Representing archaeological uncertainty in cultural informatics

This thesis sets out to explore, describe, quantify, and visualise uncertainty in a cultural informatics context, with a focus on archaeological reconstructions. For quite some time, archaeologists and heritage experts have been criticising the often toorealistic appearance of three-dimensional reconstructions. They have been highlighting one of the unique features of archaeology: the information we have on our heritage will always be incomplete. This incompleteness should be reflected in digitised reconstructions of the past. This criticism is the driving force behind this thesis. The research examines archaeological theory and inferential process and provides insight into computer visualisation. It describes how these two areas, of archaeology and computer graphics, have formed a useful, but often tumultuous, relationship through the years. By examining the uncertainty background of disciplines such as GIS, medicine, and law, the thesis postulates that archaeological visualisation, in order to mature, must move towards archaeological knowledge visualisation. Three sequential areas are proposed through this thesis for the initial exploration of archaeological uncertainty: identification, quantification and modelling. The main contributions of the thesis lie in those three areas. Firstly, through the innovative design, distribution, and analysis of a questionnaire, the thesis identifies the importance of uncertainty in archaeological interpretation and discovers potential preferences among different evidence types. Secondly, the thesis uniquely analyses and evaluates, in relation to archaeological uncertainty, three different belief quantification models. The varying ways that these mathematical models work, are also evaluated through simulated experiments. Comparison of results indicates significant convergence between the models. Thirdly, a novel approach to archaeological uncertainty and evidence conflict visualisation is presented, influenced by information visualisation schemes. Lastly, suggestions for future semantic extensions to this research are presented through the design and development of new plugins to a search engine

Towards The Development of Biobetter Therapeutic Whole Antibodies

The development of therapeutic antibodies has been revolutionary in the pharmaceutical industry due to the specificity of antibodies to a biological target and their ability to elicit a response that engages the immunological destruction of the target. As with all biologic pharmaceuticals, active antibody is lost in downstream production processes and long term storage due to intrinsic instability causing degradation and aggregation. Pharmaceutical formulations currently adopt an approach to reduce loss in aggregation through lyophilised product to be reconstituted only when in use, to large volumes appropriate for intravenous, or in some instances sub-cutaneous administration. This project explores avenues of identifying regions in the peptide structure of a model antibody (Trastuzumab) from which to improve intrinsic stability and improve affinity to its target. As many therapeutic antibody peptide structures have homologous constant regions, Adalimumab was used to show transferability and proof of concept with the modifications specific to improving antibody stability. Sites for modification were derived through in silico analysis of the crystal structures of antibody fragments. Trastuzumab and Adalimumab genes were cloned into suitable vectors to produce an optimised laboratory scale expression system. The modifications derived from in silico analysis were translated to Trastuzumab and Adalimumab through site directed mutagenesis. The mutant libraries were expressed for testing in vitro for stability and binding kinetics against their biological targets HER-2/TNF-a and Fcγ receptors. Our findings show that several of our rationally designed peptide modifications showed improvement in their targeted effect, and that can be translated to improving production and formulation strategies, as well as better treatment outcomes

Phishing and Cybercrime Risks in a University Student Community

In an exploratory quasi-experimental observational study, 138 participants recruited during a university orientation week were exposed to social engineering directives in the form of fake email or phishing attacks over several months in 2017. These email attacks attempted to elicit personal information from participants or entice them into clicking links which may have been compromised in a real-world setting. The study aimed to determine the risks of cybercrime for students by observing their responses to social engineering and exploring attitudes to cybercrime risks before and after the phishing phase. Three types of scam emails were distributed that varied in the degree of individualization: generic, tailored, and targeted or ‘spear.’ To differentiate participants on the basis of cybercrime awareness, participants in a ‘Hunter’ condition were primed throughout the study to remain vigilant to all scams, while participants in a ‘Passive’ condition received no such instruction. The study explored the influence of scam type, cybercrime awareness, gender, IT competence, and perceived Internet safety on susceptibility to email scams. Contrary to the hypotheses, none of these factors were associated with scam susceptibility. Although, tailored and individually crafted email scams were more likely to induce engagement than generic scams. Analysis of all the variables showed that international students and first year students were deceived by significantly more scams than domestic students and later year students. A Generalized Linear Model (GLM) analysis was undertaken to further explore the role of all the variables of interest and the results were consistent with the descriptive findings showing that student status (domestic compared to international) and year of study (first year student compared to students in second, third and later years of study) had a higher association to the risk of scam deception. Implications and future research directions are discussed

Phishing and Cybercrime Risks in a University Student Community

In an exploratory quasi-experimental observational study, 138 participants recruited during a university orientation week were exposed to social engineering directives in the form of fake email or phishing attacks over several months in 2017. These email attacks attempted to elicit personal information from participants or entice them into clicking links which may have been compromised in a real-world setting. The study aimed to determine the risks of cybercrime for students by observing their responses to social engineering and exploring attitudes to cybercrime risks before and after the phishing phase. Three types of scam emails were distributed that varied in the degree of individualization: generic, tailored, and targeted or ‘spear.’ To differentiate participants on the basis of cybercrime awareness, participants in a ‘Hunter’ condition were primed throughout the study to remain vigilant to all scams, while participants in a ‘Passive’ condition received no such instruction. The study explored the influence of scam type, cybercrime awareness, gender, IT competence, and perceived Internet safety on susceptibility to email scams. Contrary to the hypotheses, none of these factors were associated with scam susceptibility. Although, tailored and individually crafted email scams were more likely to induce engagement than generic scams. Analysis of all the variables showed that international students and first year students were deceived by significantly more scams than domestic students and later year students. A Generalized Linear Model (GLM) analysis was undertaken to further explore the role of all the variables of interest and the results were consistent with the descriptive findings showing that student status (domestic compared to international) and year of study (first year student compared to students in second, third and later years of study) had a higher association to the risk of scam deception. Implications and future research directions are discussed

Uncertainty in archaeological reconstructions: A 3D gaming approach

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Uncertainty in archaeological reconstructions: A 3D gaming approach

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Current advancements in addressing key challenges of therapeutic antibody design, manufacture, and formulation

Therapeutic antibody technology heavily dominates the biologics market and continues to present as a significant industrial interest in developing novel and improved antibody treatment strategies. Many noteworthy advancements in the last decades have propelled the success of antibody development; however, there are still opportunities for improvement. In considering such interest to develop antibody therapies, this review summarizes the array of challenges and considerations faced in the design, manufacture, and formulation of therapeutic antibodies, such as stability, bioavailability and immunological engagement. We discuss the advancement of technologies that address these challenges, highlighting key antibody engineered formats that have been adapted. Furthermore, we examine the implication of novel formulation technologies such as nanocarrier delivery systems for the potential to formulate for pulmonary delivery. Finally, we comprehensively discuss developments in computational approaches for the strategic design of antibodies with modulated functions

ARCO - Augmented Representation for Cultural Objects.

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Virtual reality applications for digital heritage: from multimodal interfaces to interactive environments

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Laboratory scale production and purification of a therapeutic antibody

Ensuring the successful production of a therapeutic antibody begins early on in the development process. The first stage is vector expression of the antibody genes followed by stable transfection into a suitable cell line. The stable clones are subjected to screening in order to select those clones with desired production and growth characteristics. This is a critical albeit time-consuming step in the process. This protocol considers vector selection and sourcing of antibody sequences for the expression of a therapeutic antibody. The methods describe preparation of vector DNA for stable transfection of a suspension variant of human embryonic kidney 293 (HEK-293) cell line, using polyethylenimine (PEI). The cells are transfected as adherent cells in serum-containing media to maximize transfection efficiency, and afterwards adapted to serum-free conditions. Large scale production, setup as batch overgrow cultures is used to yield antibody protein that is purified by affinity chromatography using an automated fast protein liquid chromatography (FPLC) instrument. The antibody yields produced by this method can provide sufficient protein to begin initial characterization of the antibody. This may include in vitro assay development or physicochemical characterization to aid in the time-consuming task of clonal screening for lead candidates. This method can be transferable to the development of an expression system for the production of biosimilar antibodies