Essays on robust mechanism design

Chapter 1: Under the average common value function, we select almost uniquely the mechanism that gives the seller the largest portion of the true value in the worst situation among all the direct mechanisms that are feasible, ex-post implementable and individually rational. Chapter 2: Strategy-proof, budget balanced, anonymous, envy-free linear mechanisms assign p identical objects to n agents. The efficiency loss is the largest ratio of surplus loss to efficient surplus, over all profiles of non-negative valuations. The smallest efficiency loss is uniquely achieved by the following simple allocation rule: assigns one object to each of the p−1 agents with the highest valuation, a large probability to the agent with the pth highest valuation, and the remaining probability to the agent with the (p+1)th highest valuation. When “envy freeness” is replaced by the weaker condition “voluntary participation”, the optimal mechanism differs only when p is much less than n. Chapter 3: One group is to be selected among a set of agents. Agents have preferences over the size of the group if they are selected; and preferences over size as well as the “stand-outside” option are single-peaked. We take a mechanism design approach and search for group selection mechanisms that are efficient, strategy-proof and individually rational. Two classes of such mechanisms are presented. The proposing mechanism allows agents to either maintain or shrink the group size following a fixed priority, and is characterized by group strategy-proofness. The voting mechanism enlarges the group size in each voting round, and achieves at least half of the maximum group size compatible with individual rationality.

Non-comital women of twelfth-century England: a charter based analysis

This thesis sets out to explore the place and agency of non-comital women in twelfth-century Anglo-Norman England. Until now, broad generalisations have been applied to all aristocratic women based on a long established scholarship on royal and comital women. Non-comital women have been overlooked, mainly because of an assumed lack of suitable sources from this time period. The first aim of this thesis is to demonstrate that there is a sufficient corpus of charters for a study of this social group of women. It is based on a database created from 5545 charters, of which 3046 were issued by non-comital women and men, taken from three case study counties, Oxfordshire, Suffolk and Yorkshire, and is also supported by other government records. This thesis demonstrates that non-comital women had significant social and economic agency in their own person. By means of a detailed analysis of charters and their clauses this thesis argues that scholarship on non-comital women must rethink the framework applied to the study of non-comital women to address the lifecycle as one of continuities and as active agents in a wider public society. Non-comital women’s agency and identity was not only based on land or in widowhood, which has been the one period in their life cycles where scholars have recognised some level of autonomy, and women had agency in all stages of their life cycle. Women’s agency and identity were drawn from and part of a wider framework that included their families, their kin, and broader local political, religious, and social networks. Natal families continued to be important sources of agency and identity to women long after they had married. Part A of the thesis applies modern charter diplomatic analysis methods to the corpus of charters to bring out and explore women’s presence therein. Part B contextualises these findings and explores women’s agency in their families, landholding, the gift-economy, and the wider religious and social networks of which they were a part.

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.

A III-V channel field effect transistor for non-classical CMOS: process optimisation for improved gate stack function

This thesis describes a collection of studies into the electrical response of a III-V MOS stack comprising metal/GaGdO/GaAs layers as a function of fabrication process variables and the findings of those studies. As a result of this work, areas of improvement in the gate process module of a III-V heterostructure MOSFET were identified. Compared to traditional bulk silicon MOSFET design, one featuring a III-V channel heterostructure with a high-dielectric-constant oxide as the gate insulator provides numerous benefits, for example: the insulator can be made thicker for the same capacitance, the operating voltage can be made lower for the same current output, and improved output characteristics can be achieved without reducing the channel length further. It is known that transistors composed of III-V materials are most susceptible to damage induced by radiation and plasma processing. These devices utilise sub-10 nm gate dielectric films, which are prone to contamination, degradation and damage. Therefore, throughout the course of this work, process damage and contamination issues, as well as various techniques to mitigate or prevent those have been investigated through comparative studies of III-V MOS capacitors and transistors comprising various forms of metal gates, various thicknesses of GaGdO dielectric, and a number of GaAs-based semiconductor layer structures. Transistors which were fabricated before this work commenced, showed problems with threshold voltage control. Specifically, MOSFETs designed for normally-off (VTH > 0) operation exhibited below-zero threshold voltages. With the results obtained during this work, it was possible to gain an understanding of why the transistor threshold voltage shifts as the gate length decreases and of what pulls the threshold voltage downwards preventing normally-off device operation. Two main culprits for the negative VTH shift were found. The first was radiation damage induced by the gate metal deposition process, which can be prevented by slowing down the deposition rate. The second was the layer of gold added on top of platinum in the gate metal stack which reduces the effective work function of the whole gate due to its electronegativity properties. Since the device was designed for a platinum-only gate, this could explain the below zero VTH. This could be prevented either by using a platinum-only gate, or by matching the layer structure design and the actual gate metal used for the future devices. Post-metallisation thermal anneal was shown to mitigate both these effects. However, if post-metallisation annealing is used, care should be taken to ensure it is performed before the ohmic contacts are formed as the thermal treatment was shown to degrade the source/drain contacts. In addition, the programme of studies this thesis describes, also found that if the gate contact is deposited before the source/drain contacts, it causes a shift in threshold voltage towards negative values as the gate length decreases, because the ohmic contact anneal process affects the properties of the underlying material differently depending on whether it is covered with the gate metal or not. In terms of surface contamination; this work found that it causes device-to-device parameter variation, and a plasma clean is therefore essential. This work also demonstrated that the parasitic capacitances in the system, namely the contact periphery dependent gate-ohmic capacitance, plays a significant role in the total gate capacitance. This is true to such an extent that reducing the distance between the gate and the source/drain ohmic contacts in the device would help with shifting the threshold voltages closely towards the designed values. The findings made available by the collection of experiments performed for this work have two major applications. Firstly, these findings provide useful data in the study of the possible phenomena taking place inside the metal/GaGdO/GaAs layers and interfaces as the result of chemical processes applied to it. In addition, these findings allow recommendations as to how to best approach fabrication of devices utilising these layers.

High performance terahertz resonant tunnelling diode sources and broadband antenna for air-side radiation

Resonant tunnelling diode (RTD) is known to be the fastest electronics device that can be fabricated in compact form and operate at room temperature with potential oscillation frequency up to 2.5 THz. The RTD device consists of a narrow band gap quantum well layer sandwiched between two thin wide band gap barriers layers. It exhibits negative differential resistance (NDR) region in its current-voltage (I-V) characteristics which is utilised in making oscillators. Up to date, the main challenge is producing high output power at high frequencies in particular. Although oscillation frequencies of ~ 2 THz have been already reported, the output power is in the range of micro-Watts. This thesis describes the systematic work on the design, fabrication, and characterisation of RTD-based oscillators in microwave/millimetre-wave monolithic integrated circuits (MMIC) form that can produce high output power and high oscillation frequency at the same time. Different MMIC RTD oscillator topologies were designed, fabricated, and characterised in this project which include: single RTD oscillator which employs one RTD device, double RTDs oscillator which employs two RTD devices connected in parallel, and coupled RTD oscillators which combine the powers of two oscillators over a single load, based on mutual coupling and which can employ up to four RTD devices. All oscillators employed relatively large size RTD devices for high power operation. The main challenge was to realise high oscillation frequency (~ 300 GHz) in MMIC form with the employed large sized RTD devices. To achieve this aim, proper designs of passive structures that can provide small values of resonating inductances were essential. These resonating inductance structures included shorted coplanar wave guide (CPW) and shorted microstrip transmission lines of low characteristics impedances Zo. Shorted transmission line of lower Zo has lower inductance per unit length. Thus, the geometrical dimensions would be relatively large and facilitate fabrication by low cost photolithography. A series of oscillators with oscillation frequencies in the J-band (220 – 325 GHz) range and output powers from 0.2 – 1.1 mW have been achieved in this project, and all were fabricated using photolithography. Theoretical estimation showed that higher oscillation frequencies (> 1 THz) can be achieved with the proposed MMIC RTD oscillators design in this project using photolithography with expected high power operation. Besides MMIC RTD oscillators, reported planar antennas for RTD-based oscillators were critically reviewed and the main challenges in designing high performance integrated antennas on large dielectric constant substrates are discussed in this thesis. A novel antenna was designed, simulated, fabricated, and characterised in this project. It was a bow-tie antenna with a tuning stub that has very wide bandwidth across the J-band. The antenna was diced and mounted on a reflector ground plane to alleviate the effect of the large dielectric constant substrate (InP) and radiates upwards to the air-side direction. The antenna was also investigated for integration with the all types of oscillators realised in this project. One port and two port antennas were designed, simulated, fabricated, and characterised and showed the suitability of integration with the single/double oscillator layout and the coupled oscillator layout, respectively.

Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.

An investigation into the properties of non-digestible carbohydrates that selectively promote colonic propionate production

Short chain fatty acids (SCFA), including propionate, are produced by the bacterial fermentation of carbohydrates in the colon. Propionate has many potential roles in health, including inhibiting cholesterol synthesis, de novo lipogenesis and increasing satiety. The profile of SCFA produced is determined by both the substrate available and the bacteria present and may be influenced by environmental conditions within the lumen of the colon. Whilst it may be beneficial to increase colonic propionate production, dietary strategies to achieve this are unproven. Adding propionate to food leads to poorer organoleptic properties, and oral propionate is absorbed in the small intestine. The optimum way to selectively increase colonic propionate would be to select fermentable carbohydrates that selectively promote propionate production. To date, few studies have undertaken a systematic assessment of the factors leading to increased colonic propionate production making the selection of propiogenic carbohydrates challenging. The aim of this thesis was to identify the best carbohydrates for selectively increasing propionate production, and to explore the factors which control propionate production. This work started with a systematic review of the literature for evidence of candidate carbohydrates, which led to a screen of ‘propiogenic’ substrates using in vitro batch fermentations and mechanistic analysis of the impact of pH, bond linkage and orientation using a range of sugars, polysaccharides and fibre sources. A new unit for SCFA production was developed to allow comparison of results from in vitro studies encompassing a range different methodologies found in the literature. The systematic review found that rhamnose yielded the highest rate and proportion of propionate production whereas, for polysaccharides, β-glucan ranked highest for rate and guar gum ranked highest for molar production, but this was not replicated across all studies. Thus, no single NDC was established as highly propiogenic. Some substrates appeared more propiogenic than others and when these were screened in vitro. Laminarin, and other β-glucans ranked highest for propionate production. Legume fibre and mycoprotein fibre were also propiogenic. A full complement of glucose disaccharides were tested to examine the role glycosidic bond orientation and position on propionate production. Of the glucose disaccharides tested, β(1-4) bonding was associated with increased proportion of propionate and α(1-1) and β(1-4) increased the rate and proportion of butyrate production. In conclusion, it appears that for fibre to affect satiety, high intakes of fibre are needed, and which a major mechanism is thought to occur via propionate. Within this thesis it was identified that rather than selecting specific fibres, increasing overall intakes of highly fermentable carbohydrates is as effective at increasing propionate production. Selecting carbohydrates with beta-bonding, particularly laminarin and other β(1-4) fermentable carbohydrates leads to marginal increases in propionate production. Compared with targeted delivery of propionate to the colon, fermentable carbohydrates examined in this thesis have lesser and variable effects on propionate production. A more complete understanding of the impact of bond configurations in polysaccharides, rather than disaccharides, may help selection or design of dietary carbohydrates which selectively promote colonic propionate production substrates for inclusion in functional foods. Overall this study has concluded that few substrates are selectively propiogenic and the evidence suggests that similar changes in propionate production may be achieved by modest changes in dietary fibre intake

The role of non-coding RNA in the development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries, characterised by pulmonary vascular remodelling due to excessive proliferation and resistance to apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). The increased pulmonary vascular resistance and elevated pulmonary artery pressures result in right heart failure and premature death. Germline mutations of the bone morphogenetic protein receptor-2 (bmpr2) gene, a receptor of the transforming growth factor beta (TGF-β) superfamily, account for approximately 75%-80% of the cases of heritable form of PAH (HPAH) and 20% of sporadic cases or idiopathic PAH (IPAH). IPAH patients without known bmpr2 mutations show reduced expression of BMPR2. However only ~ 20% of bmpr2-mutation carriers will develop the disease, due to an incomplete penetrance, thus the need for a ‘second hit’ including other genetic and/or environmental factors is accepted. Diagnosis of PAH occurs most frequently when patients have reached an advanced stage of disease. Although modern PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, the mortality rate from PAH remains unacceptably high. Therefore, the development of novel therapeutic approaches is required for the treatment of this multifaceted disease. Noncoding RNAs (ncRNAs) include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs are ~ 22 nucleotide long and act as negative regulators of gene ex-pression via degradation or translational inhibition of their target mRNAs. Previous studies showed extensive evidence for the role of miRNAs in the development of PAH. LncRNAs are transcribed RNA molecules greater than 200 nucleotides in length. Similar to classical mRNA, lncRNAs are translated by RNA polymerase II and are generally alternatively spliced and polyadenylated. LncRNAs are highly versatile and function to regulate gene expression by diverse mechanisms. Unlike miRNAs, which exhibit well-defined actions in negatively regulating gene expression via the 3’-UTR of mRNAs, lncRNAs play more diverse and unpredictable regulatory roles. Although a number of lncRNAs have been intensively investigated in the cancer field, studies of the role of lncRNAs in vascular diseases such as PAH are still at a very early stage. The aim of this study was to investigate the involvement of specific ncRNAs in the development of PAH using experimental animal models and cell culture. The first ncRNA we focused on was miR-143, which is up-regulated in the lung and right ventricle tissues of various animal models of PH, as well as in the lungs and PASMCs of PAH patients. We show that genetic ablation of miR-143 is protective against the development of chronic hypoxia induced PH in mice, assessed via measurement of right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. We further report that knockdown of miR-143-3p in WT mice via anti-miR-143-3p administration prior to exposure of mice to chronic hypoxia significantly decreases certain indices of PH (RVSP) although no significant changes in RVH and pulmo-nary vascular remodelling were observed. However, a reversal study using antimiR-143-3p treatment to modulate miR-143-3p demonstrated a protective effect on RVSP, RVH, and muscularisation of pulmonary arteries in the mouse chronic hypoxia induced PH model. In vitro experiments showed that miR-143-3p overexpression promotes PASMC migration and inhibits PASMC apoptosis, while knockdown miR-143-3p elicits the opposite effect, with no effects observed on cellular proliferation. Interestingly, miR-143-3p-enriched exosomes derived from PASMCs mediated cell-to-cell communication between PASMCs and PAECs, contributing to the pro-migratory and pro-angiogenic phenotype of PAECs that underlies the pathogenesis of PAH. Previous work has shown that miR-145-5p expression is upregulated in the chronic hypoxia induced mouse model of PH, as well as in PAH patients. Genetic ablation and pharmacological inhibition (subcutaneous injection) of miR-145-5p exert a protective against the de-velopment of PAH. In order to explore the potential for alternative, more lung targeted delivery strategies, miR-145-5p expression was inhibited in WT mice using intranasal-delivered antimiR-145-5p both prior to and post exposure to chronic hypoxia. The decreased expression of miR-145-5p in lung showed no beneficial effect on the development of PH compared with control antimiRNA treated mice exposed to chronic hypoxia. Thus, miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while the inhibition of miR-143-3p prevented the development of experimental pulmonary hypertension. We focused on two lncRNAs in this project: Myocardin-induced Smooth Muscle Long noncoding RNA, Inducer of Differentiation (MYOSLID) and non-annotated Myolnc16, which were identified from RNA sequencing studies in human coronary artery smooth muscle cells (HCASMCs) that overexpress myocardin. MYOSLID was significantly in-creased in PASMCs from patients with IPAH compared to healthy controls and increased in circulating endothelial progenitor cells (EPCs) from bmpr2 mutant PAH patients. Exposure of PASMCs to hypoxia in vitro led to a significant upregulation in MYOSLID expres-sion. MYOSLID expression was also induced by treatment of PASMC with BMP4, TGF-β and PDGF, which are known to be triggers of PAH in vitro. Small interfering RNA (siR-NA)-mediated knockdown MYOSLID inhibited migration and induced cell apoptosis without affecting cell proliferation and upregulated several genes in the BMP pathway in-cluding bmpr1α, bmpr2, id1, and id3. Modulation of MYOSLID also affected expression of BMPR2 at the protein level. In addition, MYOSLID knockdown affected the BMP-Smad and BMP-non-Smad signalling pathways in PASMCs assessed by phosphorylation of Smad1/5/9 and ERK1/2, respectively. In PAECs, MYOSLID expression was also induced by hypoxia exposure, VEGF and FGF2 treatment. In addition, MYOSLID knockdown sig-nificantly decreased the proliferation of PAECs. Thus, MYOSLID may be a novel modulator in pulmonary vascular cell functions, likely through the BMP-Smad and –non-Smad pathways. Treatment of PASMCs with inflammatory cytokines (IL-1 and TNF-α) significantly in-duced the expression of Myolnc16 at a very early time point. Knockdown of Myolnc16 in vitro decreased the expression of il-6, and upregulated the expression of il-1 and il-8 in PASMCs. Moreover, the expression levels of chemokines (cxcl1, cxcl6 and cxcl8) were sig-nificantly decreased with Myolnc16 knockdown. In addition, Myolnc16 knockdown decreased the MAP kinase signalling pathway assessed by phosphorylation of ERK1/2 and p38 MAPK and inhibited cell migration and proliferation in PASMCs. Thus, Myolnc16 may a novel modulator of PASMCs functions through anti-inflammatory signalling pathways. In summary, in this thesis we have demonstrated how miR-143-3p plays a protective role in the development of PH both in vivo animal models and patients, as well as in vitro cell cul-ture. Moreover, we have showed the role of two novel lncRNAs in pulmonary vascular cells. These ncRNAs represent potential novel therapeutic targets for the treatment of PAH with further work addressing to investigate the target genes, and the pathways modulated by these ncRNAs during the development of PAH.