Planting parallel program simulation on the cloud

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An agent-based visualisation system.

This thesis explores the concepts of visual supercomputing, where complex distributed systems are used toward interactive visualisation of large datasets. Such complex systems inherently trigger management and optimisation problems; in recent years the concepts of autonomic computing have arisen to address those issues. Distributed visualisation systems are a very challenging area to apply autonomic computing ideas as such systems are both latency and compute sensitive, while most autonomic computing implementations usually concentrate on one or the other but not both concurrently. A major contribution of this thesis is to provide a case study demonstrating the application of autonomic computing concepts to a computation intensive, real-time distributed visualisation system. The first part of the thesis proposes the realisation of a layered multi-agent system to enable autonomic visualisation. The implementation of a generic multi-agent system providing reflective features is described. This architecture is then used to create a flexible distributed graphic pipeline, oriented toward real-time visualisation of volume datasets. Performance evaluation of the pipeline is presented. The second part of the thesis explores the reflective nature of the system and presents high level architectures based on software agents, or visualisation strategies, that take advantage of the flexibility of the system to provide generic features. Autonomic capabilities are presented, with fault recovery and automatic resource configuration. Performance evaluation, simulation and prediction of the system are presented, exploring different use cases and optimisation scenarios. A performance exploration tool, Delphe, is described, which uses real-time data of the system to let users explore its performance

Transcriptomic phenotyping of the macrophage response to filarial nematode infection

Helminths are paraphyletic group of parasitic metazoans that collectively consist of the nematodes, trematodes, cestodes and platyhleminthes. Helminth infections are characterized, amongst other things, by IL-4 and IL-13 production from CD4* Th2 cells. IL-4 and IL-13 induce alternatively activated macrophages (AAMΦ) via their action on the IL-4Rα receptor subunit. AAMΦ are also implicated in numerous other diseases such as fibrosis, allergy, cancer and diabetes.STAT6 drives IL-4Rα-dependent transcription in AAMΦ, leading to the induction of many genes including Arg -1, YM1 and RELMα. IL-4 also induces macrophage proliferation, a phenotype observed in vivo, but not in vitro. In vitro studies have shown that IL-4 upregulates macrophage mitochondrial metabolism in a process dependent upon the Iigand-dependent transcription factor PPARγ (peroxisome proliferator activator receptor gamma). In spite of the far -reaching effects of IL-4 on macrophage biology and physiology, we are unaware of the true role(s) of AAMΦ during helminth infection.In this thesis I present two transcriptomic analyses of macrophage responses to filarial nematode infection. In the first case we define IL-4Rα-dependent components of the macrophage response to nematode infection. Using RNA-Seq, WT and IL-4Rα-/- mice implanted with the parasitic nematode Brugia malayi are compared against inflammatory - like thioglycollate-elicited macrophages. This has allowed us to infer an anti-inflammatory phenotype for nematode -elicited macrophages (NeMΦ) in vivo. We also identify an unanticipated role for NeMΦ in the production of complement components in response to B. malayi challenge. During this project I develop a method to map transcription start site (TSS) usage with RNA-Seq data, this algorithm has been developed into the software 'TSS-Predictor' and is presented in chapter 3. Using TSS-Predictor we define TSS usage in our RNA -Seq dataset, and a subsequent analysis of transcription factor binding sites in AAMΦ-associated promoters confirms a role for PPARs in AAMΦ in vivo. Furthermore, we find that PPARδ, but not PPARγ is expressed during helminth infection. A targeted lipid analysis of macrophage-derived eicosanoids identified prostacyclin (PGI2) as a candidate ligand to mediate PPARδ-dependent transcription in NeMΦ during helminth infection in vivo.Finally, we integrate flow cytometry and a microarray gene expression profiling in a time series of macrophages elicited in response to the parasitic nematode Litomosoides sigmodontis. We capitalize on the discordant kinetics of alternative activation and proliferation in this model to define gene expression signatures associated with proliferation and AAMΦ. Based upon this analysis we present a working model for IL-4-dependent macrophage proliferation in vivo and characterise candidate receptors mediating this process. We also demonstrate in vivo that AAMΦ increase mitochondrial mass in response to L. sigmodontis infection

Clinical fluorescence spectroscopy and imaging for the detection of early carcinoma by autofluorescence bronchoscopy and the study of the protoporphyrin IX pharmacokinetics in the endometrium

The aim of this thesis is to optimise and gain fundamental information on two applications of photomedicine using fluorescence imaging and spectrofluorometry: (1) the detection of early bronchial cancer by autofluorescence imaging and (2) the endometrial ablation by photodynamic therapy (PDT) based on the use of Protoporphyrin IX (PpIX). Fluorescence imaging and spectroscopy require a fluorochrome localised within the tissue. The fluorochrome can either be endogenous (naturally synthesised in the body), endogenously induced (synthesised in the body from an administered drug), or exogenous (synthesised outside the body). This thesis concentrates on the clinical applications of the endogenous and an endogenously induced fluorochrome (PpIX). Therefore, this work has been divided into two parts according to the type of fluorochromes. The numerous endogenous fluorochromes occur naturally. They are collectively responsible for the fluorescence properties of biological tissues. This tissue's intrinsic fluorescence is also referred to as autofluorescence (AF). The AF of bronchial tissues, change when they become dysplastic or neoplastic. Early neoplastic or dysplastic lesions show an overall decrease in the AF intensity as well as a distorsion of the spectral shape. Endoscopic imaging devices rely on this principle to detect early neoplastic lesions in the tracheo-bronchial tree. The first part of this thesis describes our efforts to improve the performance of AFB and to gather insight into the mechanisms at the origin of the AF contrast in the bronchi. For this purpose, we conducted a number of clinical and ex vivo studies using imaging and spectrofluorometry. Our initial clinical imaging study revealed that the detection of a red background image instead of the red AF image increased the lesion-to-healthy tissue contrast by a factor of 2. This improvement has been implemented in an AFB device that is currently commercialised by the Richard Wolf Endoskope GmbH. In a seperate clinical imaging study we investigated the influence of the excitation wavelength on the AF contrast. Using a narrowband (6 nm FWHM) excitation around 410 nm resulted in a 1.5 times higher lesion-to-healthy tissue intensity contrast than observed with a comparable broadband (80 nm FWHM) excitation. A supplemental study showed that short wavelength blue backscattered light around 430 nm has the potential to discriminate true positive lesions (i.e. early neoplastic lesions detected positive with the AFB system) from false positive lesions (i.e. benign tissue changes detected positive with the AFB system). A spectrofluorometric ex vivo study was performed to gain insight on the mechanisms at the origin of these contrasts. Five principal mechanisms are discussed, namely changes of: (1) the fluorochrome's concentration, (2) the fluorochrome's metabolic status, (3) the fluorochrome's physico-chemical microenvironment, (4) the tissue architecture such as thickening of the epithelium, and (5) the concentration of light absorbing chromophores such as haemoglobin. We measured formalin fixed human bronchial tissue samples with an optical fibre based spectrofluorometer. The formalin fixed bronchial tissue samples showed a general decrease of the AF of early lesions compared to the healthy tissues. However, no distortion of the lesions' AF spectra with respect to that of the healthy tissues was observed. These results were confirmed by imaging of the tissue samples with our AFB system. The observations from these ex vivo studies together with results obtained in clinics with our imaging system lead us to conclude that the AF contrast can be attributed to a combined effect induced by: (1) changes in the architecture of superficial tissues and (2) the concentration and spatial distribution of haemoglobin in the submucosa. Furthermore, we investigated inter-patient variations of the bronchial AF to estimate their impact on the spectral/photonic design of AFB systems. An endoscopic reference with tissue-like optical and spectral properties was designed for this purpose. Surprisingly, the AF intensities in spectroscopy of the human bronchi showed only minor (< 30 %) variations from one individual to another. The exogenously induced fluorochrome Protoporphyrin IX (PpIX) is synthesised from 5-aminolaevulinic acid (5-ALA) in the haeme biosynthetic pathway. PpIX is widely used in PDT and fluoresence detection for both malignant and benign, lesions. The second part of this thesis deals with the pharmacokinetics of 5-ALA induced PpIX in the endometrium. The final goal of this study was the optimisation of the treatment protocol for photodynamic endometrial ablation to treat menorrhagia and hypermenorrhea. The PpIX build-up in the human endometrium was measured in vivo by spectrofluorometry following intra-uterine instillation of 5-ALA. An intra-uterine optical-fibre based probe was designed for this purpose. The PpIX pharmacokinetics showed important inter-patient and intra-patient variations regarding the time interval between the drug instillation and the maximal PpIX fluorescence. Indeed, we have found that this time interval ranges between 0.5 and 5 hours. The maximal measured PpIX fluorescence intensities varied by one order of magnitude from one patient to another. Finally, no correlation was found between the characteristics of the PpIX build-up and the patient's hormonal status

An investigation of specific contributing factors affecting quality assurance in the diagnosis of conventional cervical smears

The purpose of this study is to investigate specific contributing factors affecting quality assurance in the diagnosis of conventional cervical smears. More than half of South- African women fail to have one cervical smear in their lifetime and +/- 50 percent of those who do have cervical smears taken, are lost to follow-up. Since cervical cancer is the most common malignancy amongst women in developing countries, the medical profession will have to endeavor to screen a higher rate of women and ensure a 100 percent quality assurance with every patient treated in order to reduce the unacceptable high incidence of cervical carcinoma. At this stage it seems like an impossible task to screen all women in South Africa, due to far-off rural areas, shortage of medical professionals and the lack of knowledge of some women of the necessity of cervical smears. Many newly qualified South-African doctors leave the country to go and work elsewhere. South Africa then in turn has to recruit doctors from other countries to staff the State hospitals and clinics. Some areas have one doctor to thousands of patients, insufficient nursing personnel and inadequate equipment. Doctors in some areas cannot cope with the volume of work and the long hours. One has to accept that the quality of the management of some patients is affected negatively. There are a number of medico-legal issues (world wide) in relation to aspects of cervical cancer prevention practices which are controversial and are of particular concern to all of those involved in cervical cancer prevention. Various countries have therefore formed different national organizations to address the medico-legal issues in screening for the prevention of cancer. These organizations monitors procedures, internal quality control as well as external quality control. In South Africa, medico-legal cases are not so prevalent, but may become so shortly. The South-African medical professionals therefore have to ensure that their quality of work conforms to accepted good practice in all circumstances. State hospitals serve thousands of patients per month and it is an every day occurrence to see long queues of patients sitting waiting for doctors and who often have to come back the following day. The situation appears to be much improved in private practice and since patients have medical cover and accessible medical facilities. Since cervical cancer is the most common malignancy amongst women in developing countries, the medical profession will have to endeavor to screen a higher rate of women and ensure a 100 percent quality assurance with every patient treated in order to reduce the unacceptable high incidence of cervical carcinoma. At this stage it seems like an impossible task to screen 100 percent of women in South Africa, due to far-off rural areas, the shortage of medical professionals and ignorance of patients. Quality assurance is therefore of paramount importance to every medical professional for every patient treated. Laboratories all worldwide have been, or are in the process of being accredited by their specific accreditation authorities. The main reason for this is improvement of quality control and therefore quality assurance. The South African National Accreditation Society (SANAS) now accredits various laboratories in South Africa with the view of accreditting all laboratories within a certain time limit. The Ampath laboratory Port Elizabeth was successfully accredited during 2001. Accredited laboratories have to uphold a very high degree of quality to remain accredited. A team of professionals inspects the laboratory every 2 years and other quality assurance staff inspects the laboratories every few months. All aspects of the laboratory are checked, e.g. the qualification of staff, their registration with the Health Professions Council of South Africa (HPCSA), their curriculum vitaes, equipment, safety of the laboratory etc. Since the laboratory chosen for this study, is accredited, the author evaluated every cervical smear that was received in the laboratory since the year 2000, with the following objectives in mind: · Whether the presence or absence of an endocervical component has an effect on the adequacy of cervical smears · To determine the effect of using smaller coverslips on quality assurance in the cytology laboratory · Evaluate the effect that manual re-screening of smears has on quality assurance in the cytology laboratory. As there is a shortage of cytotechnologists and pathologists worldwide, several countries make use of automated screening devices as primary screening or secondary screening for quality assurance. These devices were tested in some laboratories in South Africa but were found to be very expensive and sensitivity and specificity were not up to standard. Sensitivity is a measure of the ability of a test to detect the abnormal - Sensitivity is the ratio of true positives to true positives + false negatives. Specificity is a measure of the ability of a test to correctly identify the negative - Specificity is the ratio of true negative to true negatives + false positives. The automated screening machines failed to identify abnormal cells amongst inflammatory cells, as well as in very blood stained smears. Several other problems also occurred and an increasing number of smears had to be manually rescreened, thus making this exercise costly and not helpful as a quality assurance instrument. The slides used for this thesis, have been retrieved from the archives of the Ampath laboratory in Port Elizabeth. Fourteen specific contributing factors affecting quality assurance in the diagnosis of cervical smears are also discussed and conclusions and recommendations given

1982-1984 Xavier University College of Arts and Sciences, College of Business Administration, Edgecliff College, College of Continuing Education, Graduate School Course Catalog

https://www.exhibit.xavier.edu/coursecatalog/1120/thumbnail.jp

An examination of the neurology behind the concept of the Self with consideration given to the effects of neurological impairment

The argument that I present in this thesis is that while the idea of the Self is an illusion, a myth which our brains create, it is one that is necessary for our survival. However, by understanding its neurological origins we are able to take advantage of it without being victims of egocentricity. My first chapter, Neurology of the Self, lays down the neurological foundations for our concept of the Self and goes on to argue that, while biology and neurology must remain the basis of our understanding, we need to transcend our purely scientific concepts in order to integrate them with art and spirituality. Our transcendental view, I argue, seeks to establish values that make life worth living for and are essential to our survival. I consider some possible implications, both real and imagined, of neurological impairment. The second chapter, Consciousness and the Self, considers the neurological and chemical basis for consciousness and develops the ways in which the imagined Self can be used to create a balanced life that is not highjacked by ego. In the third chapter, Human Nature and the Self, I continue to argue for a liberated view of the Self bearing in mind its neurological origin which itself is the creator of our received reality. Compassion, which Schopenhauer's philosophy argued for as the basis of morality, is shown to be facilitated by the concept of a centred Self which I apply to the subject of morality in the fourth chapter, Morality and the Self. With the fifth chapter, Illusion and the Imagined Self. I come to the very heart of the argument to which tny considered research findings and previous chapters have lead, namely, that the illusion of the Self is neurologically created by our brains and that we do not have an unchanging Self which is other than the experiences and ideas from which our whole Being derives meaning. Nonetheless, this Self and other values we create are essential for our well being and should be cherished in themselves as being crucial for our healthy individual and collective survival. Furthermore, since we are now aware of the origin of our idea of the Self we can gain our freedom from a manipulating ego and become centred Selves able to creatively transcend and transform the limits of our neurologically given reality by being I "" .... viii actively involved in the ongoing process of change. This is the subject of my sixth chapter, Spirituality and the Creative Self, and is endorsed in my concluding chapter which, neglecting a view which carefully avoids accepting absolutes that just might be falsified tomorrow, argues that the best values that we create today should be used as absolutes from which to derive principles for living and continuing to live which could, at least, lessen the threat to our survival