Automating Data Rights

This report documents the program and the outcomes of Dagstuhl Seminar 18181 “Towards Accountable Systems”, which took place from April 29th to May 4th, 2018, at Schloss Dagstuhl – Leibniz Center for Informatics. Researchers and practitioners from academia and industry were brought together covering broad fields from computer and information science, public policy and law. Many risks and opportunities were discussed that relate to the alignment of systems technologies with developing legal and regulatory requirements and evolving user expectations. This report summarises outcomes of the seminar by highlighting key future research directions and challenges that lie on the path to developing systems that better align with accountability concerns

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Collaboration and composition:Issues for a second generation process language

Over the past decade a variety of process languages have been defined and applied to software engineering environments. The idea of using a process language to encode a software process as a "process model", and enacting this using a process-sensitive environment is now well established. Many prototype process-sensitive environments have been developed; but their use in earnest has been limited. We are designing a second generation process language which is a significant departure from current conventional thinking. Firstly a process is viewed as a set of mediated collaborations rather than a set of partially ordered activities. Secondly emphasis is given to how process models are developed, used, and enhanced over a potentially long lifetime. In particular the issue of composing both new and existing model fragments is central to our development approach. This paper outlines these features, and gives the motivations behind them. It also presents a view of process suppor..

Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway

Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several disease-associated proteins. The transcription factor NF-κB2 (p100/p52) is one of the candidate Fbw7 substrates. We show that Fbw7 interacts with p100 via a conserved degron and that it promotes degradation of p100 in a GSK3β phosphorylation-dependent manner. Fbw7 inactivation increases p100 levels, which in the presence of NF-κB pathway stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic threshold can be increased by loss of Fbw7 in a p100-dependent manner. In conclusion, Fbw7-mediated destruction of p100 is a regulatory component restricting the response to NF-κB2 pathway stimulation