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At least 1,333 records · Page 74

Inhibition of H3K9 methyltransferase G9a induces autophagy and apoptosis in oral squamous cell carcinoma

Objective: To explore whether inhibition of H3K9 Methyltransferase G9a could exert an antitumoral effect in oral squamous cell carcinoma (OSCC). Materials and methods: First we checked G9a expression in two OSCC cell lines Tca8113 and KB. Next we used a special G9a inhibitor BIX01294 (BIX) to explore the effect of inhibition of G9a on OSCC in vitro. Cell growth was tested by typlan blue staining, MTT assay and Brdu immunofluorescence staining. Cell autophagy was examined by monodansylcadaverine (MDC) staining, LC3-II immunofluorescence staining and LC3-II western blot assay. Cell apoptosis was checked by FITC Annexin-V and PI labeling, tunnel staining and caspase 3 western blot assay. Finally, the effect of inhibition of G9a on clonogenesis and tumorigenesis capacity of OSCC was analyzed by soft agar growth and xenograft model. Results: Here we showed that G9a was expressed in both Tca8113 and KB cells. Inhibition of G9a using BIX significantly reduced cell growth and proliferation in Tca8113 and KB. Inhibition of G9a induced cell autophagy with conversion of LC3-I to LC3-II and cell apoptosis with the expression of cleaved caspase 3. We also found that inhibition of G9a reduced colony formation in soft agar and repressed tumor growth in mouse xenograph model. Conclusion: Our results suggested that G9a might be a potential epigenetic target for OSCC treatment. - Highlights: • Inhibition of G9a reduced cell growth and proliferation in OSCC cells. • Inhibition of G9a induces autophagy and apoptosis in OSCC cells. • Inhibition of G9a repressed tumor growth in mouse xenograph model.

60 APPLIED LIFE SCIENCES↗

Breaking the degeneracy between polarization efficiency and cosmological parameters in CMB experiments

Accurate cosmological parameter estimates using polarization data of the cosmic microwave background (CMB) put stringent requirements on map calibration, as highlighted in the recent results from the Planck satellite. In this paper, we point out that a model-dependent determination of polarization calibration can be achieved by the joint fit of the temperature-E-mode cross-power spectrum (TE) and E-mode auto-power spectrum (EE). This provides a valuable cross-check to band-averaged polarization efficiency measurements determined using other approaches. We demonstrate that, in ΛCDM, the combination of the TE and EE constrain polarization calibration with sub-percent uncertainty with Planck data and 2% uncertainty with sptpol data. We arrive at similar conclusions when extending ΛCDM to include the amplitude of lensing A L , the number of relativistic species N eff , or the sum of the neutrino masses Σm ν . Furthermore, the uncertainties on cosmological parameters are minimally impacted when marginalizing over polarization calibration, except, as can be expected, for the uncertainty on the amplitude of the primordial scalar power spectrum ln(10 10 A s ), which increases by 20–50%. However, this information can be fully recovered by adding temperature auto-power spectrum (TT) information. For current and future ground-based experiments, SPT-3G and CMB-S4, we forecast the cosmological parameter uncertainties to be minimally degraded when marginalizing over polarization calibration parameters. In addition, CMB-S4 could constrain its polarization calibration at the level of ~0.2% by combining TE and EE, and reach ~0.06% by also including TT. We therefore conclude that relying on calibrating against Planck polarization maps, whose statistical uncertainty is limited to ~0.5%, would be insufficient for upcoming experiments.

79 ASTRONOMY AND ASTROPHYSICS↗

SU-E-T-03: 3D GPU-Accelerated Secondary Checks of Radiation Therapy Treatment Plans

Purpose: Redundant treatment verifications in conformal and intensity-modulated radiation therapy techniques are traditionally performed with single point calculations. New solutions can replace these checks with 3D treatment plan verifications. This work describes a software tool (Mobius3D, Mobius Medical Systems) that uses a GPU-accelerated collapsed cone algorithm to perform 3D independent verifications of TPS calculations. Methods: Mobius3D comes with reference beam models for common linear accelerators. The system uses an independently developed collapsed cone algorithm updated with recent enhancements. 144 isotropically-spaced cones are used for each voxel for calculations. These complex calculations can be sped up by using GPUs. Mobius3D calculate dose using DICOM information coming from TPS (CT, RT Struct, RT Plan RT Dose). DVH-metrics and 3D gamma tests can be used to compare both TPS and secondary calculations. 170 patients treated with all common techniques as 3DCFRT (including wedged), static and dynamic IMRT and VMAT have been successfully verified with this solution. Results: Calculation times are between 3–5 minutes for 3DCFRT treatments and 15–20 for most complex dMLC and VMAT plans. For all PTVs mean dose and 90% coverage differences are (1.12±0.97)% and (0.68±1.19)%, respectively. Mean dose discrepancies for all OARs is (0.64±1.00)%. 3D gamma (global, 3%/3 mm) analysis shows a mean passing rate of (97.8 ± 3.0)% for PTVs and (99.0±3.0)% for OARs. 3D gamma pasing rate for all voxels in CT has a mean value of (98.5±1.6)%. Conclusion: Mobius3D is a powerful tool to verify all modalities of radiation therapy treatments. Dose discrepancies calculated by this system are in good agreement with TPS. The use of reference beam data results in time savings and can be used to avoid the propagation of errors in original beam data into our QA system. GPU calculations permit enhanced collapsed cone calculations with reasonable calculation times.

60 APPLIED LIFE SCIENCES↗

Preclinical investigation for developing injectable fiducial markers using a mixture of BaSO{sub 4} and biodegradable polymer for proton therapy

Purpose: The aim of this study is to investigate the use of mixture of BaSO{sub 4} and biodegradable polymer as an injectable nonmetallic fiducial marker to reduce artifacts in x-ray images, decrease the absorbed dose distortion in proton therapy, and replace permanent metal markers. Methods: Two samples were made with 90 wt. % polymer phosphate buffer saline (PBS) and 10 wt. % BaSO{sub 4} (B1) or 20 wt. % BaSO{sub 4} (B2). Two animal models (mice and rats) were used. To test the injectability and in vivo gelation, a volume of 200 μl at a pH 5.8 were injected into the Sprague-Dawley rats. After sacrificing the rats over time, the authors checked the gel morphology. Detectability of the markers in the x-ray images was tested for two sizes (diameters of 1 and 2 mm) for B1 and B2. Four samples were injected into BALB/C mice. The polymer mixed with BaSO{sub 4} transform from SOL at 20 °C with a pH of 6.0 to GEL in the living body at 37 °C with a pH of 7.4, so the size of the fiducial marker could be controlled by adjusting the injected volume. The detectability of the BaSO{sub 4} marker was measured in x-ray images of cone beam CT (CBCT), on-board imager [anterior–posterior (AP), lateral], and fluoroscopy (AP, lateral) using a Novalis-TX (Varian Medical Systems, Palo Alto, CA) repeatedly over 4 months. The volume, HU, and artifacts for the markers were measured in the CBCT images. Artifacts were compared to those of gold marker by analyzing the HU distribution. The dose distortion in proton therapy was computed by using a Monte Carlo (MC) code. A cylindrical shaped marker (diameter: 1 or 2 mm, length: 3 mm) made of gold, stainless-steel [304], titanium, and 20 wt. % BaSO{sub 4} was positioned at the center of the spread-out Bragg peak (SOBP) in parallel or perpendicular to the beam entrance. The dose distortion was measured on the depth dose profile across the markers. Results: Transformation to GEL and the biodegradation were verified. All BaSO{sub 4} markers could be detected in the CBCT. In the OBI and fluoroscopy images, all markers visible in the AP, but only B2(2 mm) could be identified in the lateral images. Changes of BaSO{sub 4} position were not detected in vivo (mice). The volume of the markers decreased by up to 65% and the HU increased by 22%, on average. The mean HU values around the B1, B2, and gold markers were 121.30 [standard deviation (SD): 54.86], 126.31 (SD: 62.13), and 1070.7 (SD: 235.16), respectively. The MC-simulated dose distortion for the BaSO{sub 4} markers was less than that of the commercially used markers. The dose reduction due to the gold marker was largest (15.05%) followed by stainless steel (7.92%) and titanium (6.92%). Dose reduction by B2 (2 mm) was 4.75% and 0.53% in parallel and perpendicular orientations, respectively. Conclusions: BaSO{sub 4} mixed with PBS is a good contrast agent in biodegradable polymer marker because of minimal artifacts in x-ray images and minimal dose reduction in proton therapy. The flexibility of the size is considered to be an advantage of this material over solid type fiducials.

60 APPLIED LIFE SCIENCES↗

Analyzing fragment production in mass-asymmetric reactions as a function of density dependent part of symmetry energy

We performed a theoretical investigation of different mass-asymmetric reactions to access the direct impact of the density-dependent part of symmetry energy on multifragmentation. The simulations are performed for a specific set of reactions having same system mass and N/Z content, using isospin-dependent quantum molecular dynamics model to estimate the quantitative dependence of fragment production on themass-asymmetry factor (τ) for various symmetry energy forms. The dynamics associated with different mass-asymmetric reactions is explored and the direct role of symmetry energy is checked. Also a comparison with the experimental data (asymmetric reaction) is presented for a different equation of states (symmetry energy forms).

74 ATOMIC AND MOLECULAR PHYSICS↗

CLAS N* Excitation Results from Pion and Kaon Electroproduction

The study of the structure of excited nucleon $N^*$ states employing the electroproduction of exclusive reactions is an important avenue for exploring the nature of the non-perturbative strong interaction. The electrocouplings of $N^*$ states in the mass range below $W$=1.8~GeV have been determined from analyses of CLAS $\pi N$, $\eta N$, and $\pi \pi N$ data at four-momentum transfers $Q^2$ up to 5~GeV$^2$. The work has made it clear that consistent results from independent analyses of several exclusive channels with different couplings and non-resonant backgrounds but the same $N^*$ electroexcitation amplitudes, is essential to have confidence in the extracted results. In terms of hadronic couplings, many high-lying $N^*$ states preferentially decay through the $\pi \pi N$ channel, while couplings to $\pi N$ final states become rather small. The resonance parameters determined from $\pi N$ and $\pi \pi N$ electroproduction can be checked in independent studies of the $KY$ ($Y = \Lambda, \Sigma^0$) channels. Therefore, data from the $KY$ channels already measured with CLAS will play an important role in $N^*$ structure studies. These comparisons await the development of suitable reaction models. Starting in 2018, a program to study the structure of $N^*$ states in various exclusive electroproduction channels using the new CLAS12 spectrometer will get underway. These studies will probe the structure of $N^*$ states in the mass range up to $W$=3~GeV and $Q^2$ up to 12~GeV$^2$, thus providing a means to access $N^*$ structure information spanning a broad regime encompassing both low- and high-energy degrees of freedom.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

The binary pulsar - Post-Newtonian timing effects

Certain post-Newtonian effects may be observable in the arrival times of pulses from the binary pulsar PSR 1913+16. Such effects include the gravitational propagation delay and the post-Newtonian corrections to the elliptical binary orbit. Fitting a model of these effects as they are predicted by general relativity to the pulse arrival times permits the estimation of more parameters than are necessary to determine the orbit and masses of the system. This redundancy provides an important check of the assumption that the observed periastron precession rate is entirely due to the effect of general relativity on compact masses.

Epstein, R.↗

The friable sponge model of a cometary nucleus

The mantle/core model of cometary nuclei, first suggested by Whipple and subsequently developed by Mendis and Brin, is modified and extended. New terms are added to the heat conduction equation for the mantle, which is solved in order to obtain the temperature distribution in the mantle and the gas production rate as a function of mantle thickness and heliocentric distance. These results are then combined with some specific assumptions about the mantle structure (the friable sponge model) in order to make predictions for the variation of gas production rate and mantle thickness as functions of heliocentric distance for different comets. A solution of the time-dependent heat conduction equation is presented in order to check some of the assumptions.

Horanyi, M.↗

Accuracy Analysis on Large Blocks of High Resolution Images

Although high altitude frequencies effects are removed at the time of basic image generation, low altitude (Yaw) effects are still present in form of affinity/angular affinity. They are effectively removed by additional parameters. Bundle block adjustment based on properly weighted ephemeris/altitude quaternions (BBABEQ) are not enough to remove the systematic effect. Moreover, due to the narrow FOV of the HRSI, position and altitude are highly correlated making it almost impossible to separate and remove their systematic effects without extending the geometric model (Self-Calib.) The systematic effects gets evident on the increase of accuracy (in terms of RMSE at GCPs) for looser and relaxed ground control at the expense of large and strong block deformation with large residuals at check points. Systematic errors are most freely distributed and their effects propagated all over the block.

Passini, Richardo M.↗

Measurements and Simulations of Nadir-Viewing Radar Returns from the Melting Layer at X- and W-Bands

Simulated radar signatures within the melting layer in stratiform rain, namely the radar bright band, are checked by means of comparisons with simultaneous measurements of the bright band made by the EDOP (X-band) and CRS (W-band) airborne Doppler radars during the CRYSTAL-FACE campaign in 2002. A stratified-sphere model, allowing the fractional water content to vary along the radius of the particle, is used to compute the scattering properties of individual melting snowflakes. Using the effective dielectric constants computed by the conjugate gradient-fast Fourier transform (CGFFT) numerical method for X and W bands, and expressing the fractional water content of melting particle as an exponential function in particle radius, it is found that at X band the simulated radar bright-band profiles are in an excellent agreement with the measured profiles. It is also found that the simulated W-band profiles usually resemble the shapes of the measured bright-band profiles even though persistent offsets between them are present. These offsets, however, can be explained by the attenuation caused by cloud water and water vapor at W band. This is confirmed by the comparisons of the radar profiles made in the rain regions where the un-attenuated W-band reflectivity profiles can be estimated through the X- and W band Doppler velocity measurements. The bright-band model described in this paper has the potential to be used effectively for both radar and radiometer algorithms relevant to the TRMM and GPM satellite missions.

Liao, Liang↗

Measurements of forward jet production in polarized pp collisions at √s = 500 GeV

The A{sub N }DY project at RHIC was proposed to measure the analyzing power for Drell-Yan production. Test runs took place during polarized proton operations of RHIC in 2011 and 2012 with a model of the A {sub N }DY apparatus in place. In total, an integrated luminosity of 9 pb{sup −1} with beam polarization of 50% was sampled. The primary detector components were a hadron calorimeter (HCal) that spanned the pseudorapidity interval 2.4 < η < 4.0 and a small electromagnetic calorimeter (ECal). Basic goals for A {sub N }DY test running were to establish the impact of a third interaction region on RHIC performance and to demonstrate HCal calibration. Energy scale of HCal was established using neutral pion reconstruction and checked with hadronic response. In addition, data with a trigger based on HCal energy sum were taken to study jet events. First measurements of analyzing power in the forward jet production are reported.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Design and fabrication of an aeroelastic flap element for a Short TakeOff and Landing (STOL) aircraft model

A flap element typifying a third element in the flap system of a short takeoff and landing aircraft was designed, fabricated, and instrumented. It was delivered to NASA for flight-simulated testing. The flap element was aluminum skin-stringer-rib construction with adhesive laminated skins. The tests conducted were as follows: (1) sonic check, (2) thermal expansion, (3) end fitting stiffness, (4) material properties, (5) maximum bending stress in the skin, and (6) effective skin width and stringer spacing.

Belleman, G. W.↗

ORIGIN OF THE GALAXY MASS-METALLICITY-STAR FORMATION RELATION

We describe an equilibrium model that links the metallicity of low-redshift galaxies to stellar evolution models. It enables the testing of different stellar initial mass functions and metal yields against observed galaxy metallicities. We show that the metallicities of more than 80,000 Sloan Digital Sky Survey galaxies in the low-redshift range 0.07 ≤ z ≤ 0.3 considerably constrain stellar evolution models that simultaneously relate galaxy stellar mass, metallicity, and star formation rates to the infall rate of low-metallicity extragalactic gas and outflow of enriched matter. A feature of our model is that it encompasses both the active star forming phases of a galaxy and epochs during which the same galaxy may lie fallow. We show that the galaxy mass-metallicity-star formation relation can be traced to infall of extragalactic gas mixing with native gas from host galaxies to form stars of observed metallicities, the most massive of which eject oxygen into extragalactic space. Most consequential among our findings is that, on average, extragalactic infall accounts for one half of the gas required for star formation, a ratio that is remarkably constant across galaxies with stellar masses ranging at least from M* = 2 × 10{sup 9} to 6 × 10{sup 10} M {sub ☉}. This leads us to propose that star formation is initiated when extragalactic infall roughly doubles the mass of marginally stable interstellar clouds. The processes described may also account quantitatively for the metallicity of extragalactic space, though to check this the fraction of extragalactic baryons will need to be more firmly established.

79 ASTRONOMY AND ASTROPHYSICS↗

Modeling of Transition Through Half-Integer Resonance

In our recent experiment we measured the increase in the betatron oscillation amplitude due to crossing half-integer resonance by the beam while it performed synchrotron oscillations at NSLS-II. In this note we derive solutions of the equation of motion for a particle crossing ½ resonance and check these numerically against analytic solutions for the static detuning. We start our derivation from the first principles, i.e. from the Hill’s equation.

36 MATERIALS SCIENCE↗

Interpretation of a short-term anomaly in the gravitational microlensing event MOA-2012-BLG-486

A planetary microlensing signal is generally characterized by a short-term perturbation to the standard single lensing light curve. A subset of binary-source events can produce perturbations that mimic planetary signals, thereby introducing an ambiguity between the planetary and binary-source interpretations. In this paper, we present the analysis of the microlensing event MOA-2012-BLG-486, for which the light curve exhibits a short-lived perturbation. Routine modeling not considering data taken in different passbands yields a best-fit planetary model that is slightly preferred over the best-fit binary-source model. However, when allowed for a change in the color during the perturbation, we find that the binary-source model yields a significantly better fit and thus the degeneracy is clearly resolved. This event not only signifies the importance of considering various interpretations of short-term anomalies, but also demonstrates the importance of multi-band data for checking the possibility of false-positive planetary signals.

79 ASTRONOMY AND ASTROPHYSICS↗

Investigating the XENON1T low-energy electronic recoil excess using NEST

The search for dark matter, the missing mass of the Universe, is one of the most active fields of study within particle physics. The XENON1T experiment recently observed a 3.5⁢𝜎 excess potentially consistent with dark matter, or with solar axions. Here, we will use the Noble Element Simulation Technique (NEST) software to simulate the XENON1T detector, reproducing the excess. We utilize different detector efficiency and energy reconstruction models, but they primarily impact sub-keV energies and cannot explain the XENON1T excess. However, using NEST, we can reproduce their excess in multiple, unique ways, most easily via the addition of 31 ± 11 37 Ar decays. Furthermore, this results in new, modified background models, reducing the significance of the excess to ≤2.2⁢𝜎 at least using non-Profile Likelihood Ratio (PLR) methods. This is independent confirmation that the excess is a real effect, but potentially explicable by known physics. Many cross-checks of our 37 Ar hypothesis are presented.

particle dark matter↗

Characterization of XR-RV3 GafChromic{sup ®} films in standard laboratory and in clinical conditions and means to evaluate uncertainties and reduce errors

Purpose: To investigate the optimal use of XR-RV3 GafChromic{sup ®} films to assess patient skin dose in interventional radiology while addressing the means to reduce uncertainties in dose assessment. Methods: XR-Type R GafChromic films have been shown to represent the most efficient and suitable solution to determine patient skin dose in interventional procedures. As film dosimetry can be associated with high uncertainty, this paper presents the EURADOS WG 12 initiative to carry out a comprehensive study of film characteristics with a multisite approach. The considered sources of uncertainties include scanner, film, and fitting-related errors. The work focused on studying film behavior with clinical high-dose-rate pulsed beams (previously unavailable in the literature) together with reference standard laboratory beams. Results: First, the performance analysis of six different scanner models has shown that scan uniformity perpendicular to the lamp motion axis and that long term stability are the main sources of scanner-related uncertainties. These could induce errors of up to 7% on the film readings unless regularly checked and corrected. Typically, scan uniformity correction matrices and reading normalization to the scanner-specific and daily background reading should be done. In addition, the analysis on multiple film batches has shown that XR-RV3 films have generally good uniformity within one batch (<1.5%), require 24 h to stabilize after the irradiation and their response is roughly independent of dose rate (<5%). However, XR-RV3 films showed large variations (up to 15%) with radiation quality both in standard laboratory and in clinical conditions. As such, and prior to conducting patient skin dose measurements, it is mandatory to choose the appropriate calibration beam quality depending on the characteristics of the x-ray systems that will be used clinically. In addition, yellow side film irradiations should be preferentially used since they showed a lower dependence on beam parameters compared to white side film irradiations. Finally, among the six different fit equations tested in this work, typically used third order polynomials and more rational and simplistic equations, of the form dose inversely proportional to pixel value, were both found to provide satisfactory results. Fitting-related uncertainty was clearly identified as a major contributor to the overall film dosimetry uncertainty with up to 40% error on the dose estimate. Conclusions: The overall uncertainty associated with the use of XR-RV3 films to determine skin dose in the interventional environment can realistically be estimated to be around 20% (k = 1). This uncertainty can be reduced to within 5% if carefully monitoring scanner, film, and fitting-related errors or it can easily increase to over 40% if minimal care is not taken. This work demonstrates the importance of appropriate calibration, reading, fitting, and other film-related and scan-related processes, which will help improve the accuracy of skin dose measurements in interventional procedures.

60 APPLIED LIFE SCIENCES↗

SU-E-T-211: Comparison of Seven New TrueBeam Linacs with Enhanced Beam Data Conformance Using a Beam Comparison Software Tool

Purpose: To develop an independent software tool to assist in commissioning linacs with enhanced beam conformance, as well as perform ongoing QA for dosimetrically equivalent linacs. Methods: Linac manufacturers offer enhanced beam conformance as an option to allow for clinics to complete commissioning efficiently, as well as implement dosimetrically equivalent linacs. The specification for enhanced conformance includes PDD as well as profiles within 80% FWHM. Recently, we commissioned seven Varian TrueBeam linacs with enhanced beam conformance. We developed a software tool in Visual Basic to allow us to load the reference beam data and compare our beam data during commissioning to evaluate enhanced beam conformance. This tool also allowed us to upload our beam data used for commissioning our dosimetrically equivalent beam models to compare and tweak each of our linac beams to match our modelled data in Varian’s Eclipse TPS. This tool will also be used during annual QA of the linacs to compare our beam data to our baseline data, as required by TG-142. Results: Our software tool was used to check beam conformance for seven TrueBeam linacs that we commissioned in the past six months. Using our tool we found that the factory conformed linacs showed up to 3.82% difference in their beam profile data upon installation. Using our beam comparison tool, we were able to adjust the energy and profiles of our beams to accomplish a better than 1.00% point by point data conformance. Conclusion: The availability of quantitative comparison tools is essential to accept and commission linacs with enhanced beam conformance, as well as to beam match multiple linacs. We further intend to use the same tool to ensure our beam data conforms to the commissioning beam data during our annual QA in keeping with the requirements of TG-142.

43 PARTICLE ACCELERATORS↗