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At least 55 records · Page 3

WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)

60 APPLIED LIFE SCIENCES↗

WE-DE-202-03: Modeling of Biological Processes - What Happens After Early Molecular Damage?

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)

60 APPLIED LIFE SCIENCES↗

Four-dimensional dynamics of multirotational transition stimulated rotational Raman scattering in air

Stimulated rotational Raman scattering in air is a powerful parasitic process that degrades high intensity laser beams and pulses propagated over significant distances. Conversely, it is used beneficially in the context of Raman lasers. Through this inelastic scattering process, laser photons are converted to higher (anti-Stokes) or lower (Stokes) energies, according to rotational mode transitions in nitrogen and oxygen diatomic molecules. The full wave-mixing problem involves numerous frequencies, and it is consistently assumed that only one rotational mode contributes to the conversion process. We instead present a dynamic 4D multirotational model that is implemented in a parallelized manner within the Virtual Beamline++ optical modeling package allowing high-resolution 4D studies. We highlight the effect that spontaneous emission plays in large and small beam-width setups, even in the highly saturating regime. The weaker transition modes play a large role in the persistent dynamics and can lead to complex spatiotemporal coupling through nonlinear competition of the modes. We highlight how and why these weaker modes persist, how the size and shape of speckle patterns depends highly on the initial beam profile, and how weaker modes can transiently become stronger as a result of such competition.

47 OTHER INSTRUMENTATION↗

Exposure to ionizing radiation disrupts normal epigenetic aging in Japanese medaka

Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome (“epigenetic aging”) can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka (Oryzias latipes). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.

60 APPLIED LIFE SCIENCES↗

Direct Writing of X-ray Gratings Using Zone-Plate-Array Lithography (ZPAL)

With the objective of providing the synchrotron and free-electron-laser communities with rapid turnaround and low prices for the highest quality and most advanced gratings and diffractive-focusing optics, LumArray has made specific improvements to its ZP-150 maskless photolithography system, which is based on Zone-Plate-Array Lithography (ZPAL), a technology unique to Lumarray. ZPAL’s advantages include an ability to correct in software for systematic patterning errors. Emphasis was placed on interferometric measurements of various contributors to patterning errors using Fizeau interferometry and a Mireau technique that was developed specifically for measuring errors within a micron-scale area. Average line-placement error was reduced below 20 nm using both pattern-file distortion and address-grid modification. The preferred implementation, address-grid modification, is hardware-based and requires no user intervention while also correcting more types of error. With continued iteration and refinement of the error measurements, we anticipate achieving global line-placement error below10nm. In order to investigate line-edge smoothness and high-frequency line-placement errors, a scheme for inspecting micron-sized areas was invented and implemented based on Mireau interferometry. This enabled the various contributions to be separately evaluated and measured. These included: exposure-dose variation, pattern-writing strategy and errors in the positioning of the microlenses. Deleterious crosstalk between microlenses was minimized via a pattern-dependent software modification. The impact of exposure threshold was revealed and adjustment made. The impact of address-grid fineness on line-edge roughness was likewise shown. Lastly, techniques were developed to measure and correct errors in the positioning of microlenses within the array. We expect final calibration of microlens positions to within 5nm.

42 ENGINEERING↗

Libera Brilliance Test with Beam Signal

The purpose of the tests described below was to estimate performance of Libera Brilliance with real circulating beam signal in the accelerator environment. Tests were performed at CESR and APS. Comprehensive test of the Libera Brilliance with real beam was performed. The obtained results are in accordance with previously obtained on the stand. Single pass capabilities of the Libera Brilliance were studied and found corresponding to the requirements. There is excellent agreement between observations of beam motion with a Libera Brilliance and APS FPGA-based receiver, with the Libera Brilliance unit having less noise in the high-frequency part of spectrum. For fill pattern dependence Libera Brilliance outperformed both the APS FPGA-based unit and the Bergoz BPM receiver.

43 PARTICLE ACCELERATORS↗

Using machine learning to improve land use/cover characterization and projection for scenario-based global modeling

The characterization of the land surface in models is critical for robust estimation of the water cycle and associated extremes. Land use determines water demand, and land cover affects water availability. The interaction between water demand and availability is the key determinant of whether systems are resilient to variability in the overall water cycle. Furthermore, activities such as irrigation and deforestation or afforestation may influence regional to global precipitation patterns, depending on the extent of the activity. Thus this proposed work aims to address the following question: How does integrated land use/cover data and improved land use/cover projection, as informed by machine learning approaches, better resolve human-earth system resilience to water cycle variability and extremes?

54 ENVIRONMENTAL SCIENCES↗

Excitation of Love waves in a thin film layer by a line source.

The excitation of a Love surface wave guided by a thin film layer deposited on a semiinfinite substrate is studied in this paper. Both the thin film and the substrate are considered to be elastically isotropic. Amplitudes of the surface wave in the thin film region and the substrate are found in terms of the strength of a line source vibrating in a direction transverse to the propagating wave. In addition to the surface wave, the bulk shear wave excited by the source is also studied. Analytical expressions for the bulk wave amplitude as a function of the direction of propagation, the acoustic powers transported by the surface and bulk waves, and the efficiency of surface wave excitation are obtained. A numerical example is given to show how the bulk wave radiation pattern depends upon the source frequency, the film thickness and other important parameters of the problem. The efficiency of surface wave excitation is also calculated for various parameter values.

Tuan, H.-S.↗

Creep behavior of uranium carbide-based alloys

The present work gives the results of experiments on the influence of zirconium carbide and tungsten on the creep properties of uranium carbide. The creep behavior of high-density UC samples follows the classical time-dependence pattern of (1) an instantaneous deformation, (2) a primary creep region, and (3) a period of steady-state creep. Creep rates for unalloyed UC-1.01 and UC-1.05 are several orders of magnitude greater than those measured for carbide alloys containing a Zr-C and/or W dispersoid. The difference in creep strength between alloyed and unalloyed materials varies with temperature and applied stress.

Seltzer, M. S.↗

Towards developing robust algorithms for solving partial differential equations on MIMD machines

Methods for efficient computation of numerical algorithms on a wide variety of MIMD machines are proposed. These techniques reorganize the data dependency patterns to improve the processor utilization. The model problem finds the time-accurate solution to a parabolic partial differential equation discretized in space and implicitly marched forward in time. The algorithms are extensions of Jacobi and SOR. The extensions consist of iterating over a window of several timesteps, allowing efficient overlap of computation with communication. The methods increase the degree to which work can be performed while data are communicated between processors. The effect of the window size and of domain partitioning on the system performance is examined both by implementing the algorithm on a simulated multiprocessor system.

Saltz, J. H.↗

Towards developing robust algorithms for solving partial differential equations on MIMD machines

Methods for efficient computation of numerical algorithms on a wide variety of MIMD machines are proposed. These techniques reorganize the data dependency patterns to improve the processor utilization. The model problem finds the time-accurate solution to a parabolic partial differential equation discretized in space and implicitly marched forward in time. The algorithms are extensions of Jacobi and SOR. The extensions consist of iterating over a window of several timesteps, allowing efficient overlap of computation with communication. The methods increase the degree to which work can be performed while data are communicated between processors. The effect of the window size and of domain partitioning on the system performance is examined both by implementing the algorithm on a simulated multiprocessor system.

Saltz, Joel H.↗

A pattern jitter free AFC scheme for mobile satellite systems

This paper describes a scheme for pattern jitter free automatic frequency control (AFC) with a wide frequency acquisition range. In this scheme, equalizing signals fed to the frequency discriminator allow pattern jitter free performance to be achieved for all roll-off factors. In order to define the acquisition range, frequency discrimination characateristics are analyzed on a newly derived frequency domain model. As a result, it is shown that a sufficiently wide acquisition range over a given system symbol rate can be achieved independent of symbol timing errors. Additionally, computer simulation demonstrates that frequency jitter performance improves in proportion to E(sub b)/N(sub 0) because pattern-dependent jitter is suppressed in the discriminator output. These results show significant promise for applciation to mobile satellite systems, which feature relatively low symbol rate transmission with an approximately 0.4-0.7 roll-off factor.

Yoshida, Shousei↗

Diffraction of a Gaussian Beam by a Spherical Obstacle

The Kirchhoff integral for diffraction in the near-forward direction is derived from the exact solution of the electromagnetic boundary value problem of a focused Gaussian laser beam incident on a spherical particle. The diffracted intensity in the vicinity of the particle is computed and the way in which the features of the diffraction pattern depend on the width of the Gaussian beam is commented on.

Lock, James A.↗

Meteoritic Constraints on Models of the Solar Nebula: The Abundances of Moderately Volatile Elements

The "moderately volatile" elements are those which condense (or evaporate) in the temperature range 650 - 1350 K, as a mix of material with solar abundances is cooled (or heated) tinder equilibrium conditions. Their relative abundances in chondritic meteorites are solar (or "cosmic", as defined by the composition of Cl meteorites) to within a factor of several, but vary within that range in a way that correlates remarkably well with condensation temperature, independent of chemical affinity. It has been argued that this correlation reflects a systematically selective process which favored the accretion of refractory material over volatile material from a cooling nebula. Wasson and Chou (Meteoritics 9, 69-94, 1974, and Wasson and co-authors in subsequent papers) suggested that condensation and settling of solids contemporaneously with the cooling and removal of nebular gas could produce the observed abundance patterns, but a quantitative model has been lacking. We show that the abundance patterns of the moderately volatile elements in chondritic meteorites can be produced, in some degree of quantitative detail, by models of the solar nebula that are designed to conform to observations of T Tauri stars and the global conservation laws. For example, even if the local surface density of the nebula is not decreasing, condensation and accretion of solids from radially inflowing gas in a cooling nebula can result in depletions of volatiles, relative to refractories, like those observed, The details of the calculated abundance patterns depend on (but are not especially sensitive to) model parameters, and can exhibit the variations that distinguish the meteorite classes. Thus it appears that nebula characteristics such as cooling rates, radial flow velocities, and particle accumulation rates can be quantitatively constrained by demanding that they conform to meteoritic data; and the models, in turn, can produce testable hypotheses regarding the time and location of the formation of the chondrite parent bodies and the planets.

Cassen, Patrick↗

Meteoritic Constraints on Models of the Solar Nebula: The Abundances of Moderately Volatile Elements

The "moderately volatile" elements are those which condense (or evaporate) in the temperature range 650 - 1350 K, as a mix of material with solar abundances is cooled (or heated) under equilibrium conditions. Their relative abundances in chondritic meteorites are solar (or "cosmic", as defined by tile composition of CI meteorites) to within a factor of several, but vary within that range in a way that correlates remarkably well with condensation temperature, independent of chemical affinity. It has been argued that this correlation reflects a systematically selective process which favored the accretion of refractory material over volatile material from a cooling nebula. Wasson and Chou suggested that condensation and settling of solids contemporaneously with the cooling and removal of nebular gas could produce tile observed abundance patterns, but a quantitative model has been lacking. We show that the abundance patterns of the moderately volatile elements in chondritic meteorites can be produced, in some degree of quantitative detail, by models of the solar nebula that are designed to conform to observations of T Tauri stars and the global conservation laws. For example, even if the local surface density of the nebula is not decreasing, condensation and accretion of solids from radially inflowing gas in a cooling nebula can result in depletions of volatiles, relative to refractories, like those observed. The details of the calculated abundance patterns depend on (but are not especially sensitive to) model parameters, and can exhibit the variations that distinguish the meteorite classes. Thus it appears that nebula characteristics Such as cooling rates, radial flow velocities, and particle accumulation rates can be quantitatively constrained by demanding that they conform to meteoritic data; and the models, in turn, can produce testable hypotheses regarding the time and location of the formation of the chondrite parent bodies and the planets.

Cassen, P.↗

The response of lazy-2 tomato seedlings to curvature-inducing magnetic gradients is modulated by light

Shoots of the lazy-2 mutant of tomato (Lycopersicon esculentum Mill., cv. Ailsa Craig) exhibit negative gravitropism in the dark, but respond positively gravitropically in (red) light. In order to test whether high-gradient magnetic fields (HGMFs) exert only ponderomotive effects on amyloplasts or affect other physiological processes, we induced magnetophoretic curvature in wild-type (WT) and lazy-2 mutant seedlings. Straight hypocotyls of 4-d-old plants were selected and the tips of their hooks were placed in an HGMF near the edge of a magnetized ferromagnetic wedge [grad (H2/2) approximately 10(9)-10(10) Oe2/cm] and mounted on a 1-rpm clinostat. After 4 h in the dark, 85% of WT hypocotyls and 67% of mutant hypocotyls curved toward the wedge. When the seedlings were exposed to red light for 1 h prior to and during the application of the HGMF, 78% of the WT seedlings curved toward the magnetic gradient, but the majority of the lazy-2 seedlings (75%) curved away from the stronger field area. Intracellular amyloplast displacement in the HGMF was similar for both varieties and resembled the displacement after horizontal reorientation. The WT showed a distinct graviresponse pattern depending on the orientation of the hook, even after excision of the apex. Application of HGMFs to decapitated hypocotyls resulted in curvature consistent with that obtained after horizontal reorientation. After light exposure, decapitated lazy-2 seedlings did not respond positively gravitropically. The data imply that the lazy-2 mutants perceive the displacement of amyloplasts in a similar manner to the WT and that the HGMF does not affect the graviresponse mechanism. The study demonstrates that ponderomotive forces due to HGMFs are useful for the analysis of the gravity-sensing mechanism in plants.

NASA Discipline Plant Biology↗

Ultrasonics Equipped Crimp Tool: A New Technology for Aircraft Wiring Safety

We report on the development of a new measurement technique to quantitatively assess the condition of wire crimp connections. This ultrasonic (UT) method transmits high frequency sound waves through the joint under inspection. The wire-crimp region filters and scatters the ultrasonic energy as it passes through the crimp and wire. The resulting output (both time and frequency domains) provides a quantitative measure of the joint quality that is independent and unaffected by current. Crimps of poor mechanical and electrical quality will result in low temporal output and will distort the spectrum into unique and predictable patterns, depending on crimp "quality". This inexpensive, real-time measurement system can provide certification of crimps as they are made and recertification of existing wire crimps currently in service. The measurements for re-certification do not require that the wire be disconnected from its circuit. No other technology exists to measure in-situ the condition of wire joints (no electrical currents through the crimp are used in this analytical technique). We discuss the signals obtained from this instrument, and correlate these signals with destructive wire pull tests.

Yost, William T.↗