226 research outputs found
Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance
The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC50 value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (p = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K–Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance
Two-Proton Correlations from 14.6A GeV/c Si+Pb and 11.5A GeV/c Au+Au Central Collisions
Two-proton correlation functions have been measured in Si+Pb collisions at
14.6A GeV/c and Au+Au collisions at 11.5A GeV/c by the E814/E877 collaboration.
Data are compared with predictions of the transport model RQMD and the source
size is inferred from this comparison. Our analysis shows that, for both
reactions, the characteristic size of the system at freeze-out exceeds the size
of the projectile, suggesting that the fireball created in the collision has
expanded. For Au+Au reactions, the observed centrality dependence of the
two-proton correlation function implies that more central collisions lead to a
larger source sizes.Comment: RevTex, 12 pages, 5 figure
Proton and Pion Production Relative to the Reaction Plane in Au + Au Collisions at AGS Energies
Results are presented of an analysis of proton and charged pion azimuthal
distributions measured with respect to the reaction plane in Au + Au collisions
at a beam momentum of about 11 AGeV/c. The azimuthal anisotropy is studied as a
function of particle rapidity and transverse momentum for different
centralities of the collisions. The triple differential (in rapidity,
transverse momentum, and azimuthal angle) distributions are reconstructed. A
comparison of the results with a previous analysis of charged particle and
transverse energy flow as well as with model predictions is presented.Comment: 23 pages (LaTeX), 12 figure
Charged Particle Pseudorapidity Distributions in Au+Al, Cu, Au, and U Collisions at 10.8 AGeV/c
We present the results of an analysis of charged particle pseudorapidity
distributions in the central region in collisions of a Au projectile with Al,
Cu, Au, and U targets at an incident energy of 10.8~GeV/c per nucleon. The
pseudorapidity distributions are presented as a function of transverse energy
produced in the target or central pseudorapidity regions. The correlation
between charged multiplicity and transverse energy measured in the central
region, as well as the target and projectile regions is also presented. We give
results for transverse energy per charged particle as a function of
pseudorapidity and centrality.Comment: 31 pages + 12 figures (compressed and uuencoded by uufiles), LATEX,
Submitted to PR
Temporal behavior of the electron and negative ion densities in a pulsed radio‐frequency CF 4
Temperature and carbonate ion effects on Mg/Ca and Sr/Ca ratios in benthic foraminifera : aragonitic species Hoeglundina elegans
Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 21 (2006): PA1007, doi:10.1029/2005PA001158.Core top samples from Atlantic (Little Bahama Banks (LBB)) and Pacific (Hawaii and Indonesia) depth transects have been analyzed in order to assess the influence of bottom water temperature (BWT) and aragonite saturation levels on Mg/Ca and Sr/Ca ratios in the aragonitic benthic foraminifer Hoeglundina elegans. Both the Mg/Ca and Sr/Ca ratios in H. elegans tests show a general decrease with increasing water depth. Although at each site the decreasing trends are consistent with the in situ temperature profile, Mg/Ca and Sr/Ca ratios in LBB are substantially higher than in Indonesia and Hawaii at comparable water depths with a greater difference observed with increasing water depth. Because we find no significant difference between results obtained on “live” and “dead” specimens, we propose that these differences are due to primary effects on the metal uptake during test formation. Evaluation of the water column properties at each site suggests that in situ CO3 ion concentrations play an important role in determining the H. elegans Mg/Ca and Sr/Ca ratios. The CO3 ion effect is limited, however, only to aragonite saturation levels ([ΔCO3]aragonite) below 15 μmol kg−1. Above this level, temperature exerts a dominant effect. Accordingly, we propose that Mg/Ca and Sr/Ca in H. elegans tests can be used to reconstruct thermocline temperatures only in waters oversaturated with respect to the mineral aragonite using the following relationships: Mg/Ca = (0.034 ± 0.002)BWT + (0.96 ± 0.03) and Sr/Ca = (0.060 ± 0.002)BWT + (1.53 ± 0.03) (for [ΔCO3]aragonite > 15 μmol kg−1). The standard error associated with these equations is about ±1.1°C. Reconstruction of deeper water temperatures is complicated because in undersaturated waters, changes in Mg/Ca and Sr/Ca ratios reflect a combination of changes in [CO3] and BWT. Overall, we find that Sr/Ca, rather than Mg/Ca, in H. elegans may be a more accurate proxy for reconstructing paleotemperatures.Yair Rosenthal acknowledges the support of Amtzia
Genin and the Hebrew University, Forchheimer Fellowship, during his
sabbatical in the Inter-University Institute in Eilat, Israel. This project
has been funded by NSF Awards OCE 0220922 to Y.R. and OCE
0220776 to D.W.O. and B.K.L
Evaluation of two genera of benthic foraminifera for down-core paleotemperature studies in the western south atlantic
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A transition radiation detector which features accurate tracking and dE/dx particle identification
We describe the results of a test run involving a Transition Radiation Detector that can both distinguish electrons from pions with momenta greater than 0.7 GeV/c and simultaneously track particles passing through the detector. The particle identification is accomplished through a combination of the detection of Transition Radiation from the electron and the differences in electron and pion energy loss (dE/dx) in the detector. The dE/dx particle separation is most efficient below 2 GeV/c while particle ID utilizing Transition Radiation is effective above 1.5 GeV/c. Combined, the electron-pion separation is better than 5 [times] l0[sup 2]. The single-wire, track-position resolution for the TRD is [approximately]230[mu]m
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