained by integrating the transient displacement squared over a region of the beam and over all time. The form of the controller is chosen a priori as either one or two delayed pulses. Delays constrain the controller to be causal. The best possible control is then examined while varying the region of control and the controller location. It is found that control is always possible using either one or two control pulses. The two pulse controller gives better performance than a single pulse controller, but finding the optimal delay time for the additional controllers increases as the square of the number of control pulses.

Post, John Theodore↗

Sequence-defined structural transitions by calcium-responsive proteins

Biopolymer sequences dictate their functions, and protein-based polymers are a promising platform to establish sequence–function relationships for novel biopolymers. To efficiently explore vast sequence spaces of natural proteins, sequence repetition is a common strategy to tune and amplify specific functions. This strategy is applied to repeats-in-toxin (RTX) proteins with calcium-responsive folding behavior, which stems from tandem repeats of the nonapeptide GGXGXDXUX in which X can be any amino acid and U is a hydrophobic amino acid. To determine the functional range of this nonapeptide, we modified a naturally occurring RTX protein that forms β-roll structures in the presence of calcium. Sequence modifications focused on calcium-binding turns within the repetitive region, including either global substitution of nonconserved residues or complete replacement with tandem repeats of a consensus nonapeptide GGAGXDTLY. Some sequence modifications disrupted the typical transition from intrinsically disordered random coils to folded β rolls, despite conservation of the underlying nonapeptide sequence. Proteins enriched with smaller, hydrophobic amino acids adopted secondary structures in the absence of calcium and underwent structural rearrangements in calcium-rich environments. In contrast, proteins with bulkier, hydrophilic amino acids maintained intrinsic disorder in the absence of calcium. In conclusion, these results indicate a significant role of nonconserved amino acids in calcium-responsive folding, thereby revealing a strategy to leverage sequences in the design of tunable, calcium-responsive biopolymers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The Impact of Nonequilibrium Ionization on SDO/AIA and Hinode/EIS Observations of Impulsively Heated Plasmas

Most plasma diagnostics assume the emitting material is in a state of ionization equilibrium. For example, the AIA temperature response functions have been derived on this basis. The assumption is reasonable whenever the plasma is evolving slowly or is very dense, but these are not the conditions that apply during impulsive heating events. It is now widely believed that many coronal loops are bundles of unresolved strands that are heated quasi-randomly by nanoflares. Full blown flares are thought to have similar sub-structure. We have studied the importance of nonequilibrium effects in these circumstances by modeling nanoflare-heated loops and simulating their observation by AIA and the EIS spectrometer on Hinode. We find that the intensities of hot emission lines can be highly suppressed and that the net emission from the loop tends to be dominated by strands that have entered a slow cooling phase, well after the impulsive energy release has ended. The hottest strands are relatively invisible, both because they are tenuous and because they cool rapidly by thermal conduction. Thus, AIA channels that are normally thought of as being sensitive to hot plasma, such 131 and 94, are in fact frequently not able to detect the hot plasma that is present. The magnitude of the effect is case dependent. Great care must be exercised when using the standard temperature response functions in situations where nonequilibrium ionization is likely to be important.

Klimchuk, James A.↗

Sequence Programmable Order–Disorder Transitions in Supramolecular Assembly of Peptide Nanofibers

Protein–protein interactions determine the assembly of complexes that are responsible for numerous key biological processes. The assembly of many natural protein complexes is mediated by post-translational structural changes and environmental stimuli. In this study, we show that incorporation of adjacent lysine residues results in the pH-tunable stability of peptide secondary structure and assembly, allowing for the incorporation of complementary order-inducing motifs. The strategic placement of cysteine pairs in the same peptide sequence results in redox-dependent disulfide staple formation, inducing a transition from random coil to β-sheet conformation and subsequent supramolecular nanofiber assembly from otherwise disordered peptide monomers. Spectroscopic, imaging, molecular dynamics, and kinetic studies highlight the critical role of sequence motif location, oligomerization, and the competitive interplay between intra- and interpeptide disulfide bonding in determining assembly outcomes. We extend this approach to demonstrate phosphorylation-dependent assembly from the design of the same parent peptide sequence, suggesting a general approach to the design of diverse stimulus-responsive peptide sequences for supramolecular assembly. Furthermore, these findings also provide a framework for investigating sequence-dependent pathways in amyloid fiber formation with potential implications for neurodegenerative disease research.

Disulfides↗

Calculation of Dose Deposition in 3D Voxels by Heavy Ions and Simulation of gamma-H2AX Experiments

The biological response to high-LET radiation is different from low-LET radiation due to several factors, notably difference in energy deposition and formation of radiolytic species. Of particular importance in radiobiology is the formation of double-strand breaks (DSB), which can be detected by -H2AX foci experiments. These experiments has revealed important differences in the spatial distribution of DSB induced by low- and high-LET radiations [1,2]. To simulate -H2AX experiments, models based on amorphous track with radial dose are often combined with random walk chromosome models [3,4]. In this work, a new approach using the Monte-Carlo track structure code RITRACKS [5] and chromosome models have been used to simulate DSB formation. At first, RITRACKS have been used to simulate the irradiation of a cubic volume of 5 m by 1) 450 1H+ ions of 300 MeV (LET 0.3 keV/ m) and 2) by 1 56Fe26+ ion of 1 GeV/amu (LET 150 keV/ m). All energy deposition events are recorded to calculate dose in voxels of 20 m. The dose voxels are distributed randomly and scattered uniformly within the volume irradiated by low-LET radiation. Many differences are found in the spatial distribution of dose voxels for the 56Fe26+ ion. The track structure can be distinguished, and voxels with very high dose are found in the region corresponding to the track "core". These high-dose voxels are not found in the low-LET irradiation simulation and indicate clustered energy deposition, which may be responsible for complex DSB. In the second step, assuming that DSB will be found only in voxels where energy is deposited by the radiation, the intersection points between voxels with dose > 0 and simulated chromosomes were obtained. The spatial distribution of the intersection points is similar to -H2AX foci experiments. These preliminary results suggest that combining stochastic track structure and chromosome models could be a good approach to understand radiation-induced DSB and chromosome aberrations.

Plante, I.↗