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At least 1,135 records · Page 63

SU-G-JeP3-01: A Method to Quantify Lung SBRT Target Localization Accuracy Based On Digitally Reconstructed Fluoroscopy

Purpose: To develop a methodology based on digitally-reconstructed-fluoroscopy (DRF) to quantitatively assess target localization accuracy of lung SBRT, and to evaluate using both a dynamic digital phantom and a patient dataset. Methods: For each treatment field, a 10-phase DRF is generated based on the planning 4DCT. Each frame is pre-processed with a morphological top-hat filter, and corresponding beam apertures are projected to each detector plane. A template-matching algorithm based on cross-correlation is used to detect the tumor location in each frame. Tumor motion relative beam aperture is extracted in the superior-inferior direction based on each frame’s impulse response to the template, and the mean tumor position (MTP) is calculated as the average tumor displacement. The DRF template coordinates are then transferred to the corresponding MV-cine dataset, which is retrospectively filtered as above. The treatment MTP is calculated within each field’s projection space, relative to the DRF-defined template. The field’s localization error is defined as the difference between the DRF-derived-MTP (planning) and the MV-cine-derived-MTP (delivery). A dynamic digital phantom was used to assess the algorithm’s ability to detect intra-fractional changes in patient alignment, by simulating different spatial variations in the MV-cine and calculating the corresponding change in MTP. Inter-and-intra-fractional variation, IGRT accuracy, and filtering effects were investigated on a patient dataset. Results: Phantom results demonstrated a high accuracy in detecting both translational and rotational variation. The lowest localization error of the patient dataset was achieved at each fraction’s first field (mean=0.38mm), with Fx3 demonstrating a particularly strong correlation between intra-fractional motion-caused localization error and treatment progress. Filtering significantly improved tracking visibility in both the DRF and MV-cine images. Conclusion: We have developed and evaluated a methodology to quantify lung SBRT target localization accuracy based on digitally-reconstructed-fluoroscopy. Our approach may be useful in potentially reducing treatment margins to optimize lung SBRT outcomes. R01-184173.

60 APPLIED LIFE SCIENCES↗

Inferring protein expression changes from mRNA in Alzheimer’s dementia using deep neural networks

Identifying the molecular systems and proteins that modify the progression of Alzheimer’s disease and related dementias (ADRD) is central to drug target selection. However, discordance between mRNA and protein abundance, and the scarcity of proteomic data, has limited our ability to advance candidate targets that are mainly based on gene expression. Therefore, by using a deep neural network that predicts protein abundance from mRNA expression, here we attempt to track the early protein drivers of ADRD. Specifically, by applying the clei2block deep learning model to 1192 brain RNA-seq samples, we identify protein modules and disease-associated expression changes that were not directly observed at the mRNA level. Moreover, pseudo-temporal trajectory inference based on the predicted proteome became more closely correlated with cognitive decline and hippocampal atrophy compared to RNA-based trajectories. This suggests that the predicted changes in protein expression could provide a better molecular representation of ADRD progression. Furthermore, overlaying clinical traits on protein pseudotime trajectory identifies protein modules altered before cognitive impairment. These results demonstrate how our method can be used to identify potential early protein drivers and possible drug targets for treating and/or preventing ADRD.

60 APPLIED LIFE SCIENCES↗

Tracking Data Certification for the Lunar Reconnaissance Orbiter

This paper details the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC) Flight Dynamics Facility (FDF) tracking data certification effort of the Lunar Reconnaissance Orbiter (LRO) Space Communications Network (SCN) complement of tracking stations consisting of the NASA White Sands 1 antenna (WS1), and the commercial provider Universal Space Network (USN) antennas at South Point, Hawaii; Dongara Australia; Weilheim, Germany; and Kiruna, Sweden. Certification assessment required the cooperation and coordination of parties not under the control of either the LRO project or ground stations as uplinks on cooperating spacecraft were necessary. The LRO range-tracking requirement of 10m 1 sigma could be satisfactorily demonstrated using any typical spacecraft capable of range tracking. Though typical Low Earth Orbiting (LEO) or Geosynchronous Earth Orbiting (GEO) spacecraft may be adequate for range certification, their measurement dynamics and noise would be unacceptable for proper Doppler certification of 1-3mm/sec 1 sigma. As LRO will orbit the Moon, it was imperative that a suitable target spacecraft be utilized which can closely mimic the expected lunar orbital Doppler dynamics of +/-1.6km/sec and +/-1.5m/sq sec to +/-0.15m/sq sec, is in view of the ground stations, supports coherent S-Band Doppler tracking measurements, and can be modeled by the FDF. In order to meet the LRO metric tracking data specifications, the SCN ground stations employed previously uncertified numerically controlled tracking receivers. Initial certification testing revealed certain characteristics of the units that required resolution before being granted certification.

Morinelli, Patrick J.↗

SU-E-J-64: Feasibility Study of Surgical Clips for Fiducial Tracking in CyberKnife System

Purpose: To investigate the ability of CyberKnife to track surgical clips used as fiducial markers. Methods: The Octavius 1000SRS detector and solid water (RW3) slab phantom were used with motion platform to evaluate the study. The RW3 slab phantom was set up to measure the dose distribution from coronal plane. It consists of 9 plates and the thickness of each plate is 10mm. Among them, one plate was attached with 3 surgical clips, which are orthogonally positioned on outer region of array. The length of attached clip was represented as 1cm on planning CT. The clip plate was placed on the 1000SRS detector and 3 slabs were stacked up on the plate to build the measuring depth. Below the detector, 5 slabs were set. The two-axis motion platform was programmed with 1D sinusoidal movement (20mm peak-to-peak, 3s period) toward superior/inferior and left/right directions to simulate target motion. During delivery, two clips were extracted by two X-ray imagers, which led to translational error correction only. Synchrony was also used for dynamic tracking. After the irradiation, the measured dose distribution of coronal plane was compared with the planar dose distribution calculated by the CyberKnife treatment planning system (Multiplan) for cross verification. The results were assessed by comparing the absolute Gamma (γ) index. Results: The dose distributions measured by the 1000SRS detector were in good agreements with those calculated by Multiplan. In the dosimetric comparison using γ-function criteria based on the distance-to-agreement of 3mm and the local dose difference of 3%, the passing rate with γ- parameter ≤1 was 91% in coronal plane. Conclusion: The surgical clips can be considered as new fiducials for robotic radiosurgery delivery by considering the target margin with less than 5mm.

60 APPLIED LIFE SCIENCES↗

Effect of sun and sensor geometry, canopy structure and density, and atmospheric condition on the spectral response of vegetation, with particular emphasis on across-track pointing

A computer modeling and simulation study carried out to assess the effects of various sun and sensor geometries and atmospheric conditions on the directional reflected radiance of several vegetated targets is described. Spectral responses at two wavelengths, 0.68 micron and 0.80 micron, are simulated at nine sensor zenith angles, five sensor azimuths, and nine solar zenith angles for six vegetation canopies under three atmspheric conditions. The six canopies comprise two different geometries of grass canopies at low, medium, and high leaf density. The results suggest that off-nadir viewing effects are more pronounced in the red than in the IR. However, the use of such transformations as the normalized difference index is found to reduce much of the variability seen in the bands. The magnitude of off-nadir viewing effects is found to be a function of canopy geometry.

Schnetzler, C. C.↗

STS-70 Space Shuttle Mission Report - September 1995

The STS-70 Space Shuttle Program Mission Report summarizes the Payload activities as well as the Orbiter, External Tank (ET), Solid Rocket Booster (SRB), Reusable Solid Rocket Motor (RSRM), and the Space Shuttle main engine (SSME) systems performance during the seventieth flight of the Space Shuttle Program, the forty-fifth flight since the return-to-flight, and the twenty-first flight of the Orbiter Discovery (OV-103). In addition to the Orbiter, the flight vehicle consisted of an ET that was designated ET-71; three SSMEs that were designated as serial numbers 2036, 2019, and 2017 in positions 1, 2, and 3, respectively; and two SRBs that were designated 81-073. The RSRMs, designated RSRM-44, were installed in each SRB and were designated as 36OL044A for the left SRB, and 36OL044B for the right SRB. The primary objective of this flight was to deploy the Tracking and Data Relay Satellite-G/Inertial Upper Stage (TDRS-G/IUS). The secondary objectives were to fulfill the requirements of the Physiological and Anatomical Rodent Experiment/National Institutes of Health-Rodents (PARE/NIH-R); Bioreactor Demonstration System (BDS); Commercial Protein Crystal Growth (CPCG) experiment; Space Tissue Loss/National Institutes of Health - Cells (STL/NIH-C) experiment; Biological Research in Canisters (BRIC) experiment; Shuttle Amateur Radio Experiment-2 (SAREX-2); Visual Function Tester-4 (VFT-4); Hand-Held, Earth-Oriented, Real-Time, Cooperative, User-Friendly Location-Targeting and Environmental System (HERCULES); Microencapsulation in Space-B (MIS-B) experiment; Window Experiment (WINDEX); Radiation Monitoring Equipment-3 (RME-3); and the Military Applications of Ship Tracks (MAST) payload.

Fricke, Robert W., Jr.↗

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-set for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Flight Deck Interval Management Avionics: Eye-Tracking Analysis

Interval Management (IM) is one NexGen method for achieving airspace efficiencies. In order to initiate IM procedures, Air Traffic Control provides an IM clearance to the IM aircraft's pilots that indicates an intended spacing from another aircraft (the target to follow - or TTF) and the point at which this should be achieved. Pilots enter the clearance in the flight deck IM (FIM) system; and once the TTF's Automatic Dependent Surveillance-Broadcast signal is available, the FIM algorithm generates target speeds to meet that IM goal. This study examined four Avionics Conditions (defined by the instrumentation and location presenting FIM information) and three Notification Methods (defined by the visual and aural alerts that notified pilots to IM-related events). Current commercial pilots flew descents into Dallas/Fort-Worth in a high-fidelity commercial flight deck simulation environment with realistic traffic and communications. All 12 crews experienced each Avionics Condition, where order was counterbalanced over crews. Each crew used only one of the three Notification Methods. This paper presents results from eye tracking data collected from both pilots, including: normalized number of samples falling within FIM displays, normalized heads-up time, noticing time, dwell time on first FIM display look after a new speed, a workload-related metric, and a measure comparing the scan paths of pilot flying and pilot monitoring; and discusses these in the context of other objective (vertical and speed profile deviations, response time to dial in commanded speeds, out-of-speed-conformance and reminder indications) and subjective measures (workload, situation awareness, usability, and operational acceptability).

Latorella, Kara↗

A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm

Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [{sup 3}H]-NBTI binding affinity (K{sub i}) and [{sup 3}H]-adenosine uptake (IC{sub 50}) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥ 13.3x K{sub i}, ≥ 4x IC{sub 50}) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥ 0.1x K{sub i}, ≥ 0.05x IC{sub 50}) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds K{sub i} < 1 μM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP > 5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders. - Highlights: • ENT1 inhibition causes bronchospasm and severe dyspnoea in respiratory patients. • Neutral or basic compounds with clogP > 5 have increased promiscuity to bind ENT1. • ENT1 should be assessed within safety strategies for respiratory research programs. • Quantitative translation enables informed risk-assessment of off-target ENT1 activity.

60 APPLIED LIFE SCIENCES↗

The sweeper spectrometer for neutron invariant-mass spectroscopy at FRIB

Neutron invariant-mass spectroscopy (NIMS) is a key technique for studying unbound and weakly bound nuclei at the limits of stability. At the Facility for Rare Isotope Beams (FRIB), such measurements are performed using the Sweeper spectrometer, a large-gap, high-rigidity dipole system coupled to the MoNA-LISA neutron detector arrays. To meet the demands imposed by higher beam energies (>130 MeV/u) and the broad cocktail-beam selection available at FRIB, the spectrometer has recently been upgraded to improve particle-identification and detection performance. Upstream of the reaction target, a plastic scintillator with Silicon photomultiplier (SiPM) readout provides the global trigger and time reference, two parallel plate avalanche counters (PPACs) track the trajectories of incoming beam particles, and a silicon PIN detector measures the energy loss, ΔE, for charge (Z) identification. After the Sweeper magnet, the trajectories of the reaction products are tracked by two micro-pattern drift chambers (MPDCs), their charge (Z) is identified by a Frisch-grid ionization chamber (FG-IC), and their mass-to-charge ratio (A/Q) is deduced by time-of-flight measurement using a fast plastic scintillator read out by an array of photomultiplier tubes (PMTs). The detection system also incorporates the Modular Neutron Array (MoNA) for neutron detection and the CAESium-iodide scintillator ARray (CAESAR) for high-efficiency γ-ray measurements to enable full kinematic reconstruction. Performance was evaluated using a cocktail beam around 37 Al accelerated at E ≈ 130 MeV/u during the first FRIB campaign, demonstrating the readiness of the upgraded system for future studies of nuclei at and beyond the neutron drip line.

Particle identification methods↗

Quantum Computation of Dynamical Quantum Phase Transitions and Entanglement Tomography in a Lattice Gauge Theory

Strongly coupled gauge theories far from equilibrium may exhibit unique features that could illuminate the physics of the early universe and of hadron and ion colliders. Studying real-time phenomena has proven challenging with classical-simulation methods but is a natural application of quantum simulation. To demonstrate this prospect, we quantum compute nonequal-time correlation functions and perform entanglement tomography of nonequilibrium states of a simple lattice gauge theory, the Schwinger model, using a trapped-ion quantum computer by IonQ Inc. As an ideal target for near-term devices, a recently predicted dynamical quantum phase transition in this model is studied by preparing, quenching, and tracking the subsequent nonequilibrium dynamics in three ways: (i) overlap echos signaling dynamical transitions, (ii) nonequal-time correlation functions with an underlying topological nature, and (iii) the entanglement structure of nonequilibrium states, including entanglement Hamiltonians. These results constitute the first observation of a dynamical quantum phase transition in a lattice gauge theory on a quantum computer and are a first step toward investigating topological phenomena in nuclear and high-energy physics using quantum technologies.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

SU-G-IeP4-04: DD-Neutron Source Collimation for Neutron Stimulated Emission Computed Tomography: A Monte Carlo Simulation Study

Purpose: To optimize collimation and shielding for a deuterium-deuterium (DD) neutron generator for an inexpensive and compact clinical neutron imaging system. The envisioned application is cancer diagnosis through Neutron Stimulated Emission Computed Tomography (NSECT). Methods: Collimator designs were tested with an isotropic 2.5 MeV neutron source through GEANT4 simulations. The collimator is a 52×52×52 cm{sup 3} polyethylene block coupled with a 1 cm lead sheet in sequence. Composite opening was modeled into the collimator to permit passage of neutrons. The opening varied in shape (cylindrical vs. tapered), size (1–5 cm source-side and target-side openings) and aperture placements (13–39 cm from source-side). Spatial and energy distribution of neutrons and gammas were tracked from each collimator design. Parameters analyzed were primary beam width (FWHM), divergence, and efficiency (percent transmission) for different configurations of the collimator. Select resultant outputs were then used for simulated NSECT imaging of a virtual breast phantom containing a 2.5 cm diameter tumor to assess the effect of the collimator on spatial resolution, noise, and scan time. Finally, composite shielding enclosure made of polyethylene and lead was designed and evaluated to block 99.99% of neutron and gamma radiation generated in the system. Results: Analysis of primary beam indicated the beam-width is linear to the aperture size. Increasing source-side opening allowed at least 20% more neutron throughput for all designs relative to the cylindrical openings. Maximum throughput for all designs was 364% relative to cylindrical openings. Conclusion: The work indicates potential for collimating and shielding a DD neutron generator for use in a clinical NSECT system. The proposed collimator designs produced a well-defined collimated neutron beam that can be used to image samples of interest with millimeter resolution. Balance in output efficiency, noise reduction, and scan time should be considered to determine the optimal design for specific NSECT applications.

60 APPLIED LIFE SCIENCES↗

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging

Many breast and prostate cancers are driven by the action of steroid hormones on their cognate receptors in primary tumors and in metastases, and endocrine therapies that inhibit hormone production or block the action of these receptors provide clinical benefit to many but not all of these cancer patients. Because it is difficult to predict which individuals will be helped by endocrine therapies and which will not, positron emission tomography (PET) imaging of estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer, and androgen receptor (AR) in prostate cancer can provide useful, often functional, information on the likelihood of endocrine therapy response in individual patients. This review covers our development of three PET imaging agents, 16α-[ 18 F]fluoroestradiol (FES) for ER, 21-[ 18 F]fluoro-furanyl-nor-progesterone (FFNP) for PgR, and 16β-[ 18 F]fluoro-5α-dihydrotestosterone (FDHT) for AR, and the evolution of their clinical use. For these agents, the pathway from concept through development tracks with an emerging understanding of critical performance criteria that is needed for successful PET imaging of these low-abundance receptor targets. Progress in the ongoing evaluation of what they can add to the clinical management of breast and prostate cancers reflects our increased understanding of these diseases and of optimal strategies for predicting the success of clinical endocrine therapies.

60 APPLIED LIFE SCIENCES↗

AAA gunnermodel based on observer theory

The Luenberger observer theory is used to develop a predictive model of a gunner's tracking response in antiaircraft artillery systems. This model is composed of an observer, a feedback controller and a remnant element. An important feature of the model is that the structure is simple, hence a computer simulation requires only a short execution time. A parameter identification program based on the least squares curve fitting method and the Gauss Newton gradient algorithm is developed to determine the parameter values of the gunner model. Thus, a systematic procedure exists for identifying model parameters for a given antiaircraft tracking task. Model predictions of tracking errors are compared with human tracking data obtained from manned simulation experiments. Model predictions are in excellent agreement with the empirical data for several flyby and maneuvering target trajectories.

Kou, R. S.↗

A precision transportable tracking telemetry system

New mission requirements and the main fetures of a new generation of tracking telemetry system designed to meet these requriements are discussed. The missions include launch vehicle support, sounding rocket mission support, and LEO satellite support, which often require support from remote sites with no existing tracking resources. To meet these requirements, the new system improves on the existing capabilities in three areas: improved RF performance, automation, and target positional accuracy. Initial results of system testing are presented. Without additional adjustment, the new system routinely falls within an absolute accuracy of +/-0.075 degrees, 3 sigma, and on most passes achieves +/-0.05 degrees, 3 sigma.

Morris, R. A.↗

Centrifuge Study of Pilot Tolerance to Acceleration and the Effects of Acceleration on Pilot Performance

A research program the general objective of which was to measure the effects of various sustained accelerations on the control performance of pilots, was carried out on the Aviation Medical Acceleration Laboratory centrifuge, U.S. Naval Air Development Center, Johnsville, PA. The experimental setup consisted of a flight simulator with the centrifuge in the control loop. The pilot performed his control tasks while being subjected to acceleration fields such as might be encountered by a forward-facing pilot flying an atmosphere entry vehicle. The study was divided into three phases. In one phase of the program, the pilots were subjected to a variety of sustained linear acceleration forces while controlling vehicles with several different sets of longitudinal dynamics. Here, a randomly moving target was displayed to the pilot on a cathode-ray tube. For each combination of acceleration field and vehicle dynamics, pilot tracking accuracy was measured and pilot opinion of the stability and control characteristics was recorded. Thus, information was obtained on the combined effects of complexity of control task and magnitude and direction of acceleration forces on pilot performance. These tests showed that the pilot's tracking performance deteriorated markedly at accelerations greater than about 4g when controlling a lightly damped vehicle. The tentative conclusion was also reached that regardless of the airframe dynamics involved, the pilot feels that in order to have the same level of control over the vehicle, an increase in the vehicle dynamic stability was required with increases in the magnitudes of the acceleration impressed upon the pilot. In another phase, boundaries of human tolerance of acceleration were established for acceleration fields such as might be encountered by a pilot flying an orbital vehicle. A special pilot restraint system was developed to increase human tolerance to longitudinal decelerations. The results of the tests showed that human tolerance of longitudinal deceleration forces was considerably improved through use of the special restraint system.

Creer, Brent Y.↗

The First Flight of ATIC : Preliminary Results on CNO Nuclei

We present preliminary results on the spectra of CNO nuclei in the cosmic radiation as measured in the first flight of the Advanced Thin Ionization Calorimeter Balloon Experiment (ATIC) which lasted for 16 days, starting in December, 2000 with a launch from McMurdo, Antarctica. ATIC is a multiple, long duration balloon flight,investigation for the study of cosmic ray spectra from below 50 GeV to near 100 TeV total energy, using a fully active Bismuth Germanate (BGO) calorimeter. It is equipped with the first large area mosaic of small fully depleted silicon detector pads capable of charge identification in cosmic rays from H to Fe. As a redundancy check for the charge identification and a coarse particle tracking system, three projective layers of x-y scintillator hodoscopes were employed, above, in the center and below a Carbon interaction'target'.

Fazely, A.↗

The CNO Concentration in Cosmic Ray Spectrum as Measured From The Advanced Thin Ionization Calorimeter Experiment

We present preliminary results on the spectra of CNO nuclei in the cosmic radiation as measured in the first flight of the Advanced Thin Ionization Calorimeter Balloon Experiment (ATIC) which lasted for 16 days, starting in December, 2000 with a launch from McMurdo, Antarctica. ATIC is a multiple, long duration balloon flight, investigation for the study of cosmic ray spectra from below 50 GeV to near 100 TeV total energy, using a fully active Bismuth Germanate (BGO) calorimeter. It is equipped with the first large area mosaic of small fully depleted silicon detector pads capable of charge identification in cosmic rays from H to Fe. As a redundancy check for the charge identification and a coarse particle tracking system, three projective layers of x-y scintillator hodoscopes were employed, above, in the center and below a Carbon interaction "target".

Fazely, A. R.↗