420 research outputs found
An Agent Based Approach To Finding Expertise In The Engineering Design Environment
No full textDuring the engineering design process people need to locate colleagues with knowledge to resolve a problem. As identified by discussions with practicing designers the use of computer based systems that assist users with finding such expertise will become increasingly important. In this paper we discuss the development of an agent based Expertise Finder suitable for use within an engineering design environment. A key feature of our approach is that the Expertise Finder returns both recommended contacts and supporting documentation. The Expertise Finder bases its results on information held within the organisation, for example publications, human resource records, and not on personally compiled CVs or user maintained records. The recommendations are presented to the user with due regard to the social context. The technology used in the exemplar application allows the development of distributed, interchangeable agents that use real time data to find expertise
Approaches to maintaining provenance throughout the additive manufacturing process
No full textThe development of 3D printers has resulted in significant Intellectual Property Right issues. This work presents a model for signing printable 3D objects. The paper initially reviews the security principles of signing of objects in both digital or physical form, and the metrics for assessing signatures. 3D designs are not just a file, but actual physical objects and should be treated identically, to digital documents that have associated intellectual property rights and copyright protection. In this paper we propose a signing methodology intended to resolve issues with the adaptation of rapid prototyping and 3D printing by users both in engineering and the humanities. The proposed digital signing methodology is based on physical signing principles that follow archival principles to maintain accurate records. The new model allows the transition of provenance between digital and physical form
The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity
No full textThe hepatitis C virus (HCV) non-structural NS5A protein has been shown to associate with a variety of cellular signalling proteins. Of particular interest is the observation that a highly conserved C-terminal polyproline motif in NS5A was able to interact with the Src-homology 3 (SH3) domains of the adaptor protein Grb2. As it has previously been shown that specific polyproline motifs can interact with a range of SH3 domains, we investigated whether NS5A was capable of interacting with other SH3 domain-containing proteins. We show here that NS5A interacts with the SH3 domains of members of the Src family of tyrosine kinases: a combination of in vitro binding assays and co-immunoprecipitation experiments revealed an interaction between NS5A and Hck, Lck, Lyn and Fyn, but interestingly not Src itself. Mutational analysis confirmed that the polyproline motif responsible for binding to Grb2 also bound to the SH3 domains of Hck, Lck, Lyn and Fyn. Furthermore, a previously unidentified polyproline motif, adjacent to the first motif, was also able to mediate binding to the SH3 domain of Lyn. Using transient transfections and Huh-7 cells harbouring a persistently replicating subgenomic HCV replicon we demonstrate that NS5A bound to native Src-family kinases in vivo and differentially modulated kinase activity, inhibiting Hck, Lck and Lyn but activating Fyn. Lastly, we show that signalling pathways controlled by Src-family kinases are modulated in replicon cells. We conclude that the interactions between NS5A and Src-family kinases are physiologically relevant and may play a role in either virus replication or pathogenesis
The role of microbial-mediated genotoxicity during pathogenesis
No full textSubmission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01The student, Molly Crowder, accepted the attached license on 2025-04-23 at 09:13.The student, Molly Crowder, submitted this Dissertation for approval on 2025-04-23 at 09:18.This Dissertation was approved for publication on 2025-04-23 at 14:28.DSpace SAF Submission Ingestion Package generated from Vireo submission #21911 on 2025-10-19 at 19:53:48Pathogenic bacteria modulate host cell physiology to generate infection microenvironments suitable for colonization. Several mucosal-associated members of the Proteobacteria phylum produce a genotoxin, cytolethal distending toxin (CDT), which generates double-strand breaks in host cell DNA. Exogenous DNA damage results in changes to host cell functionality as cells attempt to repair DNA and restore homeostasis. Deviance from normal cellular function during DNA damage repair (DDR) can have vast implications on tissue function and renewal. This is especially true for dynamic tissues like the intestinal epithelium, which experiences rapid cellular turnover driven by highly proliferative cells within intestinal crypts, which replace aged cells that routinely shed into the lumen. DDR-mediated alterations to proliferative cell function impact epithelial cell function and the organization of the intestinal epithelial barrier, though the molecular mechanisms involved remain unclear. Our studies reveal that host cell autophagy, an ancient and conserved eukaryotic stress response pathway, is suppressed in cell exposed to Campylobacter jejuni CDT (Cj-CDT) through a previously undescribed p53-proteasome-LC3 axis. Suppression of autophagy in the face of DNA damage alters intestinal epithelial cell function, proteostasis, and response to stresses such as starvation. Moreover, we adopted a 3D organoid model that recapitulates the rapid cellular turnover, morphological organization, and heterogenous cell population of the physiological intestine to facilitate the study of microbial genotoxicity on epithelial barriers. Here, we show that Cj-CDT is associated with altered lineage specification in intestinal organoids, with an increased bias towards secretory lineage differentiation. Our data support the model that CDT-dependent lineage mis-specification occurs by reduction of the transcription factor SNAI1 and results in increased secretion of secretory cell factors. Together, these results suggest a role for CDT in the pathogenesis of CDT-producing bacteria: remodeling of the infection microenvironment at mucosal barriers such that CDT-producing pathogens are better able to colonize harsh epithelial environments
A Future Vision For The Engineering Design Environment: A Future Sociotechnical Scenario
No full textThis paper presents a future vision for the working practices of designers within a manufacturing organisation. By its very nature the engineering design environment is highly distributed in nature and is characterised by a large number of information sources, which together with the designers forms a complex sociotechnical system. In discussions with designers it is apparent that changes are required to this environment to reflect the changes in the design process and organisations. We have developed a scenario that incorporates many of the features requested by designers and managers to improve the design environment. The scenario sets out a route map for the development of technical and social tools that aid the designer
Harmony and discord within the English ‘counter-culture’, 1965-1975, with particular reference to the ‘rock operas’ Hair, Godspell, Tommy and Jesus Christ Superstar
No full textPhDThis thesis considers the discrete, historically-specific theatrical and musical sub-genre of ‘Rock Opera’ as a lens through which to examine the cultural, political and social changes that are widely assumed to have characterised ‘The Sixties’ in Britain. The musical and dramatic texts, creation and production of Hair (1967), Tommy (1969), Godspell (1971), Jesus Christ Superstar (1970) and other neglected ‘Rock Operas’ of the period are analysed. Their great popularity with ‘mainstream’ audiences is considered and contrasted with the overwhelmingly negative and often internally contradictory reaction towards them from the English ‘counter-culture’. This examination offers new insights into both the ‘counter-culture’ and the ‘mainstream’ against which it claimed to define and differentiate itself.
The four ‘Rock Operas’, two of which are based upon Christian scriptures, are considered as narratives of spiritual quest. The relationship between the often controversial quests for re-defined forms of faith and the apparently precipitous ‘secularization’ and ‘de-Christianization’ of British society during the 1960s and 1970s is considered.
The thesis therefore analyses the ‘Rock Operas’ as significant, enlightening prisms through which to view many of the profound societal debates – over ‘faith’ and ‘belief’ in the widest senses, sexuality, the Vietnam war, generational conflict, drugs and ‘spiritual enlightenment’, and race – which were, to some considerable extent, elevated onto the national, political agenda by the activities of the broadly-defined ‘counter-culture’. It considers subsequent representations of the ‘counter-culture’ as the root of a contested but enduring popular legacy of ‘The Sixties' as a period of profound cultural change
Fisher effect in nonlinear STAR framework: some evidence from Asia
No full textThis study tests the presence of the long run Fisher effect in eight Asian economies. Using monthly data and a variety of interest rates, the paper employs a recent nonlinear methodology to capture the long run relationship between the nominal interest rate and the inflation rate. The estimation results on the basis of the new methodology are encouraging and indicate the validity of Fisher effect in almost all the examined economies.Non-linearity, Unit Roots, Cointegration, ADF
Judicial relations between England and the Papacy before the Reformation: an appeal to the Rota, 1511-1514
No full textAn appeal to the Roman Rota launched in 1511 may seem unusual in the reign of Henry VIII because of the Statute of Praemunire, especially when the case involved prelates close to the crown. Two Statutes of Praemunire (1353 and 1393) had forbidden appeal of cases to the pope over royal objections or recognizing papal judicial authority as superior to the king’s. These statutes of Edward III and Richard II respectively had aimed at limiting papal power in England, as did the several fourteenth-century statutes against papal provisions to English benefices. A Writ of Praemunire was available in cases of illicit appeals. However, the Statute and Writ seem to have fallen into disuse by early Tudor times except as a means of exacting payments from clerics. The case discussed in this article shows a dispute being appealed to the Roman Rota early in the reign of Henry VIII, with the king intervening late in the proceedings without employing a Writ of Praemunire. Nothing was said by the king denying the bishops involved the right to appeal to Rome. This suggests that the Statute of Praemunire was revived as a political device to bring down Cardinal Wolsey in 1529, possibly on the advice of his enemies. Then it was used to promote the King’s Great Matter and used soon thereafter to force the English clergy to accept the Royal Supremacy
[Photograph 2012.201.B0997.0247]
No full textPhotograph used for a story in the Oklahoma Times newspaper. Caption: "Mrs. Juanita Owens shows off pictures of her service sons, from left, Christopher, air force; Paul, formerly aer force; Fred, army, and Franced, marine corps.
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