Mining SOM expression portraits: Feature selection and integrating concepts of molecular function

Background: 
Self organizing maps (SOM) enable the straightforward portraying of high-dimensional data of large sample collections in terms of sample-specific images. The analysis of their texture provides so-called spot-clusters of co-expressed genes which require subsequent significance filtering and functional interpretation. We address feature selection in terms of the gene ranking problem and the interpretation of the obtained spot-related lists using concepts of molecular function.

Results: 
Different expression scores based either on simple fold change-measures or on regularized Students t-statistics are applied to spot-related gene lists and compared with special emphasis on the error characteristics of microarray expression data. The spot-clusters are analyzed using different methods of gene set enrichment analysis with the focus on overexpression and/or overrepresentation of predefined sets of genes. Metagene-related overrepresentation of selected gene sets was mapped into the SOM images to assign gene function to different regions. Alternatively we estimated set-related overexpression profiles over all samples studied using a gene set enrichment score. It was also applied to the spot-clusters to generate lists of enriched gene sets. We used the tissue body index data set, a collection of expression data of human tissues, as an illustrative example. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. In addition, we display special sets of housekeeping and of consistently weak and highly expressed genes using SOM data filtering. 

Conclusions:
The presented methods allow the comprehensive downstream analysis of SOM-transformed expression data in terms of cluster-related gene lists and enriched gene sets for functional interpretation. SOM clustering implies the ability to define either new gene sets using selected SOM spots or to verify and/or to amend existing ones

Experimentation or projectification of urban change?:A critical appraisal and three steps forward

Urban experimentation has proliferated in recent years as a response to sustainability challenges and renewed pressures on urban governance. In many European cities, diverse and rapidly changing experimental forms (e.g. urban living laboratories, pilots, trials, experimental districts) are becoming commonplace, addressing ambitious goals for smartness, circularity, and liveability. Academically, there is a growing concern for moving beyond the focus on individual experiments and the insistence on upscaling their primary transformation mechanism. However, the phenomena of 'projectification' - whereby project-based forms of organising have become ubiquitous, shaping expectations about experimentation - is increasingly perceived as a barrier. Nevertheless, how specifically experimentation and projectification intersect remains unclear. Our theoretical perspective examines how the widespread tendency towards projectification shapes urban experimentation and the potential implications for urban transformations. It problematises the current wave of experimentation and how it contributes to the projectification of urban change processes. We present three steps to redress this issue and indicate directions for future research.</p

Expression cartography of human tissues using self organizing maps

Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.&#xd;&#xa;Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. &#xd;&#xa;Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.&#xd;&#xa

Alternative forms of corporate communications : the use of social media demonstrated by three exemplary companies

Der Einsatz von Social Media im Unternehmen kann auf unterschiedliche Art und Weise vollzogen werden. Diese Arbeit beschäftigt sich mit den Social-Media-Aktivitäten der drei Unternehmen mymuesli, dm und Deutsche Bahn und deren Auftritt bei Facebook, Twitter und auf YouTube. Grundlage für die Beobachtung und Auswertung der Social-Media-Maßnahmen der drei Unternehmen, sind theoretische Ausführungen zum Thema Social Media in der Unternehmenskommunikation

Impacts of urban real-world labs

Ways of evaluating the societal impact of real-world labs as a transdisciplinary and transformative research format are under discussion. We present an evaluation approach rooted in structuration theory, with a focus on structure-agency dynamics at the science-society interface. We applied the theory with its four modalities (interpretation schemes, norms, allocative and authoritative resources) to the case of the Mirke neighbourhood in Wuppertal, Germany. Six projects promoted the capacity for co-productive city-making. The effects of the projects were jointly analysed in a co-evaluation process. Previously proposed subcategories of the modalities as an empirical operationalisation were tested and confirmed as being applicable. Five new subcategories were generated. The use of the modalities seems appropriate for co-evaluation processes. The tool is practical, focused on real-world effects, and suitable for transdisciplinary interpretation processes. We encourage further empirical testing of the tool, as well as development of the subcategories.</p

Hilbert's epsilon as an Operator of Indefinite Committed Choice

Paul Bernays and David Hilbert carefully avoided overspecification of Hilbert's epsilon-operator and axiomatized only what was relevant for their proof-theoretic investigations. Semantically, this left the epsilon-operator underspecified. In the meanwhile, there have been several suggestions for semantics of the epsilon as a choice operator. After reviewing the literature on semantics of Hilbert's epsilon operator, we propose a new semantics with the following features: We avoid overspecification (such as right-uniqueness), but admit indefinite choice, committed choice, and classical logics. Moreover, our semantics for the epsilon supports proof search optimally and is natural in the sense that it does not only mirror some cases of referential interpretation of indefinite articles in natural language, but may also contribute to philosophy of language. Finally, we ask the question whether our epsilon within our free-variable framework can serve as a paradigm useful in the specification and computation of semantics of discourses in natural language.Comment: ii + 73 pages. arXiv admin note: substantial text overlap with arXiv:1104.244

The nexus of business sustainability and organizational learning: A systematic literature review to identify key learning principles for business transformation

Companies play a central role in the quest for sustainable development. Organizational learning theories have been utilized to explain sustainability-related change processes in firms. However, implications from studies at the nexus of business sustainability and organizational learning are highly dependent on varying conceptualizations. The objective of this study is to provide clarity on the plurality of conceptual underpinnings in research and to uncover principles that are associated with deeper organizational change processes, that is, business transformation. Building on insights from a systematic literature review, we develop a sustainability learning typology, from which we distill three learning principles for business transformation: (1) the deutero learning mode, (2) the societal learning scope, and (3) the cooperative advantage objective. We formulate needs for future research to further elaborate on the learning principles associated with business transformation and suggest implications for practice

The importance of familial risk factors in children with ADHD: direct and indirect effects of family adversity, parental psychopathology and parenting practices on externalizing symptoms

Background Children experiencing unfavorable family circumstances have an increased risk of developing externalizing symptoms. The present study examines the direct, indirect and total effects of family adversity, parental psychopathology, and positive and negative parenting practices on symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children with ADHD. Methods Data from 555 children (M = 8.9 years old, 80.5% boys) who participated in a multicenter study on the treatment of ADHD (ESCAschool) were analyzed using structural equation modeling (SEM). Results The SEM analyses revealed that (a) family adversity and parental psychopathology are associated with both child ADHD and ODD symptoms while negative parenting practices are only related to child ODD symptoms; (b) family adversity is only indirectly associated with child ADHD and ODD symptoms, via parental psychopathology and negative parenting practices; (c) the detrimental effect of negative parenting practices on child ADHD and ODD symptoms is stronger in girls than in boys (multi-sample SEM); (d) there are no significant associations between positive parenting practices and child ADHD or ODD symptoms. Conclusions Family adversity, parental psychopathology, and negative parenting practices should be routinely assessed by clinicians and considered in treatment planning. Trial registration (18th December 2015): German Clinical Trials Register (DRKS) DRKS00008973