3,054 research outputs found
George MacLeod’s open-air preaching: performance and counter-performance
No full textStuart Blythe uses the methodology of performance to analyse George MacLeod’s open-air preaching. He points out that MacLeod’s preaching was derived from a theology of the incarnation, and an understanding of the paradoxes and dichotomies of common human life. This preaching, Blythe suggests, was also a counter-performance in the context of outlooks and ideologies inimical to the gospel. The paper raises interesting issues related to preaching as performance, and the further question as to whether or not the life and work of the Church as a whole might now be better understood as a counter-performance.Publisher PD
Redemption in the work of Francis Stuart
No full textThe idea of redemption is central to an understanding of the work
of Francis Stuart. Through an examination of its development and
expression, it is possible to demonstrate the integrity of his work and
its distinctive qualities. Such a demonstration is necessary because
Stuart's writing has been subjected to comparatively little scholarly
inquiry, although reviews of his work, especially that produced since
1949, suggest that it is impressive and important.
First, a general background to Stuart's work, a discussion of the
special problems associated with reading it, and a summary of his corpus
is provided. This indicates that the idea of redemption is important to
his earliest writing. The state of redemption is shown to be a
necessary apotheosis for Stuart's outcast heroes; it involves spiritual
suffering through which may be found a sense of reintegration and a
higher reality. This is expressed through interrelated themes such as
those of gambler, artist and ordinary man; mystic and criminal; sacred
and profane love; and spirituality and the mundane. The nature of the
redemptive experience is further elaborated by distinctive, complex
motifs, especially the hare, the ark and the woman-Christ. Their
recurrence provides an important element in the unity of Stuart's work.
Because Stuart's idea of the outcast raises important biographical
questions, an examination of the relationship between Stuart's life and
his work is made. Finally, the way in which the idea of redemption
exists in the language structures of Stuart's novels is examined, with
especial reference to his most recent work, The High Consistory. The
thesis shows that the development of the these of redemption
demonstrates the integrity of Stuart's work
John Stuart Mill’s projected science of society: 1827-1848
No full textThe purpose of the thesis is to examine John Stuart Mill’s political thought from
about 1827 to 1848 as an exercise in intellectual history. It focuses, first, on Mill’s view,
formulated by the late 1830s, that contemporary society was ‘civilized’, and second, on
his project of a science of society, which he aspired to develop in the late 1830s and
early 1840s.
By the late 1830s, Mill came to the view that his contemporary society was a
‘commercial society or civilization’, dominated by the middle, commercial class. The
first part of my thesis, constituted by Chapters 2-4, discusses the way in which Mill
formed his notion of civilization, and what he meant by the term ‘civilization’. Mill paid
attention to the implications of the rise of the middle class, and regarded such
phenomena of contemporary society as the corruption of the commercial spirit and
excessive social conformity as an inevitable consequence of the rise of the middle class.
The second part of the thesis, constituted by Chapters 5-9, examines Mill’s
projected science of society. In the late 1830s and early 1840s, Mill attempted to
develop a new science of society whose subject-matter was the nature and prospects of
commercial, civilized society. This aspiration culminated in A System of Logic,
published in 1843. In examining Mill’s projected science, I pay particular attention to
the fact that he conceived new sciences of history and of the formation of character,
both of which were indispensable in his project, although he failed to give a complete
account of these sciences. My thesis shows that the implications of his interest both in
history and in the formation of character are more significant than Mill scholars have
assumed
Beauty for the Present: Mill, Arnold, Ruskin and Aesthetic Education
No full textThe present thesis examines the idea of aesthetic education of three eminent Victorians: John Stuart Mill, Matthew Arnold and John Ruskin. By focusing on the essence of what they meant with ‘the cultivation of the beautiful’ and, more importantly, the way their ideas of beauty informed their criticism of society, my study aims to contribute to our understanding of the idea of aesthetic education in the Victorian context and, further, to participate in a recent debate about the nature of beauty and aesthetic education.
Chapter One focuses on John Stuart Mill’s concept of ‘feeling’ in a series of essays. I will demonstrate how Mill’s idea of ‘aesthetic education’ was an ‘education of feelings,’ and moreover, how this idea was integrated into his literary criticism, his later critique of democratisation, his description of an ideal liberal society and even his own style of writing. Chapter Two contains a comparative study of Matthew Arnold and Friedrich Schiller. Through a rereading of Arnold, I will argue that his idea of aesthetic education is essentially Schillerian and that their resemblance consists primarily in their stress on the importance of aesthetic unity for modern life, which was becoming increasingly fragmentary and multitudinous. Chapter Three examines John Ruskin’s idea of aesthetic education and concentrates particularly on the cultivation of perception. Perception, as I shall show, was pivotal in Ruskin’s idea of aesthetic education. Just as what happened in Mill and Arnold, the emphasis on the education of seeing continued from his early writings well into his art and social criticisms. It not only differentiated him from his fellow art critics; the conviction that people should perceive with a pure heart also enabled him to link observation of artistic details with moral criticism of contemporary society and, thereby, to turn the cultivation of the beautiful into a moral-aesthetic experience
An Analytical Criterion for Centrifugal Instability in Non-Axisymmetric Vortices
No full textNon-axisymmetric vortices are ubiquitous in nature; examples include polar vortices in planets, the giant red spot in Jupiter, tornadoes and cyclones on Earth, mesoscale eddies in the ocean. Turbulent flows are furthermore known to be dominated by small- and large-scale vortex structures. Owing to the wide range of applications, knowledge of conditions under which a given vortex becomes unstable is beneficial. Here, the centrifugal instability of two-dimensional, non-axisymmetric vortices in the presence of an axial flow and a background rotation is studied using the local stability approach. The local stability approach, based on geometric optics and similar in formulation to the rapid distortion theory \cite{bib:godeferd2001}, considers the evolution of shortwavelength perturbations along streamlines in the base flow. This approach, developed by Lifschitz Hameiri \cite{bib:lifschitz1991}, is particularly useful for base flows for which a global stability analysis is computationally expensive. A sufficient criterion for centrifugal instability in an axisymmetric vortex with and is first derived by analytically solving the local stability equations for wave vectors that are periodic upon evolution around a closed streamline. This criterion is then heuristically extended to non-axisymmetric vortices and written in terms of integral quantities on a streamline. The criterion is then shown to be accurate in describing centrifugal instability over a reasonably large range of parameters that specify Stuart vortices and Taylor-Green vortices
A colorimetric PCR method for the detection of M. leprae in skin biopsies from leprosy patients
No full textA one-tube nested polymerase chain reaction (PCR) method for the diagnosis of paucibacillary leprosy was developed using the repetitive RLEP sequence as a target. Detection of the PCR products was simplified by the adaptation of a colorimetric method. The test was specific for Mycobacterium leprae, and the sensitivity of the assay was 1 fg of purified genomic M. leprae DNA (less than one genome). Complete concordance was seen between the development of color and resolution on agarose gels. The results of frozen skin sections from untreated patients showed that the assay could detect 100% of multibacillary samples [bacterial index (BI) of 2 or more] and 69% and 70% of the samples with Bis of 1 and 0, respectively. The use of one-tube nested PCR in assessing the effectiveness of multidrug therapy (MDT) in leprosy also was determined. The simplified colorimetric assay was found to be sensitive, rapid and specific, and is suitable for use in routing diagnostic laboratories.Peer reviewedfinal article publishe
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Discovering Molecular Patterns with Therapeutic Implications in Large-Cohort Heterogeneous Cross-Cancer Data
No full textRecent advances in high-throughput genomic technologies and high-performance computing have propelled the science of computational genomics into a new era and launched the field of precision medicine. Computational genomics is now an integral part of biomedical research and genomic testing is routinely performed in clinical settings. In the field of cancer informatics, the integration of genomics has led to invaluable insights and discoveries. We study cancers in order to better understand tumorigenesis and disease progression. This understanding can, in turn, inform and guide therapeutic decisions and suggest directions for drug development and repositioning. The ultimate goal of cancer precision medicine is to sequence and analyze every patients tumor in order to provide the most effective and least toxic treatment.Various experimental platforms are available for collection of different perspectives or views of the cell state, which help us characterize and understand molecular signals driving the cell phenotype. We collectively refer to these views as ’omics’ data. While vast amounts of ’omics’ data are being collected from tumor samples at an accelerating rate, few resources exist to aid biologists and clinicians in identifying trends in these data, finding connections within and between cancer subtypes, and matching patients to previously studied patient groups to infer therapeutic implications. In our analysis we also utilize bioinformatics methods that manipulate, transform, and integrated these views to derive new views of the cell. In my doctoral thesis, I present my work developing new tools and methods to aid the scientific community in understand- ing and interpreting cancer biology (Chapter 2). I also present my work applying such methods to contribute to cancer subtype-specific analyses as part of various projects and collaborations during my doctoral work (Chapter 3).Finally, I describe my work and contributions to the field of personalized medicine in pediatric cancer. While similar in some ways to adult cancers, pediatric cancers differ dramatically from their adult counterparts on a molecular level. For ex- ample, pediatric tumors generally have fewer genomic alterations than adult tumors. Further,childhood cancers are rarer than adult cancers and thus more difficult to study due to a lack of sufficiently large patient cohorts. While some clinics now regularly sequence pediatric tumors for bioinformatic analysis, the sequencing of patient genomes in the clinic is only beginning to impact patient care. Most computational methods for detecting differentially expressed genes are designed for analyzing patient cohorts in research settings and are thus unsuitable for interpreting RNA sequencing data from a single patient. Further, analyzing individuals genomic data leads to actionable treatment options in only fifteen percent of all childhood cancer cases. This is because pediatric cancers are often not driven by non-hereditary genomic changes, and any genomic aberrations that do exist may not be targetable by existing drugs. More sophisticated informatics tools and methods are needed in the field of personalized medicine. To this end, I describe my work developing methods for single-patient analyses in pediatric cancer (Chapter 4). While my methods were developed for pediatric cancers, they may also be used to analyze adult tumors
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Transcriptional Signatures of the Tumor and the Tumor Microenvironment Predict Cancer Patient Outcomes.
No full textPredicting the most effective cancer therapy for patients is a challenging yet very important task. In my doctoral thesis, I describe new insights gained from using transcriptional signatures from gene expression data of tumors and the tumor microenvironment. Out of different multi-omics data types, gene expression is found to be the most useful in predicting cancer drug sensitivity in a data set of cancer cell lines. Gene expression data can also be used to predict the presence of cancer driver events, genetic abnormalities responsible for tumor growth and progression. I describe the detection of rare genomic driver events found by association with known driver events using transcriptional signatures.Cancers are traditionally classified into types and subtypes by the organ- and cell-of-origin. However, more and more cancer subtypes are now being defined on a molecular basis using for example gene expression or mutation data. I perform a meta-analysis of molecular subtype classifiers for 26 different cancer cohorts that demonstrates which aspects of the input samples and input data are important to build an accurate molecular subtype classifier. In advanced prostate cancer, I use transcriptional signatures to reliably classify samples into subtypes. The gene expression data, in combination with histological review, is able to define the most at-risk patients in this cohort. However, I show that the classification of cancers into distinct subtypes is not applicable to all samples in this cohort, because they exist on a continuous spectrum between the subtypes - a finding that I was able to recapitulate in a study of lung cancer samples. I define and describe this continuum between subtypes of advanced prostate cancer using gene expression data.The tumor microenvironment, the normal cells that mix with cancer cells to form a tumor, plays an important role in cancer progression and treatment response. I built a landscape of about 10,000 cancer samples from immune cell infiltration estimated by deconvolution of gene expression profiles. However, immune cells are not the only cell types in the tumor microenvironment. I present a comprehensive deconvolution analysis of tumor patient samples using a cell type library defined from single-cell RNA sequencing data. These cell type estimates enable the detection of a pan-cancer high-risk sample group that is not detected by traditional gene expression analysis
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Sample-Specific Cancer Pathway Prediction From Genomic, Transcriptomic and Phosphoproteomic Data
No full textCancer phenotypes such as invasion, evasion of programmed cell death, and rapid growth, arise from the complex interactions of genes, proteins and extra-cellular environments. Understanding how selective alterations in the genome convert healthy cells to cancer is a critical step in developing new targeted and combination therapies. Current technology allows for detailed measurement of both genomic state as well as phenotype, through measurement of gene expression, chromatin state and protein activation. I present a method, Tied Diffusion through Interacting Events (TieDIE), that uses a “heat diffusion” model of information transfer to find pathways linking key genomic alterations to phenotypic effects, using high-throughput data collected from cohorts of cancer patients. Applying this method to four large data sets developed by The Cancer Genome Atlas (TCGA), I found key genes and interactions linking mutations related to histone modification and protein kinase signaling to gene-expression signatures of growth and proliferation. In a TCGA study of thyroid carcinoma, TieDIE found key proteins that modulate oncogenic signaling from mutant BRAF and RAS proteins to downstream MEK and ERK pathways, including the kinase suppressor of ras 1 scaffold protein.TieDIE was next applied to a study of prostate cancer that included detailed measurements of the phosphpoproteome. With collaborators at UCLA, we used tissue from lethal, metastatic castration-resistant prostate cancer (CRPC) patients obtained from rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using TieDIE, I integrated transcriptional, genomic and phosphoproteomics datasets to reveal a “map” of activated kinases and signaling pathways in CRPC. In contrast to single-dataset analyses, I show this integrative approach provides a more comprehensive and detailed look at metastatic signaling, and is generally useful in combining diverse datasets with only partially overlapping samples. Patient-specific network models were created by intersecting each sample’s data and protein activity predictions with the CRPC signaling “map.” These models reveal a hierarchy of the top kinase targets for each patient analyzed, and the corresponding therapeutic intervention, allowing for the construction of feasible strategies for patients with high activities in multiple kinases
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COMPUTATIONAL EVALUATION AND DERIVATION OF BIOLOGICAL NETWORKS IN CANCER AND STEM CELLS
No full textBiological network models have become standard tools for genome-wide analysis of both cancer disease processes and healthy differentiation from stem cells. In this thesis, I ad- dress a method for evaluating network models in terms of their ability to predict held out expression data given information about other genes in the same network. I apply this test to several extensions of our pathway database to demonstrate the transcrip- tional modeling utility of reverse phase protein array data, natural language processed literature, and transcription factor target predictions in stem cells and differentiated tissue. I then explore the addition of one new type of network data; co-localization in DNA domains. However, preexisting functional data is not the only source of networks. In the final part of the thesis, I elucidate a method to integrate prior biological knowl- edge with time series observations to infer causal relationships between phosphorylation events on proteins
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