709 research outputs found
Numerical Modeling Of Hohlraum Radiation Conditions: Spatial And Spectral Variations Due To Sample Position, Beam Pointing, And Hohlraum Geometry
View-factor simulations are presented of the spatially varying radiation conditions inside double-ended gold Hohlraums and single-ended gold Hohlraums (\u27\u27 halfraums \u27\u27) used in inertial confinement fusion and high-energy density physics experiments [J. Lindl, Phys. Plasmas 11, 339 (2004); M. D. Rosen, Phys. Plasmas 3, 1803 (1996)]. It is shown that in many circumstances, the common assumption that the Hohlraum \u27\u27 drive \u27\u27 can be characterized by a single temperature is too simplistic. Specifically, the radiation conditions seen by an experimental package can differ significantly from the wall reemission measured through diagnostic holes or laser entrance holes (LEHs) by absolutely calibrated detectors. Furthermore, even in situations where the radiation temperature is roughly the same for diagnostics and experimental packages, or for packages at different locations, the spectral energy distributions can vary significantly, due to the differing fractions of reemitting wall, laser hot spots, and LEHs seen from different locations. We find that the spatial variation of temperature and especially the differences between what diagnostics looking in the LEH measure versus the radiation temperature on wall-mounted experimental packages are generally greater for double-ended Hohlraums than for halfraums. View-factor simulations can also be used to explore experimental variables (halfraum length and geometry, sample position, and beam pointing) that can be adjusted in order to, for example, maximize the radiation flux onto a sample, or other package. In this vein, simulations of Hohlraums and halfraums with LEH shields are also presented. (c) 2005 American Institute of Physics
Influence of genomic landscape on cancer immunotherapy for newly diagnosed ovarian cancer: Biomarker analyses from the IMagyn050 randomized clinical trial
PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.
PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates.
RESULTS: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors.
CONCLUSIONS: Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors. See related commentary by Al-Rawi et al., p. 1645
Modified Bell-Plesset Effect with Compressibility: Application to Double-Shell Ignition Target Designs
The effect of spherical convergence on the fluid stability of collapsing and expanding bubbles was originally treated by Bell [Los Alamos Scientific Laboratory Report No. LA-1321 (1951)] and Plesset [J. Appl. Phys. 25, 96 (1954)]. The additional effect of fluid compressibility was also considered by Bell but was limited to the case of nonzero density on only one side of a fluid interface. A more general extension is developed which considers distinct time-dependent uniform densities on both sides of an interface in a spherically converging geometry. A modified form of the velocity potential is used that avoids an unphysical divergence at the origin [Goncharov et al., Phys. Plasmas 7, 5118 (2000); Lin et al., Phys. Fluids 14, 2925 (2002)]. Two consequences of this approach are that an instability proposed by Plesset for an expanding bubble in the limit of large interior density is now absent and application to inertial confinement fusion studies of stability becomes feasible. The model is applied to a proposed ignition double-shell target design [Amendt et al., Phys. Plasmas 9, 2221 (2002)] for the National Ignition Facility [Paisner et al., Laser Focus World 30, 75 (1994)] for studying the stability of the inner surface of an imploding high-Z inner shell. Application of the Haan [Phys. Rev. A 39, 5812 (1989)] saturation criterion suggests that ignition is possible
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Generalized x-ray scattering cross section from non-equilibrium solids and plasmas
We propose a modified x-ray form factor that describes the scattering cross section in warm dense matter valid for both the plasma and the solid (crystalline) state. Our model accounts for the effect of lattice correlations on the electron-electron dynamic structure, as well as provides a smooth transition between the solid and the plasma scattering cross sections. In addition, we generalize the expression of the dynamic structure in the case of a two-temperature system (with different electron and ion temperatures). This work provides a unified description of the x-ray scattering processes in warm and dense matter, as the one encountered in inertial confinement fusion, laboratory astrophysics, material science, and high-energy density physics and it can be used to verify temperature relaxation mechanisms in such environments
Ileo-colic hernia through the foramen of Winslow
A 60-year-old woman was admitted to hospital for acute post prandial epigastric pain and vomiting
Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder
The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium’s mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder
Tracer Spectroscopy Diagnostics Of Doped Ablators In Inertial Confinement Fusion Experiments On Omega
A technique has been developed for studying the time-dependent, local physical conditions in ablator samples in an inertial confinement fusion(ICF)hohlraum environment. This technique involves backlit point-projection absorption spectroscopy of thin tracer layers buried in the interior of solid samples mounted on laser-driven hohlraums. It is shown how detailed view-factor, atomic, hydrodynamics, and radiation-transport modeling can be used to infer time-dependent physical conditions in the interiors of these samples from the observed absorption spectra. This modeling is applied to the results of an experimental campaign on the OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] designed to compare radiation-wave velocities in doped and undoped ICF ablator materials
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