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At least 1,477 records · Page 82

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis

Background: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN. Methods and Materials: All patients presenting with brain metastasis between 1997 and 2015 who underwent SRS and subsequent radiographic follow-up at a single tertiary-care institution were eligible for inclusion. The primary outcome was the cumulative incidence of radiographic RN. Multivariate competing risks regression was used to identify biological risk factors for RN. Results: 1939 patients (5747 lesions) were eligible for inclusion; 285 patients (15%) experienced radiographic RN after the treatment of 427 (7%) lesions. After SRS, the median time to RN was 7.6 months. After multivariate analysis, graded prognostic assessment, renal pathology, lesion diameter, and the heterogeneity index remained independently predictive of RN in the pooled cohort. In subset analyses of individual pathologies, HER2-amplified status (hazard ratio [HR] 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN. Conclusions: In the present investigation constituting the largest series of RN, several novel risk factors were identified, including renal histology, lung adenocarcinoma histology, HER2 amplification, and ALK/BRAF mutational status. These risk factors may be used to guide clinical trial design incorporating biological risk stratification or dose escalation. Future studies determining the optimal timing of targeted therapies are warranted to further define the risk of RN.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A prognostic risk model for glioma patients by systematic evaluation of genomic variations

The overall survival rate of gliomas has not significantly improved despite new effective treatments, mainly due to tumor heterogeneity and drug delivery. Here, we perform an integrated clinic-genomic analysis of 1, 477 glioma patients from a Chinese cohort and a TCGA cohort and propose a potential prognostic model for gliomas. We identify that SBS11 and SBS23 mutational signatures are associated with glioma recurrence and indicate worse prognosis only in low-grade type of gliomas and IDH-Mut subtype. We also identify 42 genomic features associated with distinct clinical outcome and successfully used ten of these to develop a prognostic risk model of gliomas. The high-risk glioma patients with shortened survival were characterized by high level of frequent copy number alterations including PTEN, CDKN2A/B deletion, EGFR amplification, less IDH1 or CIC gene mutations, high infiltration levels of immunosuppressive cells and activation of G2M checkpoint and Oxidative phosphorylation oncogenic pathway.

60 APPLIED LIFE SCIENCES↗

Plasmonic hybrid core-shell (HyCoS) AgPt NP template hybridized with GQDs for SERS enhancement of 4-MBA and BT

Surface-enhanced Raman spectroscopy (SERS) is an attractive vibrational spectroscopic technique that can enable a non-destructive and ultra-sensitive detection down to the single-molecule level. Herein, a novel hybrid SERS platform is developed based on hybrid core-shell (HyCoS) AgPt nanoparticles (NPs) and graphene quantum dots (GQDs) for the enhancement of Raman vibration of 4-mercaptobenzoic acid (4-MBA) and benzenethiol (BT). The unique design of HyCoS AgPt NPs induces strong electromagnetic mechanism (EM) enhancement through the amplification of electromagnetic fields by the excitation of high-density surface plasmons and hot spots. Superior localized surface plasmon resonance (LSPR) is generated by the AgPt core-shell and background Ag NP coupling, which is systematically investigated by the optical properties and FDTD simulations. The background Ag NPs can further increase the coverage of metallic NPs, leading to higher-density hot spots and enhanced SERS response. At the same time, GQDs can provide plentiful accessible edges for the charge transfer to the HOMO and LUMO of 4-MBA and BT based on the chemical mechanism (CM) enhancement. The mixing approach of GQDs and target molecules on the HyCoS AgPt NPs can significantly amplify the Raman signals via the strong adsorption of probe molecules by the π – π interaction. The enhancement factors of proposed SERS platform can reach ~107 and ~105 for the 4-MBA and BT respectively.

36 MATERIALS SCIENCE↗

Comparing simulated and observed EMIC wave amplitudes using in situ Van Allen Probes’ measurements

In this study, we perform a statistical study calculating electromagnetic ion cyclotron (EMIC) wave amplitudes based off in situ plasma measurements taken by the Van Allen Probes’ (1.1–5.8 R e ) Helium, Oxygen, Proton, Electron (HOPE) instrument. Calculated wave amplitudes are compared to EMIC waves observed by the Electric and Magnetic Field Instrument Suite and Integrated Science on board the Van Allen Probes during the same period. The survey covers a 22-month period (1 November 2012 to 31 August 2014), a full Van Allen Probe magnetic local time (MLT) precession. The linear theory proxy was used to identify EMIC wave events with plasma conditions favorable for EMIC wave excitation. Two hundred and thirty-two EMIC wave events (103 H + -band and 129 He + -band) were selected for this comparison. Nearly all events selected are observed beyond L = 4. Results show that calculated wave amplitudes exclusively using the in situ HOPE measurements produce amplitudes too low compared to the observed EMIC wave amplitudes. Hot proton anisotropy (Ahp) distributions are asymmetric in MLT within the inner (L < 7) magnetosphere with peak (minimum) A hp , ~0.81 to 1.00 (~0.62), observed in the dawn (dusk), 0000 < MLT ≤ 1200 (1200 < MLT ≤ 2400), sectors. Measurements of A hp are found to decrease in the presence of EMIC wave activity. A hp amplification factors are determined and vary with respect to EMIC wave-band and MLT. Lastly, He + -band events generally require double (quadruple) the measured A hp for the dawn (dusk) sector to reproduce the observed EMIC wave amplitudes.

58 GEOSCIENCES↗

Multi-scale computational model of three-dimensional hemodynamics within a deformable full-body arterial network

In this article, we present a computational multi-scale model of fully three-dimensional and unsteady hemodynamics within the primary large arteries in the human. Computed tomography image data from two different patients were used to reconstruct a nearly complete network of the major arteries from head to foot. A linearized coupled-momentum method for fluid–structure-interaction was used to describe vessel wall deformability and a multi-domain method for outflow boundary condition specification was used to account for the distal circulation. We demonstrated that physiologically realistic results can be obtained from the model by comparing simulated quantities such as regional blood flow, pressure and flow waveforms, and pulse wave velocities to known values in the literature. We also simulated the impact of age-related arterial stiffening on wave propagation phenomena by progressively increasing the stiffness of the central arteries and found that the predicted effects on pressure amplification and pulse wave velocity are in agreement with findings in the clinical literature. This work demonstrates the feasibility of three-dimensional techniques for simulating hemodynamics in a full-body compliant arterial network.

97 MATHEMATICS AND COMPUTING↗

A spin-wave magnetometer with a positive feedback

In this work, we demonstrate experimentally the operation of a spin-wave magnetometer integrated into a circuit with a positive feedback. The circuit consists of the passive magnetic and active electric parts. The magnetic part includes a sensing element, which is a magnetic cross junction made of Y 3 Fe 2 (FeO 4 ) 3 . The electric part includes a non-linear amplifier and a phase shifter. The electric and magnetic parts are connected via micrometer size antennae. Spin waves are excited by two of these antennae while the output inductive voltage produced by the interfering spin waves is detected by the third antenna. Spin waves propagating in the orthogonal arms of the cross can accumulate significantly different phase shifts, depending on the direction and the strength of the external magnetic field. The output inductive voltage reaches its maximum in the case of constructive spin wave interference. The positive feedback provides further signal amplification. It appears possible to enhance the response function, compared to the passive circuits without a feedback, by a factor of ×100 without an increase in the noise level. The experimental data show a prominent response to the external magnetic field variation, exceeding 5 x 10 3 V/T. The intrinsic noise spectral density of the device can be as low as 10 -16 V 2 /Hz. The estimated sensitivity of the prototype device is 2 x 10 -12 T/√Hz at room temperature. We argue that spin-wave magnetometers can potentially be as sensitive as SQUIDs while operating at room temperature.

36 MATERIALS SCIENCE↗

Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1– 13 C]pyruvate in vivo

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1– 13 C]pyruvate. Biocompatible formulations of hyperpolarized [1– 13 C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Efficient 15 N hyperpolarization of [ 15 N 3 ]metronidazole antibiotic via spin-relayed pulsed SABRE-SHEATH

Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) is an NMR hyperpolarization technique that relies of the simultaneous exchange of parahydrogen and a to-be-hyperpolarized molecule on the metal center of a polarization-transfer catalyst in a microtesla magnetic field. Until recently, this method has been understood to perform hyperpolarization by establishing level anti-crossings between the nuclear spins of the parahydrogen derived hydrides (acting as a source of hyperpolarization) and those of the substrate. Recently, the application of highly non-intuitive pulse sequences (comprising pulses of microtesla DC fields) was predicted to hyperpolarize nuclear spins more efficiently than the canonical (static-field) SABRE-SHEATH approach. Here we show that by employing a basic “on-off” pulse sequence of rectangular microtesla pulses, it is possible to improve the hyperpolarization efficiency for SABRE-SHEATH of [ 15 N 3 ]metronidazole, an FDA-approved antibiotic (in non-enriched and non-hyperpolarized form) and potential hypoxia sensing molecule. Specifically, we demonstrate that 15N polarization of 18.5 % can be obtained in 80 s of parahydrogen bubbling parahydrogen through a solution containing 20 mM [ 15 N 3 ]metronidazole. In practice, (1.32 ± 0.14)-fold improvements in P 15N was obtained with the pulsed method described here compared to static field technique variant. These results show that pulsed SABRE-SHEATH was successfully applied to 15 N-labeled biologically relevant molecule. Moreover, we also demonstrate that although the pulsed SABRE-SHEATH sequence was designed for polarization transfer from parahydrogen derived hydrides to the metronidazole’s 15 N catalyst-binding site, all three 15 N sites of [ 15 N 3 ]metronidazole attained the hyperpolarized state. This spin-relayed polarization transfer becomes possible due to the 15 N relay network established by their spin-spin J-couplings. The feasibility of the spin-relayed polarization transfer is demonstrated here for the first time for pulsed SABRE-SHEATH (as opposed to the static-field SABRE-SHEATH reported previously) and it paves the way to broad applicability of the technique.

Hyperpolarization↗

An empirical study of I/O separation for burst buffers in HPC systems

To meet the exascale I/O requirements for the High-Performance Computing (HPC), a new I/O subsystem, Burst Buffer, based on solid state drives (SSD), has been developed. However, the diverse HPC workloads and the bursty I/O pattern cause severe data fragmentation that requires costly garbage collection (GC) and increases the number of bytes written to the SSD. To address this data fragmentation challenge, a new multi-stream feature has been developed for SSDs. In this work, we develop an I/O Separation scheme called BIOS to leverage this multi-stream feature to group the I/O streams based on the user IDs. We propose a stream-aware scheduling policy based on burst buffer pools in the workload manager, and integrate the BIOS with the workload manager to optimize the I/O separation scheme in burst buffer. We evaluate the proposed framework with a burst buffer I/O traces from Cori Supercomputer including a diverse set of applications. Experimental results show that the BIOS could improve the performance by 1.44x on average and reduce the Write Amplification Factor (WAF) by up to 1.20x. Finally, these demonstrate the potential benefits of the I/O separation scheme for solid state storage systems.

97 MATHEMATICS AND COMPUTING↗

Oxygen deficiency induced nickel based oxides for UV & IR sensitive photo-conductive devices

Ni(NO{sub 3}){sub 3}.6H{sub 2}O has been thermally decomposed to synthesize NiO{sub x} (0 3-δ synthesis. These metal oxides have been characterized by XRD, SEM, TEM, XPS and UV–vis spectroscopy for the determination of their crystal structures, structural morphologies, oxidation states and optical band gaps. The devices, made of nanocrystalline-composites or nanocomposites, have been fabricated on gold coated soda lime glasses, where the device based on NiO{sub x} has been found applicable for UV photo-conducting and LaNiO{sub 3-δ} has been recognized as a potential IR photo-conducting sensors. Their respective current amplifications have been recorded 8 and 2.2 times more than the dark current at 2 V of DC bias. The UV sensor has been explained by direct band gap semiconducting nature of NiO{sub x} and IR sensitivity of LaNiO{sub 3-δ} was explained in terms oxygen deficiency induced band gap opening.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Comparison of pectin-degrading fungal communities in temperate forests using glycosyl hydrolase family 28 pectinase primers targeting Ascomycete fungi

Here, fungi have developed a wide assortment of enzymes to break down pectin, a prevalent polymer in plant cell walls that is important in plant defense and structure. One enzyme family used to degrade pectin is the glycosyl hydrolase family 28 (GH28). In this studywe developed primers for the amplification of GH28 coding genes from a database of 293 GH28 sequences from40 fungal genomes. The primerswere used to successfully amplify GH28 pectinases from all Ascomycota cultures tested, but only three out of seven Basidiomycota cultures. In addition, we further tested the primers in PCRs on metagenomic DNA extracted from senesced tree leaves from different forest ecosystems, followed by cloning and sequencing. Taxonomic specificity for Ascomycota GH28 genes was tested by comparing GH28 composition in leaves to internal transcribed spacer (ITS) amplicon composition using pyrosequencing. All sequences obtained from GH28 primers were classified as Ascomycota; in contrast, ITS sequences indicated that fungal communitieswere up to 39% Basidiomycetes. Analysis of leaf samples indicated that both forest stand and ecosystemtype were important in structuring fungal communities. However, site played the prominent role in explaining GH28 composition, whereas ecosystem type was more important for ITS composition, indicating possible genetic drift between populations of fungi. Overall, these primers will have utility in understanding relationships between fungal community composition and ecosystem processes, as well as detection of potentially pathogenic Ascomycetes.

59 BASIC BIOLOGICAL SCIENCES↗

Cascading economic losses from port disruptions under capacity constrained multimodal freight networks

This study quantifies how throughput disruptions at major seaports cascade through capacity-constrained multimodal freight networks and interregional production systems. We couple an agent-based model (ABM) multimodal freight simulation that resolves rerouting, terminal queueing, and inventory drawdown under binding modal and facility capacities with a multiregional output loss input-output (MRIIM) model that propagates realized delivery shortfalls across regions and sectors. The framework is demonstrated for the Port of Los Angeles using Freight Analysis Framework flows and Bureau of Economic Analysis input-output accounts and is evaluated over a 52-week horizon under deterministic sector targeted shocks and stochastic disruption realizations with uncertain severity and duration. Results indicate nonlinear amplification: realized national losses concentrate in manufacturing and transportation/warehousing even when exogenous port shocks are dispersed, suggesting that congestion spillback and limited short-run substitution can dominate the initial shock allocation. We further evaluate a tabular reinforcement-learning (Q-learning) intervention layer that selects among a small set of implementable system level levers (truck-to-rail and truck-to-barge shift settings) without overriding shipper routing, finding that such interventions reduce total losses for moderate disruptions but yield diminishing returns once substitute modes approach capacity. By linking operational freight behavior to system wide impacts under uncertainty, the proposed ABM-MRIIM pipeline provides a reusable workflow for port disruption stress testing, identification of structurally critical sectors/corridors, and evaluation of resilience interventions under realistic capacity limits.

42 ENGINEERING↗

Effects of errors in velocity tilt on maximum longitudinal compression during neutralized drift compression of intense beam pulses: I. general description

Neutralized drift compression offers an effective means for particle beam pulse compression and current amplification. In neutralized drift compression, a linear longitudinal velocity tilt (head-to-tail gradient) is applied to the non-relativistic beam pulse, so that the beam pulse compresses as it drifts in the focusing section. The beam current can increase by more than a factor of 100 in the longitudinal direction. We have performed an analytical study of how errors in the velocity tilt acquired by the beam in the induction bunching module limit the maximum longitudinal compression. It is found that the compression ratio is determined by the relative errors in the velocity tilt. That is, one-percent errors may limit the compression to a factor of one hundred. However, a part of the beam pulse where the errors are small may compress to much higher values, which are determined by the initial thermal spread of the beam pulse. It is also shown that sharp jumps in the compressed current density profile can be produced due to overlaying of different parts of the pulse near the focal plane. Examples of slowly varying and rapidly varying errors compared to the beam pulse duration are studied. For beam velocity errors given by a cubic function, the compression ratio can be described analytically. In this limit, a significant portion of the beam pulse is located in the broad wings of the pulse and is poorly compressed. The central part of the compressed pulse is determined by the thermal spread. The scaling law for maximum compression ratio is derived. In addition to a smooth variation in the velocity tilt, fast-changing errors during the pulse may appear in the induction bunching module if the voltage pulse is formed by several pulsed elements. Different parts of the pulse compress nearly simultaneously at the target and the compressed profile may have many peaks. The maximum compression is a function of both thermal spread and the velocity errors. The effects of the finite gap width of the bunching module on compression are analyzed analytically.

43 PARTICLE ACCELERATORS↗

Application of atomic layer deposited microchannel plates to imaging photodetectors with high time resolution

Novel microchannel plates have been constructed using borosilicate glass micro-capillary array substrates with 20 mu m and 10 mu m pores and coated with resistive, and secondary electron emissive, layers by atomic layer deposition. Microchannel plates in 33 mm, 50 mm and 20 cm square formats have been made and tested. Although their amplification, imaging, and timing properties are comparable to standard glass microchannel plates, the background rates and lifetime characteristics are considerably improved. Sealed tube detectors based on the Planacon tube, and a 25 mm cross delay line readout tube with a GaN(Mg) opaque photocathode deposited on borosilicate microchannel plates have been fabricated. Considerable progress has also been made with 20 cm microchannel plates for a 20 cm format sealed tube sensor with strip-line readout that is being developed for Cherenkov light detection.

Siegmund, O. H. W.↗

An Internal ALD-Based High Voltage Divider and Signal Circuit for MCP-based Photodetectors

We describe a pin-less design for the high voltage (HV) resistive divider of the all-glass LAPPD (TM) 8 in,square thin photodetector module. The divider, which distributes high voltage applied to the photocathode to the two micro-channel plates (MCPs) that constitute the amplification stage, is comprised of the two MCPs and three glass mechanical spacers, each of which is coated with a resistive layer using atomic layer deposition (ALD). The three glass grid spacers and the two MCPs form a continuous resistive path between cathode and anode, with the voltages across the MCPs and the spacers determined by the resistance of each. High voltage is applied on an external tab on the top glass window that connects to the photocathode through the metal seal. The DC ground is supplied by microstrips on the bottom glass plate that form the high-bandwidth anode. The microstrips exit the package through the glass-frit seal of the anode base-plate and the package sidewall. The divider is thus completely internal, with no HV pins penetrating the low-profile flat glass package. Measurements of the performance of the divider are presented for the 8 in.-square MCP and spacer package in a custom test fixture and for an assembled externally pumped LAPPD (TM) prototype with an aluminum photocathode. (C) 2015 Elsevier B.V. All rights reserved.

Adams, Bernhard W.↗

Combination of two Gas Electron Multipliers and a Micromegas as gain elements for a time projection chamber

We measured the properties of a novel combination of two Gas Electron Multipliers with a Micromegas for use as amplification devices in high-rate gaseous time projection chambers. The goal of this design is to minimize the buildup of space charge in the drift volume of such detectors in order to eliminate the standard gating grid and its resultant dead time, while preserving good tracking and particle identification performance. To characterize this micro-pattern gas detector configuration, we measured the positive ion back-flow and energy resolution at various element gains and electric fields, using a variety of gases, and additionally studied crosstalk effects and discharge rates. At a gain of 2000, this configuration achieves an ion back-flow below 0.4% and an energy resolution better than σ / E = 12 % for 55 Fe X-rays.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Toward single electron resolution phonon mediated ionization detectors

Experiments seeking to detect rare event interactions such as dark matter or coherent elastic neutrino nucleus scattering are striving for large mass detectors with very low detection threshold. Using Neganov-Luke phonon amplification effect, the Cryogenic Dark Matter Search (CDMS) experiment is reaching unprecedented RMS resolutions of ~14 eV ee . CDMSlite is currently the most sensitive experiment to WIMPs of mass ~5 GeV/c 2 but is limited in achieving higher phonon gains due to an early onset of leakage current into Ge crystals. The contact interface geometry is particularly weak for blocking hole injection from the metal, and thus a new design is demonstrated that allows high voltage bias via vacuum separated electrode. With an increased bias voltage and a×2 Luke phonon gain, world best RMS resolution of sigma ~7 eV ee for 0.25 kg (d=75 mm, h=1 cm) Ge detectors was achieved. Since the leakage current is a function of the field and the phonon gain is a function of the applied voltage, appropriately robust interface blocking material combined with thicker substrate (25 mm) will reach a resolution of ~2.8 eV ee . In order to achieve better resolution of ~ eV, we are investigating a layer of insulator between the phonon readout surface and the semiconductor crystals.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Performance of a MICROMEGAS-based TPC in a high-energy neutron beam

The MICROMEGAS (MICRO-MEsh GAseous Structure) charge amplification structure has found wide use in many detection applications, especially as a gain stage for the charge readout of Time Projection Chambers (TPCs). We report on the behavior of a MICROMEGAS TPC when operated in a high-energy (up to 800 MeV) neutron beam. It is found that neutron-induced reactions can cause discharges in some drift gas mixtures that are stable in the absence of the neutron beam. The discharges result from recoil ions close to the MICROMEGAS that deposit high specific ionization density and have a limited diffusion time. And for a binary drift gas, increasing the percentage of the molecular component (quench gas) relative to the noble component and operating at lower pressures generally improves stability.

43 PARTICLE ACCELERATORS↗