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1.
Phys Rev Lett ; 131(16): 162501, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37925694

RESUMO

Neutrinoless double beta decay (0νßß) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νßß) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νßß decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18} yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νßß decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νßß decay.

2.
Phys Rev Lett ; 126(18): 181802, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018798

RESUMO

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νßß experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νßß decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17 kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νßß is observed. We report a new limit on the half-life of 0νßß decay in ^{100}Mo of T_{1/2}>1.5×10^{24} yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ßß}⟩<(0.31-0.54) eV, dependent on the nuclear matrix element in the light Majorana neutrino exchange interpretation.

3.
Phys Rev Lett ; 125(14): 141301, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33064531

RESUMO

We present the first Ge-based constraints on sub-MeV/c^{2} dark matter (DM) particles interacting with electrons using a 33.4 g Ge cryogenic detector with a 0.53 electron-hole pair (rms) resolution, operated underground at the Laboratoire Souterrain de Modane. Competitive constraints are set on the DM-electron scattering cross section, as well as on the kinetic mixing parameter of dark photons down to 1 eV/c^{2}. In particular, the most stringent limits are set for dark photon DM in the 6 to 9 eV/c^{2} range. These results demonstrate the high relevance of Ge cryogenic detectors for the search of DM-induced eV-scale electron signals.

4.
Cell Transplant ; 31: 9636897211070239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35170351

RESUMO

Stem cells have the capacity to ensure the renewal of tissues and organs. They could be used in the future for a wide range of therapeutic purposes and are preserved at liquid nitrogen temperature to prevent any chemical or biological activity up to several decades before their use. We show that the cryogenized cells accumulate damages coming from natural radiations, potentially inducing DNA double-strand breaks (DSBs). Such DNA damage in stem cells could lead to either mortality of the cells upon thawing or a mutation diminishing the therapeutic potential of the treatment. Many studies show how stem cells react to different levels of radiation; the effect of terrestrial cosmic rays being key, it is thus also important to investigate the effect of the natural radiation on the cryopreserved stem cell behavior over time. Our study showed that the cryostored stem cells totally shielded from cosmic rays had less DSBs upon long-term storage. This could have important implications on the long-term cryostorage strategy and quality control of different cell banks.


Assuntos
Quebras de DNA de Cadeia Dupla , Dano ao DNA , Criopreservação , Raios gama , Células-Tronco
5.
Leukemia ; 32(3): 588-596, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28819278

RESUMO

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis. To evaluate whether IL4 inhibits AML cells in vivo, we expressed IL4 ectopically in AML cells transplanted into mice and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Notably, IL4 exposure caused reduced growth and survival of primary AML CD34+CD38- patient cells from several genetic subtypes of AML, whereas normal stem and progenitor cells were less affected. The IL4-induced apoptosis of AML cells was linked to Caspase-3 activation. Our results demonstrate that IL4 selectively induces apoptosis of AML cells in a Stat6-dependent manner-findings that may translate into new therapeutic opportunities in AML.


Assuntos
Apoptose , Interleucina-4/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fator de Transcrição STAT6/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Citocinas/metabolismo , Citometria de Fluxo , Expressão Gênica , Células-Tronco Hematopoéticas , Humanos , Interleucina-4/farmacologia , Leucemia Mieloide Aguda/genética , Camundongos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Eur Phys J C Part Fields ; 77(11): 785, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31997932

RESUMO

This paper reports on the development of a technology involving 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼ 1 kg ), high optical quality, radiopure 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100 Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8 σ . Less than 10 µ Bq/kg activity of 232 Th ( 228 Th ) and 226 Ra in the crystals is ensured by boule recrystallization. The potential of 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10 kg × d exposure: the two neutrino double-beta decay half-life of 100 Mo has been measured with the up-to-date highest accuracy as T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100 Mo .

7.
Diagn Interv Imaging ; 94(12): 1279-90, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23856648

RESUMO

Microcirculation imaging in breast cancer involves studying tissue enhancement after contrast injection, which is used to calculate perfusion and permeability. The magnitude of enhancement reflects blood and interstitial volumes. This technique has benefitted from advances in MRI, which allow large volumes to be acquired with a good compromise between temporal and spatial resolution. Software has also advanced enabling microcirculation maps to be calculated and heterogeneity to be analyzed. If permeability is increased and interstitial volume is reduced, the microcirculation imaging suggests a suspicious aggressive lesion and can be used for early assessment of neoadjuvant therapies by demonstrating restoration of normal functional indices, which precede morphological changes.


Assuntos
Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética , Microcirculação , Imagem de Perfusão/métodos , Feminino , Humanos
8.
Diagn Interv Imaging ; 93(2): 104-15, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22305594

RESUMO

Breast MRI should not be used for differential diagnosis between inflammatory breast cancer and acute mastitis (AM) prior to treatment. When mastitis symptoms persist after 10 to 15 days of well-managed medical treatment, MRI may be performed in addition to an ultrasound examination, a mammogram and to taking histological samples, in order to eliminate inflammatory breast cancer (IBC). For staging, MRI would seem to be useful in looking for a contralateral lesion, PET-CT for finding information about remote metastases and in certain centres, for information about the initial extension to local/regional lymph nodes, which would guide the fields of irradiation (since patients can become lymph node negative after neoadjuvant chemotherapy). MRI and PET-CT seems to be useful for early detection of patients responding poorly to neoadjuvant chemotherapy so that the latter may be rapidly modified.


Assuntos
Imageamento por Ressonância Magnética , Mastite/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Feminino , Humanos
9.
Bull Cancer ; 97(1): 79-90, 2010 Jan.
Artigo em Francês | MEDLINE | ID: mdl-19858045

RESUMO

Angiogenesis is the process of activating dormant endothelial cells to form new vessels, after stimulation and it is essential in tumor growth. In many types of cancer, angiogenesis results from the activation of oncogenes that stimulate the production of Vascular Endothelial Growth Factor (VEGF). However, these newly formed vessels have a great number of abnormalities: increased density of fragile and hyper-permeable microvessels, arterial-venous shunts, caliber abnormalities and flow instabilities susceptible to flow direction inversion according to interstitial pressure. Anti-angiogenic treatments inhibit VEGF activity, perceived as structural and functional normalization of the microvascular pattern, such as reduced density of microvessels and restored morphology of the remaining ones. Conventional imaging techniques are not sensible to these changes, at best they show tumor size stabilization, hence the need of new techniques. Microvascularization imaging can be achieved by detecting functional disturbances to blood flow and not by showing the microvasculature per se. These techniques are based in quantifying the enhancement in tumor due to the passage of contrast agent after injection or protons labeled by a magnetic field. Through these measurements, one can derive interstitial and blood volumes as well as the tissue perfusion and capillary wall permeability. Microvascular imaging has greatly benefited from the improvements seen in CT and MRI equipment allowing large volume coverage with high spatial and temporal resolutions as from the evolutions in the methods to calculate, present and compare maps of the microcirculation and it's heterogeneity. However, software to analyze microvascularization are still rare, limiting the technique's application and validation in large scale. Nevertheless, imaging of the microcirculation is useful throughout the care of the oncological patient: it can reinforce the suspicious nature of a lesion, suggest anti-angiogenic treatment efficacy in hypervascular lesions, and show early treatment response before morphological changes as in RECIST criteria.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Permeabilidade Capilar , Humanos , Microcirculação , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neovascularização Patológica/terapia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
12.
Phys Rev B Condens Matter ; 40(13): 8700-8704, 1989 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9991347
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