The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer
. ...However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer.
We analyze the renormalization group fixed point of the two-dimensional Ising model at criticality. In contrast with expectations from tensor network renormalization (TNR), we show that a simple, ...explicit analytic description of this fixed point using operator-algebraic renormalization (OAR) is possible. Specifically, the fixed point is characterized in terms of spin-spin correlation functions. Explicit error bounds for the approximation of continuum correlation functions are given.
GRB 130427A: A Nearby Ordinary Monster Maselli, A.; Melandri, A.; Nava, L. ...
Science (American Association for the Advancement of Science),
01/2014, Letnik:
343, Številka:
6166
Journal Article
Recenzirano
Odprti dostop
Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 × 10⁵³ ...ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the γ-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropie energies.
Bright X-ray Flares in Gamma-Ray Burst Afterglows Burrows, D. N.; Romano, P.; Falcone, A. ...
Science (American Association for the Advancement of Science),
09/2005, Letnik:
309, Številka:
5742
Journal Article
Recenzirano
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Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the ...central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.
We study the second-order quantum phase transition of massive real scalar field theory with a quartic interaction in (1 + 1) dimensions on an infinite spatial lattice using matrix product states. We ...introduce and apply a naive variational conjugate gradient method, based on the time-dependent variational principle for imaginary time, to obtain approximate ground states, using a related ansatz for excitations to calculate the particle and soliton masses and to obtain the spectral density. We also estimate the central charge using finite-entanglement scaling. Our value for the critical parameter agrees well with recent Monte Carlo results, improving on an earlier study which used the related density matrix normalization group method, verifying that these techniques are well-suited to studying critical field systems. We also obtain critical exponents that agree, as expected, with those of the transverse Ising model. Additionally, we treat the special case of uniform product states (mean field theory) separately, showing that they may be used to investigate noncritical quantum field theories under certain conditions.
Timing the initiation of multiple myeloma Rustad, Even H; Yellapantula, Venkata; Leongamornlert, Daniel ...
Nature communications,
04/2020, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma ...evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2
-3
decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.
Dynamics for holographic codes Osborne, Tobias J.; Stiegemann, Deniz E.
The journal of high energy physics,
04/2020, Letnik:
2020, Številka:
4
Journal Article
Recenzirano
Odprti dostop
A
bstract
We describe how to introduce dynamics for the holographic states and codes introduced by Pastawski, Yoshida, Harlow and Preskill. This task requires the definition of a continuous limit of ...the kinematical Hilbert space which we argue may be achieved via the
semicontinuous limit
of Jones. Dynamics is then introduced by building a unitary representation of a group known as Thompson’s group
T
, which is closely related to the conformal group conf (ℝ
1
,
1
). The bulk Hilbert space is realised as a special subspace of the semicontinuous limit Hilbert space spanned by a class of distinguished states which can be assigned a discrete bulk geometry. The analogue of the group of large bulk diffeomorphisms is given by a unitary representation of the
Ptolemy group Pt
, on the bulk Hilbert space thus realising a toy model of the AdS/CFT correspondence which we call the
Pt /T
correspondence.
We present a homogeneous X-ray analysis of all 318 gamma-ray bursts detected by the X-ray telescope (XRT) on the Swift satellite up to 2008 July 23; this represents the largest sample of X-ray GRB ...data published to date. In Sections 2–3, we detail the methods which the Swift-XRT team has developed to produce the enhanced positions, light curves, hardness ratios and spectra presented in this paper. Software using these methods continues to create such products for all new GRBs observed by the Swift-XRT. We also detail web-based tools allowing users to create these products for any object observed by the XRT, not just GRBs. In Sections 4–6, we present the results of our analysis of GRBs, including probability distribution functions of the temporal and spectral properties of the sample. We demonstrate evidence for a consistent underlying behaviour which can produce a range of light-curve morphologies, and attempt to interpret this behaviour in the framework of external forward shock emission. We find several difficulties, in particular that reconciliation of our data with the forward shock model requires energy injection to continue for days to weeks.
Quantum Metropolis sampling TEMME, K; OSBORNE, T. J; VOLLBRECHT, K. G ...
Nature (London),
03/2011, Letnik:
471, Številka:
7336
Journal Article
Recenzirano
Odprti dostop
The original motivation to build a quantum computer came from Feynman, who imagined a machine capable of simulating generic quantum mechanical systems--a task that is believed to be intractable for ...classical computers. Such a machine could have far-reaching applications in the simulation of many-body quantum physics in condensed-matter, chemical and high-energy systems. Part of Feynman's challenge was met by Lloyd, who showed how to approximately decompose the time evolution operator of interacting quantum particles into a short sequence of elementary gates, suitable for operation on a quantum computer. However, this left open the problem of how to simulate the equilibrium and static properties of quantum systems. This requires the preparation of ground and Gibbs states on a quantum computer. For classical systems, this problem is solved by the ubiquitous Metropolis algorithm, a method that has basically acquired a monopoly on the simulation of interacting particles. Here we demonstrate how to implement a quantum version of the Metropolis algorithm. This algorithm permits sampling directly from the eigenstates of the Hamiltonian, and thus evades the sign problem present in classical simulations. A small-scale implementation of this algorithm should be achievable with today's technology.
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