160 research outputs found
Experimental Models of Liquid Biopsy in Hepatocellular Carcinoma Reveal Clone-Dependent Release of Circulating Tumor DNA.
Liquid biopsy, the molecular analysis of tumor components released into the bloodstream, has emerged as a noninvasive and resourceful means to access genomic information from cancers. Most data derived from translational studies showcase its numerous potential clinical applications. However, data from experimental models are scarce, and little is known about the underlying mechanisms and factors controlling the release of circulating tumor DNA (ctDNA) and cells (CTCs). This study aimed to model liquid biopsy in hepatocellular carcinoma xenografts and to study the dynamics of release of ctDNA and CTCs; this included models of intratumoral heterogeneity (ITH) and metastatic disease. We quantified ctDNA by quantitative polymerase chain reaction (PCR) targeting human long interspersed nuclear element group 1; targeted mutation analysis was performed with digital droplet PCR. CTCs were traced by flow cytometry. Results demonstrated the feasibility of detecting ctDNA, including clone-specific mutations, as well as CTCs in blood samples of mice. In addition, the concentration of ctDNA and presence of tumor-specific mutations reflected tumor progression, and detection of CTCs was associated with metastases. Our ITH model suggested differences in the release of DNA fragments impacted by the cell-clone origin and the treatment. Conclusion: These data present new models to study liquid biopsy and its underlying mechanisms and highlighted a clone-dependent release of ctDNA into the bloodstream
Measurement of Spin Correlation Parameters A, A, and A_ at 2.1 GeV in Proton-Proton Elastic Scattering
At the Cooler Synchrotron COSY/J\"ulich spin correlation parameters in
elastic proton-proton (pp) scattering have been measured with a 2.11 GeV
polarized proton beam and a polarized hydrogen atomic beam target. We report
results for A, A, and A_ for c.m. scattering angles between
30 and 90. Our data on A -- the first measurement of this
observable above 800 MeV -- clearly disagrees with predictions of available of
pp scattering phase shift solutions while A and A_ are reproduced
reasonably well. We show that in the direct reconstruction of the scattering
amplitudes from the body of available pp elastic scattering data at 2.1 GeV the
number of possible solutions is considerably reduced.Comment: 4 pages, 4 figure
Determination of Deuteron Beam Polarizations at COSY
The vector and tensor polarizations of a deuteron beam have been measured
using elastic deuteron-carbon scattering at 75.6 MeV and deuteron-proton
scattering at 270 MeV. After acceleration to 1170 MeV inside the COSY ring, the
polarizations of the deuterons were checked by studying a variety of nuclear
reactions using a cluster target at the ANKE magnet spectrometer placed at an
internal target position of the storage ring. All these measurements were
consistent with the absence of depolarization during acceleration and provide a
number of secondary standards that can be used in subsequent experiments at the
facility.Comment: 12 pages, 13 figure
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Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.
We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9}) eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation
Commissioning of the vacuum system of the KATRIN Main Spectrometer
The KATRIN experiment will probe the neutrino mass by measuring the
beta-electron energy spectrum near the endpoint of tritium beta-decay. An
integral energy analysis will be performed by an electro-static spectrometer
(Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a
volume of 1240 m^3, and a complex inner electrode system with about 120000
individual parts. The strong magnetic field that guides the beta-electrons is
provided by super-conducting solenoids at both ends of the spectrometer. Its
influence on turbo-molecular pumps and vacuum gauges had to be considered. A
system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter
strips has been deployed and was tested during the commissioning of the
spectrometer. In this paper the configuration, the commissioning with bake-out
at 300{\deg}C, and the performance of this system are presented in detail. The
vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is
demonstrated that the performance of the system is already close to these
stringent functional requirements for the KATRIN experiment, which will start
at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure
Higher Order Spin Resonances in a 2.1 GeV/c Polarized Proton Beam
Spin resonances can depolarize or spin-flip a polarized beam. We studied 1st
and higher order spin resonances with stored 2.1 GeV/c vertically polarized
protons. The 1st order vertical ({\nu}y) resonance caused almost full
spin-flip, while some higher order {\nu}y resonances caused partial
depolarization. The 1st order horizontal ({\nu}x) resonance caused almost full
depolarization, while some higher order {\nu}x resonances again caused partial
depolarization. Moreover, a 2nd order {\nu}x resonance is about as strong as
some 3rd order {\nu}x resonances, while some 3rd order {\nu}y resonances are
much stronger than a 2nd order {\nu}y resonance. One thought that {\nu}y spin
resonances are far stronger than {\nu}x, and that lower order resonances are
stronger than higher order; the data do not support this.Comment: 5 pages, 5 figures Note that Fig. 5 did not appear in the PRL due to
space limitation, but did appear in the March 2012 CERN Courier News Item
"Results from SPIN@COSY may bode well for RHIC
Suppression of Penning discharges between the KATRIN spectrometers
The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to determine the effective electron (anti)-neutrino mass with a sensitivity of 0.2eV/c by precisely measuring the endpoint region of the tritium β-decay spectrum. It uses a tandem of electrostatic spectrometers working as magnetic adiabatic collimation combined with an electrostatic (MAC-E) filters. In the space between the pre-spectrometer and the main spectrometer, creating a Penning trap is unavoidable when the superconducting magnet between the two spectrometers, biased at their respective nominal potentials, is energized. The electrons accumulated in this trap can lead to discharges, which create additional background electrons and endanger the spectrometer and detector section downstream. To counteract this problem, “electron catchers” were installed in the beamline inside the magnet bore between the two spectrometers. These catchers can be moved across the magnetic-flux tube and intercept on a sub-ms time scale the stored electrons along their magnetron motion paths. In this paper, we report on the design and the successful commissioning of the electron catchers and present results on their efficiency in reducing the experimental background
Precision measurement of the electron energy-loss function in tritium and deuterium gas for the KATRIN experiment
The KATRIN experiment is designed for a direct and model-independent
determination of the effective electron anti-neutrino mass via a high-precision
measurement of the tritium -decay endpoint region with a sensitivity on
of 0.2eV/c (90% CL). For this purpose, the -electrons
from a high-luminosity windowless gaseous tritium source traversing an
electrostatic retarding spectrometer are counted to obtain an integral spectrum
around the endpoint energy of 18.6keV. A dominant systematic effect of the
response of the experimental setup is the energy loss of -electrons from
elastic and inelastic scattering off tritium molecules within the source. We
determined the \linebreak energy-loss function in-situ with a pulsed
angular-selective and monoenergetic photoelectron source at various
tritium-source densities. The data was recorded in integral and differential
modes; the latter was achieved by using a novel time-of-flight technique.
We developed a semi-empirical parametrization for the energy-loss function
for the scattering of 18.6-keV electrons from hydrogen isotopologs. This model
was fit to measurement data with a 95% T gas mixture at 30K, as used in
the first KATRIN neutrino mass analyses, as well as a D gas mixture of 96%
purity used in KATRIN commissioning runs. The achieved precision on the
energy-loss function has abated the corresponding uncertainty of
[arXiv:2101.05253] in the KATRIN
neutrino-mass measurement to a subdominant level.Comment: 12 figures, 18 pages; to be submitted to EPJ
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