The United Kingdom Government has mandated ambitious carbon objectives, requiring an 80% reduction in emissions by 2050, and a 20% interim reduction by 2020. Their achievement will require government and large companies to work together, and for each to be assured of the other’s strategic intent. An emergent carbon accounting can provide reassurance if it produces credible information that supports the claims made by each party. This thesis investigates the extent to which carbon reduction narratives are supported or contradicted by actual carbon emissions disclosed in corporate accounting reports. It also investigates whether large corporations have delivered absolute carbon reductions in support of the government’s legally binding objectives. As a result of these and other investigations, the thesis contributes to the carbon accounting literature by critiquing the method of framing emissions employed by the Greenhouse Gas Protocol, the extent to which carbon reduction is supported by meaningful managerial incentives and the means by which analysts might rebalance financial return with carbon risk in portfolio construction. Following a middle ground approach, the research employs a numbers and narratives analysis in which critical alternative narratives are created at national, sectoral and firm levels. The analysis disaggregates macro carbon emissions data, and considers carbon emissions at a corporate meso and micro level. Narratives constituted out of these numbers, together with counter-narratives generated from corporate disclosures, are then evaluated to assess their credibility. The thesis adopts a practical approach, utilising multiple framing devices. In addition to reporting scopes 1, 2 and 3 carbon emissions, it describes a business model framework in which firms are expected to disclose their carbon-material stakeholder relations. Further recommendations are aimed at aligning the interests of corporate managers, investors and financial analysts with government carbon policy in order to modify behaviour and reduce emissions trajectories towards a lower carbon future.

The research presented herein is concerned with the exploration of tandem processes initiated by the conjugate reduction of Michael acceptors, encompassing the asymmetric reductive Dieckmann reaction and the two-carbon homologation of aldehydes by two complementary methodologies. Chapter 1 introduces the area of transition metal catalysed tandem reductive processes as a tool for carbon-carbon bond formation. An extensive discussion of this methodology is included and recent advances in the area are highlighted. Chapter 2 discusses the initial study into the asymmetric reductive Dieckmann condensation. 3,3’-Disubstituted 4-oxopyrrolidines were synthesised in up to 93% ee using both molybdenum and copper catalysis. Chapter 3 describes the novel molybdenum-catalysed two-carbon homologation of aldehydes by the reduction of alkylidene Meldrum’s acid derivatives. No over reduction to the corresponding alcohol is observed, as the aldehyde functionality remains protected until hydrolysis. Chapter 4 discusses the mild, expeditious amine promoted reduction of cyclic malonates to β-substituted propionaldehydes. The synthetic utility of the methodology is demonstrated by the synthesis of γ-substituted propylamines in a one-pot hydrosilylation/reductive amination process. Chapter 5 describes the synthesis and characterisation for the compounds discussed in chapters 2, 3 and 4.

Principal Components Analysis (PCA) is a statistical procedure commonly used for the purpose of analyzing high dimensional data. It is often used for dimensionality reduction, which is accomplished by determining orthogonal components that contribute most to the underlying variance of the data. While PCA is widely used for identifying patterns and capturing variability of data in lower dimensions, it has some known limitations. In particular, PCA represents its results as linear combinations of data attributes. PCA is therefore, often seen as difficult to interpret and because of the underlying optimization problem that is being solved it is not robust to outliers. In this thesis, we examine extensions to PCA that address these limitations. Specific techniques researched in this thesis include variations of Robust and Sparse PCA as well as novel combinations of these two methods which result in a structured low-rank approximation that is robust to outliers. Our work is inspired by the well known machine learning methods of Least Absolute Shrinkage and Selection Operator (LASSO) as well as pointwise and group matrix norms. Practical applications including robust and non-linear methods for anomaly detection in Domain Name System network data as well as interpretable feature selection with respect to a website classification problem are discussed along with implementation details and techniques for analysis of regularization parameters.

Superhydrophobic surfaces are able to entrap gas pockets in-between surface roughness elements when submerged in water. These entrapped gas pockets give these surfaces the potential to reduce drag due to the overlying flow being able to locally slip over the gas pockets, resulting in a mean slip at the surface. This thesis investigates the different effects that slip and the texturing of the surface have on turbulence over superhydrophobic surfaces. It is shown that, after filtering out the texture-induced flow, the background, overlying turbulence experiences the surface as a homogeneous slip boundary condition. For texture sizes, expressed in wall units, up to $L^+ \lesssim 20$ the only effect of the surface texture on the overlying flow is through this surface slip. The direct effect of slip does not modify the dynamics of the overlying turbulence, which remains canonical and smooth-wall-like. In these cases the flow is governed by the difference between two virtual origins, the virtual origin of the mean flow and the virtual origin experienced by the overlying turbulence. Streamwise slip deepens the virtual origin of the mean flow, while spanwise slip acts to deepen the virtual origin perceived by the overlying turbulence. The drag reduction is then proportional to the difference between the two virtual origins, reminiscent of drag reduction using riblets. The validity of slip-length models to represent textured superhydrophobic surfaces can resultantly be extended up to $L^+ \lesssim 20$. However, for $L^+ \gtrsim 25$ a non-linear interaction with the texture-coherent flow alters the dynamics of the background turbulence, with a reduction in coherence of large streamwise lengthscales. This non-linear interaction causes an increase in Reynolds stress up to $y^+ \lesssim 25$, and decreases the obtained drag reduction compared to that predicted from homogeneous slip-length models.

The aim of the work described in this thesis was to develop a more extensive knowledge of the chemistry of neptunium compounds by making rare, air- and moisture sensitive, low formal oxidation state neptunium compounds with full structural and synthetic characterization. The thesis contains three results chapters. Chapter one introduces neptunium chemistry as a background to the results presented. The first review on the molecular non-aqueous neptunium chemistry is provided and the literature reports to date discussed in the context of this. Chapter two describes exploratory synthetic and structural investigations of the organoneptunium complexes supported by the cyclopentadienyl anion, Cp = (C5H5)-, and the (trimethylsilyl)cyclopentadienyl anion, Cp' = (C5H4[Si(CH3)3])-. The syntheses of [Np(Cp)3]n and Np(Cp')3 complexes are detailed and the effect of the trimethylsilyl group of the ligand on the structure and reactivity have been investigated. Complexes were characterized by single crystal X-ray diffractometry, NMR and ATR(IR) spectroscopy. Both organoneptunium complexes were studied in reactions designed to expand the neptunium redox envelope. Notably, the complex Np(Cp')3 is reduced by KC8 in the presence of 2.2.2-cryptand to afford a product assigned as neptunium(II) complex, K(2.2.2-cryptand)[Np(Cp')3] that is thermally very unstable above approx. -10 ºC, in direct analogy to previously reported uranium, thorium and lanthanide complexes of the general formula, K(2.2.2-cryptand)[M(Cp')3]. The reaction between Np(Cp)3Cl and KCp in THF afforded the unanticipated K[NpIII(Cp)4] product as a result of a single-electron reduction presumably arising from Np–C σ-bond homolysis reactivity. This behaviour appears to be unique amongst the actinides for the An(IV)/An(III) redox couple. Chapter three focuses on oxo-bridged homo and heterometallic complexes. The reaction of NpCp3 with dioxygen afforded not only the simple oxide, (μ-O)[An(Cp)3]2, but also a small quantity of the unexpected new trinuclear oxo- neptunium(IV) compound [{(Cp3Np)(μ-O)}2{Np(Cp)2}], which interestingly contains the rare C2v-symetric [An(Cp)2]2+ structural moiety. This oxo-bridged environment is not paralleled in uranium chemistry. The two isostructural oxides, (μ-O)[An(Cp)3]2 (An = U, Np), allow a comparative study of the magnetic exchange phenomena between the two actinide centres demonstrating an exceedingly strong antiferromagnetic coupling, which is largely independent of the communicated Kramers NpIV (5f3, 4I9/2) or non-Kramers UIV (5f2, 3H4) ions. To design heterobimetallic systems, the uranyl(VI) complexes, [(UVIO2)(THF)(H2L)], supported by the calix[4]pyrrole Schiff base macrocycles, H4LOct and H4LEt, were singly-reduced to uranyl(V) with either of the actinide complexes Np(Cp)3 or U(Cp)3, affording isostructural [(Cp3)AnIVOUVO(THF)(H2L)]. Preliminary investigations of the magnetism of the AnIV-O-UV are reported, although their analysis gave counterintuitive results. Chapter four explores the redox chemistry and molecular and electronic structure of neptunium(III) complexes of the doubly deprotonated trans-calix[2]benzene[2]pyrrole, H2(LAr), macrocycle which has a unique π-bonding potential and conformational flexibility. Interestingly, the reactions with neptunium(IV) chloride yielded mono- and dinuclear neptunium(III) complexes, [(LAr)NpCl] and [(LAr)Np2Cl4(THF)3], with a subsequent elimination of the ligand radical; both complexes adopted η6:κ1:η6:κ1 bis(arene) sandwiched structural motif. In a direct analogy to the redox behaviour occurring in the salt metathesis between Np(Cp)3Cl and KCp, the spontaneous reduction derives from the favourable Np(IV)/Np(III) redox system. The reduction of complex [(LAr)NpCl] with NaK3 in DME produces near-black solutions consistent with [NpII(LAr)(DME)] that in the absence of excess NaK3 gradually convert to the metallated (LAr-H)3- neptunium(III) complex, [K(DME)(LAr-H)NpIII(OMe)]2, featuring the actinide centre bound with a ‘metallocene-type’ geometry provided by the two η5-bound pyrrolides of the ligand. The neptunium(III) compounds were characterized in the solid state by single crystal X-ray diffractometry, ATR(IR) spectroscopy and in a solution by NMR and UV-Vis-NIR spectroscopy.

Ageing and diabetes are two major healthcare concerns that used to be regarded as problems of the Western world but are now of increasing concern in developing nations. Treating elderly patients with diabetes poses issues for clinicians due to often complex, preexisting drug regimes. Research targeted at the development of novel drugs that have multiple effects on diabetes could go some way towards reducing polypharmacy in these patients. Here I present evidence that the oral Jak1/3 inhibitor, baricitinib, has effects on multiple aspects of diabetes. Baricitinib has been suggested to be a strong anti-inflammatory given the role Jak plays in transducing cytokine signals to elicit immune cell activation and maturation. Baricitinib was found to reduce urinary albumin to creatinine ratio and mesangial expansion in mice on an experimental high-fat diet with a diabetic metabolic profile when compared with naïve, non-diabetic mice. This reduction in renal impairment from diabetes was not found with a large reduction in proinflammatory cytokines and instead appears to be as a result of a direct effect on the cells of the mesangium. Baricitinib also reduced the circulating levels of cholesterol with a positive effect on the LDL: HDL ratio of diabetic mice. This reduction in cholesterol appears to be because of the abolition of GLP- 1 signalling, initiating an increase in blood insulin, preventing lipid flux and inhibiting LDL formation. Both of these changes in key diabetic complications were not accompanied by an increase in sensitivity to insulin compared with vehicle treated diabetic mice. These results show that baricitinib has a beneficial effect on two key aspects of the diabetic condition but that it does not modify insulin sensitivity itself. Baricitinib may represent a potential treatment for these diabetes-associated pathologies but only in combination with traditional anti-diabetic treatments.

by Lee Fung Yee Janet. / Thesis (M.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 257-316). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Redox chemistry is the basis for biological energy generation and anabolism. Redox conditions also serve as critical cues that modulate the development of many organisms. Roles for redox chemistry in the control of gene expression have been well characterized in multicellular eukaryotes, where oxygen availability in particular is a major developmental cue. As a gaseous metabolic substrate, oxygen becomes limiting as cellular communities grow, and can act as an indicator of aggregate size or developmental stage. In many of these cases, there are dedicated sensory and signal transduction networks that link oxygen and other redox signals to changes in gene expression and morphogenesis. The opportunistic pathogen Pseudomonas aeruginosa, like many species of microbes, forms multicellular structures called biofilms. Cells in biofilms can assume physiological states that differ from cells grown in well-mixed, homogeneous liquid cultures. They often exhibit increased resistance to environmental stresses and antibiotics, rendering biofilm physiology an important focus in the study of microbial pathogens. Biofilm development and architecture are tuned by environmental conditions. In turn, growth and survival in the community, and the specific structure of that community, give rise to internal microenvironments that are experienced by cells within a biofilm. Mechanisms that tune biofilm developmental programs in response to redox conditions are not well understood. This is due to challenges presented by most popular laboratory models of biofilm formation, which are not amenable to perturbation, characterization at the microscale, or high-throughput screening or analysis. In this thesis, I describe a standardized colony morphology assay for the study of P. aeruginosa PA14 biofilm development and use this model to address fundamental questions about the relationships between electron acceptor availability, biofilm cell physiology, and the regulation of biofilm morphogenesis. In the colony morphology assay, PA14 grows as ~1cm-diameter biofilms on agar-solidified media under controlled conditions, and displays a developmental pattern that is predictably influenced by changes in redox conditions. Microscale heterogeneity in chemical ecology can be profiled using microelectrodes, and the effects of specific mutations on development can be rigorously tested through high-throughput screening and the application of metabolic assays directly to biofilm samples. Prior to the work described here, application of the colony morphology assay had revealed that endogenous redox-active antibiotics called phenazines influence PA14 biofilm development such that defects in phenazine production promote colony wrinkling and the formation of a distinct wrinkle pattern. As phenazines can act as alternate electron acceptors for cellular metabolism, this provided an early clue to the role of redox conditions in determining biofilm architecture. The introduction to this thesis (Chapter 1) provides an overview of observations in P. aeruginosa and other microbes, drawing parallels between the physiology of colony biofilm development across phylogeny and highlighting specific preliminary studies that hint at redox-sensing mechanisms and signaling pathways that drive community morphogenesis. The associated Appendix A examines the effects of CORM-2, a synthetic compound that releases the respiratory poison carbon monoxide, on P. aeruginosa biofilm development. The inhibitory effects of CORM-2 are ameliorated by reducing agents and increased availability of electron donors for P. aeruginosa metabolism. Chapter 2 describes the foundational characterization of the P. aeruginosa PA14 colony morphology assay model, which showed that colony wrinkling is invoked under high intracellular NADH levels and electron acceptor-limiting conditions, suggesting that it is an adaptive strategy to increase access to electron acceptor. The associated Appendices B and C describe (i) a mathematical modeling approach demonstrating that wrinkle geometry is indeed optimized for efficient access to electron acceptors, and (ii) a study investigating the effects of phenazine antibiotics on the multicellular development of a eukaryotic microbe. Chapter 3 details the identification and characterization of a candidate mediator of the multicellular response to electron acceptor availability in PA14 called RmcA. RmcA contains domains that have been implicated in redox-sensitive developmental control in eukaryotic systems and domains that modulate intracellular levels of cyclic di-GMP (c-di-GMP). C-di-GMP is an important secondary messenger that controls social behaviors, including the secretion of factors required for colony biofilm structure formation, in diverse bacteria. RmcA thus bridges the gap between sensing of redox signals and colony morphogenesis. Appendix D outlines my approaches to purification and attempts to crystallize this and one other protein contributing to PA14 redox-driven colony morphogenesis. Finally, Appendix E describes the role of another protein that modulates c-di-GMP in response to metabolite-dependent signaling and physiological effects during interactions between P. aeruginosa and the fungus C. albicans. Together, the findings presented in this thesis have expanded our knowledge about the role that redox chemistry plays in biofilm development.

Neste trabalho realizaram-se reações de resolução enzimática de alcoóis secundários utilizando a enzima imobilizada lipase de Candida antarctica (NOVOZYME 435). Os alcoóis utilizados foram: (RS)-1-(4-metoxifenil)etanol (1a); (RS)-4-metil-2-pentanol (3a); (RS)-2-metil-3-hexanol (4a); (RS)-5-metil-2-hexanol (5a); (RS)-2-octanol (6a); (RS)-3-heptanol (7a); (RS)-6-metil-5-hepten-2-ol (8a); (RS)-1-octen-3-ol (9a). Todos os alcoóis foram resolvidos pela lipase, com exceção do álcool 4a. Nas resoluções enzimáticas os excessos enantioméricos dos álcoois e acetatos foram superiores a 98 %, havendo a conversão total (50 %) dos enantiômeros S nos respectivos acetatos: (S)-1-acetato-4-metoxifenil (1b); (S)-2-acetato-4-metil-pentano (3b); (S)-2-acetato-5-metil-hexano (5b); (S)-2-acetato-octano (6b); (S)-3-acetato-heptano (7b); (S)-2-acetato-6-metil-5-hepteno (8b); (S)-3-acetato-1-octeno (9b). Realizou-se ainda um estudo biocatalítico envolvendo reações de redução de cetonas com fungos de origem marinha. Foram utilizadas na reduções as cetonas: 4-metoxiacetofenona (1), 1-fenil-etanona (2), 4-metil-2-pentanona (3), 2-octanona (6) e a 6-metil-5-hetpen-2-ona (8) e como biocatalisadores três fungos de origem marinha (Bionectria sp Ce5, Aspergillus sydowii Ce15 e Aspergillus sydowii Ce19). A 4-metoxiacetofenona (1) foi reduzida pelos fungos Bionectria sp Ce5, Aspergillus sydowii Ce15 e Aspergillus sydowii Ce19 com excesso enantiomérico de 98% e rendimento de 65 %. A 2-octanona (6) e a 6-metil-5-hepten-2-ona (8) foram reduzidas pelo fungo A. sydowii Ce15 nos respectivos (S)-álcoois 6a e 8a com pureza enantiomérica > 98 %. Já a 1-fenil-etanona (2) foi reduzida somente pelo fungo Bionectria sp Ce5 com excesso enantiomérico de 50 % e rendimento de 25 %. A 4-metil-2-pentanona (3) não foi reduzida por nenhum dos microrganismos estudados. / This work carried out the enzymatic reactions of alcohols by using a lipase from immobilized Candida Antarctica (NOVOZYME 435). The alcohols used were: (RS)-1- (4-methoxyphenyl) ethanol (1a), (RS)-4-methyl-2-pentanol (3a), (RS)-2-methyl-3- hexanol (4a), (RS)-5-methyl-2-hexanol (5a), (RS)-2-octanol (6a), (RS)-3-heptanol (7a), (RS)-6-methyl-5-hepten-2-ol (8a) and (RS)-1-octen-3-ol (9a). All the alcohols were catalyzed by lipase, except for the alcohol 4a. In this enzymatic resolutions the enantiomeric excesses of alcohols and acetates were more than 98% and total conversions (50%) for enantiomers of the acetates: (R)-1-acetate-4-methoxyphenyl (1b), (R)-2-acetate-4-methyl-pentane (3b), (R)-2-acetate-5-methyl-hexane (5b), (R)-2-acetateoctane (6b), (R)-3-acetate-heptane (7b), (R)-2-acetate-6-methyl-5-hepteno (8b) and (S)- 3-acetate-1-octene (9b). In addition it was studied the biocatalytic reduction of ketones with marine-derived fungi. The ketones used were the 4-metoxyacetophenone (1), 1- phenyl-etanone (2), 4-methyl-2-pentanone (3), 2-octanone (6) and 6-methyl-5-hetpen-2- one (8). The marine-derived fungi used as biocatalysts were Bionectria sp Ce5, Aspergillus sydowii Ce15 and Aspergillus sydowii Ce19. The 4-metoxyacetophenone (1) was reduced by Bionectria sp Ce5 by Aspergillus sydowii Ce15 and Aspergillus sydowii Ce19 in high enantiomeric excess (98% e.e.) and good yield, i.g., 65%. The 2- octanone (6) and 6-methyl-5-hepten-2-one (8) were reduced by A. sydowii Ce15 in the (R)-alcohols 6a and 8a in high enantiomeric purities, > 98% e.e. However the 1-phenyletanone (2) was reduced only by the fungus Bionectria sp Ce5 with enantiomeric excess of 50% and yield of 25%. The 4-methyl-2-pentanone (3) was not reduced by the microorganisms studied.