The permissibility of the practice of inscribing graffiti in Beverley Minster, with specific reference to the eastern side of the reredos

This thesis provides an understanding of the nature of the practice of inscribing graffiti on the eastern side of the reredos in Beverley Minster in the medieval and early modern periods. It focuses on the types of graffiti that were inscribed when the upper platform of the reredos supported the shrine of Saint John of Beverley from c.1330 to 1540. This study shows that in order to interpret the meaning and significance of the graffiti for the individuals who inscribed them, it needs to be placed in a context where writing on walls was accepted and acceptable to both the clergy and the laity. The different categories of graffiti on the eastern side of the reredos are described and examined in detail.A wide range of evidence are employed to provide a holistic interpretation of the rationale behind their inscription. Comparisons with the graffiti surviving in the nave at Beverley Minster; in parish churches situated within the Humber region; and in ecclesiastical buildings from other counties across England are drawn upon to facilitate a synthesis of the graffiti on the eastern side of the reredos. Literary evidence, numismatics and objects recorded by the Portable Antiquities Scheme (PAS) are sources of evidence drawn upon throughout to supplement the lack of contextual information, and to place the practice of inscribing graffiti into a wider religious, social and cultural context. Among the types of graffiti studied are textual inscriptions, crosses, religious symbols, ships, merchants' marks and figures. The different types of graffiti are contextualised in thematic discussions based upon two aspects of religious culture, which show how graffiti can be simultaneously devotional and superstitious. In the process, this study enhances our knowledge of the ways in which individuals interacted with the fabric of church buildings on a physical level

Patterns of Education Financing and Debt: A Comparison of Two Cohorts of Canadian Post-Secondary Graduates

Using data from 1988 and 1992 National Graduates Surveys (conducted by Statistics Canada), this paper explores educational financing and debt patterns for recent graduates of Canadian community college and university programs. A majority of recent post-secondary graduates borrowed to finance their education at some point during their educational programs through the Canada Student Loans Program and/or other sources. The more recent cohort of post-secondary graduates (1990 graduates interviewed in 1992) reported markedly higher debt loads and significantly greater amounts owing two years after graduation, relative to the earlier cohort (of 1986 graduates surveyed in 1988). Multiple regression models are developed and tested to predict the amount of debt (in dollars) owed by graduates approximately two years after completion of their programs. Key explanatory variables of (1) total amount borrowed, (2) university or community college program graduate, (3) number of months not employed between graduation and time of interview, (4) current job temporary or not, and (5) current employment income were all found to be highly significant for the most recent cohort of post-secondary graduates. However, there are important differences in multiple regression results between the two cohorts which are discussed in detail in the paper.En utilisant des données tirées de l'Enquête nationale auprès des diplômés menée par Statistique Canada en 1988 et 1992, l'auteur exam- ine les tendances de divers étudiants récemment diplômés de collèges communautaires et d'universités canadiens par rapport au financement et à la dette liée à leurs études. A une moment ou à un autre pendant leur programme d'études, la majorité de ces étudiants ont eu recours à un prêt pour financier leur études, soit par l'intermédiaire du Programme canadien de prêts aux étudiants, soit d'autres sources. Comparativement à la cohorte d'étudiants postsecondaires de 1986 (sondée en 1988), celle de 1990 (sondée 1992) a déclaré des dettes beaucoup élevées et de plus importantes sommes à rembourser deux ans après l'obtention d'un diplôme. Des méthodes d'analyse par régression multiple ont été élaborées et évaluées en vue de prévoir le total de la dette (exprimée en dollars) devant être remboursée par les étudiants diplômés approxima- tivement deux ans après qu'ils auraient terminé leur programme d'études. La présence de plusieurs variables statistiques clés permet d'expliquer la situation de la plus récente cohorte d'étudiants postsec- ondaires, à savoir: 1) le total des sommes d'argent empruntées; 2) le programme d'études suivi (dans une université ou un collège commu- nautaire); 3) le nombre de mois pendant lequel l'étudiant était sans emploi entre l'obtention de son diplôme et sa première entrevue pour un poste; 4) la permanence ou non de l'emploi actuel de l'étudiant; 5) le revenue d'emploi actuel de l'étudiant. Il existe, cependant, des dif- férences considérables entre les deux cohortes en question sur le plan des résultats obtenus des analyses par régression multiple; ces dif- férences sont explicitées dans l'article

Mechanisms of Zika virus infection and neuropathogenesis

A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain–Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis

The Marmara Sea Gateway since ~16 ky BP: non-catastrophic causes of paleoceanographic events in the Black Sea at 8.4 and 7.15 ky BP

The Late Quaternary history of connection of the Black Sea to the Eastern Mediterranean has been intensely debated. Ryan, Pitman and coworkers advocate two pulses of outflow from the Black Sea to the world ocean at ~16–14.7 ky BP and ~11–10 ky BP. From ~14.7–11 ky BP and from ~10–8.4 ky BP, they suggest that the level of the Black Sea fell to ~ -100 m. At 8.4 ky BP, they further claim that a catastrophic flood occurred in a geological instant, refilling the Black Sea with saline waters from the Mediterranean. In contrast, we continue to gather evidence from seismic profiles and dated cores in the Marmara Sea which demonstrate conclusively that the proposed flood did not occur. Instead, the Black Sea has been at or above the Bosphorus sill depth and flowing into the world ocean unabated since ~10.5 ky BP. This conclusion is based on continuous Holocene water-column stratification (leading to sapropel deposition in the Marmara Sea and the Aegean Sea), proxy indicators of sea-surface salinity, and migration of endemic species across the Bosphorus in both directions whenever appropriate hydrographic conditions existed in the strait. The two pulses of outflow documented by Ryan, Pitman and coworkers find support in our data, and we have modified our earlier interpretations so that these pulses now coincide with the development of mid-shelf deltas: \Delta 2 (16–14.7 ky BP) and \Delta 1 (10.5–9 ky BP) at the southern end of the Bosphorus Strait. However, continued Black Sea outflow after 9 ky BP prevented the northward advection of Mediterranean water and the entry of open-marine species into the Black Sea for more than 1000 years. Sufficient Mediterranean water to change the Sr-isotopic composition of slope and shelf water masses was not available until ~8.4 ky BP (along with the first arrival of many varieties of marine fauna and flora), whereas euryhaline molluscs did not successfully populate the Black Sea shelves until ~7.15 ky BP. Instead of relying on catastrophic events, we recognize a slow, progressive reconnection of the Black Sea to the world ocean, accompanied by significant time lags

Human T Cell Leukemia Virus Type 1 Tax Protein Increases NF-κB Dimer Formation and Antagonizes the Inhibitory Activity of the IκBα Regulatory Protein

AbstractHuman T cell leukemia virus type 1 (HTLV-1) encodes a strong transcriptional transactivator, the Tax protein, that stimulates viral transcription through the long terminal repeat and also stimulates many cellular genes via the activation of host transcription factors. Previous studies have demonstrated that Tax activates NF-κB through binding to the Rel homology domain of NF-κB proteins. Tax was also shown to increase degradation of IκBα resulting in the induction of NF-κB DNA binding activity. We addressed the specificity and function of Tax interaction with members of the NF-κB/IκBα family by using EMSA, protein affinity chromatography, protein–protein crosslinking and co-immunoprecipitation assays. The results of the present study demonstrate that: (1) Tax enhances NF-κB binding to DNA 40- to 100-fold by increasing NF-κB dimer formation which can be detected in the absence of DNA; (2) Tax binds to all NF-κB DNA binding subunitsin vitroand to IκBα; (3) Tax physically associates with IκBαin vivo;and (4) Tax and IκBα have antagonistic effects on NF-κB binding and gene activity. These results suggest that Tax interaction with IκBα interferes with the formation of NF-κB–IκBα complexes and may play a role in targeting IκBα for degradation

Inverse problems in evolutionary biology

In this thesis, we explore three techniques which could be used to increase the efficiency of analyses in evolutionary genetics while still producing reasonably accurate results. The first of these methods improves the efficiency of analyses based on Markov chain Monte Carlo (MCMC) through the application of delayed acceptance sampling, an MCMC method with an additional proposal step in which an acceptance probability is computed from computationally less expensive approximate likelihoods. Rejection at the additional decision step should allow software like SNAPP (``SNP and AFLP Phylogenies") to avoid unnecessary computation of full likelihoods and, therefore, run more efficiently. The second method we discuss combines dynamic programming with classical numerical integration methods to compute likelihoods with respect to continuous trait models on trees. This method assumes explicitly known transition densities, but is efficient and has a relatively fast convergence rate. We apply the method to a threshold model which combines continuous traits with discrete observations. The third method we look at is another dynamic programming integration algorithm, except that this algorithm takes advantage of a basis function approximation of likelihood functions. This method allows for numerical solutions to PDEs to be applied directly and the use of Chebyshev polynomials as the basis functions make the method easy to implement. We apply this method to the computation of the likelihood given a genetic data set generated by diffusion processes

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases