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At least 703 records · Page 39

Multiple proviral integration events after virological synapse-mediated HIV-1 spread

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes.

60 APPLIED LIFE SCIENCES↗

Influence of computed tomography contrast agent on radiotherapy dose calculation for pancreatic carcinoma: A dosimetric study based on tomotherapy and volumetric-modulated arc therapy techniques

The main purpose of our investigation was to quantify the dosimetric influence of intravenous contrast agent for pancreatic cancer radiotherapy treatment. This study focused on complex modulated irradiation techniques of tomotherapy (TOMO) and volumetric-modulated arc therapy (VMAT) to investigate if novel conformal treatment methods could reduce the influence of contrast agent. In our study, patients with pancreatic cancer were enrolled to have 2 computed tomography (CT) scans in the same position without and with intravenous contrast agent for treatment planning. Then tumors and organ at risks were countered on contrast-enhanced CT (CECT) images. Each patient's CECT was assigned a TOMO plan and a VMAT plan. Then these plans were copied onto the non-CECT image and dose distribution was calculated with the same algorithm and structure sets. Finally, the dose distribution and the dose difference were analyzed for the target volume and organs at risk between the 2 sets of images. The statistic dosimetric result showed that for both TOMO and VMAT, no significant dose difference between CECT and non-CECT-based plan was observed. Dose difference was clinically negligible because the average relative percentage dose difference was 1% ± 1% for target volume, except a blurring effect at the higher dose region of the target volume. It implied that intravenous contrast agent will not affect dose calculation for pancreatic cancer radiotherapy significantly. Also the dose deviation based on TOMO showed no statistical difference compared with that on VMAT. For both superposition/conversation algorithm used by TOMO and Monte Carlo algorithm used by VMAT, the dosimetric difference was nonsignificant. A full analysis demonstrated a negligible dose difference of less than 1% between CECT-based plan and non-CECT-based plan. Therefore, contrast-enhanced CT image can be used directly for dose calculation of TOMO and VMAT plans for pancreatic cancer. It is unnecessary to scan twice then make a fusion of CECT and non-CECT, which would result to additional unnecessary radiation dose to patient and decrease work efficiency.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

AEPF: Attention-Enabled Point Fusion for 3D Object Detection

Current state-of-the-art (SOTA) LiDAR-only detectors perform well for 3D object detection tasks, but point cloud data are typically sparse and lacks semantic information. Detailed semantic information obtained from camera images can be added with existing LiDAR-based detectors to create a robust 3D detection pipeline. With two different data types, a major challenge in developing multi-modal sensor fusion networks is to achieve effective data fusion while managing computational resources. With separate 2D and 3D feature extraction backbones, feature fusion can become more challenging as these modes generate different gradients, leading to gradient conflicts and suboptimal convergence during network optimization. To this end, we propose a 3D object detection method, Attention-Enabled Point Fusion (AEPF). AEPF uses images and voxelized point cloud data as inputs and estimates the 3D bounding boxes of object locations as outputs. An attention mechanism is introduced to an existing feature fusion strategy to improve 3D detection accuracy and two variants are proposed. These two variants, AEPF-Small and AEPF-Large, address different needs. AEPF-Small, with a lightweight attention module and fewer parameters, offers fast inference. AEPF-Large, with a more complex attention module and increased parameters, provides higher accuracy than baseline models. Experimental results on the KITTI validation set show that AEPF-Small maintains SOTA 3D detection accuracy while inferencing at higher speeds. AEPF-Large achieves mean average precision scores of 91.13, 79.06, and 76.15 for the car class’s easy, medium, and hard targets, respectively, in the KITTI validation set. Results from ablation experiments are also presented to support the choice of model architecture.

Chemistry↗

Target Selection and Sample Characterization for the DESI LOW-Z Secondary Target Program

Abstract We introduce the DESI LOW- Z Secondary Target Survey, which combines the wide-area capabilities of the Dark Energy Spectroscopic Instrument (DESI) with an efficient, low-redshift target selection method. Our selection consists of a set of color and surface brightness cuts, combined with modern machine-learning methods, to target low-redshift dwarf galaxies ( z < 0.03) between 19 < r < 21 with high completeness. We employ a convolutional neural network (CNN) to select high-priority targets. The LOW- Z survey has already obtained over 22,000 redshifts of dwarf galaxies ( M * < 10 9 M ⊙ ), comparable to the number of dwarf galaxies discovered in the Sloan Digital Sky Survey DR8 and GAMA. As a spare fiber survey, LOW- Z currently receives fiber allocation for just ∼50% of its targets. However, we estimate that our selection is highly complete: for galaxies at z < 0.03 within our magnitude limits, we achieve better than 95% completeness with ∼1% efficiency using catalog-level photometric cuts. We also demonstrate that our CNN selections z < 0.03 galaxies from the photometric cuts subsample at least 10 times more efficiently while maintaining high completeness. The full 5 yr DESI program will expand the LOW- Z sample, densely mapping the low-redshift Universe, providing an unprecedented sample of dwarf galaxies, and providing critical information about how to pursue effective and efficient low-redshift surveys.

79 ASTRONOMY AND ASTROPHYSICS↗

SIMBAD : a sequence-independent molecular-replacement pipeline

The conventional approach to finding structurally similar search models for use in molecular replacement (MR) is to use the sequence of the target to search against those of a set of known structures. Sequence similarity often correlates with structure similarity. Given sufficient similarity, a known structure correctly positioned in the target cell by the MR process can provide an approximation to the unknown phases of the target. An alternative approach to identifying homologous structures suitable for MR is to exploit the measured data directly, comparing the lattice parameters or the experimentally derived structure-factor amplitudes with those of known structures. Here, SIMBAD , a new sequence-independent MR pipeline which implements these approaches, is presented. SIMBAD can identify cases of contaminant crystallization and other mishaps such as mistaken identity (swapped crystallization trays), as well as solving unsequenced targets and providing a brute-force approach where sequence-dependent search-model identification may be nontrivial, for example because of conformational diversity among identifiable homologues. The program implements a three-step pipeline to efficiently identify a suitable search model in a database of known structures. The first step performs a lattice-parameter search against the entire Protein Data Bank (PDB), rapidly determining whether or not a homologue exists in the same crystal form. The second step is designed to screen the target data for the presence of a crystallized contaminant, a not uncommon occurrence in macromolecular crystallography. Solving structures with MR in such cases can remain problematic for many years, since the search models, which are assumed to be similar to the structure of interest, are not necessarily related to the structures that have actually crystallized. To cater for this eventuality, SIMBAD rapidly screens the data against a database of known contaminant structures. Where the first two steps fail to yield a solution, a final step in SIMBAD can be invoked to perform a brute-force search of a nonredundant PDB database provided by the MoRDa MR software. Through early-access usage of SIMBAD , this approach has solved novel cases that have otherwise proved difficult to solve.

59 BASIC BIOLOGICAL SCIENCES↗

SU-E-T-24: A Dose Volume Comparison in Stereotactic Body Radiation Therapy Using Flattened and Un-Flattened Photon Beams

Purpose: Aim of this study is to compare the dose volume characteristics of 6X FFF (flattening Free Filter) Arc and 6X FB (flattened Beam) arc photon plans in SBRT technique. Methods: Eight patients who received linear Accelearator-based SBRT were retrospectively included in this study. A dose of 50 Gy was given to the target in five fractions. Same data set was used to generate plans for both FFF and FB. ITV was generated using maximum intensity projection and critical structures were derived using average intensity projection. PTV obtained by giving 0.5cm margin to ITV. Results: While both modalities can provide satisfactory target dose coverage, the dose to PTV was more heterogeneous in FFF than 6X FB plans in all cases. The doses in all plans were well below institutional constraints for both modalities. Comparing the results of Homogeneity Index(HI), Conformity Index(CI), PTV-D80% volume, D50% volume and D20% volume (Table-1 ) for both techniques, found all the indices are within limits of RTOG guidelines but the 6X FFF is superior in sparing normal tissues in compare with FB. In all cases studied, more treatment time was required for FB treatment delivery for a given prescription. The results indicate that for large dose delivery FFF is preferable as volumetric parameters like HI and CI are better and dose can be delivered in a short span of time. Conclusion: Both Flattened and Unflattened beam SBRT systems can provide adequate dose coverage for target tumor. While the unflattened beams deliver less normal tissue dose than Flattened beams in all cases. The magnitude of differences in normal tissue dose between both modalities was due to beam characterization of the beams. Flattened beam requires more Monitor Units to deliver similar target prescription to the tumor than unflattened beam SBRT systems. The results of this study may provide a general guideline for patient and treatment modality selection based on volumetric, tumor control and normal tissue sparing considerations.

60 APPLIED LIFE SCIENCES↗

Zero Energy University Campuses: A 2018 Progress Update on Reaching Campus Energy Goals: Preprint

Many universities have aggressive energy-reduction and climate action plans. To reach these goals, leading universities have developed a suite of common energy-efficiency and renewable generation strategies. In this paper, we present a common set of approaches across the following areas: zero energy campus definitions and planning, best practices for including energy targets in new construction procurement contracts and design guidelines, implementing pilot new construction zero energy projects, aggressively implementing best-in-class laboratory energy-efficiency strategies, planning for and optimizing on-site and off-site renewable energy projects, and high-performance district energy systems. Best practices are compiled from various experiences, including programs funded by the U.S. Department of Energy, Energy Efficiency and Renewable Energy program. The summary of these best practices is to reduce campus energy use and then meet the remaining campus energy needs with renewable energy. The fivestep process to developing and implementing campus energy-reduction plans is described: 1) determine baseline energy consumption, 2) analyze technology options, 3) develop a plan and set priorities, 4) implement the plan, and 5) evaluate progress. The process follows a logical hierarchy of actions to evaluate options by energy sector and set specific targets. It encompasses all energy systems on campus, recognizing that campus-wide measures have increased potential for reducing energy use. Common strategies are explained along with examples and results.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Zero Energy University Campuses: A 2018 Progress Update on Reaching Campus Energy Goals

Many universities have aggressive energy-reduction and climate action plans. To reach these goals, leading universities have developed a suite of common energy-efficiency and renewable generation strategies. In this paper, we present a common set of approaches across the following areas: zero energy campus definitions and planning, best practices for including energy targets in new construction procurement contracts and design guidelines, implementing pilot new construction zero energy projects, aggressively implementing best-in-class laboratory energy-efficiency strategies, planning for and optimizing on-site and off-site renewable energy projects, and high-performance district energy systems. Best practices are compiled from various experiences, including programs funded by the U.S. Department of Energy, Energy Efficiency and Renewable Energy program. The summary of these best practices is to reduce campus energy use and then meet the remaining campus energy needs with renewable energy. The fivestep process to developing and implementing campus energy-reduction plans is described: 1) determine baseline energy consumption, 2) analyze technology options, 3) develop a plan and set priorities, 4) implement the plan, and 5) evaluate progress. The process follows a logical hierarchy of actions to evaluate options by energy sector and set specific targets. It encompasses all energy systems on campus, recognizing that campus-wide measures have increased potential for reducing energy use. Common strategies are explained along with examples and results.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Simultaneous and Constrained Calibration of Multiple Hyperspectral Images Through a New Generalized Empirical Line Model

The empirical line (EL) calibration method is commonly used for atmospheric correction of remotely sensed spectral images and recovery of surface reflectance. The current EL-based methods are applicable to calibrate only single images. Therefore, the use of the EL calibration is impractical for imaging campaigns, where many (partially overlapped) images are acquired to cover a large area. In addition, the EL results are unconstrained and an undesired reflectance with negative values or larger than 100% can be obtained. In this paper, we use the standard EL model to formulate a new generalized empirical line (GEL) model. Based on the GEL, we present a novel method for simultaneous and constrained calibration of multiple images. This new method allows for calibration through multiple image constrained empirical line (MIcEL) and three additional calibration modes. Given a set of images, we use the available ground targets and automatically extracted tie points between overlapping images to calibrate all the images in the set simultaneously. Quantitative and visual assessments of the proposed method were carried out relatively to the off-the-shelf method quick atmospheric correction (QUAC), using real hyperspectral images and field measurements. The results clearly show the superiority of MIcEL with respect to the minimization of the difference between the reflectance values of the same object in different overlapping images. An assessment of the absolute accuracy, with respect to 11 field measurement points, shows that the accuracy of MIcEL, with an average mean absolute error (MAE) of ~11%, is comparable with respect to the QUAC.

47 OTHER INSTRUMENTATION↗

Maximize, minimize or target - optimization for a fitted response from a designed experiment

One of the common goals of running and analyzing a designed experiment is to find a location in the design space that optimizes the response of interest. Depending on the goal of the experiment, we may seek to maximize or minimize the response, or set the process to hit a particular target value. After the designed experiment, a response model is fitted and the optimal settings of the input factors are obtained based on the estimated response model. Furthermore, the suggested optimal settings of the input factors are then used in the production environment.

97 MATHEMATICS AND COMPUTING↗

Cycle accurate and cycle reproducible memory for an FPGA based hardware accelerator

A method, system and computer program product are disclosed for using a Field Programmable Gate Array (FPGA) to simulate operations of a device under test (DUT). The DUT includes a device memory having a number of input ports, and the FPGA is associated with a target memory having a second number of input ports, the second number being less than the first number. In one embodiment, a given set of inputs is applied to the device memory at a frequency Fd and in a defined cycle of time, and the given set of inputs is applied to the target memory at a frequency Ft. Ft is greater than Fd and cycle accuracy is maintained between the device memory and the target memory. In an embodiment, a cycle accurate model of the DUT memory is created by separating the DUT memory interface protocol from the target memory storage array.

97 MATHEMATICS AND COMPUTING↗

Cycle accurate and cycle reproducible memory for an FPGA based hardware accelerator

A method, system and computer program product are disclosed for using a Field Programmable Gate Array (FPGA) to simulate operations of a device under test (DUT). The DUT includes a device memory having a number of input ports, and the FPGA is associated with a target memory having a second number of input ports, the second number being less than the first number. In one embodiment, a given set of inputs is applied to the device memory at a frequency Fd and in a defined cycle of time, and the given set of inputs is applied to the target memory at a frequency Ft. Ft is greater than Fd and cycle accuracy is maintained between the device memory and the target memory. In an embodiment, a cycle accurate model of the DUT memory is created by separating the DUT memory interface protocol from the target memory storage array.

42 ENGINEERING↗

Cycle accurate and cycle reproducible memory for an FPGA based hardware accelerator

A method, system and computer program product are disclosed for using a Field Programmable Gate Array (FPGA) to simulate operations of a device under test (DUT). The DUT includes a device memory having a number of input ports, and the FPGA is associated with a target memory having a second number of input ports, the second number being less than the first number. In one embodiment, a given set of inputs is applied to the device memory at a frequency Fd and in a defined cycle of time, and the given set of inputs is applied to the target memory at a frequency Ft. Ft is greater than Fd and cycle accuracy is maintained between the device memory and the target memory. In an embodiment, a cycle accurate model of the DUT memory is created by separating the DUT memory interface protocol from the target memory storage array.

Asaad, Sameh W.↗

Closed Loop Control Compact Exercise Device for Use on MPCV

Long duration space travel to Mars or to an asteroid will expose astronauts to extended periods of reduced gravity. To combat spaceflight physiological deconditioning, astronauts will use resistive and aerobic exercise regimens for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the mass and volume available for an exercise device in the next generation of spacecraft is limited. Therefore, compact exercise device prototypes are being developed for human in the loop evaluations. The NASA Human Research Program (HRP) is managing Advanced Exercise Concepts (AEC) requirements development and candidate technology maturation for all exploration mission profiles from Multi-Purpose Crew Vehicle (MPCV) exploration missions (e.g., EM-2, up to 21 day) to Mars Transit (up to 1000 day) missions. Numerous technologies have been considered and evaluated against HRP-approved functional requirements and include flywheel, pneumatic and closed-loop microprocessor-controlled motor driven power plants. Motor driven technologies offer excellent torque density and load accuracy characteristics as well as the ability to create custom mechanical impedance (the dynamic relationship between force and velocity) and custom load versus position exercise algorithms. Further, closed-loop motor-driven technologies offer the ability to monitor exercise dose parameters and adapt to the needs of the crewmember for real time optimization of exercise prescriptions. A simple proportional-integral-derivative (PID) controller is demonstrated in a prototype motor driven exercise device with comparison to resistive static and dynamic load set points and aerobic work rate targets. The resistive load term in the algorithm includes a constant force component (Fcmg) as well as inertial component (Fima) and a discussion of system tuning is presented in terms of addressing key functional requirements and human interfaces. The device aerobic modality is modelled as a rowing exercise using ground data sets obtained from Concept 2 rowers as well as competitive rowing1. A discussion of software and electronic implementations are presented which demonstrate unique approaches to meeting the constrained mass, volume and power requirements of the MPCV. . In addition to utilizing traditional PID control, controllers utilizing state feedback with gains solved using a Linear Quadratic Regulator will be developed. Controllability and observability will be utilized to investigate the need for state measurement in the design. As the control system directly interacts with human test subjects, robust methods such as H-infinity are also being investigated.1. Kleshnev V. Biomechanics. In: Rowing, Handbook of Sports Medicine and Science. ed. by Secher N., Voliantis S. IOC Medical Commission, Blackwell Pub. pp. 22-34, 2007

microgravity↗

Predicting kinase inhibitors using bioactivity matrix derived informer sets

Prediction of compounds that are active against a desired biological target is a common step in drug discovery efforts. Virtual screening methods seek some active-enriched fraction of a library for experimental testing. Where data are too scarce to train supervised learning models for compound prioritization, initial screening must provide the necessary data. Commonly, such an initial library is selected on the basis of chemical diversity by some pseudo-random process (for example, the first few plates of a larger library) or by selecting an entire smaller library. These approaches may not produce a sufficient number or diversity of actives. An alternative approach is to select an informer set of screening compounds on the basis of chemogenomic information from previous testing of compounds against a large number of targets. We compare different ways of using chemogenomic data to choose a small informer set of compounds based on previously measured bioactivity data. We develop this Informer-Based-Ranking (IBR) approach using the Published Kinase Inhibitor Sets (PKIS) as the chemogenomic data to select the informer sets. We test the informer compounds on a target that is not part of the chemogenomic data, then predict the activity of the remaining compounds based on the experimental informer data and the chemogenomic data. Through new chemical screening experiments, we demonstrate the utility of IBR strategies in a prospective test on three kinase targets not included in the PKIS.

59 BASIC BIOLOGICAL SCIENCES↗

Cumulative short-lived photofission product yields for nuclear forensic application

Experiments have long been carried out with linear accelerator (linac) produced bremsstrahlung X-rays to study high-energy photon-induced fission, known as “photofission”. One benefit of photofission, when compared with neutron-induced fission, is the ability to investigate fundamental physics of fission at excitation energies lower than what is possible with neutrons [1]. Absorption of an incident neutron results in a compound nucleus with an excitation energy at least equal to the neutron binding energy; thus, the lowest energy region of the fission barrier cannot be studied. Fission product yield distributions are dependent on the incident particle energy and the target nucleus mass. They are generally represented by a double-humped curve, with low and high mass “peaks” and an intermediate mass “valley”. As incident particle energy increases, the excitation energy of the nucleus increases, thereby increasing the overall yield of isotopes in the valley with respect to the two maxima or peaks of the fission product curve [3]. Photofission is most probable for incident photons around 14 MeV due to the giant dipole resonance. Induced photofission around this energy results in a fission product yield distribution that resembles 14 MeV DT neutron fission more than thermal or fast (500 keV) neutron fission. In post-detonation nuclear forensics, the peak-to-valley ratio of the fission product yield curve could be used for characterizing device type by providing an indication of the neutron energy spectrum that had induced fission (e.g., 500 keV vs. 14 MeV). The goal of this work is to improve nuclear data for isotopes of interest in nuclear forensics and special nuclear material (SNM) detection, specifically the fission product yield data via photofission experiments for the isotopes of 238U and 232Th. Photofission has been proposed as a less costly and more flexible production method for the valley isotopes that are representative of DT neutron fission product yield distributions, which would benefit nuclear forensics exercises in testing for analysis techniques. Natural uranium and thorium targets were irradiated with bremsstrahlung photons (nominal endpoint energies of 8, 14, and 20 MeV), generated via impingement of high-energy electrons on a tungsten electron-to-photon radiator. Gamma-ray spectroscopy was used to observe and identify the decay of the resulting fission products. The photofission yields of 102 fission products were measured for the set of the 238U and 232Th targets at the three bremsstrahlung X-ray endpoint energies 8, 14, and 20 MeV. These fragments included masses ranging from A=84 to A=144, with half-lives as short as 1.07 seconds.

07 ISOTOPE AND RADIATION SOURCES↗

Evaluating vaccination strategies for tuberculosis in endemic and non-endemic settings

According to the World Health Organization, tuberculosis (TB) is the leading cause of death from infectious disease worldwide. While there is no effective vaccine against adult pulmonary TB, more than a dozen vaccine candidates are in the clinical trial pipeline. These include both pre-exposure vaccines to prevent initial infections and post-exposure vaccines to prevent reactivation of latent disease. Many epidemiological models have been used to study TB, but most have not included a continuous age structure and the possibility of both pre- and post-exposure vaccination. Incorporating age-dependent death rates, disease properties, and social contact data allows for more realistic modeling of disease spread. Here, we propose a continuous age-structured model for the epidemiology of tuberculosis with pre- and post-exposure vaccination. We use uncertainty and sensitivity analysis to make predictions about the efficacy of different vaccination strategies in a non-endemic setting (United States) and an endemic setting (Cambodia). In particular, we determine optimal age groups to target for pre-exposure and post-exposure vaccination in both settings. We find that the optimal age groups tend to be younger for Cambodia than for the US, and that post-exposure vaccination has a significantly larger effect than pre-exposure vaccination in the US.

60 APPLIED LIFE SCIENCES↗

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently, the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗