Monasticism and its limits: rematerialising monastic space in early medieval Ireland

This thesis creates a multi-faceted archaeological context for early Irish monasticism, so as to ‘rematerialise’ a phenomenon that has been neglected by recent archaeological scholarship. Following revision of earlier models of the early Irish Church, archaeologists are now faced with redefining monasticism and distinguishing it from other diverse forms of Christian lifestyle. This research addresses this challenge, exploring the ways in which material limits can be set on the monastic phenomenon. The evidence for early Irish monasticism does not always conform to modern expectations of its character, and monastic space must be examined as culturally unique in its own right - though this thesis demonstrates that early Irish monasticism was by no means as unorthodox in its contemporary European setting as has previously been suggested. The research is informed by theories of the body, habitus and space, drawing on a wide body of archaeological, religious, sociological and anthropological thought. The data-set comprises evidences gathered through field-survey, reassessment of archaeological scholarship, historical research and cartographic research, enabling consideration of the ways in which early Irish monastics engaged with their environments. A sample of thirty-one early Irish ecclesiastical sites plus Iona forms the basis for discussion of the location and layout of monastic space, the ways in which monastics used buildings and space in their daily lives, the relationship of monasticism and material culture, the setting of mental and physical limits on monastic space and monastic bodies, and the variety of monastic lifestyles that pertained in early medieval Ireland. The study then examines the Christian landscapes of two case-studies in mid-Western Ireland in order to illustrate how monasticism functioned on the ground in these areas. As this research shows, the material complexities of early Irish monastic life are capable of archaeological definition in terms of both communal and personal lived experience.

New phosphorescence based probes and techniques for the analysis of cellular oxygen and respiration

Real time monitoring of oxygenation and respiration is on the cutting edge of bioanalysis, including studies of cell metabolism, bioenergetics, mitochondrial function and drug toxicity. This thesis presents the development and evaluation of new luminescent probes and techniques for intracellular O2 sensing and imaging. A new oxygen consumption rate (OCR) platform based on the commercial microfluidic perfusion channel μ-slides compatible with extra- and intracellular O2 sensitive probes, different cell lines and measurement conditions was developed. The design of semi-closed channels allowed cell treatments, multiplexing with other assays and two-fold higher sensitivity to compare with microtiter plate. We compared three common OCR platforms: hermetically sealed quartz cuvettes for absolute OCRs, partially sealed with mineral oil 96-WPs for relative OCRs, and open 96-WPs for local cell oxygenation. Both 96-WP platforms were calibrated against absolute OCR platform with MEF cell line, phosphorescent O2 probe MitoXpress-Intra and time-resolved fluorescence reader. Found correlations allow tracing of cell respiration over time in a high throughput format with the possibility of cell stimulation and of changing measurement conditions. A new multimodal intracellular O2 probe, based on the phosphorescent reporter dye PtTFPP, fluorescent FRET donor and two-photon antennae PFO and cationic nanoparticles RL-100 was described. This probe, called MM2, possesses high brightness, photo- and chemical stability, low toxicity, efficient cell staining and high-resolution intracellular O2 imaging with 2D and 3D cell cultures in intensity, ratiometric and lifetime-based modalities with luminescence readers and FLIM microscopes. Extended range of O2 sensitive probes was designed and studied in order to optimize their spectral characteristics and intracellular targeting, using different NPs materials, delivery vectors, ratiometric pairs and IR dyes. The presented improvements provide useful tool for high sensitive monitoring and imaging of intracellular O2 in different measurement formats with wide range of physiological applications.

Preserving patent policy space and securing access to medicines in developing countries: the role of states and pharmaceutical corporations

This thesis examines the tension between patent rights and the right to health and it recognizes patent rights on pharmaceutical products as one of the factors responsible for the problem of lack of access to affordable medicines in developing countries. The thesis contends that, in order to preserve their patent policy space and secure access to affordable medicines for their citizens, developing countries should incorporate a model of human rights into the design, implementation, interpretation, and enforcement of their national patent laws. The thesis provides a systematic analysis of court decisions from four key developing countries (Brazil, India, Kenya, and South Africa) and it assesses how the national courts in these countries resolve the tension between patent rights and the right to health. Essentially, this thesis demonstrates how a model of human rights can be incorporated into the adjudication of disputes involving patent rights in national courts. Focusing specifically on Brazil, the thesis equally demonstrates how policy makers and law makers at the national level can incorporate a model of human rights into the design or amendment of their national patent law. This thesis also contributes to the ongoing debate in the field of business and human rights with regard to the mechanisms that can be used to hold corporate actors accountable for their human rights responsibilities. This thesis recognizes that, while states bear the primary responsibility to respect, protect, and fulfil the right to health, corporate actors such as pharmaceutical companies also have a baseline responsibility to respect the right to health. This thesis therefore contends that pharmaceutical companies that own patent rights on pharmaceutical products can be held accountable for their right to health responsibilities at the national level through the incorporation of a model of civic participation into a country’s patent law system.

Characterisation of bifunctional ruthenium(ii) complexes, potential DNA photo-probes. Presence of folded and unfolded conformers

Novel bifunctional ruthenium(n) complexes, [Ru(TAP)2(POQ-Nmet)]2+ and [Ru(BPY)2(POQ-Nmet)]2+(la, 2a), containing a metallic and an organic moiety, have been prepared as photoprobes and photoreagents of DNA(TAP = 1,4,5,8-tetraazaphenanthrene, POQ-Nmet = 5-[6-(7-chloroquinolin-4-yl)-3-thia-6-azaheptanamido]-l,10phenanthroline). The ES mass spectrometry and 'H NMR data in organic solvents indicate that the quinoline moiety exists in both the protonated and non-protonated form. Moreover, the comparison of the NMR data with those of the corresponding monofunctional complexes(without quinoline) evidences that [Ru(TAP).2(POQ-Nmet)]2+ and [Ru(BPY)J(POQ-Nmet)]2+ are unfolded when the quinoline unit is protonated whereas deprotonation permits folding of the molecule. In the folded state the spatial proximity of the electron donor(the organic moiety) and electron acceptor(the metallic moiety) in [Ru(TAP)2(POQ-Nmet)]2+ favours intramolecular photo-induced electron transfer, which has been shown in a previous study to be responsible for the very low luminescence of la in non-protonating solutions. The restoration of the luminescence by protonation of the quinoline moiety as observed previously is in agreement with the unfolding of the molecule demonstrated in this work. The existence of such folding-unfolding processes related to protonation is crucial for studies of la with DNA. © The Royal Society of Chemistry 2000.

Adaptive Mixture Modelling Metropolis Methods for Bayesian Analysis of Non-linear State-Space Models.

We describe a strategy for Markov chain Monte Carlo analysis of non-linear, non-Gaussian state-space models involving batch analysis for inference on dynamic, latent state variables and fixed model parameters. The key innovation is a Metropolis-Hastings method for the time series of state variables based on sequential approximation of filtering and smoothing densities using normal mixtures. These mixtures are propagated through the non-linearities using an accurate, local mixture approximation method, and we use a regenerating procedure to deal with potential degeneracy of mixture components. This provides accurate, direct approximations to sequential filtering and retrospective smoothing distributions, and hence a useful construction of global Metropolis proposal distributions for simulation of posteriors for the set of states. This analysis is embedded within a Gibbs sampler to include uncertain fixed parameters. We give an example motivated by an application in systems biology. Supplemental materials provide an example based on a stochastic volatility model as well as MATLAB code.

Different stimuli, different spatial codes: a visual map and an auditory rate code for oculomotor space in the primate superior colliculus.

Maps are a mainstay of visual, somatosensory, and motor coding in many species. However, auditory maps of space have not been reported in the primate brain. Instead, recent studies have suggested that sound location may be encoded via broadly responsive neurons whose firing rates vary roughly proportionately with sound azimuth. Within frontal space, maps and such rate codes involve different response patterns at the level of individual neurons. Maps consist of neurons exhibiting circumscribed receptive fields, whereas rate codes involve open-ended response patterns that peak in the periphery. This coding format discrepancy therefore poses a potential problem for brain regions responsible for representing both visual and auditory information. Here, we investigated the coding of auditory space in the primate superior colliculus(SC), a structure known to contain visual and oculomotor maps for guiding saccades. We report that, for visual stimuli, neurons showed circumscribed receptive fields consistent with a map, but for auditory stimuli, they had open-ended response patterns consistent with a rate or level-of-activity code for location. The discrepant response patterns were not segregated into different neural populations but occurred in the same neurons. We show that a read-out algorithm in which the site and level of SC activity both contribute to the computation of stimulus location is successful at evaluating the discrepant visual and auditory codes, and can account for subtle but systematic differences in the accuracy of auditory compared to visual saccades. This suggests that a given population of neurons can use different codes to support appropriate multimodal behavior.

Measurements of Epidural Space Depth Using Preexisting CT Scans Correlate with Loss of Resistance Depth during Thoracic Epidural Catheter Placement.

Background. Thoracic epidural catheters provide the best quality postoperative pain relief for major abdominal and thoracic surgical procedures, but placement is one of the most challenging procedures in the repertoire of an anesthesiologist. Most patients presenting for a procedure that would benefit from a thoracic epidural catheter have already had high resolution imaging that may be useful to assist placement of a catheter. Methods. This retrospective study used data from 168 patients to examine the association and predictive power of epidural-skin distance (ESD) on computed tomography (CT) to determine loss of resistance depth acquired during epidural placement. Additionally, the ability of anesthesiologists to measure this distance was compared to a radiologist, who specializes in spine imaging. Results. There was a strong association between CT measurement and loss of resistance depth (P < 0.0001); the presence of morbid obesity (BMI > 35) changed this relationship (P = 0.007). The ability of anesthesiologists to make CT measurements was similar to a gold standard radiologist (all individual ICCs > 0.9). Conclusions. Overall, this study supports the examination of a recent CT scan to aid in the placement of a thoracic epidural catheter. Making use of these scans may lead to faster epidural placements, fewer accidental dural punctures, and better epidural blockade.

When the library is located in prime real estate: a case study on the loss of space from the Duke University Medical Center Library and Archives.

The Duke University Medical Center Library and Archives is located in the heart of the Duke Medicine campus, surrounded by Duke Hospital, ambulatory clinics, and numerous research facilities. Its location is considered prime real estate, given its adjacency to patient care, research, and educational activities. In 2005, the Duke University Library Space Planning Committee had recommended creating a learning center in the library that would support a variety of educational activities. However, the health system needed to convert the library's top floor into office space to make way for expansion of the hospital and cancer center. The library had only five months to plan the storage and consolidation of its journal and book collections, while working with the facilities design office and architect on the replacement of key user spaces on the top floor. Library staff worked together to develop plans for storing, weeding, and consolidating the collections and provided input into renovation plans for users spaces on its mezzanine level. The library lost 15,238 square feet (29%) of its net assignable square footage and a total of 16,897 (30%) gross square feet. This included 50% of the total space allotted to collections and over 15% of user spaces. The top-floor space now houses offices for Duke Medicine oncology faculty and staff. By storing a large portion of its collection off-site, the library was able to remove more stacks on the remaining stack level and convert them to user spaces, a long-term goal for the library. Additional space on the mezzanine level had to be converted to replace lost study and conference room spaces. While this project did not match the recommended space plans for the library, it underscored the need for the library to think creatively about the future of its facility and to work toward a more cohesive master plan.

An Exploration into Fern Genome Space.

Ferns are one of the few remaining major clades of land plants for which a complete genome sequence is lacking. Knowledge of genome space in ferns will enable broad-scale comparative analyses of land plant genes and genomes, provide insights into genome evolution across green plants, and shed light on genetic and genomic features that characterize ferns, such as their high chromosome numbers and large genome sizes. As part of an initial exploration into fern genome space, we used a whole genome shotgun sequencing approach to obtain low-density coverage (∼0.4X to 2X) for six fern species from the Polypodiales (Ceratopteris, Pteridium, Polypodium, Cystopteris), Cyatheales (Plagiogyria), and Gleicheniales (Dipteris). We explore these data to characterize the proportion of the nuclear genome represented by repetitive sequences (including DNA transposons, retrotransposons, ribosomal DNA, and simple repeats) and protein-coding genes, and to extract chloroplast and mitochondrial genome sequences. Such initial sweeps of fern genomes can provide information useful for selecting a promising candidate fern species for whole genome sequencing. We also describe variation of genomic traits across our sample and highlight some differences and similarities in repeat structure between ferns and seed plants.

Radiolabeled inhibitors as probes for imaging mutant IDH1 expression in gliomas: Synthesis and preliminary evaluation of labeled butyl-phenyl sulfonamide analogs.

INTRODUCTION: Malignant gliomas frequently harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Studies suggest that IDH mutation contributes to tumor pathogenesis through mechanisms that are mediated by the neomorphic metabolite of the mutant IDH1 enzyme, 2-hydroxyglutarate (2-HG). The aim of this work was to synthesize and evaluate radiolabeled compounds that bind to the mutant IDH1 enzyme with the goal of enabling noninvasive imaging of mutant IDH1 expression in gliomas by positron emission tomography (PET). METHODS: A small library of nonradioactive analogs were designed and synthesized based on the chemical structure of reported butyl-phenyl sulfonamide inhibitors of mutant IDH1. Enzyme inhibition assays were conducted using purified mutant IDH1 enzyme, IDH1-R132H, to determine the IC50 and the maximal inhibitory efficiency of the synthesized compounds. Selected compounds, 1 and 4, were labeled with radioiodine ((125)I) and/or (18)F using bromo- and phenol precursors, respectively. In vivo behavior of the labeled inhibitors was studied by conducting tissue distribution studies with [(125)I]1 in normal mice. Cell uptake studies were conducted using an isogenic astrocytoma cell line that carried a native IDH1-R132H mutation to evaluate the potential uptake of the labeled inhibitors in IDH1-mutated tumor cells. RESULTS: Enzyme inhibition assays showed good inhibitory potency for compounds that have iodine or a fluoroethoxy substituent at the ortho position of the phenyl ring in compounds 1 and 4 with IC50 values of 1.7 μM and 2.3 μM, respectively. Compounds 1 and 4 inhibited mutant IDH1 activity and decreased the production of 2-HG in an IDH1-mutated astrocytoma cell line. Radiolabeling of 1 and 4 was achieved with an average radiochemical yield of 56.6 ± 20.1% for [(125)I]1 (n = 4) and 67.5 ± 6.6% for [(18)F]4 (n = 3). [(125)I]1 exhibited favorable biodistribution characteristics in normal mice, with rapid clearance from the blood and elimination via the hepatobiliary system by 4 h after injection. The uptake of [(125)I]1 in tumor cells positive for IDH1-R132H was significantly higher compared to isogenic WT-IDH1 controls, with a maximal uptake ratio of 1.67 at 3 h post injection. Co-incubation of the labeled inhibitors with the corresponding nonradioactive analogs, and decreasing the normal concentrations of FBS (10%) in the incubation media substantially increased the uptake of the labeled inhibitors in both the IDH1-mutant and WT-IDH1 tumor cell lines, suggesting significant non-specific binding of the synthesized labeled butyl-phenyl sulfonamide inhibitors. CONCLUSIONS: These data demonstrate the feasibility of developing radiolabeled probes for the mutant IDH1 enzyme based on enzyme inhibitors. Further optimization of the labeled inhibitors by modifying the chemical structure to decrease the lipophilicity and to increase potency may yield compounds with improved characteristics as probes for imaging mutant IDH1 expression in tumors.

Mapping 2-D defects in a conductive half-space by eigenfunction expansions in K-space of Fourier-Laplace transforms

info:eu-repo/semantics/published

The Euroregional discourse. Increasing evidence towards legitimizing an institutional space

From a multilingual corpus composed of institutional websites published by the Euroregions, this article attempts to explore the discursive indications which tend to legitimize the notion of Euroregional space. The lexicometric and qualitative observations lead to a compliance to the normative objectives of the European politics and to the standardization of the euroregional representations, in spite of languages and issuing cross-border areas.

Hopf hypersurfaces in pseudo-Riemannian complex and para-complex space forms

The study of real hypersurfaces in pseudo-Riemannian complex space forms and para-complex space forms, which are the pseudo-Riemannian generalizations of the complex space forms, is addressed. It is proved that there are no umbilic hypersurfaces, nor real hypersurfaces with parallel shape operator in such spaces. Denoting by J be the complex or para-complex structure of a pseudo-complex or para-complex space form respectively, a non-degenerate hypersurface of such space with unit normal vector field N is said to be Hopf if the tangent vector field JN is a principal direction. It is proved that if a hypersurface is Hopf, then the corresponding principal curvature (the Hopf curvature) is constant. It is also observed that in some cases a Hopf hypersurface must be, locally, a tube over a complex (or para-complex) submanifold, thus generalizing previous results of Cecil, Ryan and Montiel.

Case base adaptation using solution-space metrics

In this paper we propose a generalisation of the k-nearest neighbour (k-NN) retrieval method based on an error function using distance metrics in the solution and problem space. It is an interpolative method which is proposed to be effective for sparse case bases. The method applies equally to nominal, continuous and mixed domains, and does not depend upon an embedding n-dimensional space. In continuous Euclidean problem domains, the method is shown to be a generalisation of the Shepard's Interpolation method. We term the retrieval algorithm the Generalised Shepard Nearest Neighbour (GSNN) method. A novel aspect of GSNN is that it provides a general method for interpolation over nominal solution domains. The performance of the retrieval method is examined with reference to the Iris classification problem,and to a simulated sparse nominal value test problem. The introducion of a solution-space metric is shown to out-perform conventional nearest neighbours methods on sparse case bases.

Case base reduction using solution-space metrics

In this paper we propose a case base reduction technique which uses a metric defined on the solution space. The technique utilises the Generalised Shepard Nearest Neighbour (GSNN) algorithm to estimate nominal or real valued solutions in case bases with solution space metrics. An overview of GSNN and a generalised reduction technique, which subsumes some existing decremental methods, such as the Shrink algorithm, are presented. The reduction technique is given for case bases in terms of a measure of the importance of each case to the predictive power of the case base. A trial test is performed on two case bases of different kinds, with several metrics proposed in the solution space. The tests show that GSNN can out-perform standard nearest neighbour methods on this set. Further test results show that a caseremoval order proposed based on a GSNN error function can produce a sparse case base with good predictive power.