Investement appraisal in a deregulated electricity market

This thesis analyses the impact of deregulation on the theory and practice of investment decision making in the electricity sector and appraises the likely effects on its long term future inefficiency. Part I describes the market and its shortcomings in promoting an optimal generation margin and plant mix and in reducing prices through competition. A full size operational model is developed to simulate hour by hour operation of the market and analyse its features. A relationship is established between the SMP and plant mix and between the LOLP and plant margin and it is shown bow a theoretical optimum can be derived when the combined LOLP payments and the capital costs of additional generation reach a minimum. A comparison of prices against an idealised bulk supply tariff is used to show how energy prices have risen some 12% in excess of what might have occurred under the CEGB regime. This part concludes with proposals to improve the marlderegulation to demonstrate their appropriateness. It is shown that the current market mechanisms could lead to suboptimal investment. Part 3 discusses the essential role of transmission in enabling competition and reviews worldwide practices illustrating little consensus on charging for its use. Basic costing principles are described and a new model is developed to demonstrate bow a generator may strike supply agreements either side of an interconnector to influence prices so as to maximise his income. The optimal pricing strategy for the transmitter is also derived and consumer response is simulated .The concept of transmission uplift is developed and the operational model is extended to include transmission constraints and then used to establish monthly incremental transmission constraint cost functions. It is shown how these can be used to appraise investment options and optimally plan outages. Part 4 concludes by discussing the regulatory framework and its limitations in improving efficiency or encouraging the optimum levels of investment. The principal findings of the thesis are reviewed and potential market improvement are described. This part concludes with a discussion of alternative market structures and likely future developments.

Benefits from competition:some illustrative UK cases

This study provides a powerful demonstration of the real world impact of increasedcompetition. By presenting six market case studies drawn from a variety of sectors itgives evidence of the type and magnitude of the benefits following marketinterventions to develop competition and free up the operation of these sectors. In discussing the types and form such interventions take, whether competition policy,deregulation or liberalisation, this report explores market conditions before and afterintervention, paying careful attention to both the envisaged benefits and the potentialfor negative side effects. Overall, the evidence suggests these benefits materialised,and in a number of instances proved more sizeable than anticipated. Concerns aboutharmful side effects have proved unfounded, with market stimuli impacting not only onthe price and range of goods available but also acting as a motivating force to productand process innovation. As Professor Davies points out, although active competition policy proves an importantcomponent in the competitive process, it is not sufficient in its own right. In order todeliver greater productivity, of which competition is a key driver, the UK needs a pool of resourceful entrepreneurs able to exploit changing market conditions. In order togive these people the best chance of success the framework conditions need to becorrect with strength in the complementary capabilities of innovation, investment, skillsand enterprise. Ensuring the competition framework is world class is central to the DTI’s strategy. The most recent peer review of the UK competition regime demonstrates that the UK isa strong performer, ranked third in the 2004 study, with the US first and Germanysecond. This study provides further evidence of the important role played by thatframework in delivering tangible benefits to consumers.

How important is ownership in a market with a level playing field? The Indian banking sector revisited

Private ownership of firms is often argued to lead to better firm performance than public ownership. However, the theoretical literature and the empirical evidence indicate that agency problems may affect the performance of privately owned firms. At the same time, competition and hard budget constraints can induce state-owned firms to operate efficiently. In India, banking sector reforms and deregulation were initiated in 1992, encouraging entry and establishing a level playing field for all banks. Data for the financial years 1995–1996 through 2000–2001 suggest that, by 1999–2000, ownership was no longer a significant determinant of performance. Rather, competition induced public-sector banks to eliminate the performance gap that existed between them and both domestic and foreign private-sector banks.

Expression profiling of type 2 diabetes susceptibility genes in the pancreatic islets, adipose tissue and liver of obese mice

Type 2 diabetes (T2D) is characterized by impaired beta cell function and insulin resistance. T2D susceptibility genes identified by Genome-wide association studies (GWAS) are likely to have roles in both impaired insulin secretion from the beta cell as well as insulin resistance. The aim of this study was to use gene expression profiling to assess the effect of the diabetic milieu on the expression of genes involved in both insulin secretion and insulin resistance. We measured the expression of 43 T2D susceptibility genes in the islets, adipose and liver of leptin-deficient Ob/Ob mice compared with Ob/+ littermates. The same panel of genes were also profiled in cultured rodent adipocytes, hepatocytes and beta cells in response to high glucose conditions, to distinguish expression effects due to elevated glycemia from those on the causal pathway to diabetes or induced by other factors in the diabetic microenviroment. We found widespread deregulation of these genes in tissues from Ob/Ob mice, with differential regulation of 23 genes in adipose, 18 genes in liver and one gene (Tcf7l2) in islets of diabetic animals (Ob/Ob) compared to control (Ob/+) animals. However, these expression changes were in most cases not noted in glucose-treated adipocyte, hepatocyte or beta cell lines, indicating that they may not be an effect of hyperglycemia alone. This study indicates that expression changes are apparent with diabetes in both the insulin producing beta cells, but also in peripheral tissues involved in insulin resistance. This suggests that incidence or progression of diabetic phenotypes in a mouse model of diabetes is driven by both secretory and peripheral defects. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York.

Exploring chain, network and cluster collaborative practices:implications for SMEs

Collaboration among enterprises has been rendered as one of the most important issues in the business agenda, either as a result of the globalisation and deregulation of markets or as a result of the Information and Communication Technology (ICT) revolution. Both factors have created a business reality where success in the collaboration practices followed, may result in improvements in the competitive position of enterprises. This paper starts from the basic business activity of the individual enterprise, looks into the chain, network and cluster collaborative practices and analyses their characteristics and the implications for Small-Medium Enterprises (SMEs). In addition, it provides insights regarding the opportunities, benefits, requirements and risks related to each collaborative practice. This paper finally argues that different collaboration practices are required, as enterprises and the industrial sectors where they operate, present distinctive characteristics.

Transglutaminases:nature's biological glues

Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

Do labour laws protect labour in India? Union experiences of workplace employment regulations in Maharashtra India

The debate over labour market regulations in India is highly polarised. Advocates of labour market deregulation suggest that the labour law framework in the country confers disproportionate powers on workers and trade unions in the formal sector of the economy, resulting in industrial conflicts and poor productivity. Using workplace union survey data from the state of Maharashtra, this paper examines the veracity of these claims. Maharashtra is recognised as a state with a broadly pro-worker labour law framework. We find that even pro-worker labour laws at best offer only weak protection to workers and unions in the formal sector establishments. Unions find themselves increasingly vulnerable to employer hostility. We discuss these findings in the context of the role of state and judiciary in employment relations and of union links with political parties.

Anarchy In The Airways

In his dialogue - Anarchy In The Airways - Joseph C. Von Kornfeld, Assistant Professor, College of Hotel Administration, University of Nevada, Las Vegas initially states: “Deregulation of the airline industry has brought about financial vulnerability for the traveling public. The author analyzes the situation since that point in time and makes recommendations for some solutions.” In this article, Assistant Professor Von Kornfeld, first defines the airline industry in its pre-regulated form. Then he goes into the ramifications and results of deregulating the industry, both in regards to the consumer, and in deregulation’s impact on the airlines themselves. “The most dramatic consequence of the pressures and turbulence of airline deregulation has been the unprecedented proliferation of airline bankruptcies,” Von Kornfeld informs. “Prior to the deregulation of the U.S. airline industry in 1978, U.S. air carriers operated in a business environment that was insulated from the normal stresses and strains of open competition. They were restricted from actively competing with fares and routings by the Civil Aeronautics Board (CAB),” Von Kornfeld says. In leveling the playing field, Von Kornfeld offers, “Each carrier was restricted to specific geographic routes, with those routes limited to two or three competing carriers. The only thing that set carriers apart in this CAB defined atmosphere was their ability to either advertise, or to enhance their level of service; or both. “…ultimately paid for by the passenger through fare increases sanctioned by the CAB,” Von Kornfeld states. “Airline service standards were unquestionably superior during the regulated environment,” Von Kornfeld renders an interesting observation. He does mention, however, that carrier safety was also considered a concern immediately prior to, and then after deregulation. “The major controversy focused on the allegation that safety and maintenance standards would be compromised due to the financial pressures brought about by an openly competitive environment,” Von Kornfeld says. Pricing, as well as labor unions are important factors in the equation, and Von Kornfeld addresses their relevance in the deregulated environment. “The primary rationalization for deregulation was to facilitate a more openly competitive environment. The increased competition was to ultimately have benefitted the consumer. Ironically, that’s not entirely the case, Von Kornfeld elaborates. In addressing some of the negative aspects of airline deregulation, Von Kornfeld suggests that some sort of federal re-regulation may be in order.

International Air Transporation: Some Challenges

In a Spring 1984 article in the FIU Hospitality Review, new developments in the domestic airline industry were discussed, particularly those relating to the forces of deregulation and the changes brought about by this phenomenon. This article takes a wider perspective in examining the global air transportation scene, the changes that have been wrought recently on air carriers flying international routes, and the carriers' responses to these changes.

A Look Back To Look Forward: New Patterns In The Supply/Demand Equation In The Lodging Industry

In his dialogue entitled - A Look Back to Look Forward: New Patterns In The Supply/Demand Equation In The Lodging Industry - by Albert J. Gomes, Senior Principal, Pannell Kerr Forster, Washington, D.C. What the author intends for you to know is the following: “Factors which influence the lodging industry in the United States are changing that industry as far as where hotels are being located, what clientele is being served, and what services are being provided at different facilities. The author charts these changes and makes predictions for the future.” Gomes initially alludes to the evolution of transportation – the human, animal, mechanical progression - and how those changes, in the last 100 years or so, have had a significant impact on the hotel industry. “A look back to look forward treats the past as prologue. American hoteliers are in for some startling changes in their business,” Gomes says. “The man who said that the three most important determinants for the success of a hotel were “location, location, location” did a lot of good only in the short run.” Gomes wants to make you aware of the existence of what he calls, “locational obsolescence.” “Locational obsolescence is a fact of life, and at least in the United States bears a direct correlation to evolutionary changes in transportation technology,” he says. “…the primary business of the hospitality industry is to serve travelers or people who are being transported,” Gomes expands the point. Tied to the transportation element, the author also points out an interesting distinction between hotels and motels. In addressing, “…what clientele is being served, and what services are being provided at different facilities,” Gomes suggests that the transportation factor influences these constituents as well. Also coupled with this discussion are oil prices and shifts in transportation habits, with reference to airline travel being an ever increasing method of travel; capturing much of the inter-city travel market. Gomes refers to airline deregulation as an impetus. The point being, it’s a fluid market rather than a static one, and [successful] hospitality properties need to be cognizant of market dynamics and be able to adjust to the variables in their marketplace. Gomes provides many facts and figures to bolster his assertions. Interestingly and perceptively, at the time of this writing, Gomes alludes to America’s deteriorating road and bridge network. As of right now, in 2009, this is a major issue. Gomes rounds out this study by comparing European hospitality trends to those in the U.S.

The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool.

Associação da imunoexpressão das proteínas XRCC1, TFIIH E XPF com características clinicopatológicas e sobrevida em carcinoma epidermoide de língua oral

DNA repair systems, genes and proteins are essential for genome integrity maintenance, avoiding serious diseases such as cancer. Deregulation in the expression of those proteins has been associated with both the risk of development and evolution of various human cancers, including oral squamous cell carcinoma. The purpose of this study was to analyze the immunoreactivity of the DNA repair proteins XRCC1, THIIF and XPF in oral tongue squamous cell carcinoma (OTSCC) and to investigate its association with clinical and histopathological parameters, outcome and 5-year survival rate. Seventy-four cases of OTSCC were analyzed semi-quantitatively through immunohistochemistry. We observed that DNA repair proteins were highly expressed in parenchymal cells; however, we only observed a significant association between XRCC1 high expression and better clinical staging (p=0,02). Cox regression showed that tumor size (p<0,01), lymph node involvement (p=0,04), tumor stage (p=0,02) and depth of invasion> 4mm (p=0,05) were prognostic factors. The results of this experiment suggest that XRCC1, TFIIH and XPF participate in the tumorigenic process, however, their immunoexpression may not be used as an independent prognostic indicator for OTSCC.

Associação da imunoexpressão das proteínas XRCC1, TFIIH E XPF com características clinicopatológicas e sobrevida em carcinoma epidermoide de língua oral

DNA repair systems, genes and proteins are essential for genome integrity maintenance, avoiding serious diseases such as cancer. Deregulation in the expression of those proteins has been associated with both the risk of development and evolution of various human cancers, including oral squamous cell carcinoma. The purpose of this study was to analyze the immunoreactivity of the DNA repair proteins XRCC1, THIIF and XPF in oral tongue squamous cell carcinoma (OTSCC) and to investigate its association with clinical and histopathological parameters, outcome and 5-year survival rate. Seventy-four cases of OTSCC were analyzed semi-quantitatively through immunohistochemistry. We observed that DNA repair proteins were highly expressed in parenchymal cells; however, we only observed a significant association between XRCC1 high expression and better clinical staging (p=0,02). Cox regression showed that tumor size (p<0,01), lymph node involvement (p=0,04), tumor stage (p=0,02) and depth of invasion> 4mm (p=0,05) were prognostic factors. The results of this experiment suggest that XRCC1, TFIIH and XPF participate in the tumorigenic process, however, their immunoexpression may not be used as an independent prognostic indicator for OTSCC.

Defining the Role of the Histone Methyltransferase, PR-Set7, in Maintaining the Genome Integrity of Drosophila Melanogaster

The complete and faithful duplication of the genome is essential to ensure normal cell division and organismal development. Eukaryotic DNA replication is initiated at multiple sites termed origins of replication that are activated at different time through S phase. The replication timing program is regulated by the S-phase checkpoint, which signals and repairs replicative stress. Eukaryotic DNA is packaged with histones into chromatin, thus DNA-templated processes including replication are modulated by the local chromatin environment such as post-translational modifications (PTMs) of histones.

One such epigenetic mark, methylation of lysine 20 on histone H4 (H4K20), has been linked to chromatin compaction, transcription, DNA repair and DNA replication. H4K20 can be mono-, di- and tri-methylated. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7 and subsequent di-/tri- methylation is catalyzed by Suv4-20. Prior studies have shown that PR-Set7 depletion in mammalian cells results in defective S phase progression and the accumulation of DNA damage, which may be partially attributed to defects in origin selection and activation. Meanwhile, overexpression of mammalian PR-Set7 recruits components of pre-Replication Complex (pre-RC) onto chromatin and licenses replication origins for re-replication. However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 impacts the replication program on a genomic scale. Finally, the methylation substrates of PR-Set7 include both histone (H4K20) and non-histone targets, therefore it is necessary to directly test the role of H4K20 methylation in PR-Set7 regulated phenotypes.

I employed genetic, cytological, and genomic approaches to better understand the role of H4K20 methylation in regulating DNA replication and genome stability in Drosophila melanogaster cells. Depletion of Drosophila PR-Set7 by RNAi in cultured Kc167 cells led to an ATR-dependent cell cycle arrest with near 4N DNA content and the accumulation of DNA damage, indicating a defect in completing S phase. The cells were arrested at the second S phase following PR-Set7 downregulation, suggesting that it was an epigenetic effect that coupled to the dilution of histone modification over multiple cell cycles. To directly test the role of H4K20 methylation in regulating genome integrity, I collaborated with the Duronio Lab and observed spontaneous DNA damage on the imaginal wing discs of third instar mutant larvae that had an alanine substitution on H4K20 (H4K20A) thus unable to be methylated, confirming that H4K20 is a bona fide target of PR-Set7 in maintaining genome integrity.

One possible source of DNA damage due to loss of PR-Set7 is reduced origin activity. I used BrdU-seq to profile the genome-wide origin activation pattern. However, I found that deregulation of H4K20 methylation states by manipulating the H4K20 methyltransferases PR-Set7 and Suv4-20 had no impact on origin activation throughout the genome. I then mapped the genomic distribution of DNA damage upon PR-Set7 depletion. Surprisingly, ChIP-seq of the DNA damage marker γ-H2A.v located the DNA damage to late replicating euchromatic regions of the Drosophila genome, and the strength of γ-H2A.v signal was uniformly distributed and spanned the entire late replication domain, implying stochastic replication fork collapse within late replicating regions. Together these data suggest that PR-Set7-mediated monomethylation of H4K20 is critical for maintaining the genomic integrity of late replicating domains, presumably via stabilization of late replicating forks.

In addition to investigating the function of H4K20me, I also used immunofluorescence to characterize the cell cycle regulated chromatin loading of Mcm2-7 complex, the DNA helicase that licenses replication origins, using H4K20me1 level as a proxy for cell cycle stages. In parallel with chromatin spindown data by Powell et al. (Powell et al. 2015), we showed a continuous loading of Mcm2-7 during G1 and a progressive removal from chromatin through S phase.

Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma.

We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111.