189 research outputs found
Mapping transcription mechanisms from multimodal genomic data
Background
Identification of expression quantitative trait loci (eQTLs) is an emerging area in genomic study. The task requires an integrated analysis of genome-wide single nucleotide polymorphism (SNP) data and gene expression data, raising a new computational challenge due to the tremendous size of data.
Results
We develop a method to identify eQTLs. The method represents eQTLs as information flux between genetic variants and transcripts. We use information theory to simultaneously interrogate SNP and gene expression data, resulting in a Transcriptional Information Map (TIM) which captures the network of transcriptional information that links genetic variations, gene expression and regulatory mechanisms. These maps are able to identify both cis- and trans- regulating eQTLs. The application on a dataset of leukemia patients identifies eQTLs in the regions of the GART, PCP4, DSCAM, and RIPK4 genes that regulate ADAMTS1, a known leukemia correlate.
Conclusions
The information theory approach presented in this paper is able to infer the dependence networks between SNPs and transcripts, which in turn can identify cis- and trans-eQTLs. The application of our method to the leukemia study explains how genetic variants and gene expression are linked to leukemia.National Human Genome Research Institute (U.S.) (R01HG003354)National Institute of Allergy and Infectious Diseases (U.S.) (U19 AI067854-05)National Heart, Lung, and Blood Institute (grant T32 HL007427-28)National Institutes of Health (U.S.) (grant K99 LM009826
Structural approach to the description and planning of universities
Available from British Library Document Supply Centre- DSC:D32876/80 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Network models in the study of metabolism
The systematic study of the genetic fingerprint (genomics) and the
biochemistry (metabolites) that goes with a specific cellular process
requires the characterization of all the small molecules that form the
profile of metabolites and the associated genes. The metabolome
represents the collection of all the metabolites during certain process
in an organism. The transcriptome represents the gene expression
profile, all the messengers RNA in a defined condition. Then to
understand the whole process, the studies of metabolites must be
accompanied with studies of the gene expression, hence the metabolome
must be accompanied by the transcriptome, so we can identify genes and
metabolites whose synthesis is induced by a specific process, an
infection or stress. Studies of metabolomics generate an enormous
amount of data, then they need mathematical and computational tools to
establish the correlations between the biochemical and genetic data,
and to build up networks that represent the complex metabolic
interactions that occur in each case, using tools like Graph and
Networks Theory to elucidate the emergent properties inherent to the
complex interactions of the metabolic maps. This paper describes the
major mathematical tools that can be used for these studies, with
emphasis on a semi-qualitative proposal known as the kinetic structural
model
Complex Adaptive Systems & Urban Morphogenesis:
This thesis looks at how cities operate as Complex Adaptive Systems (CAS). It focuses on how certain characteristics of urban form can support an urban environment's capacity to self-organize, enabling emergent features to appear that, while unplanned, remain highly functional. The research is predicated on the notion that CAS processes operate across diverse domains: that they are âgeneralized' or âuniversal'. The goal of the dissertation is then to determine how such generalized principles might âplay out' within the urban fabric. The main thrust of the work is to unpack how elements of the urban fabric might be considered as elements of a complex system and then identify how one might design these elements in a more deliberate manner, such that they hold a greater embedded capacity to respond to changing urban forces. The research is further predicated on the notion that, while such responses are both imbricated with, and stewarded by human actors, the specificities of the material characteristics themselves matter. Some forms of material environments hold greater intrinsic physical capacities (or affordances) to enact the kinds of dynamic processes observed in complex systems than others (and can, therefore, be designed with these affordances in mind). The primary research question is thus:
What physical and morphological conditions need to be in place within an urban environment in order for Complex Adaptive Systems dynamics arise - such that the physical components (or âbuilding blocks') of the urban environment have an enhanced capacity to discover functional configurations in space and time as a response to unfolding contextual conditions?
To answer this question, the dissertation unfolds in a series of parts. It begins by attempting to distill the fundamental dynamics of a Complex Adaptive System. It does so by means of an extensive literature review that examines a variety of highly cited âdefining principles' or âkey attributes' of CAS. These are cross-referenced so as to extract common features and distilled down into six major principles that are considered as the generalized features of any complex system, regardless of domain. In addition, this section considers previous urban research that engages complexity principles in order to better position the distinctive perspective of this thesis. This rests primarily on the dissertation's focus on complex urban processes that occur by means of materially enabled in situ processes. Such processes have, it is argued, remained largely under-theorized. The opening section presents introductory examples of what might be meant by a âmaterially enabling' environment.
The core section of the research then undertakes a more detailed unpacking of how complex processes can be understood as having a morphological dimension. This section begins by discussing, in broad terms, the potential âphase space' of a physical environment and how this can be expanded or limited according to a variety of factors. Drawing insights from related inquiries in the field of Evolutionary Economic Geography, the research argues that, while emergent capacity is often explored in social, economic, or political terms, it is under-theorized in terms of the concrete physical sub-strata that can also act to âcarry' or âmoor' CAS dynamics. This theme is advanced in the next article, where a general framework for speaking about CAS within urban environments is introduced. This framework borrows from the terms for âimageability' that were popularized by Kevin Lynch: paths, edges, districts, landmarks, and nodes. These terms are typically associated with physical or âobject-like features' of the urban environment â that is to say, their image. The terminology is then co-opted such that it makes reference not simply to physical attributes, but rather to the complex processes these attributes enable. To advance this argument, the article contrasts the static and âimageable' qualities of New Urbanism projects with the âunfolding' and dynamic qualities of complex systems - critiquing NU proponents as failing to appreciate the underlying forces that generate the environments they wish to emulate. Following this, the efficacy of the re-purposed âLynchian' framework is tested using the case study of Istanbul's Grand Bazaar. Here, specific elements of the Bazaar's urban fabric are positioned as holding material agency that enables particular emergent spatial phenomena to manifest. In addition, comparisons are drawn between physical dynamics unfolding within the Bazaar's morphological setting (leading to emergent merchant districts) and parallel dynamics explored within Evolutionary Economic Geography).
The last section of the research extends this research to consider digitally augmented urban elements that hold an enhanced ability to receive and convey information. A series of speculative thought-experiments highlight how augmented urban entities could employ CAS dynamics to âsolve for' different kinds of urban optimization scenarios, leading these material entities to self-organize (with their users) and discover fit regimes. The final paper flips the perspective, considering how, not only material agency, but also human agency is being augmented by new information processing technologies (smartphones), and how this can lead to new dances of agency that in turn generate novel emergent outcomes.
The dissertation is based on a compilation of articles that have, for the most part, been published in academic journals and all the research has been presented at peer-reviewed academic conferences. An introduction, conclusion, and explanatory transitions between sections are provided in order to clarify the narrative thread between the sections and the articles. Finally, a brief âcoda' on the spatial dynamics afforded by Turkish Tea Gardens is offered
Sacred Space: Spatial Communications Patterns in an Irish American and Slovak American Roman Catholic Parish
This ethnographic study provides contextual definitions of religious-centered frames for communication in an Irish-American and a Slovak-American parish. Spatial behavior patterns which appear incident to ethnic traditions and patterns associated with Roman Catholicism which do not appear to vary significantly across ethnic parishes are both described. The context control methodology employed is adapted from the microanalytic study of multimodal communication behavior. A detailed explication of the evolving methodological process reveals relevant cultural contrasts in interview negotiations and hospitality patterns. Data analyses include informant interviews and observations made in analogously controlled conditions in a variety of comparable locations in each church and in the dwelling space of both clergy and laity. Historical depth to empirical observations is provided by a through-time description of the two cultural groups and their migration and settlement patterns. Church doctrine and architectural history provides technical insights regarding the liturgical significance of ritual behaviors patterns
Contemporary Surface Architecture : The correspondence between surface and space
This thesis aims to investigate aspects of contemporary architecture that concentrate on the role of surface, in sense of demateriality. The word 'demateriality' denotes the spatiality rather than a physical substance; it does not refer to the actual absence of matter or the abolishment of the solid materials of construction. Rather it describes the phenomenal perception of a particular spatialisation that the surface creates through either the way it is formed or through the optical quality of its materials. The terms surface and surface architecture discussed in this thesis thus have specific meanings beyond the generally received understanding of 'architectural surface', 'material surface' and so on. What is focused on is the particular role of surface architecture as a spatial boundary, especially between inside and outside spaces. In this context, the research aims to explore the correspondence between the surface and space, between the forms of the surface and the experience that they induce.
As a programme of PhD with design, this research includes both theoretical and practical approaches, including a design research project supported by an extensive literature review and theoretical argument. The thesis mainly consists of five parts. It begins from an Introduction including subject and questions, context, definition and methodology of the research. Chapter One is about a critical review of history of surface-space architecture, both in theory and design will be considered first. This will mainly focus on the architecture of 20th century modernism. Chapter Two focus on contemporary theories and practices of surface architecture, as well as the conception of surface in other intellectual areas such as philosophy and cultural theory. Based on a rigorous theoretical framework built by the historical and contemporary research, a series of design works will be developed in Chapter Three, and attempt to offer a further understanding and rethinking of the knowledge gained from the first phase. Finally, at the end of the thesis, there is a brief Conclusion
An aesthetics of touch: investigating the language of design relating to form
How well can designers communicate qualities of touch?
This paper presents evidence that they have some capability to do so, much of which appears to have been learned, but at present make limited use of such language. Interviews with graduate designer-makers suggest that they are aware of and value the importance of touch and materiality in their work, but lack a vocabulary to fully relate to their detailed explanations of other aspects such as their intent or selection of materials. We believe that more attention should be paid to the verbal dialogue that happens in the design process, particularly as other researchers show that even making-based learning also has a strong verbal element to it. However, verbal language alone does not appear to be adequate for a comprehensive language of touch. Graduate designers-makersâ descriptive practices combined non-verbal manipulation within verbal accounts. We thus argue that haptic vocabularies do not simply describe material qualities, but rather are situated competences that physically demonstrate the presence of haptic qualities. Such competencies are more important than groups of verbal vocabularies in isolation. Design support for developing and extending haptic competences must take this wide range of considerations into account to comprehensively improve designersâ capabilities
Architecture and the creation of worlds
This thesis is an enquiry by creative practice into the academic and aesthetic
(avant-garde) practice of architecture. It explores the notion of the virtual as
pure potentiality following an event, and defines architecture as the site of such
potentiality. (Alain Badiou names event as the moment /encounter which initiates
a radical break from a given situation /state of affairs. There are four types of
event: artistic, political, scientific and amorous).The thesis follows two parallel strands of enquiry. One, into the material
production of the architectural object and topological space, this is titled the
actual; and the other, an investigation into the philosophical and antagonistic
nature of the virtual, this is titled the virtual. The actual deals with the literature
review, methodology, context of study and proposal for (the site of) actual
engagement with theory, including a design element (House of the Chinese
Mantis); while the virtual explores (through a series of five international and
interdisciplinary conference papers) the philosophical problems of emergence.
The 'context of study' in the actual centres around the move from the fetish of
commodities to seduction and concludes with eroticism, while the body of work
in the virtual concentrates on the notions of sovereignty, becoming, and concrete
subjectivity.Following the technological practices of the avant-garde between hypersurface
theory and catalytic formations in architecture, the thesis rejects the claims of
virtual space as the digital space of computer -based design, and of emergence as
mimetic and /or algorithm based design. It argues that the virtual is the
intangible space of creative unfolding following Bergson and Deleuze, but
resists the claim in Deleuze that event is a chance occurring. Also, it resists the
claim in Baudrillard that seduction and /or enchanted simulation are event and
abandons them to focus on the amorous (one of the four events in Badiou). This
creates an inflection in the enquiry, moving the thesis towards Plato and the
Renaissance, and a contemporary resurrection in architecture, of the tragic, as
concrete manifestation of the amorous encounter.The method of inquiry is structured after the nomadic logic of the War Machine
in the philosophy of Deleuze and Guattari, and of the revolutionary nature of
fidelity to the scientific event in Badiou, which argues that new knowledge is
created by 'revolutions' and from the anomalies and collaborations which arise
as a result of such 'detours'; it is a strategy justified by the science historians
Feyerabend, Kuhn and Lakatos.The thesis takes the form of two books (the actual and the virtual), and concludes
that the avant-garde practice of architecture, with its infinite potentialities is
distinct from the bureaucratic or State apparatus of building, and that the
commonplace appropriation of the avant-garde by the State, as seen in the
institutional recourse to parametrics, appears unproductive and uncreative with
regard to knowledge
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