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At least 109 records · Page 6

Quantitation of amiodarone and N-desethylamiodarone in single HepG2 cells by single-cell printing-liquid vortex capture-mass spectrometry

Quantitative measure of a drug and its associated metabolite(s) with single-cell resolution is often limited by sampling throughput or other compromises that limit broad use. Here, we demonstrate the use of single-cell printing-liquid vortex capture-mass spectrometry (SCP-LVC-MS) to quantitatively measure the intracellular concentrations of amiodarone (AMIO) and its metabolite, N-desethylamiodarone (NDEA), from thousands of single cells across several AMIO incubation concentrations ranging from 0 to 10 μM. Concentrations obtained by SCP-LVC-MS were validated through comparison with average assays and traditional measurement of cells in bulk. Average of SCP-LVC-MS measurements and aggregate vial collection assay the concentrations differed by < 5%. Both AMIO and NDEA had clear log-normal distributions with similar standard deviation of concentrations in the cell population. The mean of both AMIO and NDEA intracellular concentrations were positively correlated with AMIO incubation concentration, increasing from 0.026 to 0.520 and 0.0055 to 0.048 mM for AMIO and NDEA, respectively. The standard deviation of AMIO and NDEA log-normal distribution fits were relatively similar in value across incubation concentrations, 0.15–0.19 log 10 (mM), and exhibited a linear trend with respect to each other. The single cell-resolved conversion ratio of AMIO to NDEA increased with decreasing incubation concentration, 7 ± 2%, 18 ± 3%, and 20 ± 7% for 10.0, 1.0, and 0.1 μM AMIO incubation concentrations, respectively. Finally, association with simultaneously measured lipids had several ions with statistically significant difference in intensity but no clear correlations with AMIO intracellular content was observed.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Slant path L- and S-Band tree shadowing measurements

This contribution presents selected results from simultaneous L- and S-Band slant-path fade measurements through a pecan, a cottonwood, and a pine tree employing a tower-mounted transmitter and dual-frequency receiver. A single, circularly-polarized antenna was used at each end of the link. The objective was to provide information for personal communications satellite design on the correlation of tree shadowing between frequencies near 1620 and 2500 MHz. Fades were measured along 10 m lateral distance with 5 cm spacing. Instantaneous fade differences between L- and S-Band exhibited normal distribution with means usually near 0 dB and standard deviations from 5.2 to 7.5 dB. The cottonwood tree was an exception, with 5.4 dB higher average fading at S- than at L-Band. The spatial autocorrelation reduced to near zero with lags of about 10 lambda. The fade slope in dB/MHz is normally distributed with zero mean and standard deviation increasing with fade level.

Vogel, Wolfhard J.↗

Fermi/GBM Observations of SGRJ0501 + 4516 Bursts

We present our temporal and spectral analyses of 29 bursts from SGRJ0501+4516, detected with the Gamma-ray Burst Monitor onboard the Fermi Gamma-ray Space Telescope during the 13 days of the source activation in 2008 (August 22 to September 3). We find that the T(sub 90) durations of the bursts can be fit with a log-normal distribution with a mean value of approx. 123 ms. We also estimate for the first time event durations of Soft Gamma Repeater (SGR) bursts in photon space (i.e., using their deconvolved spectra) and find that these are very similar to the T(sub 90)s estimated in count space (following a log-normal distribution with a mean value of approx. 124 ms). We fit the time-integrated spectra for each burst and the time-resolved spectra of the five brightest bursts with several models. We find that a single power law with an exponential cutoff model fits all 29 bursts well, while 18 of the events can also be fit with two black body functions. We expand on the physical interpretation of these two models and we compare their parameters and discuss their evolution. We show that the time-integrated and time-resolved spectra reveal that E(sub peak) decreases with energy flux (and fluence) to a minimum of approx. 30 keV at F = 8.7 x 10(exp -6)erg/sq cm/s, increasing steadily afterwards. Two more sources exhibit a similar trend: SGRs J1550 - 5418 and 1806 - 20. The isotropic luminosity, L(sub iso), corresponding to these flux values is roughly similar for all sources (0.4 - l.5 x 10(exp 40) erg/s.

Lin, Lin↗

Statistical Properties of Maximum Likelihood Estimators of Power Law Spectra Information

A simple power law model consisting of a single spectral index, a is believed to be an adequate description of the galactic cosmic-ray (GCR) proton flux at energies below 10(exp 13) eV, with a transition at the knee energy, E(sub k), to a steeper spectral index alpha(sub 2) greater than alpha(sub 1) above E(sub k). The Maximum likelihood (ML) procedure was developed for estimating the single parameter alpha(sub 1) of a simple power law energy spectrum and generalized to estimate the three spectral parameters of the broken power law energy spectrum from simulated detector responses and real cosmic-ray data. The statistical properties of the ML estimator were investigated and shown to have the three desirable properties: (P1) consistency (asymptotically unbiased). (P2) efficiency asymptotically attains the Cramer-Rao minimum variance bound), and (P3) asymptotically normally distributed, under a wide range of potential detector response functions. Attainment of these properties necessarily implies that the ML estimation procedure provides the best unbiased estimator possible. While simulation studies can easily determine if a given estimation procedure provides an unbiased estimate of the spectra information, and whether or not the estimator is approximately normally distributed, attainment of the Cramer-Rao bound (CRB) can only he ascertained by calculating the CRB for an assumed energy spectrum-detector response function combination, which can be quite formidable in practice. However. the effort in calculating the CRB is very worthwhile because it provides the necessary means to compare the efficiency of competing estimation techniques and, furthermore, provides a stopping rule in the search for the best unbiased estimator. Consequently, the CRB for both the simple and broken power law energy spectra are derived herein and the conditions under which they are attained in practice are investigated. The ML technique is then extended to estimate spectra information from an arbitrary number of astrophysics data sets produced by vastly different science instruments. This theory and its successful implementation will facilitate the interpretation of spectral information from multiple astrophysics missions and thereby permit the derivation of superior spectral parameter estimates based on the combination of data sets.

Howell, L. W.↗

Statistical Properties of Maximum Likelihood Estimators of Power Law Spectra Information

A simple power law model consisting of a single spectral index, sigma(sub 2), is believed to be an adequate description of the galactic cosmic-ray (GCR) proton flux at energies below 10(exp 13) eV, with a transition at the knee energy, E(sub k), to a steeper spectral index sigma(sub 2) greater than sigma(sub 1) above E(sub k). The maximum likelihood (ML) procedure was developed for estimating the single parameter sigma(sub 1) of a simple power law energy spectrum and generalized to estimate the three spectral parameters of the broken power law energy spectrum from simulated detector responses and real cosmic-ray data. The statistical properties of the ML estimator were investigated and shown to have the three desirable properties: (Pl) consistency (asymptotically unbiased), (P2) efficiency (asymptotically attains the Cramer-Rao minimum variance bound), and (P3) asymptotically normally distributed, under a wide range of potential detector response functions. Attainment of these properties necessarily implies that the ML estimation procedure provides the best unbiased estimator possible. While simulation studies can easily determine if a given estimation procedure provides an unbiased estimate of the spectra information, and whether or not the estimator is approximately normally distributed, attainment of the Cramer-Rao bound (CRB) can only be ascertained by calculating the CRB for an assumed energy spectrum- detector response function combination, which can be quite formidable in practice. However, the effort in calculating the CRB is very worthwhile because it provides the necessary means to compare the efficiency of competing estimation techniques and, furthermore, provides a stopping rule in the search for the best unbiased estimator. Consequently, the CRB for both the simple and broken power law energy spectra are derived herein and the conditions under which they are stained in practice are investigated.

Howell, L. W., Jr.↗

Solution of an integral equation encountered in studies on radiative transfer in completely absorbing leaf canopies

The leaf normal distribution function is related to the extinction coefficient of direct solar radiation by a Fredholm integral equation of the first kind. The integral equation is solved by the method of constrained least squares. The solutions are stable and correct only in extreme cases and, in general, it is not possible to recover an arbitrary leaf normal distribution function.

Myneni, Ranga B.↗

The Nickel Mass Distribution of Normal Type II Supernovae

Core-collapse supernova (SN) explosions expose the structure and environment of massive stars at the moment of their death. We use the global fitting technique of Pejcha and Prieto to estimate a set of physical parameters of 19 normal SNe II, such as their distance moduli, reddenings, {sup 56}Ni masses M{sub Ni}, and explosion energies E{sub exp} from multicolor light curves and photospheric velocity curves. We confirm and characterize known correlations between M{sub Ni} and bolometric luminosity at 50 days after the explosion, and between M{sub Ni} and E{sub exp}. We pay special attention to the observed distribution of M{sub Ni} coming from a joint sample of 38 SNe II, which can be described as a skewed-Gaussian-like distribution between 0.005 M{sub ⊙} and 0.280 M{sub ⊙}, with a median of 0.031 M{sub ⊙}, mean of 0.046 M{sub ⊙}, standard deviation of 0.048 M{sub ⊙}, and skewness of 3.050. We use a two-sample Kolmogorov–Smirnov test and two-sample Anderson–Darling test to compare the observed distribution of M{sub Ni} to results from theoretical hydrodynamical codes of core-collapse explosions with the neutrino mechanism presented in the literature. Our results show that the theoretical distributions obtained from the codes tested in this work, KEPLER and Prometheus Hot Bubble, are compatible with the observations irrespective of different pre-SN calibrations and different maximum mass of the progenitors.

79 ASTRONOMY AND ASTROPHYSICS↗

Testing Nesting DXTRAN Spheres for Neutron Transport in Air

The deterministic transport sphere (DXTRAN sphere) is a technology that can be utilized in MCNP for improving sampling in the vicinity of a particular geometry, when the solid angle, between the source and particular geometry, is small. At a collision event, a DXTRAN particle is created and deterministically transported to the DXTRAN sphere, while the colliding particle (NONDXTRAN particle) continues transporting as if no DXTRAN event had occurred. Weight is balanced by killing the NONDXTRAN particle when traversing the DXTRAN sphere. If set up correctly, the DXTRAN particle placed on the DXTRAN sphere has a high probability of interacting with the geometry within the DXTRAN sphere. The Central Limit Theorem (CLT) states that the estimated mean approaches a normal distribution with known variance as the number of random samples grows sufficiently large. In reality the variance is seldom known and therefore must be estimated. In a Monte Carlo calculation, one must determine when the number of random samples is sufficiently large for the CLT to be satisfied. For the CLT to be satisfied, the first two moments (mean and variance) must exist. The second moment, the variance of a normal distribution is estimated. The slope test, which uses the largest 201 history scores of each tally fluctuation chart (TFC) bin fit to a Pareto function, is used to determine if the largest history scores decrease faster than 1/x{sup 3}. If the slope is less than 3, then enough histories have not yet been sampled such to meet the second moment existence requirement of the CLT. Usually, a slope of less than 3 indicates that the effects of high weight scores have not been satisfactorily sampled; such a consequence can also be manifested in examining trends in the 4. moment, the variance of the variance (VOV). For example, when examining the TFC, if the VOV is monotonically decreasing for a few sets of histories and then drastically increases for the next set of histories, chances are a rare high weight score, significantly greater than the average score, was encountered. As a result of the 1/R{sup 2} term, a point detector can achieve an extremely high weight, much greater than the average, as the distance from collision to point detector approaches zero. To remedy this difficulty, a 'radius of exclusion' is applied, where within the radius of exclusion 'the point detector estimate is assumed to be the average flux uniformly distributed'. A DXTRAN sphere can suffer from the same weight fluctuation as collisions in the vicinity of the DXTRAN sphere produce much larger weights than collisions happening far from the DXTRAN sphere. If the rare large weight put on the DXTRAN sphere then scores in a tally, there will be a significant increase in the VOV and the slope may drop below 3. To compliment that analysis, here we utilize an air composition and density that varies as a function of altitude, detailing the trials and tribulations of attempting to pass the 10 statistical checks for a variety of single and nested DXTRAN sphere approaches. The objective here is to illuminate important considerations for radiation transport problems with small solid angles in a scatter medium of few mean free paths (MFPs)

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Formulation of autoconversion and drop spectra shape in shallow cumulus clouds

Two-moment autoconversion parameterizations as compared to accretion parameterizations exhibit significant errors suggesting that additional moments are needed to increase their accuracy. We develop a three-moment autoconversion parameterization using output from an LES model with size-resolved microphysics. Adding the third moment decreases the errors of parameterization and improves precipitation prediction. However, the errors are still significantly larger than errors of accretion rate. An analysis of the cloud drop size distributions (DSDs) in the simulated tropical convective cloud system reveals that most of DSDs have a significant fraction of cloud liquid water content (qc) in the mid-size droplet range (radii from 20 to 40 microns). Our data indicates that more than 30% of DSDs have over half of qc contained in the mid-size range and about 60% of spectra have, at least, one third of qc in this range. Even when the rain/drizzle mode is small (radar reflectivity Z < -10 dBZ), there is a significant number of spectra in which fraction of qc in the mid-size range is as large as 60%. These DSDs are more complex than the frequently used single-mode Gamma or Log-normal distributions, which usually do not have a considerable tail extending to the mid-size range and can be defined by three microphysical moments. The need to define DSDs by more than three moments explains the large errors in the three-moment autoconversion parameterization. The limitation of three-parameter Gamma or Log-normal distributions should be kept in mind when applying them in precipitating shallow Cu clouds.

Kogan, Yefim↗

On the statistics of El Nino occurrences and the relationship of El Nino to volcanic and solar/geomagnetic activity

El Nino is conventionally defined as an anomalous and persistent warming of the waters off the coasts of Ecuador and Peru in the eastern equatorial Pacific, having onset usually in Southern Hemispheric summer/fall. Some of the statistical aspects of El Nino occurrences are examined, especially as they relate to the normal distribution and to possible associations with volcanic, solar, and geomagnetic activity. With regard to the very strong El Nino of 1982 to 1983, it is noted that, although it may very well be related to the 1982 eruptions of El Chichon, the event occurred essentially on time (with respect to the past behavior of elapsed times between successive El Nino events; a moderate-to-stronger El Nino was expected during the interval 1978 to 1982, assuming that El Nino occurrences are normally distributed, having a mean elapsed time between successive onsets of 4 years and a standard deviation of 2 years and a last known occurrence in 1976). Also, although not widely recognized, the whole of 1982 was a record year for geomagnetic activity (based on the aa geomagnetic index, with the aa index registering an all time high in February 1982), perhaps, important for determining a possible trigger for this and other El Nino events. A major feature is an extensive bibliography (325 entries) on El Nino and volcanic-solar-geomagnetic effects on climate. Also, included is a tabular listing of the 94 major volcanic eruptions of 1835 to 1986.

Wilson, Robert M.↗

SU-E-J-176: Characterization of Inter-Fraction Breast Variability and the Implications On Delivered Dose

Purpose: To systematically characterize inter-fraction breast variability and determine implications on delivered dose. Methods: Weekly port films were used to characterize breast setup variability. Five evenly spaced representative positions across the contour of each breast were chosen on the electronic port film in reference to graticule, and window and level was set such that the skin surface of the breast was visible. Measurements from the skin surface to treatment field edge were taken on each port film at each position and compared to the planning DRR, quantifying the variability. The systematic measurement technique was repeated for all port films for 20 recently treated breast cancer patients. Measured setup variability for each patient was modeled as a normal distribution. The distribution was randomly sampled from the model and applied as isocentric shifts in the treatment planning computer, representing setup variability for each fraction. Dose was calculated for each shifted fraction and summed to obtain DVHs and BEDs that modeled the dose with daily setup variability. Patients were categorized in to relevant groupings that were chosen to investigate the rigorousness of immobilization types, treatment techniques, and inherent anatomical difficulties. Mean position differences and dosimetric differences were evaluated between planned and delivered doses. Results: The setup variability was found to follow a normal distribution with mean position differences between the DRR and port film between − 8.6–3.5 mm with sigma range of 5.3–9.8 mm. Setup position was not found to be significantly different than zero. The mean seroma or whole breast PTV dosimetric difference, calculated as BED, ranged from a −0.23 to +1.13Gy. Conclusion: A systematic technique to quantify and model setup variability was used to calculate the dose in 20 breast cancer patients including variable setup. No statistically significant PTV or OAR BED differences were found between immobilization, treatment or anatomical differences investigated.

60 APPLIED LIFE SCIENCES↗

Identification of Accretion as Grain Growth Mechanism in Astrophysically Relevant Water–Ice Dusty Plasma Experiment

The grain growth process in the Caltech water–ice dusty plasma experiment has been studied using a high-speed camera and a long-distance microscope lens. It is observed that (i) the ice grain number density decreases fourfold as the average grain major axis increases from 20 to 80 μ m, (ii) the major axis length has a log-normal distribution rather than a power-law dependence, and (iii) no collisions between ice grains are apparent. The grains have a large negative charge resulting in strong mutual repulsion and this, combined with the fractal character of the ice grains, prevents them from agglomerating. In order for the grain kinetic energy to be sufficiently small to prevent collisions between ice grains, the volumetric packing factor (i.e., ratio of the actual volume to the volume of a circumscribing ellipsoid) of the ice grains must be less than ∼0.1 depending on the exact relative velocity of the grains in question. Thus, it is concluded that direct accretion of water molecules is very likely to dominate the observed ice grain growth.

79 ASTRONOMY AND ASTROPHYSICS↗

Constraining baryon annihilation in the hadronic phase of heavy-ion collisions via event-by-event fluctuations

We point out that the variance of net-baryon distribution normalized by the Skellam distribution baseline, κ 2 [$B-\overline{B}$]/$\langle B+\overline{B} \rangle$, is sensitive to the possible modification of (anti)baryon yields due to $B\overline{B}$ annihilation in the hadronic phase. The corresponding measurements can thus place stringent limits on the magnitude of the $B\overline{B}$ annihilation and its inverse reaction. We perform Monte Carlo simulations of the hadronic phase in Pb-Pb collisions at the LHC via the recently developed subensemble sampler + UrQMD afterburner and show that the effect survives in net-proton fluctuations, which are directly accessible experimentally. The available experimental data of the ALICE Collaboration on net-proton fluctuations disfavors a notable suppression of (anti)baryon yields in $B\overline{B}$ annihilations predicted by the present version of UrQMD if only global baryon conservation is incorporated. On the other hand, the annihilations improve the data description when local baryon conservation is imposed. The two effects can be disentangled by measuring κ 2 [$B-\overline{B}$]/$\langle B+\overline{B} \rangle$, which at the LHC is notably suppressed by annihilations but virtually unaffected by baryon number conservation.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Quantifying the unknown impact of segmentation uncertainty on image-based simulations

Abstract Image-based simulation, the use of 3D images to calculate physical quantities, relies on image segmentation for geometry creation. However, this process introduces image segmentation uncertainty because different segmentation tools (both manual and machine-learning-based) will each produce a unique and valid segmentation. First, we demonstrate that these variations propagate into the physics simulations, compromising the resulting physics quantities. Second, we propose a general framework for rapidly quantifying segmentation uncertainty. Through the creation and sampling of segmentation uncertainty probability maps, we systematically and objectively create uncertainty distributions of the physics quantities. We show that physics quantity uncertainty distributions can follow a Normal distribution, but, in more complicated physics simulations, the resulting uncertainty distribution can be surprisingly nontrivial. We establish that bounding segmentation uncertainty can fail in these nontrivial situations. While our work does not eliminate segmentation uncertainty, it improves simulation credibility by making visible the previously unrecognized segmentation uncertainty plaguing image-based simulation.

42 ENGINEERING↗

Ion heating, burnout of the high-frequency field, and ion sound generation under the development of a modulation instability of an intense Langmuir wave in a plasma

The development of one-dimensional parametric instabilities of intense long plasma waves is considered in terms of the so-called hybrid models, with electrons being treated as a fluid and ions being regarded as particles. The analysis is performed for both cases when the average plasma field energy is lower (Zakharov's hybrid model—ZHM) or greater (Silin's hybrid model—SHM) than the plasma thermal energy. The efficiency of energy transfer to ions and to ion perturbations under the development of the instability is considered for various values of electron-to-ion mass ratios. The energy of low-frequency oscillations (ion-sound waves) is found to be much lower than the final ion kinetic energy. We also discuss the influence of the changes in the damping rate of the high-frequency (HF) field on the instability development. The decrease of the absorption of the HF field inhibits the HF field burnout within plasma density cavities and gives rise to the broadening of the HF spectrum. At the same time, the ion velocity distribution tends to the normal distribution in both ZHM and SHM.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Linewidth broadening and tunneling of excitons bound to N pairs in dilute GaAs:N

The exciton bound to a pair of nitrogen atoms situated at nearby lattice sites in dilute GaAs:N provides an energetically uniform electronic system, spectrally distinct from pairs with larger or smaller separations, and can even be grown with a uniform pair orientation in the crystal. We use photoluminescence excitation spectroscopy on an ensemble of N pairs to study the narrow continuous energy distribution within two of the individual exchange- and symmetry-split exciton states. Inhomogeneous linewidths of 50-60 ueV vary across the crystal on a mesoscopic scale and can be 30 ueV at microscopic locations indicating that the homogeneous linewidth inferred from previous time-domain measurements is still considerably broadened. While excitation and emission linewidths are similar, results show a small energy shift between them indicative of exciton transfer via phonon-assisted tunneling between spatially separated N pairs. We numerically simulate the tunneling in a spatial network of randomly distributed pairs having a normal distribution of bound exciton energies. Comparing the ensemble excitation-emission energy shift with the measured results shows that the transfer probability is higher than expected from the dilute pair concentration and what is known of the exciton wavefunction spatial extent. Both the broadening and the exciton transfer have implications for the goal of pair-bound excitons as a single- or multi-qubit system.

36 MATERIALS SCIENCE↗

TH-CD-BRA-02: 3D Remote Dosimetry for MRI-Guided Radiation Therapy: A Hybrid Approach

Purpose: To validate the dosimetric accuracy of a commercially available MR-IGRT system using a combination of 3D dosimetry measurements (with PRESAGE(R) radiochromic plastic and optical-CT readout) and an in-house developed GPU-accelerated PENELOPE Monte-Carlo dose calculation system. Methods: {sup 60}Co IMRT subject to a 0.35T lateral magnetic field has recently been commissioned in our institution following AAPM’s TG-119 recommendations. We performed PRESAGE(R) sensitivity studies in 4ml cuvettes to verify linearity, MR-compatibility, and energy-independence. Using 10cm diameter PRESAGE(R), we delivered an open calibration field to examine the percent depth dose and a symmetrical 3-field plan with three adjacent regions of varying dose to determine uniformity within the dosimeter under a magnetic field. After initial testing, TG-119 plans were created in the TPS and then delivered to 14.5cm 2kg PRESAGE(R) dosimeters. Dose readout was performed via optical-CT at a second institution specializing in remote 3D dosimetry. Absolute dose was measured using an IBA CC01 ion chamber and the institution standard patient-specific QA methods were used to validate plan delivery. Calculated TG-119 plans were then compared with an independent Monte Carlo dose calculation (gPENELOPE). Results: PRESAGE(R) responds linearly (R{sup 2}=0.9996) to {sup 60}Co irradiation, in the presence of a 0.35T magnetic field, with a sensitivity of 0.0305(±0.003)cm{sup −1}Gy{sup −1}, within 1% of a 6MV non-MR linac irradiation (R{sup 2}=0.9991) with a sensitivity of 0.0302(±0.003)cm{sup −1}Gy{sup −1}. Analysis of TG-119 clinical plans using 3D-gamma (3%/3mm, 10% threshold) give passing rates of: HN 99.1%, prostate 98.0%, C-shape 90.8%, and multi-target 98.5%. The TPS agreed with gPENELOPE with a mean gamma passing rate of 98.4±1.5% (2%/2mm) with the z-score distributions following a standard normal distribution. Conclusion: We demonstrate for the first time that 3D remote dosimetry using both experimental and computational methods is a feasible and reliable approach to commissioning MR-IMRT, which is particularly useful for less specialized clinics in adopting this new treatment modality.

60 APPLIED LIFE SCIENCES↗