Alloying effects and the development of Co-Ni superalloys

This thesis presents the development of cobalt/nickel-based polycrystalline superalloys for gas turbine applications. The optimisation of the hot isostatic pressing (HIP) process and subsequent heat treatments has been investigated. Additionally, two powder alloys V208E and V208F have been characterised and investigated to determine the effects of 1.5at% titanium and 1at% niobium substitutions. Finally six alloys based on V208C, developed by M. Knop [113], were developed and characterised. Additions of 1at% chromium, 1at% aluminium, 1 and 2at% molybdenum, 0.5at% niobium and a swap in the carbon and boron level (0.20 and 0.15at% respectively) were investigated. Introducing a lower temperature stage of 950°C during the HIP process caused the carbides that form to reduce in size from approximately 1μm to 80-150nm, as well as confining them to grain boundaries. STEM-EDS confirmed that the small carbides formed are rich in tantalum and zirconium. Upon cooling from above the γ’ solvus, cooling rates below 0.5°C/s were found to cause grain boundary serration, which resulted in an increase in room temperature strength of approximately 100MPa. Titanium was found to increase the γ’ solvus by around 30°C, whereas niobium had little effect. Both alloys had an acceptable low cycle fatigue (LCF) strength with a life of over 0.25 million cycles at 650°C and 774MPa, which was above the yield stress. Titanium was detrimental to oxidation performance, with a damage depth of 4.7μm, compared to niobium with 1.1μm. Both titanium and niobium improved creep strength compared to Knop’s alloy V208C. In the V208C-based alloy series, niobium and aluminium were found to increase the γ’ fraction and solvus, with molybdenum and chromium reducing them. All additions improved oxidation performance except niobium. Molybdenum and niobium were found to be particularly beneficial to high temperature strength. Substitution of carbon for boron significantly improved both high temperature strength and oxidation performance.Open Acces

The effects of alloying additions in polycrystalline Co-Ni Superalloys

New Co-Ni superalloys are being considered as a potential replacement for current Ni superalloys used in gas turbine applications. Utilizing the stable L12 phase Co3(Al,W) discovered in 20061 M.Knop et al. developed the new γ/γ’ polycrystalline superalloy V208C, which exhibited favourable strength and oxidation performance when compared to existing Ni and Co superalloys2. Further work has now been done to evolve the alloy chemistry of V208C in order to make a step towards the next iteration of a potential candidate alloy. Using the nominal composition of V208C, 36Co-35Ni-15Cr-10Al-3W-1Ta-0.15C-0.2B-0.04Zr (at%), further additions of 1Cr, 1Al, 1Mo, 2Mo, 0.5Nb and a swap of the C/B content were investigated using a laboratory-scale cast and wrought process to produce a series of ingots for characterization. Differential scanning calorimetry (DSC) was used to determine the γ’ solvus temperatures of each alloy, with the 1Al addition providing the most significant increase from 1000°C to 1020°C. The oxidation performance of each alloy at 800°C for 100 hours was examined via a combination of thermogravimetric analysis (TGA) and focused ion beam (FIB) cross-sectioning of the oxide layers. The 1Al addition, again, exhibited the best oxidation performance, with the 1Mo addition also performing well. High-temperature tensile testing determined the yield strength of each specimen at room temperature and at 50°C intervals from 650-900°C. The alloys all displayed the flow stress anomaly; with 2Mo possessing the highest yield stress at room temperature and 1Al at the high-temperature peak. The γ’ fraction, size and distribution were observed using electron microscopy, indicating that the addition of 1Al caused the most significant rise in γ’ fraction from 50% to 53%. Special consideration was given to the C/B content swap in order to understand how it may effect the mechanisms of grain boundary precipitate formation, as well as the subsequent impact on strength performance. References: J. Sato, T. Omori, K. Oikawa, I Ohnuma, R. Kainuma and K. Ishida. Cobalt-base high-temperature alloys. Science, p90-91, 2007 M. Knop, P. Mulvey, F. Ismail, A. Radecka, K.M. Rahman, T.C. Lindley, B.A. Shollock, M.C. Hardy, M.P. Moody, T.L. Martin, P.A.J. Bagot and D. Dye. New Polycrystalline Co-Ni Superalloy. JOM, 201

Reappraisal of Temporary Levodopa Withdrawal ("Drug Holiday") in Parkinson's Disease

Transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients. We then compared the subsequent clinical course of these patients over one year with that of 30 other randomly selected, similar patients with Parkinson's disease. In both groups the disease progressed; there was no difference in disease severity, capacity for daily living activities, or total amounts of dopamine agonists eventually used. For some patients, it was possible to reduce dopamine agonists used immediately after the drug holiday without causing deterioration, but a pulmonary embolus and other complications occurred. Subsequent complications related to long-term dopamine-agonist therapy during the follow-up period were similar in the two groups. This investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration

Probing the black box : experiments in design and design education

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2000.Includes bibliographical references (leaves 75-77).Conventional analysis and design methods based on preexisting methods and assumptions preconditions and limits the designer's level of engagement with the specific context that is under investigation. A structural analysis is concerned with the disclosure of [subconscious] tendencies and agendas from within a form or site. This thesis develops methods that facilitate the organization and evaluation of 'design information' gathered from a structural analysis. The methodologies developed in this thesis place an equal emphasis on excavating the logic and tendencies of both the physical context and the logic of the conceptual structuring of the designer's processes. This approach acknowledges that each situation offers its own specific truths and that each project needs to readdress the issue as to what constitutes the discipline of architecture. The methodologies developed in this thesis analyze the site through the lens of events as a means to suspend preconceptions and investigate the tendencies of the designer. It takes as axiom that some thoughts and intentions cannot be reached frontally, but rather require analogies, metaphors or other such strategies to uncover the subconscious meaning. The design methodology developed in this research is a proposal for such a strategy. This suspension allows for the emergence of intuitions and strategies directly from site and the context. These methods also become a means to elicit, record and classify the 'conceptual schema' or the structure of the designer's thought. They attempt, in a constructivist manner, to aid the students in clarifying their thought processes. This thesis will explore the mapping of concepts and approaches clearly and externally as a means to create an intellectual space for the designer to work within. This space becomes a way to test and evaluate ideas, and intuitions within a 'conversational approach'. This approach defines the role of the designer as both writer and reader.by Christopher P. Mulvey.S.M

Truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates does not predict increased biological activity of Toxin B or Toxin A

<p>Abstract</p> <p>Background</p> <p>The increased severity of disease associated with the NAP1 strain of <it>Clostridium difficile </it>has been attributed to mutations to the <it>tcdC </it>gene which codes for a negative regulator of toxin production. To assess the role of hyper-production of Toxins A and B in clinical isolates of <it>Clostridium difficile</it>, two NAP1-related and five NAP1 non-related strains were compared.</p> <p>Methods</p> <p>Sequencing was performed on <it>tcdC</it>, <it>tcdR</it>, and <it>tcdE</it> to determine if there were differences that might account for hyper-production of Toxin A and Toxin B in NAP1-related strains. Biological activity of Toxin B was evaluated using the HFF cell CPE assay and Toxin A biological activity was assessed using the Caco-2 Trans-membrane resistance assay.</p> <p>Results</p> <p>Our results confirm that Toxin A and Toxin B production in NAP1-related strains and ATCC 43255 occurs earlier in the exponential growth phase compared to most NAP1-nonrelated clinical isolates. Despite the hyper-production observed in ATCC 43255 it had no mutations in <it>tcdC</it>, <it>tcdR </it>or <it>tcdE</it>. Analysis of the other clinical isolates indicated that the kinetics and ultimate final concentration of Toxin A and B did not correlate with the presence or lack of alterations in <it>tcdC</it>, <it>tcdR </it>or <it>tcdE</it>.</p> <p>Conclusion</p> <p>Our data do not support a direct role for alterations in the <it>tcdC </it>gene as a predictor of hyperproduction of Toxin A and B in NAP1-related strains.</p

A Bayesian mixture modelling approach for spatial proteomics.

Analysis of the spatial sub-cellular distribution of proteins is of vital importance to fully understand context specific protein function. Some proteins can be found with a single location within a cell, but up to half of proteins may reside in multiple locations, can dynamically re-localise, or reside within an unknown functional compartment. These considerations lead to uncertainty in associating a protein to a single location. Currently, mass spectrometry (MS) based spatial proteomics relies on supervised machine learning algorithms to assign proteins to sub-cellular locations based on common gradient profiles. However, such methods fail to quantify uncertainty associated with sub-cellular class assignment. Here we reformulate the framework on which we perform statistical analysis. We propose a Bayesian generative classifier based on Gaussian mixture models to assign proteins probabilistically to sub-cellular niches, thus proteins have a probability distribution over sub-cellular locations, with Bayesian computation performed using the expectation-maximisation (EM) algorithm, as well as Markov-chain Monte-Carlo (MCMC). Our methodology allows proteome-wide uncertainty quantification, thus adding a further layer to the analysis of spatial proteomics. Our framework is flexible, allowing many different systems to be analysed and reveals new modelling opportunities for spatial proteomics. We find our methods perform competitively with current state-of-the art machine learning methods, whilst simultaneously providing more information. We highlight several examples where classification based on the support vector machine is unable to make any conclusions, while uncertainty quantification using our approach provides biologically intriguing results. To our knowledge this is the first Bayesian model of MS-based spatial proteomics data.LG was supported by the BBSRC Strategic Longer and Larger grant (Award BB/L002817/1) and the Wellcome Trust Senior Investigator Award 110170/Z/15/Z awarded to KSL. PDWK was supported by the MRC (project reference MC_UP_0801/1). CMM was supported by a Wellcome Trust Technology Development Grant (Grant number 108467/Z/15/Z). OMC is a Wellcome Trust Mathematical Genomics and Medicine student supported financially by the School of Clinical Medicine, University of Cambridge. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The ecology and evolution of Japanese encephalitis virus

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus mainly spread by Culex mosquitoes that currently has a geographic distribution across most of Southeast Asia and the Western Pacific. Infection with JEV can cause Japanese encephalitis (JE), a severe disease with a high mortality rate, which also results in ongoing sequalae in many survivors. The natural reservoir of JEV is ardeid wading birds, such as egrets and herons, but pigs commonly play an important role as an amplifying host during outbreaks in human populations. Other domestic animals and wildlife have been detected as hosts for JEV, but their role in the ecology and epidemiology of JEV is uncertain. Safe and effective JEV vaccines are available, but unfortunately, their use remains low in most endemic countries where they are most needed. Increased surveillance and diagnosis of JE is required as climate change and social disruption are likely to facilitate further geographical expansion of Culex vectors and JE risk areas

Brexit: implications for the rural North of England

This study has been commissioned by Northumberland County Council to consider the implications of Brexit on the rural north of England. Brexit is a ‘once in a generation’ event which will have a significant and long-lasting impact on all parts of the UK. The area covered by this report is primarily the rural parts of the county of Northumberland, but inevitably, what happens in the neighbouring areas will have a significant impact on rural Northumberland so a wider focus on the rural north is employed where necessary. The report’s structure is as follows. Following the Introduction, Chapter One sets out the wider context of the rural north, its economic and social profile and wider challenges and opportunities and locates the Northumberland economy within this. Chapter 2 looks specifically at policy literature on the potential implications of Brexit across a series of pan-regional, regional and local scales, while Chapter 3 provides a more in-depth analysis of the key sectors relevant to Northumberland’s rural strategy and the potential opportunities and constraints created by Brexit. The policy review considered both academic and policy documents. It looked at policy responses to Brexit on both a national and regional level coupled with a comprehensive sectoral analysis taking account of the most important sectors for the rural north east of England. This was then triangulated using the material gleaned from the primary data described in the next three chapters. Building on the material covered in the first 3 sections, Chapter 4 explains how a foresight methodology was used to engage a panel of experts from across the region in imagining what rural Northumberland will be like in 2030. This panel of experts wasset the seemingly simple question of: “what will Brexit mean for the rural north of England?” Within this question, the complexity of Brexit soon reveals itself as the impact will be felt across all sectors of the economy and within every community in the region. To structure this seemingly impossible task, the Delphi Method was adopted. The Delphi Method provides a systematic way of thinking about the future. Chapter 5 captures how it first identifies the key drivers for change and then starts to build an understanding of the systems and processes that are driving change in the region. The final stage of the foresight process – contained in Chapter 6 - is to build a set of scenarios imagining what the rural north of England will be like in 2030. These are not intended to be predictions but are provocations to stimulate a debate about the kind of future to aim for and conversely the kind of future to avoid

Regioselective zincation of indazoles using TMP2Zn and Negishi cross-coupling with aryl and heteroaryl iodides.

The metalation of various SEM-protected functionalized indazoles with TMP2Zn provides 3-zincated indazoles which undergo palladium-catalyzed Negishi cross-couplings in good yields