RESUMEN
Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. SIGNIFICANCE: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.
Asunto(s)
Edema Encefálico , Neoplasias Encefálicas , Glioma , Adulto , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Edema Encefálico/genética , Edema Encefálico/diagnóstico , Edema Encefálico/patología , Glioma/patología , Edema , Mutación , Microambiente TumoralRESUMEN
We demonstrate the possibility to generate squeezed vacuum states of light by four wave mixing (FWM) enabled coherent population trapping in a metastable helium cell at room temperature. Contrary to usual FWM far detuned schemes, we work at resonance with an atomic transition. We investigate the properties of such states and show that the noise variances of the squeezed and anti-squeezed quadratures cannot be explained by the simple presence of losses. A specific model allows us to demonstrate the role played by spontaneous emitted photons, which experience squeezing while propagation inside of the cell. This theoretical model, which takes into account both residual absorption and spontaneous emission, leads to an excellent agreement with the experimental data without any adjusted parameter.
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We theoretically study the propagation and storage of a classical field in a Λ-type atomic medium using coherent population oscillations (CPOs). We show that the propagation eigenmodes strongly relate to the different CPO modes of the system. Light storage in such modes is discussed by introducing a "populariton" quantity, a mixture of populations and field, by analogy to the dark state polariton used in the context of electromagnetically induced transparency light storage protocol. As experimentally shown, this memory relies on populations and is then-by contrast with usual Raman coherence optical storage protocols-robust to dephasing effects.
RESUMEN
Electromagnetically induced transparency (EIT) in a ladder system involving a Rydberg level is known to yield giant optical nonlinearities for the probe field, even in the few-photon regime. This enhancement is due to the strong dipole-dipole interactions between Rydberg atoms and the resulting excitation blockade phenomenon. In order to study such highly correlated media, ad hoc models or low-excitation assumptions are generally used to tackle their dynamical response to optical fields. Here, we study the behavior of a cavity Rydberg-EIT setup in the nonequilibrium quantum field formalism, and we obtain analytic expressions for elastic and inelastic components of the cavity transmission spectrum, valid up to higher excitation numbers than previously achieved. This allows us to identify and interpret a polaritonic resonance structure, to our knowledge unreported so far.
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In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.
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We propose to use a collective excitation blockade mechanism to identify errors that occur due to disturbances of single atoms in ensemble quantum registers where qubits are stored in the collective population of different internal atomic states. A simple error correction procedure and a simple decoherence-free encoding of ensemble qubits in the hyperfine states of alkali-metal atoms are presented.
RESUMEN
The very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon or satellite based instruments in the detection of very-high-energy (>600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.
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We propose a new physical approach for encoding and processing of quantum information in ensembles of multilevel quantum systems, where the different bits are not carried by individual particles but associated with the collective population of different internal levels. One- and two-bit gates are implemented by collective internal state transitions taking place in the presence of an excitation blockade mechanism, which restricts the population of each internal state to the values zero and unity. Quantum computers with 10-20 bits can be built via this scheme in single trapped clouds of ground state atoms subject to the Rydberg excitation blockade mechanism, and the linear dependence between register size and the number of internal quantum states in atoms offers realistic means to reach larger registers.