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At least 19 records

Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles

A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials. - Highlights: • Cell penetrable human scFvs (transbodies) to Ebolavirus (EBOV) VP40 were produced. • The transbodies inhibited egress of EBOV-like particles (VLPs) from human hepatocytes. • They interacted with VP40 CTD basic residues important for plasma membrane binding. • And hence interfere with viral matrix assembly and viral progeny budding. • This is the first report on human antibodies that target intracellular EBOV VP40.

60 APPLIED LIFE SCIENCES↗

WE-A-207-00: In Memoriam of Jacques Ovadia - Reinvigorating Scientific Excellence: Electron Beam Therapy - Past, Present and Future

The Medical Physics community lost one of its early pioneers in radiation oncology physics, Jacques Ovadia, who passed away in April of 2014 at the age of 90. Jacques received his Ph.D. in Nuclear Physics from the University of Illinois at Urbana in 1951. Subsequently, under the guidance of John Laughlin, he was introduced to the field of Medical Physics. When John moved to Memorial Sloan Kettering, Jacques followed him. There he gained clinical experience and expertise in the then cutting-edge field of high energy electron beam therapy. In 1956, Jacques joined Dr. Erich Uhlmann at Michael Reese Hospital in Chicago where one of the country’s first high energy medical linear accelerators had just been installed. During his 35 year tenure, Dr. Ovadia built a strong Medical Physics department that merged in 1984 with that of the University of Chicago. Jacques pioneered the use of high energy electron beams to treat deep seated tumors, multiple-field chest wall irradiation with variable electron energies, and even anticipated the current interest in high energy electron beam grid-therapy. At an early stage, he introduced a simulator, computerized treatment planning and in-house developed record and verify software. He retired in 1990 as Professor emeritus in Radiation and Cellular Biology at the University of Chicago. Dr. Ovadia was an early and strong supporter of AAPM. He was present at the Chicago ROMPS meeting where the decision was made to form an independent professional society for medical physics. He served as AAPM president in 1976. Jacques Ovadia is survived by his wife of 58 years, Florence, their daughter Corinne Graefe and son Marc Ovadia, MD, as well as four grandchildren and one great-grandchild. Jacques’ dynamic and ever enthusiastic personality inspired all who collaborated with him. He will be greatly missed.

60 APPLIED LIFE SCIENCES↗

WE-A-207-01: Memorial Lecturer

The Medical Physics community lost one of its early pioneers in radiation oncology physics, Jacques Ovadia, who passed away in April of 2014 at the age of 90. Jacques received his Ph.D. in Nuclear Physics from the University of Illinois at Urbana in 1951. Subsequently, under the guidance of John Laughlin, he was introduced to the field of Medical Physics. When John moved to Memorial Sloan Kettering, Jacques followed him. There he gained clinical experience and expertise in the then cutting-edge field of high energy electron beam therapy. In 1956, Jacques joined Dr. Erich Uhlmann at Michael Reese Hospital in Chicago where one of the country’s first high energy medical linear accelerators had just been installed. During his 35 year tenure, Dr. Ovadia built a strong Medical Physics department that merged in 1984 with that of the University of Chicago. Jacques pioneered the use of high energy electron beams to treat deep seated tumors, multiple-field chest wall irradiation with variable electron energies, and even anticipated the current interest in high energy electron beam grid-therapy. At an early stage, he introduced a simulator, computerized treatment planning and in-house developed record and verify software. He retired in 1990 as Professor emeritus in Radiation and Cellular Biology at the University of Chicago. Dr. Ovadia was an early and strong supporter of AAPM. He was present at the Chicago ROMPS meeting where the decision was made to form an independent professional society for medical physics. He served as AAPM president in 1976. Jacques Ovadia is survived by his wife of 58 years, Florence, their daughter Corinne Graefe and son Marc Ovadia, MD, as well as four grandchildren and one great-grandchild. Jacques’ dynamic and ever enthusiastic personality inspired all who collaborated with him. He will be greatly missed.

60 APPLIED LIFE SCIENCES↗

Utility of the Virtual Liver Parenchymal Perfusion Area Using a Commercially Available Workstation in Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose: To evaluate the accuracy of the virtual liver parenchymal perfusion area using a commercially available workstation and liver analysis software in conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC). Materials and Methods: This method was retrospectively applied to 29 treated HCCs in 23 patients. The virtual embolic area (VEA) was estimated based on cone beam computed tomography during hepatic arteriography using a commercially available workstation and liver analysis software by two observer groups (group A: experts; group B: semi-experts). The real embolic area (REA) was defined as the area where iodized oil accumulated on computed tomography at 1 week after cTACE. The REA was estimated by each of the two groups, and the mean REA between the groups (mREA) was used as a standard reference. Agreement of volume and cross-sectional area in three orthogonal planes between the VEA and mREA were analyzed using intraclass correlation coefficients (ICCs) and Bland–Altman plots. Results: The ICCs for volume between VEA and mREA were 0.97 and 0.88 for groups A and B, respectively, and those for cross-sectional area were 0.94 and 0.88 for the axial plane, 0.95 and 0.83 for the coronal plane, and 0.87 and 0.74 for the sagittal plane, respectively. Thus, the overall agreement was excellent, except for the sagittal imaging plane in group B. Conclusion: This method using a commercially available workstation and liver analysis software can be useful for estimating the embolic area in cTACE.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Three dimensional (3D) microstructure-based finite element modeling of Al-SiC nanolaminates using focused ion beam (FIB) tomography

Al-SiC nanolaminate composites show promise as high performance coating materials due to their combination of strength and toughness. Although a significant amount of modeling effort has been focused on materials with an idealized flat nanostructure, experimentally these materials exhibit complex undulating layer geometries. This work utilizes FIB tomography to characterize this nanostructure in 3D and finite element modeling to determine the effect that this complex structure has on the mechanical behavior of these materials. A sufficiently large volume was characterized such that a 1 × 2 μm micropillar could be generated from the dataset and compared directly to experimental results. The mechanical response from this nanostructure was then compared to pillar models using simplified structures with perfectly flat layers, layers with sinusoidal waviness, and layers with arc segment waviness. The arc segment based layer geometry showed the best agreement with the experimentally determined structure, indicating it would be the most appropriate geometry for future modeling efforts. - Highlights: •FIB tomography was used to determine the structure of an Al-SiC nanolaminate in 3D. •FEM was used to compare the deformation of the nanostructure to experimental results. •Idealized structures from literature were compared to the FIB determined structure. •Arc segment based structures approximated the FIB determined structure most closely.

36 MATERIALS SCIENCE↗

Automated correlative segmentation of large Transmission X-ray Microscopy (TXM) tomograms using deep learning

Highlights: • A unique automated segmentation approach for large 3D nanotomography datasets obtained by Transmission X-ray Microscopy (TXM) in an Al-Cu alloy. • Automated segmentation using a Convolutional Neural Network (CNN) architecture based on a deep learning approach was employed. • This extremely versatile technique is capable of emulating the manual segmentation process effectively. • Quantitative comparison between manual segmentation and CNN architecture established the accuracy of this automated technique. • Its ability to robustly process ultra-large volumes of data in relatively small time frames can exponentially accelerate tomographic data analysis. - Abstract: A unique correlative approach for automated segmentation of large 3D nanotomography datasets obtained using Transmission X-ray Microscopy (TXM) in an Al-Cu alloy has been introduced. Automated segmentation using a Convolutional Neural Network (CNN) architecture based on a deep learning approach was employed. This extremely versatile technique is capable of emulating the manual segmentation process effectively. Coupling this technique with post-scanning SEM imaging ensured precise estimation of 3D morphological parameters from nanotomography. The segmentation process as well as subsequent analysis was expedited by several orders of magnitude. Quantitative comparison between segmentation performed manually and using the CNN architecture established the accuracy of this automated technique. Its ability to robustly process ultra-large volumes of data in relatively small time frames can exponentially accelerate tomographic data analysis, possibly opening up novel avenues for performing 4D characterization experiments with finer time steps.

36 MATERIALS SCIENCE↗

Three-dimensional grain mapping of open-cell metallic foam by integrating synthetic data with experimental data from high-energy X-ray diffraction microscopy

Highlights: • High-energy X-ray measurements are made for ligaments of an open-cell aluminum foam. • Grain centroids and orientations are measured using high-energy X-ray diffraction. • 3D grain map is virtually reconstructed by integrating measured and synthetic data. - Abstract: The complex mechanical response of open-cell foams depends strongly on the hierarchy of length scales inherent in them, from engineering-part scale to the ligament scale through the grain scale down to the crystal-lattice scale. A first step toward understanding and predicting the coordinated mechanical response across length scales requires characterizing the open-cell foam structure in three dimensions at relevant scales. Here, we present an initial attempt to digitally represent a physically-realized aluminum alloy foam in terms of both its geometry/topology as well as its underlying crystallographic orientations by integrating several advanced techniques. Specifically, we use a combination of X-ray computed tomography and X-ray diffraction microscopy in conjunction with synthetic grain mapping. Experimental investigation of the foam shows relatively large grain sizes with respect to the ligament length scale, implying that competing mechanics at different length scales (i.e. grain scale vs. ligament scale) will need to be fully incorporated to understand the mechanical behavior of the foam. The integration of non-destructive measurement techniques with synthetic-data generation provides a path toward realistic modeling of bulk samples of open-cell metal foam resolved at the scale of individual grains.

36 MATERIALS SCIENCE↗

Flow characteristics in narrowed coronary bypass graft

Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Structure of a Deformed Inhomogeneous Material on the Data of Acoustic Emission and X-Ray Computer Microtomography

Accumulation of defects at various stages of the deformation of a structurally inhomogeneous material (granite) has been studied using two nondestructive methods: acoustic emission (AE) and X-ray computer microtomorgaphy (CT). The quasi-static testing of cylindrical samples of a Westerly granite was carried out under uniaxial compression. The control of the defect formation was realized using the real-time monitoring of acoustic emission. For each sample under study, several steps of the loading and tomographic imaging have been performed. We have found that an exponential or power-law function of the energy distribution of the AE signals makes it possible to select a sample region, in which the system of defects has transited into a self-organized criticality state and large cracks have been formed. This result coincides with the data of the X-ray tomography Computer Microtomography.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Uniaxial Compression of Cellular Materials at a 10 -1 s -1 Strain Rate Simultaneously with Synchrotron X-ray Computed Tomographic Imaging

The topic is presented as a series of slides. Motivation for the work included the following: X-ray tomography is a fantastic technique for characterizing a material’s starting structure as well as for non-destructive, in situ experiments to investigate material response; 3D X-ray tomography is needed to fully characterize the morphology of cellular materials; and synchrotron micro-CT can capture 3D images without pausing experiment. Among the conclusions reached are these: High-rate radiographic and tomographic imaging (0.25 s 3D frame rate) using synchrotron CT can capture full 3D images of hyper-elastic materials at a 10 -2 strain rate; dynamic true in situ uniaxial loading can be accurately captured; the three stages of compression can be imaged: bending, buckling, and breaking; implementation of linear modeling is completed; meshes have been imported into LANL modeling codes--testing and validation is underway and direct comparison and validation between in situ data and modeled mechanical response is possible.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Frontiers for Laboratory Research of Magnetic Reconnection

Magnetic reconnection occcurs throughout heliophysical and astrophysical plasmas as well as in laboratory fusion plasmas. Two broad categories of reconnection models exist: collisional MHD and collisionless kinetic. Eight major questions with respect to magnetic connection are set down, and past and future devices for studying them in the laboratory are described. Results of some computerized simulations are compared with experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Historical Building Stability Monitoring by Means of a Cosmic Ray Tracking System

Cosmic ray radiation is mostly composed, at sea level, by high energy muons, which are highly penetrating particles capable of crossing kilometers of rock. The ubiquitous and steady presence at the Earth's surface and the high penetration capability have motivated the use of cosmic ray radiation also in fields beyond particle physics, from geology, archaeology, speleology to industrial applications and homeland security. In particular, in recent years, the novel technique of muon tomography has been proposed, with the aim of performing non invasive inspection of large non accessible volumes, material atomic number Z and density discrimination, and three dimension image reconstruction of the inspected volume. In the present paper, after a short recall of the physical principles and mathematical formalism on which muon tomography is based, a number of examples of application of the novel technique in industry and homeland security issues is given. Moreover, a new application of cosmic rays detection techniques in the field of civil engineering is proposed. The aim is the monitoring of the stability of large structures, in particular the static monitoring of historical buildings, where conservation constraints are more severe and the time evolution of the deformation phenomena under study may be of the order of months or years. The new technique may be seen, in some way, as the reverse problem of muon tomography. As a significant case study, the monitoring of the wooden vaulted roof of the Palazzo della Loggia in the town of Brescia, in Italy, has been considered. The feasibility as well as the performances and limitations of a monitoring system based on cosmic ray tracking have been studied by Monte Carlo simulation and discussed in comparison with more traditional monitoring systems. (authors)

42 ENGINEERING↗

Partial relay selection in mixed RF/FSO dual-hop system over unified M-distributed fading channel with non-zero boresight pointing errors

In this paper, the performance of a partial relay selection-based amplify-and-forward mixed radio frequency/free space optical (RF/FSO) system with a direct RF link and outdated channel state information (CSI) is presented. The source-to-relay and source-to-destination RF links are subjected to Rayleigh distributions while the relay-to-destination FSO link experiences Malaga (M)-distribution with generalized non-zero boresight pointing errors. It is also assumed that selection combining diversity with heterodyne detection is considered for the signal reception at the destination. Moreover, the cumulative distribution functions of the end-to-end signal-to-noise under the influence of with/or without a direct link are then derived for the concerned system. Through this, the closed-form expressions for the system outage probability and average bit error rate are obtained. Thus, the influence of atmospheric turbulence, outdated CSI and relay selection are evaluated for the system under zero boresight and non-zero boresight displacement pointing errors scenarios. The results illustrated that the mixed RF/FSO system with a direct link offers better performance than the one without a direct link. The accuracy of the presented results is validated by Monte-Carlo simulation.

42 ENGINEERING↗

Cosmic bubble and domain wall instabilities II: fracturing of colliding walls

We study collisions between nearly planar domain walls including the effects of small initial nonplanar fluctuations. These perturbations represent the small fluctuations that must exist in a quantum treatment of the problem. In a previous paper, we demonstrated that at the linear level a subset of these fluctuations experience parametric amplification as a result of their coupling to the planar symmetric background. Here we study the full three-dimensional nonlinear dynamics using lattice simulations, including both the early time regime when the fluctuations are well described by linear perturbation theory as well as the subsequent stage of fully nonlinear evolution. We find that the nonplanar fluctuations have a dramatic effect on the overall evolution of the system. Specifically, once these fluctuations begin to interact nonlinearly the split into a planar symmetric part of the field and the nonplanar fluctuations loses its utility. At this point the colliding domain walls dissolve, with the endpoint of this being the creation of a population of oscillons in the collision region. The original (nearly) planar symmetry has been completely destroyed at this point and an accurate study of the system requires the full three-dimensional simulation.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Polychromatic sparse image reconstruction and mass attenuation spectrum estimation via B-spline basis function expansion

We develop a sparse image reconstruction method for polychromatic computed tomography (CT) measurements under the blind scenario where the material of the inspected object and the incident energy spectrum are unknown. To obtain a parsimonious measurement model parameterization, we first rewrite the measurement equation using our mass-attenuation parameterization, which has the Laplace integral form. The unknown mass-attenuation spectrum is expanded into basis functions using a B-spline basis of order one. We develop a block coordinate-descent algorithm for constrained minimization of a penalized negative log-likelihood function, where constraints and penalty terms ensure nonnegativity of the spline coefficients and sparsity of the density map image in the wavelet domain. This algorithm alternates between a Nesterov’s proximal-gradient step for estimating the density map image and an active-set step for estimating the incident spectrum parameters. Numerical simulations demonstrate the performance of the proposed scheme.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

SU-G-IeP4-03: Cone Beam X-Ray Luminescence Computed Tomography Based On Generalized Gaussian Markov Random Field

Purpose: Cone beam X-ray luminescence computed tomography (CB-XLCT), which aims to achieve molecular and functional imaging by X-rays, has recently been proposed as a new imaging modality. However, the inverse problem of CB-XLCT is seriously ill-conditioned, hindering us to achieve good image quality. In this work, a novel reconstruction method based on Bayesian theory is proposed to tackle this problem Methods: Bayesian theory provides a natural framework for utilizing various kinds of available prior information to improve the reconstruction image quality. A generalized Gaussian Markov random field (GGMRF) model is proposed here to construct the prior model of the Bayesian theory. The most important feature of GGMRF model is the adjustable shape parameter p, which can be continuously adjusted from 1 to 2. The reconstruction image tends to have more edge-preserving property when p is slide to 1, while having more noise tolerance property when p is slide to 2, just like the behavior of L1 and L2 regularization methods, respectively. The proposed method provides a flexible regularization framework to adapt to a wide range of applications. Results: Numerical simulations were implemented to test the performance of the proposed method. The Digimouse atlas were employed to construct a three-dimensional mouse model, and two small cylinders were placed inside to serve as the targets. Reconstruction results show that the proposed method tends to obtain better spatial resolution with a smaller shape parameter, while better signal-to-noise image with a larger shape parameter. Quantitative indexes, contrast-to-noise ratio (CNR) and full-width at half-maximum (FWHM), were used to assess the performance of the proposed method, and confirmed its effectiveness in CB-XLCT reconstruction. Conclusion: A novel reconstruction method for CB-XLCT is proposed based on GGMRF model, which enables an adjustable performance tradeoff between L1 and L2 regularization methods. Numerical simulations were conducted to demonstrate its performance.

60 APPLIED LIFE SCIENCES↗

SU-E-T-761: TOMOMC, A Monte Carlo-Based Planning VerificationTool for Helical Tomotherapy

Purpose: Present a new Monte Carlo code (TOMOMC) to calculate 3D dose distributions for patients undergoing helical tomotherapy treatments. TOMOMC performs CT-based dose calculations using the actual dynamic variables of the machine (couch motion, gantry rotation, and MLC sequences). Methods: TOMOMC is based on the GEPTS (Gama Electron and Positron Transport System) general-purpose Monte Carlo system (Chibani and Li, Med. Phys. 29, 2002, 835). First, beam models for the Hi-Art Tomotherpy machine were developed for the different beam widths (1, 2.5 and 5 cm). The beam model accounts for the exact geometry and composition of the different components of the linac head (target, primary collimator, jaws and MLCs). The beams models were benchmarked by comparing calculated Pdds and lateral/transversal dose profiles with ionization chamber measurements in water. See figures 1–3. The MLC model was tuned in such a way that tongue and groove effect, inter-leaf and intra-leaf transmission are modeled correctly. See figure 4. Results: By simulating the exact patient anatomy and the actual treatment delivery conditions (couch motion, gantry rotation and MLC sinogram), TOMOMC is able to calculate the 3D patient dose distribution which is in principal more accurate than the one from the treatment planning system (TPS) since it relies on the Monte Carlo method (gold standard). Dose volume parameters based on the Monte Carlo dose distribution can also be compared to those produced by the TPS. Attached figures show isodose lines for a H&N patient calculated by TOMOMC (transverse and sagittal views). Analysis of differences between TOMOMC and TPS is an ongoing work for different anatomic sites. Conclusion: A new Monte Carlo code (TOMOMC) was developed for Tomotherapy patient-specific QA. The next step in this project is implementing GPU computing to speed up Monte Carlo simulation and make Monte Carlo-based treatment verification a practical solution.

60 APPLIED LIFE SCIENCES↗