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At least 883 records · Page 49

Quantum Hall Effect Measurement of Spin–Orbit Coupling Strengths in Ultraclean Bilayer Graphene/WSe 2 Heterostructures

Here, we study proximity-induced spin–orbit coupling (SOC) in bilayer graphene/few-layer WSe 2 heterostructure devices. Contact mode atomic force microscopy (AFM) cleaning yields ultraclean interfaces and high-mobility devices. In a perpendicular magnetic field, we measure the quantum Hall effect to determine the Landau level structure in the presence of out-of-plane Ising and in-plane Rashba SOC. A distinct Landau level crossing pattern emerges when tuning the charge density and displacement field independently with dual gates, originating from a layer-selective SOC proximity effect. Analyzing the Landau level crossings and measured inter-Landau level energy gaps yields the proximity-induced SOC energy scale. The Ising SOC is ~2.2 meV, 100 times higher than the intrinsic SOC in graphene, whereas its sign is consistent with theories predicting a dependence of SOC on interlayer twist angle. The Rashba SOC is ~15 meV. Finally, we infer the magnetic field dependence of the inter-Landau level Coulomb interactions. These ultraclean bilayer graphene/WSe 2 heterostructures provide a high mobility system with the potential to realize novel topological electronic states and manipulate spins in nanostructures.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Amphitrite ornata Dehaloperoxidase (DHP): Investigations of Structural Factors That Influence the Mechanism of Halophenol Dehalogenation Using ;Peroxidase-like; Myoglobin Mutants and ;Myoglobin-like; DHP Mutants

Dehaloperoxidase (DHP), discovered in the marine terebellid polychaete Amphitrite ornata, is the first heme-containing globin with a peroxidase activity. The sequence and crystal structure of DHP argue that it evolved from an ancient O{sub 2} transport and storage globin. Thus, DHP retains an oxygen carrier function but also has the ability to degrade halophenol toxicants in its living environment. Sperm whale myoglobin (Mb) in the ferric state has a peroxidase activity {approx}10 times lower than that of DHP. The catalytic activity enhancement observed in DHP appears to have been generated mainly by subtle changes in the positions of the proximal and distal histidine residues that appeared during DHP evolution. Herein, we report investigations into the mechanism of action of DHP derived from examination of 'peroxidase-like' Mb mutants and 'Mb-like' DHP mutants. The dehalogenation ability of wild-type Mb is augmented in the peroxidase-like Mb mutants (F43H/H64L, G65T, and G65I Mb) but attenuated in the Mb-like T56G DHP variant. X-ray crystallographic data show that the distal His residues in G65T Mb and G65I are positioned {approx}0.3 and {approx}0.8 {angstrom}, respectively, farther from the heme iron compared to that in the wild-type protein. The H93K/T95H double mutant Mb with the proximal His shifted to the 'DHP-like' position has an increased peroxidase activity. In addition, a better dehaloperoxidase (M86E DHP) was generated by introducing a negative charge near His89 to enhance the imidazolate character of the proximal His. Finally, only minimal differences in dehalogenation activities are seen among the exogenous ligand-free DHP, the acetate-bound DHP, and the distal site blocker L100F DHP mutant. Thus, we conclude that binding of halophenols in the internal binding site (i.e., distal cavity) is not essential for catalysis. This work provides a foundation for a new structure-function paradigm for peroxidases and for the molecular evolution of the dual-function enzyme DHP.

59 BASIC BIOLOGICAL SCIENCES↗

Deformation Precursors to Catastrophic Failure in Rocks

Forecasting the timing of catastrophic failure, such as crustal earthquakes, has been a central concern for centuries. Such forecasting requires identifying signals that evolve or accelerate in the precursory phase leading to failure, and the subset of signals that may be detected in the crust. We develop machine learning models to predict the proximity of catastrophic failure in synchrotron X-ray tomography triaxial compression experiments on rocks using characteristics of evolving fracture networks. We then examine the characteristics that most strongly influence the model results, and thus may be considered the best predictors of the proximity of macroscopic failure. Finally, the resulting suite of predictive parameters underscores the importance of dilation in the precursory phase leading to catastrophic failure. The results indicate that the evolution of the strain energy density field may provide more robust predictions of the proximity of failure than other existing metrics of rock deformation.

58 GEOSCIENCES↗

How type II CRISPR–Cas establish immunity through Cas1–Cas2-mediated spacer integration

CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby Cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR–Cas systems, the spacer integration mechanism is essentially identical. The conserved Cas1 and Cas2 proteins form an integrase complex consisting of two distal Cas1 dimers bridged by a Cas2 dimer. The prespacer is bound by Cas1–Cas2 as a dual-forked DNA, and the terminal 3'-OH of each 3' overhang serves as an attacking nucleophile during integration. The prespacer is preferentially integrated into the leader-proximal region of the CRISPR array, guided by the leader sequence and a pair of inverted repeats inside the CRISPR repeat. Spacer integration in the well-studied Escherichia coli type I–E CRISPR system also relies on the bacterial integration host factor. In type II–A CRISPR, however, Cas1–Cas2 alone integrates spacers efficiently in vitro; other Cas proteins (such as Cas9 and Csn2) have accessory roles in the biogenesis phase of prespacers. Here we present four structural snapshots from the type II–A system of Enterococcus faecalis Cas1 and Cas2 during spacer integration. Enterococcus faecalis Cas1–Cas2 selectively binds to a splayed 30-base-pair prespacer bearing 4-nucleotide 3' overhangs. Three molecular events take place upon encountering a target: first, the Cas1–Cas2–prespacer complex searches for half-sites stochastically, then it preferentially interacts with the leader-side CRISPR repeat, and finally, it catalyses a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3' overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. Here, we derive a mechanistic framework to explain the stepwise spacer integration process and the leader-proximal preference.

59 BASIC BIOLOGICAL SCIENCES↗

Increased enhancer–promoter interactions during developmental enhancer activation in mammals

Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here, in this study, we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer-promoter and enhancer-enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer-promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer-promoter physical proximity for developmental gene activation in mammals.

59 BASIC BIOLOGICAL SCIENCES↗

Low background signal readout electronics for the MAJORANA DEMONSTRATOR

The MAJORANA Collaboration will seek neutrinoless double beta decay (0νββ) in {sup 76}Ge using isotopically enriched p-type point contact (PPC) high purity Germanium (HPGe) detectors. A tonne-scale array of HPGe detectors would require background levels below 1 count/ROI-tonne-year in the 4 keV region of interest (ROI) around the 2039 keV Q-value of the decay. In order to demonstrate the feasibility of such an experiment, the MAJORANA DEMONSTRATOR, a 40 kg HPGe detector array, is being constructed with a background goal of < 3 count/ROI-tonne-year, which is expected to scale down to < 1 count/ROI-tonne-year for a tonne-scale experiment. The signal readout electronics, which must be placed in close proximity to the detectors, present a challenge toward reaching this background goal. This talk will discuss the materials and design used to construct signal readout electronics with low enough backgrounds for the MAJORANA DEMONSTRATOR.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Flow and heat transfer in the wake of a triangular arrangement of spheres

This research work seeks to investigate the influence of spacing and heat transfer on the wake behavior of a triangular arrangement of spheres. Four experimental configurations have been investigated at three Reynolds numbers, Re 1 = 350, Re 2 = 700, and Re 3 = 1050. Two isothermal cases were investigated with spacing between the spheres of zero and one sphere diameter, and two cases were investigated with an applied heat flux at the same spacing conditions. The time resolved particle image velocimetry results revealed various flow phenomena including flow separations, von Karman vortex shedding, and Kelvin–Helmholtz instabilities. The turbulent statistics reveal the effect of proximity and heat transfer on the time averaged values of the wake size, turbulent strengths, and Reynolds shear stress in the wake of each sphere, namely, the laminarization effects from the addition of heat and the suppression of the lead sphere wake from the proximity of the trailing spheres. These results are complemented by the application of proper orthogonal decomposition (POD) to the flow fields, which extracts the coherent structures from the flow. Here the modes that describe the coherent structures are extracted and described in detail, which provide further insight into effects of the experimental conditions on the temporal behavior of the flow. Many of the low order modes are found to be associated in pairs, corresponding to asymmetric structures or advection of a given structure downstream. The capability of POD to produce reduced order models of the flow is then utilized to facilitate vortex identification analysis. A turbulent kinetic energy based mode truncation criteria, which has been found to enhance vortex identification capability, is applied to select the POD modes and temporal coefficients to be used in the reduced order modeling. The reconstructed velocity fields are then analyzed with vortex identification algorithms to extract the vortex cores and boundaries. The combination of these approaches allows the study of the effect of proximity and heat transfer on the vortex characteristics, such as size, strength, and distribution.

42 ENGINEERING↗

Overview and status of the Long-Baseline Neutrino Facility Far Site cryogenics system

The Sanford Underground Research Facility (SURF) will host the Far Detector of the Deep Underground Neutrino Experiment (DUNE), an international multi-kiloton Long-Baseline neutrino experiment that will be installed about one and a half kilometers underground in Lead, SD. Detectors will be located inside four cryostats filled with almost 70,000 metric tons of ultrapure liquid argon, with a level of impurities lower than 100 parts per trillion of oxygen equivalent contamination. The cryogenics infrastructure supporting this experiment is provided by the Long-Baseline Neutrino Facility (LBNF). This contribution presents modes of operation, layout, and main features of the LBNF Far Site cryogenic system, which is composed of three subsystems: Infrastructure, Proximity, and Internal cryogenics. The Infrastructure cryogenics supports the needs of the cryostat and Proximity cryogenics. It includes the equipment to receive the argon in liquid phase, vaporize it and transfer it underground as a gas, the nitrogen system (composed of the refrigeration system, liquid nitrogen buffer tanks and liquid and gaseous nitrogen distribution), liquid and gaseous argon distribution and process controls. The Proximity cryogenics receives fluids from the Infrastructure cryogenics and delivers them to the Internal cryogenics at the required temperature, pressure, purity and mass flow rate. It includes the argon condensers, liquid and gaseous argon purification and regeneration systems, nitrogen and argon phase separators, piping, valves, and instrumentation. The Internal cryogenics comprises the liquid and gaseous argon distribution inside the cryostats for the commissioning, cool down, fill, and steady state operations of the cryostats and detectors. An international engineering team is designing these systems and will manufacture, install, commission, and qualify them. This contribution describes the main features, performance, functional requirements, and modes of operation of the LBNF Far Site cryogenics system. It also presents the status of the design, along with present and future needs to support the DUNE experiment.

43 PARTICLE ACCELERATORS↗

High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.

59 BASIC BIOLOGICAL SCIENCES↗

Co-locality to co-functionality: Eukaryotic gene neighborhoods as a resource for function

Diverging from the classic paradigm of random gene order in eukaryotes, gene proximity can be leveraged to systematically identify functionally related gene neighborhoods in eukaryotes, utilizing techniques pioneered in bacteria. Current methods of identifying gene neighborhoods typically rely on sequence similarity to characterized gene products. However, this approach is not robust for non model organisms like algae, which are evolutionarily distant from well-characterized model organisms. Here, we utilize a comparative genomic approach to identify evolutionarily conserved Proximal Orthologous Gene (POG) pairs conserved across at least two taxonomic classes of green algae. A total of 317 gene neighborhoods were identified. In some cases, gene proximity appears to have been conserved since before the streptophyte-chlorophyte split, 1,000 million years ago. Using functional inferences derived from reconstructed evolutionary relationships, we identified several novel functional clusters. A putative mycosporine-like amino acid (MAA), "sunscreen", neighborhood contains genes similar to either vertebrate or cyanobacterial pathways, suggesting a novel mosaic biosynthetic pathway in green algae. One of two putative arsenic-detoxification neighborhoods includes an organoarsenical transporter (ArsJ), a glyceraldehyde 3-phosphate dehydrogenase-like gene, homologs of which are involved in arsenic detoxification in bacteria, and a novel algal-specific phosphoglycerate kinase-like gene (PGK). Mutants of the ArsJ-like transporter and PGK-like genes in Chlamydomonas reinhardtii were found to be sensitive to arsenate, providing experimental support for the role of these identified neighbors in resistance to arsenate. Potential evolutionary origins of neighborhoods are discussed, and updated annotations for formerly poorly annotated genes are presented, highlighting the potential of this strategy for functional annotation.

59 BASIC BIOLOGICAL SCIENCES↗

Effect of intervalley interaction on band topology of commensurate graphene/EuO heterostructures

Recent experiments demonstrating proximity induced ferromagnetism in graphene motivate this study of commensurate graphene/EuO heterostructures. Due to the commensurability of graphene with the (111)-EuO layer, graphene’s Dirac points are mapped to the Γ point of the commensurate Brillouin zone. The Eu atoms not only induce proximity exchange on the graphene layer, but they also introduce intervalley interactions resulting in a nonlinear dispersion at Γ. Here, we develop a model Hamiltonian, consistent with the lattice symmetries, that includes proximity induced exchange splitting, spin-orbit coupling, and intervalley interactions with parameters fitted to ab initio calculations. The intervalley interaction opens up a trivial gap preventing the system from crossing into a nontrivial state. The model Hamiltonian is analyzed to determine the conditions under which the heterostructures can exhibit topologically nontrivial bands.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

High Landau levels of two-dimensional electrons near the topological transition caused by interplay of spin-orbit and Zeeman energy shifts

In the presence of spin-orbit coupling two branches of the energy spectrum of two-dimensional electrons get shifted in the momentum space. Application of an in-plane magnetic field causes the splitting of the branches in energy. When both spin-orbit coupling and Zeeman splitting are present, the branches of the energy spectrum cross at a certain energy. Near this energy, the Landau quantization becomes peculiar since semiclassical trajectories, corresponding to individual branches, get coupled. We study this coupling as a function of the proximity to the topological transition. Remarkably, the dependence on the proximity is strongly asymmetric, reflecting the specifics of the behavior of the trajectories near the crossing. Equally remarkable, on one side of the transition, the magnitude of coupling is an oscillating function of this proximity. These oscillations can be interpreted in terms of the Stückelberg interference. Scaling of characteristic detuning with magnetic length is also unusual. Furthermore, this unusual behavior cannot be captured by simply linearizing the Fermi contours near the crossing point.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Ferroelectric Semimetals with α-Bi/SnSe van der Waals Heterostructures and Their Topological Currents

We show that proximity effects can be utilized to engineer van der Waals heterostructures (vdWHs) displaying semimetallic spin-ferroelectricity locking, where ferroelectricity and semimetallic spin states are confined to different layers, but are correlated by means of proximity effects. Our findings are supported by first principles calculations involving α-Bi/SnSe bilayers. We show that such systems support ferroelectrically switchable nonlinear anomalous Hall effect originating from large Berry curvature dipoles as well as direct and inverse spin Hall effects with giant bulk spin-charge interconversion efficiencies. In conclusion, the giant efficiencies are consequences of the proximity-induced semimetallic nature of low energy electron states, which are shown to behave as two-dimensional pseudo-Weyl fermions by means of symmetry analysis and first principles calculations as well as direct angle-resolved photoemission spectroscopy measurements.

2-dimensional systems↗

Discovering the Whole by the Coarse: A topological paradigm for data analysis

The increasing interest in big data applications is ushering in a large effort in seeking new, efficient, and adapted data models to reduce complexity, while preserving maximal intrinsic information. Graph-based models have recently been getting a lot of attention on account of their intuitive and direct connection to the data. The cost of these models, however, is to some extent giving up geometric insight as well as algebraic flexibility. Topology, as an intermediate analysis medium, focuses on coarse structures of an object/signal in general. It affords a formalism of transitioning from a local to a global description of an object, while providing significant information, which respects the local structure of measurements. It may also support a global visualization (e.g., data variation trends) and enhances the understanding of the underlying phenomenon. Throughout this article, measurements may be considered proximal in various ways, depending on the specific application, and the selected proximity metrics are subsequently used in the construction of a graph structure, thus highlighting various groups of neighboring data. As described later, these groups, often based on proximity criteria, are represented by n-simplices, where n + 1 corresponds to the number of points in an associated group. Collectively, they form what is (and will be throughout) referred to as a simplicial complex, a special representation of a topological space. We find the key advantage of computational topology is its inherently algebraic structure on the basic elements of the resulting graph-like structure.

97 MATHEMATICS AND COMPUTING↗

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

60 APPLIED LIFE SCIENCES↗

Electrostatic focal spot correction for x-ray tubes operating in strong magnetic fields

Purpose: A close proximity hybrid x-ray/magnetic resonance (XMR) imaging system offers several critical advantages over current XMR system installations that have large separation distances (∼5 m) between the imaging fields of view. The two imaging systems can be placed in close proximity to each other if an x-ray tube can be designed to be immune to the magnetic fringe fields outside of the MR bore. One of the major obstacles to robust x-ray tube design is correcting for the effects of the MR fringe field on the x-ray tube focal spot. Any fringe field component orthogonal to the x-ray tube electric field leads to electron drift altering the path of the electron trajectories. Methods: The method proposed in this study to correct for the electron drift utilizes an external electric field in the direction of the drift. The electric field is created using two electrodes that are positioned adjacent to the cathode. These electrodes are biased with positive and negative potential differences relative to the cathode. The design of the focusing cup assembly is constrained primarily by the strength of the MR fringe field and high voltage standoff distances between the anode, cathode, and the bias electrodes. From these constraints, a focusing cup design suitable for the close proximity XMR system geometry is derived, and a finite element model of this focusing cup geometry is simulated to demonstrate efficacy. A Monte Carlo simulation is performed to determine any effects of the modified focusing cup design on the output x-ray energy spectrum. Results: An orthogonal fringe field magnitude of 65 mT can be compensated for using bias voltages of +15 and −20 kV. These bias voltages are not sufficient to completely correct for larger orthogonal field magnitudes. Using active shielding coils in combination with the bias electrodes provides complete correction at an orthogonal field magnitude of 88.1 mT. Introducing small fields (<10 mT) parallel to the x-ray tube electric field in addition to the orthogonal field does not affect the electrostatic correction technique. However, rotation of the x-ray tube by 30° toward the MR bore increases the parallel magnetic field magnitude (∼72 mT). The presence of this larger parallel field along with the orthogonal field leads to incomplete correction. Monte Carlo simulations demonstrate that the mean energy of the x-ray spectrum is not noticeably affected by the electrostatic correction, but the output flux is reduced by 7.5%. Conclusions: The maximum orthogonal magnetic field magnitude that can be compensated for using the proposed design is 65 mT. Larger orthogonal field magnitudes cannot be completely compensated for because a pure electrostatic approach is limited by the dielectric strength of the vacuum inside the x-ray tube insert. The electrostatic approach also suffers from limitations when there are strong magnetic fields in both the orthogonal and parallel directions because the electrons prefer to stay aligned with the parallel magnetic field. These challenging field conditions can be addressed by using a hybrid correction approach that utilizes both active shielding coils and biasing electrodes.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-T-322: Dosimetric Evaluation of Rib Dose in Peripheral Lung Tumors Treated with X-Ray Voxel Monte Carlo (XVMC) Based Lung Stereotactic Body Radiotherapy (SBRT) Following RTOG 0915 Guidelines

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dose to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.

60 APPLIED LIFE SCIENCES↗

WE-EF-303-11: Activity Distributions of Positron-Emitting-Isotopes Activated by Modulated Spot-Scanning Particle Beams

Purpose: To present the characteristics of positron-emitting-isotope (PEI) activity distributions on homogeneous and CIRS thorax phantoms irradiated by modulated spot-scanning carbon-ions and protons in Siemens IONTRIS system. Methods and Materials: Cylindrical homogeneous wax was irradiated by carbon-ions and protons of 10cm uniform square field with single-energy-layer ranges of 7cm, 16cm and 29cm. Images of PEI distributions were acquired over a period of 30 minutes at 10 minutes after each irradiation. Optimized uniform biological-equivalent doses of carbon-ions over a 5.0cm spherical target was delivered to CIRS phantom. Doses with range shifts in depths from 1mm to 6mm were also calculated and delivered to evaluate the accuracy of measuring activated PEI distributions. Results: Activated PEI distribution on homogeneous phantoms showed sharper peak near distal edge with flatter distribution toward proximal depth by carbon-ions than by protons. For depths near at Bragg-peak, penetration-depth spreading for energies from 10MeV/u to 60 MeV/u are from 0.4mm to 10.3mm, and 1.2mm to 30.4mm for projectile-fragments by carbon-ions and target-fragments by protons, respectively. For depths proximal to Bragg-peak, target-fragments for both carbon-ions and protons had minimal energy dependence in depth. For complex dose distributions delivered to CIRS thorax phantom, similar PEI peak-like distributions were still observed for carbon-ions. And, the changes at locations and edges of measured PEI peak were correlated within 0.5mm of shifted ranges. Mean activities over 5.0cm spherical target were similar for CISR phantom irradiated by doses with various range shifts. Conclusions: Peak-like PEI distributions by carbon-ions with good correlation to distal edges in both homogeneous and CIRS thorax phantoms present the potential for the in-vivo range verification while additional efforts is needed for protons. Due to flat distributions for depths at 6mm proximal to distal edges, mean activity at target might be used for in-vivo dose verification of target.

60 APPLIED LIFE SCIENCES↗