RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers ...clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice.
RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated.RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients.
Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment.
The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.
Permanent electric dipole moments (EDMs) of fundamental particles provide powerful probes for physics beyond the Standard Model. We propose to search for the EDM of strange and charm baryons at LHC, ...extending the ongoing experimental program on the neutron, muon, atoms, molecules and light nuclei. The EDM of strange
Λ
baryons, selected from weak decays of charm baryons produced in
p
p
collisions at LHC, can be determined by studying the spin precession in the magnetic field of the detector tracking system. A test of
C
P
T
symmetry can be performed by measuring the magnetic dipole moment of
Λ
and
Λ
¯
baryons. For short-lived
Λ
c
+
and
Ξ
c
+
baryons, to be produced in a fixed-target experiment using the 7
TeV
LHC beam and channeled in a bent crystal, the spin precession is induced by the intense electromagnetic field between crystal atomic planes. The experimental layout based on the LHCb detector and the expected sensitivities in the coming years are discussed.
We propose a unique program of measurements of electric and magnetic dipole moments of charm, beauty and strange charged baryons at the LHC, based on the phenomenon of spin precession of channeled ...particles in bent crystals. Studies of crystal channeling and spin precession of positively- and negatively-charged particles are presented, along with feasibility studies and expected sensitivities for the proposed experiment using a layout based on the LHCb detector.
A novel method for the direct measurement of the elusive magnetic and electric dipole moments of the τ lepton is presented. The experimental approach relies on the production of τ^{+} leptons from ...D_{s}^{+}→τ^{+}ν_{τ} decays, originating in fixed-target collisions at the LHC. A sample of polarized τ^{+} leptons is kinematically selected and subsequently channeled in a bent crystal. The magnetic and electric dipole moments of the τ^{+} lepton are measured by determining the rotation of the spin-polarization vector induced by the intense electromagnetic field between crystal atomic planes. The experimental technique is discussed along with the expected sensitivities.
The electric and magnetic dipole moment of charm and bottom baryons can be measured for the first time by using bent crystal technology at the LHC. The experimental method, proposed in recent years, ...suffers from limited statistics, which dominates the uncertainty of the measurement. In this work, we present an alternative experimental layout, based on the use of crystal lenses, that improves the trapping efficiency by about a factor 15 (35) for a 2-cm (5-mm) target with respect to the nominal layout, with plain crystal faces. The efficiencies are evaluated taking into account the constraints from the LHC machine, and the technical challenges to realize this novel experimental method are discussed.
New bounds on the electric dipole moment (EDM) of charm and bottom quarks are derived using the stringent limits on their chromo-EDMs. The new limits, | dc | < 1.5 × 10−21 e cm and | db | < 1.2 × ...10−20 e cm, improve the previous ones by about 3 orders of magnitude. These indirect bounds have implications for different models of new physics, including two-Higgs-doublet, leptoquarks, and supersymmetry models.
In this Erratum, an improved simulation of the channeling efficiency of protons and antiprotons as a function of the particle momentum is shown in for different configurations
Electromagnetic dipole moments of short-lived particles are sensitive to physics within and beyond the Standard Model of particle physics but have not been accessible experimentally to date. To ...perform such measurements it has been proposed to exploit the spin precession of channeled particles in bent crystals at the LHC. Progress that enables the first measurement of charm baryon dipole moments is reported. In particular, the design and characterization on beam of silicon and germanium bent crystal prototypes, the optimization of the experimental setup, and advanced analysis techniques are discussed. Sensitivity studies show that first measurements of Λc+ and Ξc+ baryon dipole moments can be performed in two years of data taking with an experimental setup positioned upstream of the LHCb detector.
Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is ...essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.
•Acidic organelles are high Ca2+ content stores that can take up and release Ca2+ upon cell activation.•The optimal Ca2+ indicator for acidic organelles should be pH resistant and of low Ca2+ affinity.•Aequorin probes have been engineered for monitoring Ca2+ in several mildly acidic organelles across kingdoms of life.•Ca2+ measurements in more acidic compartments are limited.
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