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At least 1,117 records · Page 62

Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy

Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

Despite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune response to SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase 1-2 Study of Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation in Patients With High-Risk Prostate Cancer (SATURN): Early Toxicity and Quality of Life

Five-fraction stereotactic ablative radiation therapy appears to be gaining popularity in treatment of prostate cancer, but it has not been extensively tested in the context of pelvic radiation. The objective of this prospective prostate and pelvic SABR study is to report the acute toxicity, late toxicity, and quality of life (QoL) after study completion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Comparison of Non-coplanar Three-dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy, and Volumetric Modulated Radiation Therapy for the Delivery of Stereotactic Ablative Radiation Therapy to Peripheral Lung Cancer

The objective of the study was to compare three noncoplanar delivery techniques (three-dimensional conformal radiation therapy [3DCRT], intensity-modulated radiation therapy [IMRT], and volumetric-modulated arc therapy [VMAT]) for the delivery of lung stereotactic ablative radiation therapy to peripheral lung tumours.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effect of different breathing patterns in the same patient on stereotactic ablative body radiotherapy dosimetry for primary renal cell carcinoma: A case study

Stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) targets requires motion management strategies to verify dose delivery. This case study highlights the effect of a change in patient breathing amplitude on the dosimetry to organs at risk and target structures. A 73-year-old male patient was planned for receiving 26 Gy of radiation in 1 fraction of SABR for a left primary RCC. The patient was simulated with four-dimensional computed tomography (4DCT) and the tumor internal target volume (ITV) was delineated using the 4DCT maximum intensity projection. However, the initially planned treatment was abandoned at the radiation oncologist's discretion after pretreatment cone-beam CT (CBCT) motion verification identified a greater than 50% reduction in superior to inferior diaphragm motion as compared with the planning 4DCT. This patient was resimulated with respiratory coaching instructions. To assess the effect of the change in breathing on the dosimetry to the target, each plan was recalculated on the data set representing the change in breathing condition. A change from smaller to larger breathing showed a 46% loss in planning target volume (PTV) coverage, whereas a change from larger breathing to smaller breathing resulted in an 8% decrease in PTV coverage. ITV coverage was similarly reduced by 8% in both scenarios. This case study highlights the importance of tools to verify breathing motion prior to treatment delivery. 4D image guided radiation therapy verification strategies should focus on not only verifying ITV margin coverage but also the effect on the surrounding organs at risk.

61 RADIATION PROTECTION AND DOSIMETRY↗

A modified formula for dose calculations of stereotactic ablative body radiotherapy for non–small cell lung cancer

To provide a modified formula consistent with the Monte Carlo (MC) algorithm for dose calculations during stereotactic ablative body radiotherapy for non–small cell lung cancer. Seventy CyberKnife treatment plans were calculated and analyzed by MC and ray-tracing (RT) algorithms, separately. Parameters of treatment plans were compared, and those associated with differences of dose distributions were analyzed to establish a modified formula. Gross tumor volume and tumor tracking volume (TTV) were defined as the evident disease on the sequences of the window width and level of the lung and the mediastinum. Additionally, the formula was validated by another 20 plans. The prescription dose of the 90 patients was 60 Gy/5f. The RT algorithm overestimated the planning target volume (PTV) D{sub 95} by an average of 8.59 Gy and the gross tumor volume D{sub 99} by an average of 5.84 Gy. The homogeneity index of PTV was underestimated by 0.11 on average, whereas the conformity index and new conformity index was underestimated by 0.05. The RT algorithm overestimated the dose distribution to the spinal cord by 2.23 Gy, the esophagus by 1.96 Gy, the trachea by 1.89 Gy, the left-sided bronchus by 1.77 Gy, the right-sided bronchus by 1.64 Gy, and the heart by 2.16 Gy. The average whole-lung dose volumes of lung tissues and dose volumes of V{sub 5} were overestimated by 2.69 Gy and 7.52%, respectively. A power function distribution (R{sup 2} = 0.8626) was confirmed between PTV D{sub 95} and TTV volumes. PTV D{sub 95} calculated by the MC algorithm could be computed easily with TTV and PTV D{sub 95} calculated by the RT algorithm based on the formula. The modified equation was more consistent with MC algorithm than with other formula, which could be a reference to those not accessible to the MC algorithm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Laser Ablation Positive-Ion AMS of Neutron Activated Actinides

At Argonne we have enhanced the AMS capabilities of the Argonne Tandem Linac Accelerator System (ATLAS) to attempt to minimize crosstalk between samples and to quickly move from one (M/Q) setting to another in order to make measurements on a large number of samples provided by the MANTRA (Measurement of Actinide Neutron Transmutation Rates by Accelerator mass spectrometry) project. Those improvements include the use of a picosecond laser to ablate actinide material into the source, a new 20- sample holder that can switch samples within 1-2 minutes, and a number of accelerator configuration improvements that allow quick and precise switching between species. In principle, AMS can provide production yields of actinide isotopes produced during the irradiation period at a sensitivity exceeding other mass spectrometry techniques. A total of 27 irradiated samples of a variety of actinides have been provided for measurement. We discuss our experience with these facility improvements and how well we have met our performance goals. In addition, we present preliminary results on a number of the irradiated actinide samples with this approach and compare those results to Multi- Collector ICPMS measurements.

Pardo, R. C.↗

Reduction of spectral interferences and noise effects in laser ablation molecular isotopic spectrometry with partial least square regression – a computer simulation study

The fundamental analytical accuracies and precisions attainable by laser ablation molecular isotopic spectrometry (LAMIS), with emphasis on the impacts from spectral interferences and measurement noise, were investigated by means of computer simulation. The study focused on the analysis of a minor isotope at sub- to single-percentage abundance level. With a natural abundance about 1.1% for 13 C, the C 2 Swan band (d 3 II g - a 3 II u ) with Δν = + 1 was selected as a representative system. The characteristics (e.g., noise amplitude and distribution, signal strength, and signal-to-background ratio) of the simulated spectra were experimentally characterized. Partial least square (PLS) regression was used to extract isotopic information from the simulated molecular spectra. In the absence of any spectral interference and with the use of a calibration set consisting of eleven isotopic standards, the theoretical accuracies and precisions with signal accumulation from 100 laser shots are about 0.002% and 0.001%, respectively, in absolute percentage abundance of 13 C. The theoretical analytical accuracies slightly degrade, but are adequate for many applications, to 0.004% and 0.008% respectively, for calibrations involving only three and two isotopic standards. It was found that PLS regression is not only immune to both source-flicker and photon-shot noise, but is also effective in differentiating the spectral patterns from the analyte against those from spectral interferences. The influences of spectral interference from single or multiple atomic emission lines were simulated, and new ways to minimize their impacts were formulated and demonstrated. It was found that the wavelength range selected for the computation of the normalization factor should not contain any spectral-interfering peak, and a properly chosen wavelength range increases the tolerance of spectral interference by at least one order of magnitude. With matrix-matched calibration standards, the precisions (expressed as RSDs of the determined 13 C isotopic abundances) degrade from ~ 1% in the absence of spectral interference, to ~ 3&#8240, 10&#8240 and 20&#8240 with multiple spectral-interfering peaks that are 10 ×, 100 × and 1000 ×, respectively, stronger than the molecular bandhead of the analyte. The study concluded that PLS regression is a powerful and indispensable tool for extraction of isotopic information from LAMIS spectra.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Internal mixing dynamics of Cu/Sn-Pb plasmas produced by femtosecond laser ablation

Chemical imaging applications using Laser Induced Breakdown Spectroscopy (LIBS) involve laser ablation sampling at interfaces or boundaries between materials with different thermophysical and optical properties, leading to the formation of two initially isolated plasmas. The mechanisms of mixing in these plasmas and their direct implications on spectral emission and chemical imaging remain largely unknown. We investigate the mixing dynamics of isolated plasmas produced using femtosecond (fs) laser pulses at the interface between two different model Cu and Sn–Pb samples. Specifically, we study the spatial and temporal mixing dynamics and outer plasma expansion dynamics of the fs plasma components. The time-resolved degree of component mixing, horizontal and vertical expansion, mixing speed, and temperature and electron density of the heterogeneous plasma are characterized. Mixing processes are initiated early on, <100 ns after the laser pulse, and continue taking place until the end of plasma emission persistence at a constant velocity of 10 4 cm/s. In conclusion, these findings demonstrate that proper selection of detection timing parameters and signal collection position are critically important in precise LIBS measurements to ensure that full plasma mixing has taken place and that homogeneous spectral emission is properly detected.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Time-resolved formation of uranium and silicon oxides subsequent to the laser ablation of U 3 Si 2

The early-time kinetic behavior of species in a plume produced from laser ablation of U 3 Si 2 in an environment containing 2% O 2 is characterized using time-resolved absorption spectroscopy. The UO band around 593.55 nm and the SiO band around 230 nm is observed as well as various atomic and ionic uranium transitions. Temperatures and concentrations of these species are tracked and reported as well.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Remote isotope detection and quantification using femtosecond filament-laser ablation molecular isotopic spectrometry

We demonstrate the detection and quantification of isotopes from solid samples remotely at a distance of 36 m. This was accomplished through the combination of femtosecond filaments and laser ablation molecular isotopic spectrometry (F 2 -LAMIS). Isotopically enriched graphite samples with varying 13 C concentration were used and the F 2 -LAMIS emission was measured remotely using a portable spectrometer system. A standardless quantification approach was used to determine the corresponding isotopic ratios. The use of F 2 -LAMIS for the detection and quantification of isotopes at atmospheric pressure without the use of calibration standards opens the possibility to implement this technology for remote sensing of isotopes in field applications

07 ISOTOPE AND RADIATION SOURCES↗

Incomplete radiofrequency ablation induced chemoresistance by up-regulating heat shock protein 70 in hepatocellular carcinoma

Highlights: • iRFA treatment inhibited cisplatin-induced pyroptosis of HCC cells. • Heat shock protein 70 was involved in the suppression of NLRP3 activation. • iRFA treatment decreased the cisplatin sensitivity of HCC through regulating HSP70. Radiofrequency ablation (RFA) is a common minimally invasive treatment for hepatocellular carcinoma (HCC). Incomplete RFA (iRFA) due to the sub-lethal heat shock challenge of some cell populations leads to the generation of transformed survivor cells with enhanced chemoresistance. However, the underlying mechanism of iRFA on HCCs chemoresistance remains unknown. In the present study, we investigated the effect of iRFA on HCCs sensitivity to cisplatin. Cells treated with the sub-lethal heat shock challenge were used to mimic iRFA treatment in vitro. An orthotopic implantation HCC model was established and also performed iRFA treatment. Flow cytometry, transwell assay, and cell counting kit-8 assay were used to determine the effect of iRFA treatment on cisplatin-induced HCC cell apoptosis, invasion, and cell viability. ELISA and Western blot were used to detect the effect of iRFA treatment on cisplatin-induced HCC cell pyroptosis. We found that iRFA treatment increased the HCC cell proliferation and invasion ability, and inhibited cisplatin-induced pyroptosis. Further experiments showed that iRFA treatment induced upregulation of HSP70, which inhibited the cisplatin-induced NLRP3 inflammasome activation, leading to inhibition of pyroptosis. HSP70 knockdown or NLRP3 overexpression could reverse the effect of iRFA treatment in vitro. In vivo, HSP70 knockdown reversed the chemosensitivity of HCC to cisplatin, which was decreased by iRFA. In conclusion, we demonstrated that iRFA induced drug resistance by HSP70-mediated inhibition of cell pyroptosis in HCC.

60 APPLIED LIFE SCIENCES↗

Isotopic Heterogeneity Imaged in a Uranium Fuel Pellet with Extreme Ultraviolet Laser Ablation and Ionization Time-of-Flight Mass Spectrometry

We use extreme ultraviolet laser ablation and ionization time-of-flight mass spectrometry (EUV TOF) to map uranium isotopic heterogeneity at the nanoscale (=100 nm). Using low-enriched uranium fuel pellets that were made by blending two isotopically distinct feedstocks, we show that EUV TOF can map the 235U/238U content in 100 nm-sized pixels. The two-dimensional (2D) isotope maps reveal U ratio variations in sub-microscale to =1 µm areas of the pellet that had not been fully exposed by microscale or bulk mass spectrometry analyses. Compared to the ratio distribution measured in a homogeneous U reference material, the ratios in the enriched pellet follow a ~3× wider distribution. These results indicate U heterogeneity in the fuel pellet from incomplete blending of the different source materials. EUV TOF results agree well with those obtained on the same enriched pellets by nanoscale secondary ionization mass spectrometry (NanoSIMS), which reveals a comparable U isotope ratio distribution at the same spatial scale. EUV TOF’s ability to assess and map isotopic heterogeneity at the nanoscale makes it a promising tool in fields such as nuclear forensics, geochemistry, and biology that could benefit from uncovering sub-microscale sources of chemical modifications.

Rush, Lydia A.↗

Rapid assessment of human amylin aggregation and its inhibition by copper(II) ions by laser ablation electrospray ionization mass spectrometry with ion mobility separation

Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta-cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreas that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. In this paper, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin–copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the β-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the —HSSNN– residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of β-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of β-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin–copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of potential inhibitors of amylin oligomerization and fibril formation. Finally and more generally, this rapid technique opens the door for high-throughput screening of potential inhibitors of amyloid protein aggregation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Calibration-free analysis of Li isotope ratios using laser ablation and laser absorption spectroscopy

We introduce a rapid, calibration-free, all-optical method for high-precision lithium isotope ratio measurements in solid materials using laser ablation combined with tunable laser absorption spectroscopy. A new asynchronous acquisition method is used to acquire time-resolved, high-resolution spectra of the 6Li and 7Li D1 and D2 transitions near 671 nm. Isotope ratios and atomic column densities are extracted from measured spectra via a physics-based fitting model including hyperfine structure. Under 1 Torr air, spectra recorded = 0.75 ms after plasma onset exhibit narrow linewidths corresponding to Doppler temperatures = 400 K, enabling resolution of the isotope peaks with high signal-to-noise ratios. Analysis of LiAlO2 samples with varying 6Li:7Li ratios demonstrates isotopic precisions of 0.6–1.7% for spectra acquired in 30 s. Isotope ratios determined from the spectral fits show accuracy within –0.3% to –1.7% of reference ICP-MS measurements without requiring calibration to external standards. By eliminating sample preparation and enabling spatially resolved isotopic mapping, this method offers a rapid analysis approach to lithium isotope determination in solid materials relevant to nuclear energy, safeguards, and geochemistry.

Phillips, Mark C.↗

Ambient Single-Cell Analysis and Native Tissue Imaging Using Laser-Ablation Electrospray Ionization Mass Spectrometry with Increased Spatial Resolution

Laser ablation electrospray ionization mass spectrometry (LAESI-MS) is an emerging method that has the potential to transform the field of metabolomics. This is in part due to LAESI-MS being an ambient ionization method that requires minimal sample preparation and uses (endogenous) water for in situ analysis. This application note details the employment of the ‘LAESI microscope’ source to perform spatially resolved MS analysis of cells and MS imaging (MSI) of tissues at high spatial resolution. This source configuration utilizes a long-working distance reflective objective that permits both visualization of the sample and a smaller LAESI laser beam profile than conventional LAESI setups. In this work, we analyzed 200 single cells of Allium cepa (red onion) and imaged Fittonia argyroneura (nerve plant) in high spatial resolution using this source coupled to a Fourier transform mass spectrometer for high mass resolution and high mass accuracy metabolomics.

59 BASIC BIOLOGICAL SCIENCES↗

A Self-Limiting Electro-Ablation Technique for the Top-Down Synthesis of Large-Area Monolayer Flakes of 2D Materials

We report the discovery of an electrochemical process that converts two dimensional layered materials of arbitrary thicknesses into monolayers. The lateral dimensions of the monolayers obtained by the process within a few seconds time at room temperature were as large as 0.5 mm. The temporal and spatial dynamics of this physical phenomenon, studied on MoS2 flakes using ex-situ AFM imaging, Raman mapping, and photoluminescence measurements trace the origin of monolayer formation to a substrate-assisted self-limiting electrochemical ablation process. Electronic structure and atomistic calculations point to the interplay between three essential factors in the process: (1) strong covalent interaction of monolayer MoS2 with the substrate; (2) electric-field induced differences in Gibbs free energy of exfoliation; (3) dispersion of MoS2 in aqueous solution of hydrogen peroxide. This process was successful in obtaining monolayers of other 2D transition metal dichalcogenides, like WS2 and MoTe2 as well.

36 MATERIALS SCIENCE↗