Advancing Climate Change Research and Hydrocarbon Leak Detection : by Combining Dissolved Carbon Dioxide and Methane Measurements with ADCP Data

With the emergence of largescale, comprehensive environmental monitoring projects, there is an increased need to combine state-of-the art technologies to address complicated problems such as ocean acidifi cation and hydrocarbon leak detection

Blockchain electricity trading using tokenised power delivery contracts. ESRI Working Paper No. 649 December 2019

This paper proposes a new mechanism for forward selling renewable electricity generation. In this transactive framework, a wind or solar farm may directly sell to consumers a claim on their future power output in the form of nonfungible blockchain tokens. Using the flexibility of smart contract code, which executes irrevocably on a blockchain, the realised generation levels will offset the token holders’ electricity consumption in near real-time. To elucidate the flexibility offered by such smart contracts, two ways of structuring these power delivery instruments are considered: firstly, an exotic tranched system, where more senior tokens holders enjoy priority claims on power, as compared against a simpler pro-rata scheme, where the realised output of a generator is equally apportioned between token holders. A notional market simulation is provided to explore whether, for instance, consumers could exploit the flatter power delivery profiles of more senior tranches to better schedule their responsive demands

The British Way of War in North West Europe 1944-45: A Study of Two Infantry Divisions

This thesis will examine the British way of war as experienced by two British Infantry Divisions - the 43rd ‘Wessex’ and 53rd ‘Welsh’ - during the Overlord campaign in North West Europe in 1944 and 1945. The main locus of research centres on the fighting components of those divisions; the infantry battalions and their supporting regiments. In order to understand the way the British fought this part of the war, the thesis will consider the British Army’s history since 1918: its level of expertise at the end of the First World War; the impact of inter-war changes, and the experience of the early part of the Second World War, as these factors were fundamental in shaping how the British Army operated during the period covered in this study. These themes will be considered in the first chapter. The following seven chapters will study each of the two infantry divisions in turn, to maintain a chronological order. This is so that the experiences of each division can be examined in a logical way, from their initial experiences of combat in late June 1944 through to March 1945. Naturally, their major battles will be considered but so will their minor engagements and day-to-day experiences, as this will give a good, detailed, overview of each division’s campaign. This layout of chapters is also convenient for allowing comparisons between the two divisions as the campaign progressed. This thesis contains several strands of enquiry which will consider how Montgomery’s prosecution of the war actually translated to the smaller units of the division (the battalions, 4 companies, platoons and sections). The historiography for this campaign tends to suggest that the British Army fought the war in a cautious way, and that this approach was characterised by the use of overwhelming material superiority and rehearsed set piece attacks; tactics that were designed not only to destroy the enemy, but also to avoid the heavy casualties of the major battles of the First World War; a factor that was perceived to be vital to the maintenance of fragile infantry morale. Although the basic premise of a ‘cautious’ British way of war is generally accepted (along with its attendant emphasis on consolidation of objectives rather than exploitation of opportunities, and a reliance on adherence to lengthy orders), this study will conclude that the way the war was fought at sub-divisional levels was frequently at a pace that did not allow for such caution. Instead, it was characterised by command pressure to achieve results quickly, hasty planning and a reliance on massive artillery and mortar contributions to compensate for deficiencies in anti-tank and armoured support. This thesis will further conclude that a conscious policy of casualty conservation appears not to have been a priority at divisional command level, but was instead a consideration for company, platoon and section commanders and the men that they led

Reliability improvement project decision making : water cooling system redesign

Thesis (S.M.)--Massachusetts Institute of Technology, System Design and Management Program, June 2006.Includes bibliographical references (p. 66).Deciding on which reliability & performance improvement projects to launch or to reject has historically been an extremely challenging responsibility of Teradyne management. Incorrect decisions can lead to major customer dissatisfaction, which may subsequently lead to loss of market share. Teradyne Engineering and Marketing team have been trying to develop a tool that would assist in their reliability improvement project decision making. The challenge is the dynamic aspects of the reliability improvement projects. Like most engineering projects, reliability improvement projects have variables such as internal workforce, productivity, skill sets, customer expectations and many others that are in constant motion. These variables make the assessment of reliability projects extremely difficult in a static framework. This research will incorporate these key variables into a dynamic framework to help assess individual reliability improvement projects.by Paul Devine.S.M

Role of the engineer in international development : a case study in water supply service delivery models in Sierra Leone

The eradication of global poverty is central to the concept of sustainable development. In developing nations the lack of essential infrastructure and technologies, which are necessary to provide people with their basic human rights, offer a central role for the engineer. These needs are increasing as new global threats, such as the pressures caused by population growth, the harmful effects of climate change or the increasing frequency and intensity of disasters, have only heightened the difficulties which threaten the world’s poorest nations. Decades of development practice has allowed the profession of engineering to engage with many of these global issues. Over this period the engineering approaches, particularly in Sub-Saharan Africa, have gradually moved from high impact and short-term disasters relief interventions to long-term endogenous solutions. This change in overall aims has raised awareness of the sustainability of current engineering interventions. Many of the results are not entirely positive. For example, in water supply engineering, certain national estimates of sustainability of hand-pump wells for countries in Sub-Saharan Africa can range from 30- 80%. The role that the engineer could provide in addressing the concerns of poorer nations has not yet been fully realised. This thesis evaluates the current engineering models of service delivery that are used by Non-Governmental Organisations (NGOs) in developing nations. These models of technology transfer are supposed to provide communities in developing nations with a sustainable access to technologies that can provide for their basic rights. It is from within these models that engineers, who in many cases are foreign to the socio-cultural systems of the host nation, perform their engineering function and activities. The field research focuses on a case study of water supply engineering projects that have been carried out within the rural District of Tonkolili in Sierra Leone. To address the complex socio-cultural and socio-technical systems in Sierra Leone this field research adopted a combination of qualitative and quantitative assessment methods. This involved investigating both the technical and social sustainability issues found in Sierra Leone. The research visits were both inductive and deductive. They covered 150 spatially distributed villages in the rural district of Tonkolili. The methodologies used as part of this study involved; interviews, focus group discussions, community mapping, transect walks and technical observations, to provide a broad understanding of the sustainability issues affecting engineering projects. A total of 309 hand-pump wells, pulley systems and borehole water points were evaluated as part of the research. The study investigated the technical, socio-technical and socio-cultural consequences of these technology transfers - as well as the current condition of the social support mechanisms that are designed to sustain the water schemes. The results of the technical observations demonstrated that there are a diverse range of failures, from extreme to moderate, that have occurred at many of the water points. During the field visits observations of water supply solutions found to have urgent technical problems were frequent occurrences. The majority of the water points (96%) were found to have at least one technical failing that required immediate maintenance or further engineering assistance. The social research also indicated that, of the 4,700 individual categories monitored, a significant proportion (49%) were technical problems that were within the capacities of village members to address locally. These technical problems found to be ignored by the host communities. The NGO trained support mechanisms, which were designed to provide sustainability to the systems, for innumerable reasons, were unable to operate effectively. The breakdown in function of these supporting systems highlighted the serious weakness of current service delivery models in their ability to achieve sustainable engineering solutions. Investigating the relationship between the households and the water points suggests that the communities are not acting rationally towards their water sources. The majority of households were found to have unsafe water practices regardless of the provision of their improved sources. For example, many households that had access to improved water sources were found to still use their unimproved sources (30%). Many more (53%) complemented, and mixed, their unimproved water with water from their improved wells. This attitude towards safe water suggested that there were fundamentally flawed assumptions about how communities would receive and interact with their technologies. These household decisions, and the associated technical concerns, are directly attributable to the actions of the engineers from the project implementing development agencies. The results of these misinterpretations have undermined the long term sustainability of water supplies in Sierra Leone. The research indicated that to address sustainability the engineering profession is at a crossroads in determining its future in international development. Engineers have the capacity to acknowledge that the complexities of development limit their efficacy and therefore seek support from other professions. This would narrow the scope of their interventions. They are also capable of actively seeking the opposite; to broaden the scope as well as the responsibilities, expectations and skills of the engineers. It is this decision that will define the role of the engineer in international development

Defining the mechanism behind the self-association of therapeutic monoclonal antibodies using mass spectrometric techniques

Protein aggregation is responsible for a vast array of life-threatening protein based diseases as well as being an economic hurdle in biopharmaceutical development and manufacturing. Monoclonal antibodies represent the fastest growing class of biotherapeutics, with 53 antibodies in late phase clinical trials as of late 2015. Antibodies serve as ideal therapeutics due to their exquisite specificity and favourable safety profile. However, further therapeutic antibody development is hamstringed by uncontrolled self-association and aggregation which can occur at all stages of biotherapeutic development. Therefore, there is an urgent need for methods to dissect the mechanisms that drive uncontrolled self-association and protein aggregation. This thesis presents techniques which were applied to address the identification of aggregated material of a therapeutically relevant monoclonal antibody, and to characterise the mechanism responsible for driving oligomerisation. A combination of mass spectrometric techniques were employed to visualise the oligomeric species. Ion mobility spectrometry coupled to nanoelectrospray ionisation mass spectrometry was utilised to identify the oligomeric species formed under native conditions and to define the oligomers in terms of their mass and collision cross-sectional area. To characterise the regions responsible for driving oligomer formation, chemical cross-linking was employed to capture the oligomeric species in solution which were then analysed using tandem mass spectrometry. The initial dimer interaction was modelled using distance restraints obtained from the chemical cross-linking results and a model proposed that explains the oligomerisation events, and how runaway polymerisation can occur at higher concentrations. Finally, a powerful in vivo assay in the E. coli periplasm was developed to differentiate between aggregation and non-aggregation-prone sequences using single chain variable fragments (scFv) of the antibodies studied. The results presented demonstrate the applicability of the assay to molecules relevant to the biopharmaceutical sector; as an upstream platform for the identification of aggregation-prone sequences, prior to antibody production and development. Overall, the work presented within this thesis describes techniques that can be successfully applied to define the mechanism that underpins the self-association of a therapeutically-relevant monoclonal antibody. Furthermore, the study presents a novel in vivo assay that can be used to identify aggregation-prone sequences, and to develop them further by mutagenesis, which could be useful in protein development in the biopharmaceutical sector

Factors associated with public knowledge of and attitudes to dementia: A cross-sectional study

IntroductionDementia is a major public health concern but one that continues to be stigmatised. We examine lay knowledge of dementia and attitudes to people with dementia as potential precursors of public anxiety, focusing on the social characteristics associated with (a) the formation of these attitudes, and (b) the perception of the need for restriction and control for people with dementia.MethodsAnalysis of the 2014 Northern Ireland Life and Times survey, which included questions on knowledge of, attitudes to and personal experience with dementia. We used (a) latent class analysis and (b) logistic regression to examine factors associated with respondent attitudes towards dementia.ResultsRespondents (n = 1211) had relatively good general knowledge of dementia, but limited knowledge of specific risk factors. Negative perceptions of dementia were mitigated somewhat by personal contact. A high proportion of respondents felt that high levels of control were appropriate for people diagnosed with dementia, even at early stages of the disease.ConclusionPersonal antipathy to dementia was highly prevalent despite ongoing public campaigns to increase public awareness of developments in its prevention, treatment and consequent care pathways and hampering efforts to widen social inclusion. Fresh thinking and more resources may be needed to challenge persisting common misapprehension of the condition and the formation of entrenched stigma

Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR

'Food hates' over the life course : an analysis of food narratives from the UK Mass Observation Archive

This article presents data from the UK Mass Observation Archive drawn from the 1982 Winter Food Directive, which focuses on memories of childhood food ‘hates’. Through our analysis of these data, we identify three main findings: (a) there is a discrepancy between individual-level and collective aggregate level food hates, which problematises the notion of commensality; (b) a small but powerful ‘outlier’ group of respondents, which we refer to as ‘visceral repulsors’, show relatively extreme reactions to certain foods throughout their lives; and (c) the duration and temporalities of food hates can be used to sketch a rough model of change and continuity of food hates over the life course. Finally, the discussion focuses on the food hate trajectories through the life course, situated in a social context, to explore the implications the findings may have for food and health policy more generally

Metabolic Engineering of the Chloroplast Genome Using the Echerichia coli ubiC Gene Reveals That Chorismate Is a Readily Abundant Plant Precursor for p-Hydroxybenzoic Acid Biosynthesis1

p-Hydroxybenzoic acid (pHBA) is the major monomer in liquid crystal polymers. In this study, the Escherichia coli ubiC gene that codes for chorismate pyruvate-lyase (CPL) was integrated into the tobacco (Nicotiana tabacum) chloroplast genome under the control of the light-regulated psbA 5′ untranslated region. CPL catalyzes the direct conversion of chorismate, an important branch point intermediate in the shikimate pathway that is exclusively synthesized in plastids, to pHBA and pyruvate. The leaf content of pHBA glucose conjugates in fully mature T1 plants exposed to continuous light (total pooled material) varied between 13% and 18% dry weight, while the oldest leaves had levels as high as 26.5% dry weight. The latter value is 50-fold higher than the best value reported for nuclear-transformed tobacco plants expressing a chloroplast-targeted version of CPL. Despite the massive diversion of chorismate to pHBA, the plastid-transformed plants and control plants were indistinguishable. The highest CPL enzyme activity in pooled leaf material from adult T1 plants was 50,783 pkat/mg of protein, which is equivalent to approximately 35% of the total soluble protein and approximately 250 times higher than the highest reported value for nuclear transformation. These experiments demonstrate that the current limitation for pHBA production in nuclear-transformed plants is CPL enzyme activity, and that the process becomes substrate-limited only when the enzyme is present at very high levels in the compartment of interest, such as the case with plastid transformation. Integration of CPL into the chloroplast genome provides a dramatic demonstration of the high-flux potential of the shikimate pathway for chorismate biosynthesis, and could prove to be a cost-effective route to pHBA. Moreover, exploiting this strategy to create an artificial metabolic sink for chorismate could provide new insight on regulation of the plant shikimate pathway and its complex interactions with downstream branches of secondary metabolism, which is currently poorly understood