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- Martel, I., et al.
(author)
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An innovative Superconducting Recoil Separator for HIE-ISOLDE
- 2023
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In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : ELSEVIER. - 0168-583X .- 1872-9584. ; 541, s. 176-179
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Journal article (peer-reviewed)abstract
- The ISOLDE Scientific Infrastructure at CERN offers a unique range of post-accelerated radioactive beams. The scientific program can be improved with the “Isolde Superconducting Recoil Separator” (ISRS), an innovative spectrometer able to deliver unprecedented (A, Z) resolution. In this paper we present an overview of the physics and ongoing technical developments.
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2. |
- Kotmayer, L, et al.
(author)
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Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Journal article (peer-reviewed)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
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3. |
- Camacho-Neves, Yssavo, et al.
(author)
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Over 500 Days in the Life of the Photosphere of the Type Iax Supernova SN 2014dt
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 951:1
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Journal article (peer-reviewed)abstract
- Type Iax supernovae (SNe Iax) are the largest known class of peculiar white dwarf SNe, distinct from normal Type Ia supernovae (SNe Ia). The unique properties of SNe Iax, especially their strong photospheric lines out to extremely late times, allow us to model their optical spectra and derive the physical parameters of the long-lasting photosphere. We present an extensive spectral timeseries, including 21 new spectra, of SN Iax 2014dt from +11 to +562 days after maximum light. We are able to reproduce the entire timeseries with a self-consistent, nearly unaltered deflagration explosion model from Fink et al. using TARDIS, an open source radiative-transfer code. We find that the photospheric velocity of SN 2014dt slows its evolution between +64 and +148 days, which closely overlaps the phase when we see SN 2014dt diverge from the normal spectral evolution of SNe Ia (+90 to +150 days). The photospheric velocity at these epochs, ∼400–1000 km s−1, may demarcate a boundary within the ejecta below which the physics of SNe Iax and normal SNe Ia differ. Our results suggest that SN 2014dt is consistent with a weak deflagration explosion model that leaves behind a bound remnant and drives an optically thick, quasi-steady-state wind creating the photospheric lines at late times. The data also suggest that this wind may weaken at epochs past +450 days, perhaps indicating a radioactive power source that has decayed away.
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