Paternalism and Competent Patient Choice in the Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People

In 2016 physicians in Ontario will be granted the authority to refer patients with gender dysphoria for sex reassignment surgery. In order to be granted this authority physicians must be trained in the World Professional Association for Transgender Health’s Standards of Care, which outlines healthcare procedures for the treatment of gender dysphoria and provides background information concerning transgender health. The Standards of Care require that patients undergo a process of 12 months of continuous living in a gender role that is congruent with their gender identity prior to being given access to sex reassignment surgery. While this requirement can sometimes be helpful it can also cause more harm than benefit. This paper argues that the requirement is strongly paternalistic in its current form and should no longer be mandatory in most cases.

The evolution of lactase persistence in Europe. A synthesis of archaeological and genetic evidence

Lactase persistence, the ability to digest the milk sugar lactose in adulthood, is highly associated with a T allele situated 13,910 bp upstream from the actual lactase gene in Europeans. The frequency of this allele rose rapidly in Europe after transition from hunter–gatherer to agriculturalist lifestyles and the introduction of milkable domestic species from Anatolia some 8000 years ago. Here we first introduce the archaeological and historic background of early farming life in Europe, then summarize what is known of the physiological and genetic mechanisms of lactase persistence. Finally, we compile the evidence for a co-evolutionary process between dairying culture and lactase persistence. We describe the different hypotheses on how this allele spread over Europe and the main evolutionary forces shaping this process. We also summarize three different computer simulation approaches, which offer a means of developing a coherent and integrated understanding of the process of spread of lactase persistence and dairying.

Correlation between anxiety and academic self-concept in interpreter trainees

This paper focuses on two basic issues: the anxiety-generating nature of the interpreting task and the relevance of interpreter trainees’ academic self-concept. The first has already been acknowledged, although not extensively researched, in several papers, and the second has only been mentioned briefly in interpreting literature. This study seeks to examine the relationship between the anxiety and academic self-concept constructs among interpreter trainees. An adapted version of the Foreign Language Anxiety Scale (Horwitz et al., 1986), the Academic Autoconcept Scale (Schmidt, Messoulam & Molina, 2008) and a background information questionnaire were used to collect data. Students’ t-Test analysis results indicated that female students reported experiencing significantly higher levels of anxiety than male students. No significant gender difference in self-concept levels was found. Correlation analysis results suggested, on the one hand, that younger would-be interpreters suffered from higher anxiety levels and students with higher marks tended to have lower anxiety levels; and, on the other hand, that younger students had lower self-concept levels and higher-ability students held higher self-concept levels. In addition, the results revealed that students with higher anxiety levels tended to have lower self-concept levels. Based on these findings, recommendations for interpreting pedagogy are discussed.

Settlement Duration and Materiality:Formal Chronological Models for the Development of Barnhouse, a Grooved Ware Settlement in Orkney

Radiocarbon dating and Bayesian chronological modelling, undertaken as part of the investigation by the Times of Their Lives project into the development of Late Neolithic settlement and pottery in Orkney, has provided precise new dating for the Grooved Ware settlement of Barnhouse, excavated in 1985–91. Previous understandings of the site and its pottery are presented. A Bayesian model based on 70 measurements on 62 samples (of which 50 samples are thought to date accurately the deposits from which they were recovered) suggests that the settlement probably began in the later 32nd century cal bc (with Houses 2, 9, 3 and perhaps 5a), possibly as a planned foundation. Structure 8 – a large, monumental structure that differs in character from the houses – was probably built just after the turn of the millennium. Varied house durations and replacements are estimated. House 2 went out of use before the end of the settlement, and Structure 8 was probably the last element to be abandoned, probably during the earlier 29th century cal bc. The Grooved Ware pottery from the site is characterised by small, medium-sized, and large vessels with incised and impressed decoration, including a distinctive, false-relief, wavy-line cordon motif. A considerable degree of consistency is apparent in many aspects of ceramic design and manufacture over the use-life of the settlement, the principal change being the appearance, from c. 3025–2975 cal bc, of large coarse ware vessels with uneven surfaces and thick applied cordons, and of the use of applied dimpled circular pellets. The circumstances of new foundation of settlement in the western part of Mainland are discussed, as well as the maintenance and character of the site. The pottery from the site is among the earliest Grooved Ware so far dated. Its wider connections are noted, as well as the significant implications for our understanding of the timing and circumstances of the emergence of Grooved Ware, and the role of material culture in social strategies.

Situation Background Assessment Recommendation (SBAR): Undergraduate Perspectives

Situation Background Assessment and Recommendation (SBAR): Undergraduate Perspectives C Morgan, L Adams, J Murray, R Dunlop, IK Walsh. Ian K Walsh, Centre for Medical Education, Queen’s University Belfast, Mulhouse Building, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6DP Background and Purpose: Structured communication tools are used to improve team communication quality.1,2 The Situation Background Assessment and Recommendation (SBAR) tool is widely adopted within patient safety.3 SBAR effectiveness is reportedly equivocal, suggesting use is not sustained beyond initial training.4-6 Understanding perspectives of those using SBAR may further improve clinical communication. We investigated senior medical undergraduate perspectives on SBAR, particularly when communicating with senior colleagues. Methodology: Mixed methods data collection was used. A previously piloted questionnaire with 12 five point Lickert scale questions and 3 open questions was given to all final year medical students. A subgroup also participated in 10 focus groups, deploying strictly structured audio-recorded questions. Selection was by convenience sampling, data gathered by open text questions and comments transcribed verbatim. In-vivo coding (iterative, towards data saturation) preceded thematic analysis. Results: 233 of 255 students (91%) completed the survey. 1. There were clearly contradictory viewpoints on SBAR usage. A recurrent theme was a desire for formal feedback and a relative lack of practice/experience with SBAR. 2. Students reported SBAR as having variable interpretation between individuals; limiting use as a shared mental model. 3. Brief training sessions are insufficient to embed the tool. 4. Most students reported SBAR helping effective communication, especially by providing structure in stressful situations. 5. Only 18.5% of students felt an alternative resource might be needed. Sub analysis of the themes highlighted: A. Lack of clarity regarding what information to include and information placement within the acronym, B. Senior colleague negative response to SBAR C. Lack of conciseness with the tool. Discussion and Conclusions: Despite a wide range of contradictory interpretation of SBAR utility, most students wish to retain the resource. More practice opportunities/feedback may enhance user confidence and understanding. References: (1) Leonard M, Graham S, Bonacum D. The human factor: the critical importance of effective teamwork and communication in providing safe care. Quality & Safety in Health Care 2004 Oct;13(Suppl 1):85-90. (2) d'Agincourt-Canning LG, Kissoon N, Singal M, Pitfield AF. Culture, communication and safety: lessons from the airline industry. Indian J Pediatr 2011 Jun;78(6):703-708. (3) Dunsford J. Structured communication: improving patient safety with SBAR. Nurs Womens Health 2009 Oct;13(5):384-390. (4) Compton J, Copeland K, Flanders S, Cassity C, Spetman M, Xiao Y, et al. Implementing SBAR across a large multihospital health system. Jt Comm J Qual Patient Saf 2012 Jun;38(6):261-268. (5) Ludikhuize J, de Jonge E, Goossens A. Measuring adherence among nurses one year after training in applying the Modified Early Warning Score and Situation-Background-Assessment-Recommendation instruments. Resuscitation 2011 Nov;82(11):1428-1433. (6) Cunningham NJ, Weiland TJ, van Dijk J, Paddle P, Shilkofski N, Cunningham NY. Telephone referrals by junior doctors: a randomised controlled trial assessing the impact of SBAR in a simulated setting. Postgrad Med J 2012 Nov;88(1045):619-626.

New methods for movement technique development in cross-country skiing using mathematical models and simulation

This Licentiate Thesis is devoted to the presentation and discussion of some new contributions in applied mathematics directed towards scientific computing in sports engineering. It considers inverse problems of biomechanical simulations with rigid body musculoskeletal systems especially in cross-country skiing. This is a contrast to the main research on cross-country skiing biomechanics, which is based mainly on experimental testing alone. The thesis consists of an introduction and five papers. The introduction motivates the context of the papers and puts them into a more general framework. Two papers (D and E) consider studies of real questions in cross-country skiing, which are modelled and simulated. The results give some interesting indications, concerning these challenging questions, which can be used as a basis for further research. However, the measurements are not accurate enough to give the final answers. Paper C is a simulation study which is more extensive than paper D and E, and is compared to electromyography measurements in the literature. Validation in biomechanical simulations is difficult and reducing mathematical errors is one way of reaching closer to more realistic results. Paper A examines well-posedness for forward dynamics with full muscle dynamics. Moreover, paper B is a technical report which describes the problem formulation and mathematical models and simulation from paper A in more detail. Our new modelling together with the simulations enable new possibilities. This is similar to simulations of applications in other engineering fields, and need in the same way be handled with care in order to achieve reliable results. The results in this thesis indicate that it can be very useful to use mathematical modelling and numerical simulations when describing cross-country skiing biomechanics. Hence, this thesis contributes to the possibility of beginning to use and develop such modelling and simulation techniques also in this context.

Stressful Life Events and their Trajectories among Midlife Women: Observations from the Seattle Midlife Women's Health Study

Thesis (Ph.D.)--University of Washington, 2016-08

Ferulates and lignin structural composition in cork

The structure of lignin and suberin, and ferulic acid (FA) content in cork from Quercus suber L. were studied. Extractive-free cork (Cork), suberin, desuberized cork (Cork(sap)), and milled-cork lignins (MCL) from Cork and Cork(sap) were isolated. Suberin composition was determined by GC-MS/FID, whereas the polymers structure in Cork, Corksap, and MCL was studied by Py-TMAH and 2D-HSQC-NMR. Suberin contained 94.4% of aliphatics and 3.2% of phenolics, with 90% of omega-hydroxyacids and alpha,omega-diacids. FA represented 2.7% of the suberin monomers, overwhelmingly esterified to the cork matrix. Py-TMAH revealed significant FA amounts in all samples, with about 3% and 6% in cork and cork lignins, respectively. Py-TMAH and 2D-HSQC-NMR demonstrated that cork lignin is a G-lignin (>96% G units), with a structure dominated by beta-O-4' alkyl-aryl ether linkages (80% and 77% of all linkages in MCL and MCLsap, respectively), followed by phenylcoumarans (18% and 20% in MCL and MCLsap, respectively), and smaller amounts of resinols (ca. 2%) and dibenzodioxocins (1%). HSQC also revealed that cork lignin is heavily acylated (ca. 50%) exclusively at the side-chain gamma-position. Ferulates possibly have an important function in the chemical assembly of cork cell walls with a cross-linking role between suberin, lignin and carbohydrates.

Towards guidelines for curriculum design and development in English language teacher education in Cambodian higher education institutions

In the current Cambodian higher education sector, there is little regulation of standards in curriculum design of undergraduate degrees in English language teacher education. The researcher, in the course of his professional work in the Curriculum and Policy Office at the Department of Higher Education, has seen evidence that most universities tend to copy their curriculum from one source, the curriculum of the Institute of Foreign Languages, the Royal University of Phnom Penh. Their programs fail to impose any entry standards, accepting students who pass the high school exam without any entrance examination. It is possible for a student to enter university with satisfactory scores in all subjects but English. Therefore, not many graduates are able to fulfil the professional requirements of the roles they are supposed to take. Neau (2010) claims that many Cambodian EFL teachers do not reach a high performance standard due to their low English language proficiency and poor background in teacher education. The main purpose of this study is to establish key guidelines for developing curricula for English language teacher education for all the universities across the country. It examines the content of the Bachelor‘s degree of Education in Teaching English as a Foreign Language (B Ed in TEFL) and Bachelor‘s degree of Arts in Teaching English to Speakers of Other Languages (BA in TESOL) curricula adopted in Cambodian universities on the basis of criteria proposed in current curriculum research. It also investigates the perspectives of Cambodian EFL teachers on the areas of knowledge and skill they need in order to perform their English teaching duties in Cambodia today. The areas of knowledge and skill offered in the current curricula at Cambodian higher education institutions (HEIs), the framework of the knowledge base for EFL teacher education and general higher education, and the areas of knowledge and skill Cambodian EFL teachers perceive to be important, are compared so as to identify any gaps in the current English language teacher education curricula in the Cambodian HEIs. The existence of gaps show what domains of knowledge and skill need to be included in the English language teacher education curricula at Cambodian HEIs. These domains are those identified by previous curriculum researchers in both general and English language teacher education at tertiary level. Therefore, the present study provides useful insights into the importance of including appropriate content in English language teacher education curricula. Mixed methods are employed in this study. The course syllabi and the descriptions within the curricula in five Cambodian HEIs are analysed qualitatively based on the framework of knowledge and skills for EFL teachers, which is formed by looking at the knowledge base for second language teachers suggested by the methodologists and curriculum specialists whose work is elaborated on the review of literature. A quantitative method is applied to analyse the perspectives of 120 Cambodian EFL teachers on areas of knowledge and skills they should possess. The fieldwork was conducted between June and August, 2014. The analysis reveals that the following areas are included in the curricula at the five universities: communication skills, general knowledge, knowledge of teaching theories, teaching skills, pedagogical reasoning and decision making skills, subject matter knowledge, contextual knowledge, cognitive abilities, and knowledge of social issues. Additionally, research skills are included in three curricula while society and community involvement is in only one. Further, information and communication technology, which is outlined in the Education Strategies Plan (2006-2010), forms part of four curricula while leadership skills form part of two. This study demonstrates ultimately that most domains that are directly and indirectly related to language teaching competence are not sufficiently represented in the current curricula. On the basis of its findings, the study concludes with a set of guidelines that should inform the design and development of TESOL and TEFL curricula in Cambodia.

Controlling Nanostructures for in-situ TEM Characterization

Low dimensional nanostructures, such as nanotubes and 2D sheets, have unique and promising material properties both from a fundamental science and an application standpoint. Theoretical modelling and calculations predict previously unobserved phenomena that experimental scientists often struggle to reproduce because of the difficulty in controlling and characterizing the small structures under real-world constraints. The goal of this dissertation is to controlling these structures so that nanostructures can be characterized in-situ in transmission electron microscopes (TEM) allowing for direct observation of the actual physical responses of the materials to different stimuli. Of most interest to this work are the thermal and electrical properties of carbon nanotubes, boron nitride nanotubes, and graphene. The first topic of the dissertation is using surfactants for aqueous processing to fabricate, store, and deposit the nanostructures. More specifically, thorough characterization of a new surfactant, ammonium laurate (AL), is provided and shows that this new surfactant outperforms the standard surfactant for these materials, sodium dodecyl sulfate (SDS), in almost all tested metrics. New experimental set-ups have been developed by combining specialized in-situ TEM holders with innovative device fabrication. For example, electrical characterization of graphene was performed by using an STM-TEM holder and depositing graphene from aqueous solutions onto lithographically patterned, electron transparent silicon nitride membranes. These experiments produce exciting information about the interaction between graphene and metal probes and the substrate that it rests on. Then, by adding indium to the backside of the membrane and employing the electron thermal microscopy (EThM) technique, the same type of graphene samples could be characterized for thermal transport with high spatial resolution. It is found that reduced graphene oxide sheets deposited onto a silicon nitride membrane and displaying high levels of wrinkling have higher than expected electrical and thermal conduction properties. We are clearly able to visualize the ability of graphene to spread heat away from an electronic hot spot and into the substrate.

The Scots in Ireland: culture, colonialism and memory, 1315-1826

This thesis examines three key moments in the intersecting histories of Scotland, Ireland and England, and their impact on literature. Chapter one Robert Bruce and the Last King of Ireland: Writing the Irish Invasion, 1315- 1826‘, is split into two parts. Part one, Barbour‘s (other) Bruce‘ focuses on John Barbour‘s The Bruce (1375) and its depiction of the Bruce‘s Irish campaign (1315-1318). It first examines the invasion material from the perspective of the existing Irish and Scottish relationship and their opposition to English authority. It highlights possible political and ideological motivations behind Barbour‘s negative portrait of Edward Bruce - whom Barbour presents as the catalyst for the invasion and the source of its carnage and ultimate failure - and his partisan comparison between Edward and his brother Robert I. It also probes the socio-polticial and ideological background to the Bruce and its depiction of the Irish campaign, in addition to Edward and Robert. It peers behind some of the Bruce‘s most lauded themes such as chivalry, heroism, loyalty, and patriotism, and exposes its militaristic feudal ideology, its propaganda rich rhetoric, and its illusions of freedom‘. Part one concludes with an examination of two of the Irish section‘s most marginalised figures, the Irish and a laundry woman. Part two, Cultural Memories of the Bruce Invasion of Ireland, 1375-1826‘, examines the cultural memory of the Bruce invasion in three literary works from the Medieval, Early Modern and Romantic periods. The first, and by far the most significant memorialisation of the invasion is Barbour‘s Bruce, which is positioned for the first time within the tradition of ars memoriae (art of memory) and present-day cultural memory theories. The Bruce is evaluated as a site of memory and Barbour‘s methods are compared with Icelandic literature of the same period. The recall of the invasion in late sixteenth century Anglo-Irish literature is then considered, specifically Edmund Spenser‘s A View of the State of Ireland, which is viewed in the context of contemporary Ulster politics. The final text to be considered is William Hamilton Drummond‘s Bruce’s Invasion of Ireland (1826). It is argued that Drummond‘s poem offers an alternative Irish version of the invasion; a counter-memory that responds to nineteenth-century British politics, in addition to the controversy surrounding the publication of the Ossian fragments. Chapter two, The Scots in Ulster: Policies, Proposals and Projects, 1551-1575‘, examines the struggle between Irish and Scottish Gaels and the English for dominance in north Ulster, and its impact on England‘s wider colonial ideology, strategy, literature and life writing. Part one entitled Noisy neighbours, 1551-1567‘ covers the deputyships of Sir James Croft, Sir Thomas Radcliffe, and Sir Henry Sidney, and examines English colonial writing during a crucial period when the Scots provoked an increase in militarisation in the region. Part two Devices, Advices, and Descriptions, 1567-1575‘, deals with the relationship between the Scots and Turlough O‘Neill, the influence of the 5th Earl of Argyll, and the rise of Sorley Boy MacDonnell. It proposes that a renewed Gaelic alliance hindered England‘s conquest of Ireland and generated numerous plantation proposals and projects for Ulster. Many of which exhibit a blurring‘ between the documentary and the literary; while all attest to the considerable impact of the Gaelic Scots in both motivating and frustrating various projects for that province, the most prominent of which were undertaken by Sir Thomas Smith in 1571 and Walter Devereux, 1st Earl of Essex in 1573.

The interplay between tectonics, sediment dynamics and gateways evolution in the Danube system from the Pannonian Basin to the western Black Sea

Understanding the natural evolution of a river–delta–sea system is important to develop a strong scientific basis for efficient integrated management plans. The distribution of sediment fluxes is linked with the natural connection between sediment source areas situated in uplifting mountain chains and deposition in plains, deltas and, ultimately, in the capturing oceans and seas. The Danube River–western Black Sea is one of the most active European systems in terms of sediment re-distribution that poses significant societal challenges. We aim to derive the tectonic and sedimentological background of human-induced changes in this system and discuss their interplay. This is obtained by analysing the tectonic and associated vertical movements, the evolution of relevant basins and the key events affecting sediment routing and deposition. The analysis of the main source and sink areas is focused in particular on the Miocene evolution of the Carpatho-Balkanides, Dinarides and their sedimentary basins including the western Black Sea. The vertical movements of mountains chains created the main moments of basin connectivity observed in the Danube system. Their timing and effects are observed in sediments deposited in the vicinity of gateways, such as the transition between the Pannonian/Transylvanian and Dacian basins and between the Dacian Basin and western Black Sea. The results demonstrate the importance of understanding threshold conditions driving rapid basins connectivity changes superposed over the longer time scale of tectonic-induced vertical movements associated with background erosion and sedimentation. The spatial and temporal scale of such processes is contrastingly different and challenging. The long-term patterns interact with recent or anthropogenic induced modifications in the natural system and may result in rapid changes at threshold conditions that can be quantified and predicted. Their understanding is critical because of frequent occurrence during orogenic evolution, as commonly observed in the Mediterranean area and discussed elsewhere.

Grain coarsening in contact metamorphic carbonates: effects of second-phase particles, fluid flow and thermal perturbations

Under contact metamorphic conditions, carbonate rocks in the direct vicinity of the Adamello pluton reflect a temperature-induced grain coarsening. Despite this large-scale trend, a considerable grain size scatter occurs on the outcrop-scale indicating local influence of second-order effects such as thermal perturbations, fluid flow and second-phase particles. Second-phase particles, whose sizes range from nano- to the micron-scale, induce the most pronounced data scatter resulting in grain sizes too small by up to a factor of 10, compared with theoretical grain growth in a pure system. Such values are restricted to relatively impure samples consisting of up to 10 vol.% micron-scale second-phase particles, or to samples containing a large number of nano-scale particles. The obtained data set suggests that the second phases induce a temperature-controlled reduction on calcite grain growth. The mean calcite grain size can therefore be expressed in the form D 1⁄4 C2 eQ*/RT(dp/fp)m*, where C2 is a constant, Q* is an activation energy, T the temperature and m* the exponent of the ratio dp/fp, i.e. of the average size of the second phases divided by their volume fraction. However, more data are needed to obtain reliable values for C2 and Q*. Besides variations in the average grain size, the presence of second-phase particles generates crystal size distribution (CSD) shapes characterized by lognormal distributions, which differ from the Gaussian-type distributions of the pure samples. In contrast, fluid-enhanced grain growth does not change the shape of the CSDs, but due to enhanced transport properties, the average grain sizes increase by a factor of 2 and the variance of the distribution increases. Stable d18O and d13C isotope ratios in fluid-affected zones only deviate slightly from the host rock values, suggesting low fluid/rock ratios. Grain growth modelling indicates that the fluid-induced grain size variations can develop within several ka. As inferred from a combination of thermal and grain growth modelling, dykes with widths of up to 1 m have only a restricted influence on grain size deviations smaller than a factor of 1.1.To summarize, considerable grain size variations of up to one order of magnitude can locally result from second-order effects. Such effects require special attention when comparing experimentally derived grain growth kinetics with field studies.

Components and circuits for tunneling diode based high frequency sources

Terahertz (THz) technology has been generating a lot of interest because of the potential applications for systems working in this frequency range. However, to fully achieve this potential, effective and efficient ways of generating controlled signals in the terahertz range are required. Devices that exhibit negative differential resistance (NDR) in a region of their current-voltage (I-V ) characteristics have been used in circuits for the generation of radio frequency signals. Of all of these NDR devices, resonant tunneling diode (RTD) oscillators, with their ability to oscillate in the THz range are considered as one of the most promising solid-state sources for terahertz signal generation at room temperature. There are however limitations and challenges with these devices, from inherent low output power usually in the range of micro-watts (uW) for RTD oscillators when milli-watts (mW) are desired. At device level, parasitic oscillations caused by the biasing line inductance when the device is biased in the NDR region prevent accurate device characterisation, which in turn prevents device modelling for computer simulations. This thesis describes work on I-V characterisation of tunnel diode (TD) and RTD (fabricated by Dr. Jue Wang) devices, and the radio frequency (RF) characterisation and small signal modelling of RTDs. The thesis also describes the design and measurement of hybrid TD oscillators for higher output power and the design and measurement of a planar Yagi antenna (fabricated by Khalid Alharbi) for THz applications. To enable oscillation free current-voltage characterisation of tunnel diodes, a commonly employed method is the use of a suitable resistor connected across the device to make the total differential resistance in the NDR region positive. However, this approach is not without problems as the value of the resistor has to satisfy certain conditions or else bias oscillations would still be present in the NDR region of the measured I-V characteristics. This method is difficult to use for RTDs which are fabricated on wafer due to the discrepancies in designed and actual resistance values of fabricated resistors using thin film technology. In this work, using pulsed DC rather than static DC measurements during device characterisation were shown to give accurate characteristics in the NDR region without the need for a stabilisation resistor. This approach allows for direct oscillation free characterisation for devices. Experimental results show that the I-V characterisation of tunnel diodes and RTD devices free of bias oscillations in the NDR region can be made. In this work, a new power-combining topology to address the limitations of low output power of TD and RTD oscillators is presented. The design employs the use of two oscillators biased separately, but with the combined output power from both collected at a single load. Compared to previous approaches, this method keeps the frequency of oscillation of the combined oscillators the same as for one of the oscillators. Experimental results with a hybrid circuit using two tunnel diode oscillators compared with a single oscillator design with similar values shows that the coupled oscillators produce double the output RF power of the single oscillator. This topology can be scaled for higher (up to terahertz) frequencies in the future by using RTD oscillators. Finally, a broadband Yagi antenna suitable for wireless communication at terahertz frequencies is presented in this thesis. The return loss of the antenna showed that the bandwidth is larger than the measured range (140-220 GHz). A new method was used to characterise the radiation pattern of the antenna in the E-plane. This was carried out on-wafer and the measured radiation pattern showed good agreement with the simulated pattern. In summary, this work makes important contributions to the accurate characterisation and modelling of TDs and RTDs, circuit-based techniques for power combining of high frequency TD or RTD oscillators, and to antennas suitable for on chip integration with high frequency oscillators.

An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.