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1.
Ann Oncol ; 29(4): 966-972, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365086

RESUMO

Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and methods: Patients with absence of disease progression for over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genetic landscape. Microarray analysis, comparing US-CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.


Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Estudos de Coortes , Variações do Número de Cópias de DNA , Progressão da Doença , Genes p53 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Sequenciamento do Exoma
3.
Phys Rev Lett ; 116(14): 143603, 2016 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-27104710

RESUMO

We explore the phase diagram of the dissipative Rabi-Hubbard model, as could be realized by a Raman-pumping scheme applied to a coupled cavity array. There exist various exotic attractors, including ferroelectric, antiferroelectric, and incommensurate fixed points, as well as regions of persistent oscillations. Many of these features can be understood analytically by truncating to the two lowest lying states of the Rabi model on each site. We also show that these features survive beyond mean field, using matrix product operator simulations.

4.
Phys Rev Lett ; 109(5): 053601, 2012 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-23006171

RESUMO

Systems of strongly interacting atoms and photons, which can be realized wiring up individual cavity QED systems into lattices, are perceived as a new platform for quantum simulation. While sharing important properties with other systems of interacting quantum particles, here we argue that the nature of light-matter interaction gives rise to unique features with no analogs in condensed matter or atomic physics setups. By discussing the physics of a lattice model of delocalized photons coupled locally with two-level systems through the elementary light-matter interaction described by the Rabi model, we argue that the inclusion of counterrotating terms, so far neglected, is crucial to stabilize finite-density quantum phases of correlated photons out of the vacuum, with no need for an artificially engineered chemical potential. We show that the competition between photon delocalization and Rabi nonlinearity drives the system across a novel Z(2) parity symmetry-breaking quantum criticality between two gapped phases that share similarities with the Dicke transition of quantum optics and the Ising critical point of quantum magnetism. We discuss the phase diagram as well as the low-energy excitation spectrum and present analytic estimates for critical quantities.

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