Modeling biochemical transformation processes and information processing with Narrator

BACKGROUND: Software tools that model and simulate the dynamics of biological processes and systems are becoming increasingly important. Some of these tools offer sophisticated graphical user interfaces (GUIs), which greatly enhance their acceptance by users. Such GUIs are based on symbolic or graphical notations used to describe, interact and communicate the developed models. Typically, these graphical notations are geared towards conventional biochemical pathway diagrams. They permit the user to represent the transport and transformation of chemical species and to define inhibitory and stimulatory dependencies. A critical weakness of existing tools is their lack of supporting an integrative representation of transport, transformation as well as biological information processing. RESULTS: Narrator is a software tool facilitating the development and simulation of biological systems as Co-dependence models. The Co-dependence Methodology complements the representation of species transport and transformation together with an explicit mechanism to express biological information processing. Thus, Co-dependence models explicitly capture, for instance, signal processing structures and the influence of exogenous factors or events affecting certain parts of a biological system or process. This combined set of features provides the system biologist with a powerful tool to describe and explore the dynamics of life phenomena. Narrator's GUI is based on an expressive graphical notation which forms an integral part of the Co-dependence Methodology. Behind the user-friendly GUI, Narrator hides a flexible feature which makes it relatively easy to map models defined via the graphical notation to mathematical formalisms and languages such as ordinary differential equations, the Systems Biology Markup Language or Gillespie's direct method. This powerful feature facilitates reuse, interoperability and conceptual model development. CONCLUSION: Narrator is a flexible and intuitive systems biology tool. It is specifically intended for users aiming to construct and simulate dynamic models of biology without recourse to extensive mathematical detail. Its design facilitates mappings to different formal languages and frameworks. The combined set of features makes Narrator unique among tools of its kind. Narrator is implemented as Java software program and available as open-source from

Comparative study of three commonly used continuous deterministic methods for modeling gene regulation networks

BACKGROUND: A gene-regulatory network (GRN) refers to DNA segments that interact through their RNA and protein products and thereby govern the rates at which genes are transcribed. Creating accurate dynamic models of GRNs is gaining importance in biomedical research and development. To improve our understanding of continuous deterministic modeling methods employed to construct dynamic GRN models, we have carried out a comprehensive comparative study of three commonly used systems of ordinary differential equations: The S-system (SS), artificial neural networks (ANNs), and the general rate law of transcription (GRLOT) method. These were thoroughly evaluated in terms of their ability to replicate the reference models' regulatory structure and dynamic gene expression behavior under varying conditions. RESULTS: While the ANN and GRLOT methods appeared to produce robust models even when the model parameters deviated considerably from those of the reference models, SS-based models exhibited a notable loss of performance even when the parameters of the reverse-engineered models corresponded closely to those of the reference models: this is due to the high number of power terms in the SS-method, and the manner in which they are combined. In cross-method reverse-engineering experiments the different characteristics, biases and idiosynchracies of the methods were revealed. Based on limited training data, with only one experimental condition, all methods produced dynamic models that were able to reproduce the training data accurately. However, an accurate reproduction of regulatory network features was only possible with training data originating from multiple experiments under varying conditions. CONCLUSIONS: The studied GRN modeling methods produced dynamic GRN models exhibiting marked differences in their ability to replicate the reference models' structure and behavior. Our results suggest that care should be taking when a method is chosen for a particular application. In particular, reliance on only a single method might unduly bias the results

Shhhuicide Stories: A Crip Critical Analysis of Attempt Survivors\u27 Narrations of Suicidality

Estimations suggest that one person in the United States tries to take their own life every 38 seconds (Yeager & Roberts, 2015, p. 38), making suicide the 10th leading cause of death in the nation (AFSP, 2016). Despite the prevalence of this issue, communication surrounding suicidality remains scarce - as do concrete understandings of what causes the desire to die in the first place. Dominant understandings link suicidality to chemical/neurobiological issues in the brain (mental illnesses), but these claims have not yet been scientifically proven (Hjelmeland, Dieserud, Dyregrov, Knizek, & Leenaars, 2012) and, as this study suggests, biomedical aspects of suicide are only part of a much larger picture. In critically analyzing firsthand narratives of suicidality as they are shared by attempt survivors, this work blends crip theory frameworks with narrative methods to better understand how people experience suicidality, what brings them to attempt, and how treatment for survivors could be improved. Within these narratives, survivors make sense of their suicidality in hybrid forms by utilizing biomedical frameworks while also describing social causes for their attempts, notably including the ableist Othering of people deemed mentally ill. Through this analysis, what results is a fuller understanding of how people make sense of suicidal inclinations from an insider-perspective, as well as a set of crip critiques that implicate psychiatric hospitals and other biomedical care facilities as sites of oppression and abuse

Authorizing the self : negotiating normality in contemporary American memoir

Writing a better story : authorizing a vivid and valid self -- Lauren Slater's Prozac diary : the medical model and the suppression of the patient -- Maxine Hong Kingston's The woman warrior : the spectacular subjugation of the dually oppressed and dis-abled body -- The three memoirs : no prosthesis needed.This study examines the contemporary American memoirs Goat (2004) by Brad Land, Prozac Diary (1998) by Lauren Slater, and The Woman Warrior: Memoirs of a Girlhood Among Ghosts (1976) by Maxine Hong Kingston to reveal how these texts push traditional thematic and genre boundaries as well as conceptions of minority identity. Their inclusion of fictional aspects, episodic structure, narrative excesses, and non-teleological endings work to enhance their status as sociocultural critique and protest. This dissertation utilizes a social oppression angle within disability studies to demonstrate the overlapping processes and experiences of marginalization faced by these disparate protagonists who are dis-abled due to their undesired bodily variations and their failure to meet sociocultural standards of appropriate embodied behavior. Society is ideologically unwilling to accommodate or accept the differences the protagonists possess. Such a frame expands the artificial and culturally constructed notion of disability by illustrating the ways that discourse and ideologies of embodied normalcy intersect to constitute various minority identities as incompetent and unworthy. The texts bear witness to each protagonists’ struggle to cultivate meaningful subjectivity and reject passive victim status; however, their resulting survivor subjectivities are both resistant to and complicit with hegemonic tenets. This literary project augments ongoing work in minority, identity, autobiography, cultural, and disability studies that deconstructs essentialist paradigms while reinforcing the important cultural and literary work of contemporary memoir. Moreover, it fills a critical gap with respect to Goat and Prozac Diary, bringing these two texts into the critical discussion of autobiography. Finally, this dissertation illustrates that memoir is uniquely positioned within literary genres to navigate the interconnectedness of identity, subjectivity, and ideology, thus challenging readers to confront the injustice of a sociocultural structure that sanctions these inequities in the first placeThesis (Ph. D.)Department of EnglishWriting a better story : authorizing a vivid and valid self -- Lauren Slater's Prozac diary : the medical model and the suppression of the patient -- Maxine Hong Kingston's The woman warrior : the spectacular subjugation of the dually oppressed and dis-abled body -- The three memoirs : no prosthesis needed

Systems Biology Markup Language (SBML) Level 2: Structures and Facilities for Model Definitions

Not applicabl

Visual Support for the Modeling and Simulation of Cell Biological Processes

This dissertation aims at bringing information visualization closer to the demands of analytical problem solving for the specific domain of modeling and simulating cell biological systems. To this end, main segments of visual support in the domain are identified. For one of these segments, the visual analysis of simulation data, new concepts are developed. First, this includes the visualization of simulation data in the context of data generation. Second, new multiple view techniques for large and complex simulation data are introduced.Diese Arbeit verfolgt das Ziel, Informationsvisualisierung näher an die Anforderungen des Analyseprozesses heranzuführen, mit Blick auf die konkrete Anwendung der Modellierung und Simulation zellbiologischer Systeme. Dazu werden wesentliche Teilbereiche der visuellen Unterstützung identifiziert. Für den Teilbereich der visuellen Analyse von Simulationsdaten werden neue Konzepte entwickelt. Dies beinhaltet zum einen die Visualisierung von Simulationsdaten im Kontext der Datengenerierung. Zum anderen werden neue Multiple-View-Techniken für große und komplexe Simulationsdaten vorgestellt

Washington University Senior Undergraduate Research Digest (WUURD), Spring 2018

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 13, 05-01-2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Scien

Systems Biology Markup Language (SBML) Level 2: Structures and Facilities for Model Definitions

We present the Systems Biology Markup Language (SBML) SBML Level 2 Version 2, a model representation formalism for systems biology. SBML is oriented towards describing systems of biochemical reactions of the sort common in research on a number of topics, including cell signaling pathways, metabolic pathways, biochemical reactions, gene regulation, and many others. SBML is defined in a neutral fashion with respect to programming languages and software encoding; however, it is primarily oriented towards allowing models to be encoded using XML, the eXtensible Markup Language (Bosak and Bray, 1999; Bray et al., 2000). This document contains many examples of SBML models written in XML, as well as the text of an XML Schema (Biron and Malhotra, 2000; Fallside, 2000; Thompson et al., 2000) that defines SBML Level 2 Version 2. A downloadable copy of the XML Schema and other related documents and software are also available from the SBML project web site, http://sbml.org/. The SBML project is not an attempt to define a universal language for representing quantitative models. The rapidly evolving views of biological function, coupled with the vigorous rates at which new computational techniques and individual tools are being developed today, are incompatible with a one-size-fits-all idea of a universal language. A more realistic alternative is to acknowledge the diversity of approaches and methods being explored by different software tool developers, and seek a common intermediate format—a lingua franca—enabling communication of the most essential aspects of the models. The definition of the model description language presented here does not specify how programs should communicate or read/write SBML. We assume that for a simulation program to communicate a model encoded in SBML, the program will have to translate its internal data structures to and from SBML, use a suitable transmission medium and protocol, etc., but these issues are outside of the scope of this document

Writing Emotions: Theoretical Concepts and Selected Case Studies in Literature

After a long period of neglect, emotions have become an important topic within literary studies. This collection of essays stresses the complex link between aesthetic and non-aesthetic emotional components and discusses emotional patterns by focusing on the practice of writing as well as on the impact of such patterns on receptive processes. Readers interested in the topic will be presented with a concept of aesthetic emotions as formative both within the writing and the reading process. Essays, ranging in focus from the beginning of modern drama to digital formats and theoretical questions, examine examples from English, German, French, Russian and American literature

A psychoanalytic exploration into the memory and aesthetics of everyday life: Photographs, recollections, and encounters with loss

The project at hand explores some of the psychological functions of photography as both an everyday and an artistic cultural practice from a psychoanalytic perspective. It is proposed that, contrary to commonsensical opinion, photographs are not accurate depositories of memory, but rather function as a functional equivalent of screen memories, thus channeling the subject\u27s memory in ways that are objectively distorted and distorting, but psychologically meaningful and important; moreover, they are a special kind of screen memory in that they are often created pre-emptively and are physically instantiated. Additionally, it is suggested that, by dint of their materiality, photographs achieve a degree of autonomy from the purposes of their creators and viewers, with the result that they can also trigger unwanted and potentially traumatic recollections, along the lines of the Freudian notion of `deferred action\u27. Specifically, different ways in which photographs can enter into the experiencing and processing of loss are explored. It is proposed that photographs can either facilitate normal mourning or impede it. They can be used to either disavow loss, to repetitively fixate on it in a sadomasochistic manner, or to facilitate the transition to an acceptance of loss and moving on. Parallels are drawn between these various uses of photographs and three types of physical/emotionally charged objects: fetishes, transitional objects, and what I term `masochistic objects\u27. The paradox of the accrual of aesthetic value on certain photographs and not others is explored next. The attainment of aesthetic value is separated from the conscious intentions of the photographer, and is instead linked to certain underlying psychological parameters, primarily, the acceptance of the depressive position and of the separateness of the libidinal object, as well as the capacity to achieve a controlled surrender to primary-process functioning. These conceptualizations are illustrated by reference to specific photographs (taken by the author, who is also a recognized photographer), as well as through an analysis of several poems of the Greek poet Kiki Dimoula, in whose oeuvre photography is a prominent and recurrent theme