7 research outputs found
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
The Enigma of Mind: A Theory of Evolution and Conscious Experience
Focusing on human capacity to design, the volume's final chapter draws attention to the fascinating role imagination can play in human life. The relationship between human consciousness and the evolution of the species continues to captivate and puzzle scholars. By revisiting the dialogue between consciousness and evolution, the authors demonstrate how enigmas often necessitate dynamic collaboration between sciences, arts, and humanities. Archaeology provides evidence that the drive for diverse conscious experiences is no new phenomenon, while neuroscience illuminates the ways in which altered states of consciousness can enhance the variety of mental experience. Art, design, and cognitive technologies can build on this picture by providing innovative ways of exploring conscious experience. Inspired by insights from a range of academic disciplines and reflecting on personal experience, this chapter proposes the role of ‘harmony’ as another enigmatic angle of research with potential to shed further light on the functioning both of human society and of the human mind.Design Aesthetic
Resonance as a Design Strategy for AI and Social Robots
Resonance, a powerful and pervasive phenomenon, appears to play a major role in human interactions. This article investigates the relationship between the physical mechanism of resonance and the human experience of resonance, and considers possibilities for enhancing the experience of resonance within human–robot interactions. We first introduce resonance as a widespread cultural and scientific metaphor. Then, we review the nature of “sympathetic resonance” as a physical mechanism. Following this introduction, the remainder of the article is organized in two parts. In part one, we review the role of resonance (including synchronization and rhythmic entrainment) in human cognition and social interactions. Then, in part two, we review resonance-related phenomena in robotics and artificial intelligence (AI). These two reviews serve as ground for the introduction of a design strategy and combinatorial design space for shaping resonant interactions with robots and AI. We conclude by posing hypotheses and research questions for future empirical studies and discuss a range of ethical and aesthetic issues associated with resonance in human–robot interactions.Design AestheticsHuman Information Communication Desig
Current and future trends in topology optimization for additive manufacturing
Manufacturing-oriented topology optimization has been extensively studied the past two decades, in particular for the conventional manufacturing methods, for example, machining and injection molding or casting. Both design and manufacturing engineers have benefited from these efforts because of the close-to-optimal and friendly-to-manufacture design solutions. Recently, additive manufacturing (AM) has received significant attention from both academia and industry. AM is characterized by producing geometrically complex components layer-by-layer, and greatly reduces the geometric complexity restrictions imposed on topology optimization by conventional manufacturing. In other words, AM can make near-full use of the freeform structural evolution of topology optimization. Even so, new rules and restrictions emerge due to the diverse and intricate AM processes, which should be carefully addressed when developing the AM-specific topology optimization algorithms. Therefore, the motivation of this perspective paper is to summarize the state-of-art topology optimization methods for a variety of AM topics. At the same time, this paper also expresses the authors’ perspectives on the challenges and opportunities in these topics. The hope is to inspire both researchers and engineers to meet these challenges with innovative solutions.Accepted author manuscriptMaterials and Manufacturin
Search for anomaly-mediated supersymmetry breaking with the ATLAS detector based on a disappearing-track signature in pp collisions at sqrt(s) = 7TeV$
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