Autonomic Performance-Aware Resource Management in Dynamic IT Service Infrastructures

Model-based techniques are a powerful approach to engineering autonomic and self-adaptive systems. This thesis presents a model-based approach for proactive and autonomic performance-aware resource management in dynamic IT infrastructures. Core of the approach is an architecture-level modeling language to describe performance and resource management related aspects in such environments. With this approach, it is possible to autonomically find suitable system configurations at the model level

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

AUTNES Content Analysis of Party Manifestos: Cumulative File (SUF edition)

Full edition for scientific use. The AUTNES dataset on party manifestos covers the manifestos of the relevant parties that competed in the Austrian national elections 2002-2017. All natural sentences within the manifestos are part of the dataset. The units of analysis are standardized statements derived from these natural sentences by means of a set of unitizing rules. The coding procedure applies the AUTNES relational approach of recording subjects, predicates, and objects to party manifestos. The subject actor is usually the party, but it can also be another actor being cited in the manifesto. There are two types of objects: issues and object actors. Issues are recorded by coders selecting from the AUTNES issue coding scheme the one issue that fits the content of the statement best. One object actor can be recorded per statement, each with their name (if an individual is present) and organizational affiliation. The issue predicate numerically records whether the subject's position towards the issue (if present) is one of (conditional) support, (conditional) rejection, or conveys a neutral stance. Similarly, the object actor predicate numerically records whether the subject's position towards the object actor is one of support, rejection, or conveys a neutral stance. In addition to the basic subject–predicate–object structure we code character traits for all subject and object actors as well as the party record and pledges. Variables: sentence (the text of the natural sentence); statement derived from the natural sentence; page number of the manifesto where the natural sentence can be found; organizational affiliation of the subject actor (usually the party); name of the subject actor if an individual; attributes of the subject actor; issue predicate (the relation between subject and issue); issue category selected for the statement; statement refers to regulation of the issue on the European level; reference to a party's own or a political opponent's past behavior or achievements at different levels of governance (national level, land level, international level, historical); pledge (subjective pledges: promises whose evaluation requires a value judgement, objective pledges: promises that can be objectively tested); object actor predicate (relation between subject and object actor); organization of the object actor (usually the party); name of the object actor if individual; characteristics of the object actor (attributes: competence, character, leadership, appearance); year of election for which the manifesto was published; party authoring the manifesto; title of the manifesto. Additionally coded was: ID number for each observation; sentence-ID

AUTNES Content Analysis of Party Press Releases: Cumulative File (SUF edition)

Full edition for scientific use. The AUTNES coding of party press releases covers all press releases that were issued by parties gaining at least two percent of the votes in the national elections 2002, 2006, 2008, 2013 and 2017. The coding procedure applies the AUTNES relational approach of recording subjects, predicates, and objects to press releases. The subject is the person or party that features as the sender of the message in the title of the press release. There are two types of objects: issues and object actors. Issues are recorded by coders selecting from the AUTNES issue coding scheme the one issue that fits the content of the press release’s title best. The issue predicate numerically records whether the subject’s position towards the issue is one of support, rejection, or conveys a neutral/ambivalent stance. This procedure (coding of predicate and issue) is repeated for the subtitle of the press release. Up to three object actors are recorded from the information in the title of the press release, each with their name (if an individual is present) and organisational affiliation, as well as the evaluation by the subject actor (positive, negative or neutral). In addition to the basic subject–predicate–object structure we code four more variables for specific years: character traits for all object actors, party records for all subject and object actors, justifications for issue statements, and the incident that triggered the press release. Variables: party authoring the press release; sender (the three-letter APA channel through which the press release was sent); keywords of the press release; title; subtitle; text; name of first and second subject actor; organisational affiliation of these subject actors; reference to subject actor’s record; issue of title and subtitle; issue predicate of title and subtitle (position towards the coded issue of title and subtitle); reference of title and subtitle to policy at the EU level; justification of issue; up to three object actors: name and organisational affiliation; object actor predicates (the relation between the subject and each object actor as support, criticism/rejection, or neutral); reference to object actor’s record; reference to object actor’s attributes; trigger variables: arena in which the press release was triggered; name and organisational affiliation of the individual who triggered the press release; bipartisan press release (press release was issued in by politicians from two different parties). Additionally coded was: ID of individual press releases; coder-ID

First operation of the KATRIN experiment with tritium

The determination of the neutrino mass is one of the major challenges in astroparticle physics today. Direct neutrino mass experiments, based solely on the kinematics of β β -decay, provide a largely model-independent probe to the neutrino mass scale. The Karlsruhe Tritium Neutrino (KATRIN) experiment is designed to directly measure the effective electron antineutrino mass with a sensitivity of 0.2 eV 0.2 eV (90% 90% CL). In this work we report on the first operation of KATRIN with tritium which took place in 2018. During this commissioning phase of the tritium circulation system, excellent agreement of the theoretical prediction with the recorded spectra was found and stable conditions over a time period of 13 days could be established. These results are an essential prerequisite for the subsequent neutrino mass measurements with KATRIN in 2019

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

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.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 (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

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