The Hilbert space of Chern-Simons theory on the cylinder. A Loop Quantum Gravity approach

As a laboratory for loop quantum gravity, we consider the canonical quantization of the three-dimensional Chern-Simons theory on a noncompact space with the topology of a cylinder. Working within the loop quantization formalism, we define at the quantum level the constraints appearing in the canonical approach and completely solve them, thus constructing a gauge and diffeomorphism invariant physical Hilbert space for the theory. This space turns out to be infinite dimensional, but separable.Comment: Minor changes and some references added. Latex, 16 pages, 1 figur

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Simetrias escondidas em teorias de calibre & quasi-integrabilidade

This thesis is about some extensions of the ideas and techniques used in integrable field theories to deal with non-integrable theories. It is presented in two parts. The first part deals with gauge theories in 3 and 4 dimensional space-time; we propose what we call the integral formulation of them, which at the end give us a natural way of defining the conserved charges that are gauge invariant and do not depend on the parametrisation of space-time. The definition of gauge invariant conserved charges in non-Abelian gauge theories is an open issue in physics and we think our solution might be a first step into its full understanding. The integral formulation shows a deeper connection between different gauge theories: they share the same basic structure when written in the loop space. Moreover, in our construction the arguments leading to the conservation of the charges are dynamical and independent of the particular solution. In the second part we discuss the recently introduced concept called quasi-integrability: one observes soliton-like configurations evolving through non-integrable equations having properties similar to those expected for integrable theories. We study the case of a model which is a deformation of the non-linear Schr¨odinger equation consisting of a more general potential, connected in a way with the integrable one. The idea is to develop a mathematical approach to treat more realistic theories, which is in particular very important from the point of view of applications; the NLS model appears in many branches of physics, specially in optical fibres and Bose-Einstein condensation. The problem was treated analytically and numerically, and the results are interesting. Indeed, due to the fact that the model is not integrable one does not find an infinite number of conserved charges but, instead, a set of infinitely many charges that are asymptotically conserved, i.e., when two solitons undergo a scattering process the charges they carry before the collision change, but after the collision their values are recovered.Essa tese discute algumas extensões de ideias e técnicas usadas em teorias de campos integráveis para tratar teorias que não são integráveis. Sua apresentação é feita em duas partes. A primeira tem como tema teorias de calibre em 3 e 4 dimensões; propomos o que chamamos de equação integral para uma tal teoria, o que nos permite de maneira natural a construção de suas cargas invariantes de calibre, e independentes da parametrização do espaço-tempo. A definição de cargas conservadas in variantes de calibre em teorias não-Abelianas ainda é um assunto em aberto e acreditamos que a nossa solução pode ser um primeiro passo em seu entendimento. A formulação integral mostra uma conexão profunda entre diferentes teorias de calibre: elas compartilham da mesma estrutura básica quando formuladas no espaço dos laços. Mais ainda, em nossa construção os argumentos que levam `a conservação das cargas são dinâmicos e independentes de qualquer solução particular. Na segunda parte discutimos o recentemente introduzido conceito de quasi-integrabilidade: em (1 + 1) dimensões existem modelos não integráveis que admitem soluções solitonicas com propriedades similares `aquelas de teorias integráveis. Estudamos o caso de um modelo que consiste de uma deformação (não-integrável) da equação de Schrödinger não-linear (NLS), proveniente de um potencial mais geral, obtido a partir do caso integrável. O que se busca é desenvolver uma abordagem matemática sistemática para tratar teorias mais realistas (e portanto não integráveis), algo bastante relevante do ponto de vista de aplicações; o modelo NLS aparece em diversas áreas da física, especialmente no contexto de fibra ótica e condensação de Bose-Einstein. O problema foi tratado de maneira analítica e numérica, e os resultados se mostram interessantes. De fato, sendo a teoria não integrável não é encontrado um conjunto com infinitas cargas conservadas, mas, pode-se encontrar um conjunto com infinitas cargas assintoticamente conservadas, i.e., quando dois solitons colidem as cargas que eles tinham antes tem os seus valores alterados, mas após a colisão, os valores inicias, de antes do espalhamento, são recobrados