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105 result(s) for "Drouet, F."
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Candidates for low-lying octupole isovector (mixed-symmetry) excitations
The spectroscopic properties of low-lying octupole states, previously proposed to be candidates for isovector (mixed-symmetry) states, were investigated in 95 Mo( n th , γ ) and 143 Nd( n th , γ ) thermal neutron capture reactions. The experiments used eight Clover detectors that made up the central ring of the EXILL setup and the high thermal neutron flux of the research reactor at ILL. These measurements allowed a determination of branching ratios and multipole mixing ratios for the transitions of interest connecting the isovector candidate and the lowest-lying J π = 3 − 1 state, the octupole phonon. Furthermore, for 144 Nd the lifetime of the third excited 3 − 3 level was remeasured using the Gamma-Ray Induced Doppler-shift method to be τ = 31 +10 −25 . While calculations in the Quasi-particle Phonon Model indicate that the 3 − 3 state in 144 Nd remains a good candidate for an isovector state, a simple model approach indicates that for 96 Mo the isovector state must be higher in energy than the proposed 3 − 2 candidate at 3178 keV.
A new ER-specific photosensitizer unravels ¹O.sub.2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT
Photosensitizers (PS) are ideally devoid of any activity in the absence of photoactivation, and rely on molecular oxygen for the formation of singlet oxygen (¹[O.sub.2]) to produce cellular damage. Off-targets and tumor hypoxia therefore represent obstacles for the use of PS for cancer photodynamic therapy. Herein, we describe the characterization of OR141, a benzophenazine compound identified through a phenotypic screening for its capacity to be strictly activated by light and to kill a large variety of tumor cells under both normoxia and hypoxia. This new class of PS unraveled an unsuspected common mechanism of action for PS that involves the combined inhibition of the mammalian target of rapamycin (mTOR) signaling pathway and proteasomal deubiquitinases (DUBs) USP14 and UCH37. Oxidation of mTOR and other endoplasmic reticulum (ER)-associated proteins drives the early formation of high molecular weight (MW) complexes of multimeric proteins, the concomitant blockade of DUBs preventing their degradation and precipitating cell death. Furthermore, we validated the antitumor effects of OR141 in vivo and documented its highly selective accumulation in the ER, further increasing the ER stress resulting from ¹[O.sub.2] generation upon light activation.
A new ER-specific photosensitizer unravels 1O2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT
Photosensitizers (PS) are ideally devoid of any activity in the absence of photoactivation, and rely on molecular oxygen for the formation of singlet oxygen ( 1 O 2 ) to produce cellular damage. Off-targets and tumor hypoxia therefore represent obstacles for the use of PS for cancer photodynamic therapy. Herein, we describe the characterization of OR141, a benzophenazine compound identified through a phenotypic screening for its capacity to be strictly activated by light and to kill a large variety of tumor cells under both normoxia and hypoxia. This new class of PS unraveled an unsuspected common mechanism of action for PS that involves the combined inhibition of the mammalian target of rapamycin (mTOR) signaling pathway and proteasomal deubiquitinases (DUBs) USP14 and UCH37. Oxidation of mTOR and other endoplasmic reticulum (ER)-associated proteins drives the early formation of high molecular weight (MW) complexes of multimeric proteins, the concomitant blockade of DUBs preventing their degradation and precipitating cell death. Furthermore, we validated the antitumor effects of OR141 in vivo and documented its highly selective accumulation in the ER, further increasing the ER stress resulting from 1 O 2 generation upon light activation.
EXOGAM at the ILL: the EXILL campaign
A combination of germanium detectors has been installed at the PF1B neutron guide of the ILL to perform the prompt spectroscopy of neutron-rich nuclei produced in the neutron-capture induced-fission of 235U and 241Pu. Radiative capture reactions on rare targets have also been performed. LaBr3 detectors from the FATIMA collaboration have also been installed in complement with the EXOGAM clovers to measure lifetimes of low-lying excited states. The measured characteristics indicate very good performances of the overall setup. Some recent results will be discussed.
From EXILL (EXogam at the ILL) to FIPPS (FIssion Product Prompt γ -ray Spectrometer)
Within the EXILL campaign a large and efficient cluster of Ge-detectors was installed around a very well collimated neutron beam. This has allowed to carry out rather complete spectroscopic studies close to the line of stability using the (n,γ) reaction. Neutron rich isotopes were produced by neutron induced fission and prompt spectroscopy was carried out. The isotope selection in this setup was based on a partially known level scheme and the use of triple coincidences. The latter is limiting the statistical sensitivity in the case of weak production yields. Based on the experiences of these campaigns we are currently developing a new setup: FIPPS (FIssion Product Prompt Spectroscopy). This setup combines a collimated neutron beam, a highly efficient cluster of Ge detectors, a gas filled magnet and auxiliary detectors. The presence of the gas filled magnet will allow us to identify fission products directly and should give access to a new quality of studies if compared to the EXILL campaign. The EXILL campaign and the FIPPS project are presented.
Lifetime measurement in neutron-rich A~100 nuclei
Lifetimes of excited states of the 98;100;102 Zr nuclei were measured by using the Generalized Centroid Difference Method. The nuclei of interest were populated via neutron-induced fission of 241 Pu and 235 U during the EXILL-FATIMA campaign. The obtained lifetimes were used to calculate the B(E2) transition strengths and β deformation parameters which were then compared with the recent theoretical predictions obtained with Monte Carlo Shell Model.
The Generalized Centroid Difference method for lifetime measurements via γ-γ coincidences using large fast-timing arrays
A novel method for direct electronic “fast-timing” lifetime measurements of nuclear excited states via γ-γ coincidences using an array equipped with N very fast high-resolution LaBr3(Ce) scintillator detectors is presented. The generalized centroid difference method provides two independent “start” and “stop” time spectra obtained without any correction by a superposition of the N(N – 1)/2 calibrated γ-γ time difference spectra of the N detector fast-timing system. The two fast-timing array time spectra correspond to a forward and reverse gating of a specific γ-γ cascade and the centroid difference as the time shift between the centroids of the two time spectra provides a picosecond-sensitive mirror-symmetric observable of the set-up. The energydependent mean prompt response difference between the start and stop events is calibrated and used as a single correction for lifetime determination. These combined fast-timing array mean γ-γ zero-time responses can be determined for 40 keV < Eγ < 1.4 MeV with a precision better than 10 ps using a 152Eu γ-ray source. The new method is described with examples of (n,γ) and (n,f,γ) experiments performed at the intense cold-neutron beam facility PF1B of the Institut Laue-Langevin in Grenoble, France, using 16 LaBr3(Ce) detectors within the EXILL&FATIMA campaign in 2013. The results are discussed with respect to possible systematic errors induced by background contributions.
The (n, γ ) campaigns at EXILL
At the PF1B cold neutron beam line at the Institut Laue Langevin, the EXILL array consisting of EXOGAM, GASP and ILL-Clover detectors was used to perform (n,γ) measurements at very high coincidence rates. About ten different reactions were measured in autumn 2012 using a highly collimated cold neutron beam. In spring 2013, the EXOGAM array was combined with 16 LaBr3(Ce) scintillators in the EXILL&FATIMA campaign for the measurement of lifetimes using the generalised centroid difference method. We report on the properties of the set-ups and present first results from both campaigns.
A new ER-specific photosensitizer unravels super(1)O sub(2)-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT
Photosensitizers (PS) are ideally devoid of any activity in the absence of photoactivation, and rely on molecular oxygen for the formation of singlet oxygen ( super(1)O sub(2)) to produce cellular damage. Off-targets and tumor hypoxia therefore represent obstacles for the use of PS for cancer photodynamic therapy. Herein, we describe the characterization of OR141, a benzophenazine compound identified through a phenotypic screening for its capacity to be strictly activated by light and to kill a large variety of tumor cells under both normoxia and hypoxia. This new class of PS unraveled an unsuspected common mechanism of action for PS that involves the combined inhibition of the mammalian target of rapamycin (mTOR) signaling pathway and proteasomal deubiquitinases (DUBs) USP14 and UCH37. Oxidation of mTOR and other endoplasmic reticulum (ER)-associated proteins drives the early formation of high molecular weight (MW) complexes of multimeric proteins, the concomitant blockade of DUBs preventing their degradation and precipitating cell death. Furthermore, we validated the antitumor effects of OR141 in vivo and documented its highly selective accumulation in the ER, further increasing the ER stress resulting from super(1)O sub(2) generation upon light activation.