Formalizing graphical notations

The thesis describes research into graphical notations for software engineering, with a principal interest in ways of formalizing them. The research seeks to provide a theoretical basis that will help in designing both notations and the software tools that process them. The work starts from a survey of literature on notation, followed by a review of techniques for formal description and for computational handling of notations. The survey concentrates on collecting views of the benefits and the problems attending notation use in software development; the review covers picture description languages, grammars and tools such as generic editors and visual programming environments. The main problem of notation is found to be a lack of any coherent, rigorous description methods. The current approaches to this problem are analysed as lacking in consensus on syntax specification and also lacking a clear focus on a defined concept of notated expression. To address these deficiencies, the thesis embarks upon an exploration of serniotic, linguistic and logical theory; this culminates in a proposed formalization of serniosis in notations, using categorial model theory as a mathematical foundation. An argument about the structure of sign systems leads to an analysis of notation into a layered system of tractable theories, spanning the gap between expressive pictorial medium and subject domain. This notion of 'tectonic' theory aims to treat both diagrams and formulae together. The research gives details of how syntactic structure can be sketched in a mathematical sense, with examples applying to software development diagrams, offering a new solution to the problem of notation specification. Based on these methods, the thesis discusses directions for resolving the harder problems of supporting notation design, processing and computer-aided generic editing. A number of future research areas are thereby opened up. For practical trial of the ideas, the work proceeds to the development and partial implementation of a system to aid the design of notations and editors. Finally the thesis is evaluated as a contribution to theory in an area which has not attracted a standard approach

Modelling genetic networks involved in the activity-dependent modulation of adult neurogenesis

Die Bildung neuen Nervenzellen im erwachsenen Gehirn—adulte Neurogenese—ist bei Säugetieren auf spezifische Regionen beschränkt. Eine der beiden bekannten ist der Hippokampus, eine Gehirnstruktur, die eine wichtige Rolle beim Lernen sowie der Gedächtnisbildung spielt. Ein Reservoir von neuralen Stammzellen befindet sich in der subgranulären Zone des hippokampalen Gyrus dentatus. Diese Zellen teilen sich fortwährend und bilden neue Nervenzellen. Die Regulation adulter hippokampaler Neurogenese wird sowohl von der Umgebung beeinflusst als auch von mehreren Genen gesteuert. In der vorliegenden Arbeit wurden mittels Hochdurchsatz- Genexpressionsverfahren die an der Neurogenese beteiligten Gene identifiziert und ihr Zusammenspiel untersucht. Anhand von genetischen, umgebungsbedingten und zeitlichen Angaben und Variationen wurde ein vielseitiger Datensatz erstellt, der einen multidimensionalen Blick auf den proliferativen Phänotyp verschafft. Netzwerke aus Gen-Gen und Gen-Phänotyp Interaktionen wurden beschrieben und in einer mehrschichtigen Ressource zusammengefasst. Ein Kern-Netzwerk bestehend aus immerwiederkehrenden Modulen aus verschiedenen Ebenen wurde anhand von Proliferation als Keim-Phänotyp identifiziert. Aus diesem Kern-Netzwerk sind neue Gene und ihre Interaktionen hervorgegangen, die potentiell bei der Regulierung adulter Neurogenesis beteiligt sind.:Zusammenfassung i Abstract iii Acknowledgements vii Contents ix Preface xiii General Introduction 1 Adult Neurogenesis 1 Historical setting 1 Neurogenesis exists in two regions of the adult mammalian brain 1 Implications of neurogenesis in the hippocampus 1 The Hippocampal Formation 2 Function of the hippocampus in learning and memory 2 The functional role of adult neurogenesis 2 Anatomy of the hippocampal formation 2 Neural Precursor Biology 3 The subgranular zone as a neurogenic niche 3 Neuronal maturation is a multi-step pathway 3 Regulation of Adult Neurogenesis 3 Neurogenesis is modulated by age 3 Neurogenesis is modulated by environmental factors 4 Neurogenesis is modulated by genetic background 4 Genetics of the BXD RI Cross 5 C57BL/6 and DBA/2 5 Recombinant Inbred Lines 5 The BXD panel 6 Quantitative genetics 6 Microarray Analysis 7 The concept of ‘whole genome’ expression analysis 7 Technical considerations 8 Theoretical considerations 9 Current Analytical Methods 9 Network Analysis 10 Network Description and Terminology 10 Graph Theory 10 Multiple-Network Comparison 11 Biological networks 11 Types of Biological Network 11 Sources of Network Data 12 Biological Significance of Networks 12 Aim of the current work 13 Methods and Materials 15 Animals 15 BXD panel 15 Progenitor strains 15 Animal behaviour 15 Running wheel activity 15 Enriched environment 16 Morris water maze 16 Open field test 16 Corticosterone assay 16 Histology 17 Tissue collection 17 BrdU staining 17 Statistics 17 Cell culture 18 Maintenance and differentiation 18 Immunostaining 18 RNA isolation 18 Microarray processing 18 Affymetrix arrays 18 M430v2 probe reannotation 19 Illumina arrays 19 Illumina probe reannotation 19 Bioinformatics 19 Translating the STRING network 19 QTL mapping 20 Network graph layout 20 Triplot 20 Enrichment analysis 20 Mammalian Adult Neurogenesis Gene Ontology 21 Introduction 21 Results 25 The cell stage ontology 25 The process ontology 25 Genes known to regulate hippocampal adult neurogenesis 26 Enrichment analysis 27 The MANGO gene network 27 Discussion 28 Hippocampal Coexpression Networks from the BXD Panel 31 Introduction 31 Results 32 Variation and covariation of gene expression across a panel of inbred lines 32 A hippocampal expression correlation network 32 Diverse neurogenesis phenotypes associate with discrete transcript networks 34 Discussion 34 Interactions Between Gene Expression Phenotypes and Genotype 37 Introduction 37 Results 39 QTL analysis and interval definitions 39 Pleiotropic loci and ‘trans-bands’ 39 Transcript expression proxy-QTLs can help in dissection of complex phenotypes 41 Interaction network 43 Discussion 43 Strain-Dependent Effects of Environment 47 Introduction 47 Results 48 Effects of strain and environment on precursor cell proliferation 48 Effects of strain and environment on learning behaviour 52 Transcript expression associated with different housing environments 53 Strain differences in transcript regulation 55 Distance-weighted coexpression networks 57 Discussion 58 Expression Time Course from Differentiating Cell Culture 61 Introduction 61 Results 63 Differentiation of proliferating precursors into neurons in vitro 63 Transcripts associated with stages of differentiation 63 Early events in NPC differentiation 64 A network of transcript coexpression during in vitro differentiation 66 Discussion 67 Integrated Gene Interaction Networks 71 Introduction 71 Results 72 Description of network layers 72 Merging of network layers to a multigraph 74 A network of genes controls neural precursor proliferation in the adult hippocampus 75 Novel candidate regulators of adult hippocampal neurogenesis 77 Novel pathways regulating adult hippocampal neurogenesis 77 Discussion 79 General Discussion 81 References 89 Selbständigkeitserklärung 107Neurogenesis, the production of new neurons, is restricted in the adult brain of mammals to only a few regions. One of these sites of adult neurogenesis is the hippocampus, a structure essential for many types of learning. A pool of stem cells is maintained in the subgranular zone of the hippocampal dentate gyrus which proliferate and can differentiate into new neurons, astrocytes and oligodendroctytes. Regulation of adult hippocampal neurogenesis occurs in response to en- vironmental stimuli and is under the control of many genes. This work employs high-throughput gene expression technologies to identify these genes and their interactions with each other and the neurogenesis phenotype. Harnessing variation from genetic, environmental and temporal sources, a multi-faceted dataset has been generated which offers a multidimensional view of the neural precursor proliferation phenotype. Networks of gene-gene and gene-phenotype interac- tions have been described and merged into a multilayer resource. A core subnetwork derived from modules recurring in the different layers has been identified using the proliferation phenotype as a seed. This subnetwork has suggested novel genes and interactions potentially involved in the regulation of adult hippocampal neurogenesis.:Zusammenfassung i Abstract iii Acknowledgements vii Contents ix Preface xiii General Introduction 1 Adult Neurogenesis 1 Historical setting 1 Neurogenesis exists in two regions of the adult mammalian brain 1 Implications of neurogenesis in the hippocampus 1 The Hippocampal Formation 2 Function of the hippocampus in learning and memory 2 The functional role of adult neurogenesis 2 Anatomy of the hippocampal formation 2 Neural Precursor Biology 3 The subgranular zone as a neurogenic niche 3 Neuronal maturation is a multi-step pathway 3 Regulation of Adult Neurogenesis 3 Neurogenesis is modulated by age 3 Neurogenesis is modulated by environmental factors 4 Neurogenesis is modulated by genetic background 4 Genetics of the BXD RI Cross 5 C57BL/6 and DBA/2 5 Recombinant Inbred Lines 5 The BXD panel 6 Quantitative genetics 6 Microarray Analysis 7 The concept of ‘whole genome’ expression analysis 7 Technical considerations 8 Theoretical considerations 9 Current Analytical Methods 9 Network Analysis 10 Network Description and Terminology 10 Graph Theory 10 Multiple-Network Comparison 11 Biological networks 11 Types of Biological Network 11 Sources of Network Data 12 Biological Significance of Networks 12 Aim of the current work 13 Methods and Materials 15 Animals 15 BXD panel 15 Progenitor strains 15 Animal behaviour 15 Running wheel activity 15 Enriched environment 16 Morris water maze 16 Open field test 16 Corticosterone assay 16 Histology 17 Tissue collection 17 BrdU staining 17 Statistics 17 Cell culture 18 Maintenance and differentiation 18 Immunostaining 18 RNA isolation 18 Microarray processing 18 Affymetrix arrays 18 M430v2 probe reannotation 19 Illumina arrays 19 Illumina probe reannotation 19 Bioinformatics 19 Translating the STRING network 19 QTL mapping 20 Network graph layout 20 Triplot 20 Enrichment analysis 20 Mammalian Adult Neurogenesis Gene Ontology 21 Introduction 21 Results 25 The cell stage ontology 25 The process ontology 25 Genes known to regulate hippocampal adult neurogenesis 26 Enrichment analysis 27 The MANGO gene network 27 Discussion 28 Hippocampal Coexpression Networks from the BXD Panel 31 Introduction 31 Results 32 Variation and covariation of gene expression across a panel of inbred lines 32 A hippocampal expression correlation network 32 Diverse neurogenesis phenotypes associate with discrete transcript networks 34 Discussion 34 Interactions Between Gene Expression Phenotypes and Genotype 37 Introduction 37 Results 39 QTL analysis and interval definitions 39 Pleiotropic loci and ‘trans-bands’ 39 Transcript expression proxy-QTLs can help in dissection of complex phenotypes 41 Interaction network 43 Discussion 43 Strain-Dependent Effects of Environment 47 Introduction 47 Results 48 Effects of strain and environment on precursor cell proliferation 48 Effects of strain and environment on learning behaviour 52 Transcript expression associated with different housing environments 53 Strain differences in transcript regulation 55 Distance-weighted coexpression networks 57 Discussion 58 Expression Time Course from Differentiating Cell Culture 61 Introduction 61 Results 63 Differentiation of proliferating precursors into neurons in vitro 63 Transcripts associated with stages of differentiation 63 Early events in NPC differentiation 64 A network of transcript coexpression during in vitro differentiation 66 Discussion 67 Integrated Gene Interaction Networks 71 Introduction 71 Results 72 Description of network layers 72 Merging of network layers to a multigraph 74 A network of genes controls neural precursor proliferation in the adult hippocampus 75 Novel candidate regulators of adult hippocampal neurogenesis 77 Novel pathways regulating adult hippocampal neurogenesis 77 Discussion 79 General Discussion 81 References 89 Selbständigkeitserklärung 10

Probabilidades Variacionales y Propensiones del Desarrollo: Un Estudio Filosófico del Azar en la Variación Evolutiva

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Filosofía, leída el 09/11/2020The ongoing debate over a possible extension of the explanatory corpus of evolutionary biology touches many aspects of philosophical interest, among which is the role that chance plays in its models and explanations. In particular, how evolutionary variation relates to chance seems to differ under the classical and the evo-devo perspectives. While some tools of the philosophy of probability and chance have been incorporated into important aspects of evolutionary biology, this discrepancy has not been considered from this perspective. In this dissertation, Iintend to bridge part of this gap by endorsing a conception of chance in the generation of evolutionary variation that is the result of incorporating several conceptual tools from the philosophy of probability and chance into different views over the nature of evolutionary variation. My aim is to clarify the distinct roles that chance in variation plays in the field of evo-devo as compared with classical evolutionary genetics. I depart from the construction of a suitable philosophical framework about the representative role of probabilities in evolutionary disciplines and the type of explanatory causes that are responsible for them...El actual debate sobre una posible extensión del corpus explicativo de la biología evolutiva recoge muchos aspectos de interés filosófico, entre los que se encuentra el rol del azar en sus modelos y explicaciones. En particular, la relación entre la variación evolutiva y el azar parece ser muy distinto bajo las perspectivas clásica y dela evo-devo. Mientras que algunas herramientas de la filosofía de la probabilidad y el azar han sido incorporadas en aspectos importantes de la biología evolutiva, esta disparidad no ha sido considerada desde esta perspectiva. En esta tesis, mi intención es aliviar parcialmente esta carencia defendiendo una noción de azar en la generación de la variación evolutiva que es el resultado de incorporar varias herramientas conceptuales de la filosofía de la probabilidad a distintas perspectivas sobre su naturaleza. Mi objetivo es clarificar los distintos roles que el azar en la variación juega en el campo de la evo-devo en comparación con la genética evolutiva clásica. Comienzo con la construcción de un marco filosófico que considera el rol representativo de la probabilidad en las disciplinas evolutivas y el tipo de causas explicativas que son responsables de ella...Fac. de FilosofíaTRUEunpu

Meaningful lines : Social semiotic investigations of the graphical line, used as a connector in digital data visualizations

The paper III is not published yet.The dissertation investigates the graphical line, used as a connector in digital data visualizations (DVs), from a social semiotic perspective. It explores the semiotic functions of connecting lines in digital DVs, building empirically on two corpus analyses. These analyses are concerned with how two key semiotic functions are graphically realized in the selected lines and whether graphical conventions regulating these realizations can be identified. In the dissertation the connecting line is researched as a central element of several different DV types – line graphs, timelines, route maps, connection maps, network diagrams, etc. Today, DVs are used in a broad range of social contexts and thus play an essential role in society. New digital technologies make it possible to apply other visual characteristics to graphical lines in DVs than was previously possible, for example, when they were hand-drawn or printed. This change may have influenced the DV design practice, a situation calling for updated research. The dissertation is article-based, comprising three articles and an extended abstract. The extended abstract frames the three articles and includes an introduction, definitions of key terms, more comprehensive sections on the theoretical framework, earlier research and methodology, as well as ethical considerations, reflections on methodological decisions and a conclusion. The two overall research questions addressed in the dissertation are: (1) What characterizes the graphical forms and semiotic functions of connecting lines in current, publicly available digital DVs? (2) What conventions, regulating the relations between these forms and functions, can be observed in such DVs?publishedVersio

Khronika: Soviet Newsreel at the Dawn of the Information Age

This dissertation considers ten years in the life of one word. Between 1918 and 1928, khronika—the Russian word that describes newsreel filmmaking—became the site of extensive debates about the aesthetics and social responsibilities of the documentary film. Following the February revolution of 1917, khronika was promoted as the privileged record keeper of a new historical era, catalyzing a period of unprecedented formal innovation. During this period, Soviet documentarians transform the relationship between text and image, developing a film style that integrated verbal and visual material. In newsreel journal such as Kino-Pravda, images cease to be passive illustrations accompanying text and are for the first time treated as equally capable of delivering propositional content. Like other modernist art practices, khronika develops in dialogue with attempts to define its essence as a film genre and its medium specificity. Falling under the influence of competing strains within Constructivism, khronika is first conceived as a purely visual medium and then again as a purely factual one. Made up of seventeen variations on the social, political, and aesthetic aspects of khronika's evolution, the dissertation makes a crucial revision of documentary history. Rather than focus on the first instances of non-fiction films that adapt the narrative conventions of fiction film, Khronika examines the origins of documentary as an informational medium. Drawing on film theory, history of science, and philosophy, Khronika asks what it was that film learned to express during the first tumultuous decade when documentaries ceased to be windows onto a world and become the active interpreters of the reality captured by motion picture cameras.Slavic Languages and Literature

World and Logic

What is the relationship between the world and logic, between intuition and language, between objects and their quantitative determinations? Rationalists, on the one hand, hold that the world is structured in a rational way. Representationalists, on the other hand, assume that language, logic, and mathematics are only the means to order and describe the intuitively given world. In World and Logic, Jens Lemanski takes up three surprising arguments from Arthur Schopenhauer’s hitherto undiscovered Berlin Lectures, which concern the philosophy of language, logic, and mathematics. Based on these arguments, Lemanski develops a new position entitled ‘rational representationalism’: the world is always structured by human beings according to linguistic, logical, and mathematical principles, but the basic vocabulary of these structural descriptions already contains metaphors taken from the world around us

Making a name for Anonymous. Digital culture , anonymous publics and transgressie subjectivities

Recently, researchers from various domains of social sciences have been particularly concerned with the social, cultural, and political impacts of digital media. To give an account of the specific processes behind the formation of Anonymous, I develop a microsociological framework for the analysis of disembodied global forms – anchoring such forms in intersubjective reciprocity. In order to move beyond interpretative sociology’s emphasis on language as society’s integrative function, I privileged the dimensions of temporality, rhythms and patterns. I also focused on how “disembodied” internet collectives are enacted and assembled within computer screens, terminals, and the digital networks that connect them. My analysis takes into account those temporalities, projections and reflections, which point to the non-symbolic components of mediated sociality. Those dynamic interconnections behind the Anonymous collective are approached through the notions of publics, networks or even swarms.Recientemente, investigadores de diversos campos de las ciencias sociales se han enfocado en los impactos sociales, culturales y políticos de los medios digitales. Para dar cuenta de los procesos específicos detrás de la formación de Anonymous, yo desarrollo un marco microsociológico para el análisis de formas globales “desencarnadas” de sociabilidad, anclando estas formas en la reciprocidad intersubjetiva mediada. Para ir más allá del énfasis en el lenguaje como función integrativa de la sociedad de la sociología interpretativa, privilegié las dimensiones de la temporalidad, los ritmos y los patrones en mi análisis. También me enfoqué a ver cómo los colectivos de Internet "desencarnados" se construyen en pantallas de computadora, terminales y las redes digitales que los conectan. Mi análisis tiene en cuenta esas temporalidades, proyecciones y reflexiones, que apuntan a los componentes no simbólicos de la socialidad mediada. Esas interconexiones dinámicas detrás del colectivo Anónimo se acercan a través de las nociones de públicos, redes y enjambres.Recentment, investigadors de diversos camps de les ciències socials s'han enfocat en els impactes socials, culturals i polítics dels mitjans digitals. Per donar compte dels processos específics darrere de la formació d'Anonymous, jo desenvolupament un marc miocrosociològic per a l'anàlisi de formes globals "desencarnades" de sociabilitat, ancorant aquestes formes en la reciprocitat intersubjectiva intervinguda. Per anar més enllà de l'èmfasi en el llenguatge com a funció integrativa de la societat de la sociologia interpretativa, privilegiï les dimensions de la temporalitat, els ritmes i els patrons en la meva anàlisi. També vaig focalitzar a veure com els col·lectius d'Internet "desencarnats" es construeixen en pantalles d'ordinador, terminals i les xarxes digitals que els connecten. La meva anàlisi té en compte aquestes temporalitats, projeccions i reflexions, que apunten als components no simbòlics de la socialitat intervinguda. Aquestes interconnexions dinàmiques darrere del col·lectiu Anònim s'acosten a través de les nocions de públics, xarxes i eixams