Exploring the Epigenome of Neurons and Glia in Vitro to Determine their Utility as a Model for Alzheimer's Disease

Alzheimer’s disease is a progressive neurodegenerative condition that is characterised by distinct neuropathological changes. Within the last decade post mortem human brain samples have been used to show that there are robust epigenetic changes occurring in the brain during disease. However, as these samples are collected shortly after death they are a reflection of only the very end stages of disease. Through the exposure of differentiated adult cells to exogenous reprogramming factors it is now possible to generate induced pluripotent stem cells which have the potential to differentiate into any cell type in the body. Over recent years reseach has moved towards using these stem cells to generate neurons or microglia in order to study diseases of ageing such as Alzheimer’s disease. However, there are relatively few epigenetic studies that have been undertaken using induced pluripotent stem cells. As there are global cellular epigenetic changes occurring during the induction of pluripotency and re-differentiation it is critical to ensure we understand the DNA methylation changes occurring during normal neuronal differentiation before using these as a model of Alzheimer’s disease or other diseases of ageing. The aim of this thesis is to first characterise the DNA methylation changes that are occurring in neuronal and microglial models that are exposed to AD-relevant exposures such as differentiation and maturation, drug treatment and immune challenge. This will largely be achieved through measuring DNA methylation using the Illumina Infinium HumanMethylationEPIC BeadChip array which provides information on the DNA methylation levels at over 850,000 loci across the genome.Alzheimers Research UKAlzheimer's Societ

Effects Of Ownership Structure, Motives And Premiums Paid On Bidding Firms' Performance [HD2746.55.M2 S698 2007 f rb].

Secara umumnya literatur mengenai pengambilan korporat menyimpulkan bahawa pembida rugi atau tidak untung di sekitar pengumuman pengambilalihan. Walaupun begitu, statistik telah menunjukkan bahawa pengambilan korporat masih menjadi suatu strategi yang popular oleh firma-firma untuk pertumbuhan. Generally literature on take-overs highlight that bidders lose or do not gain upon the announcement of a take-over. Despite the negative empirical findings, take-over activities are still a major corporate maneuver for growth as can be seen from the increasing trend in the statistics

Lexical borrowing in Malaysian English: Influences of Malay

During its evolution in the region that is today Malaysia, English has come into contact with a range of diverse, typologically-distinct languages. All these languages have influenced the lexicon of Malaysia English (ME), but it is Malay that has contributed to some of the most remarkable characteristics of this variety of English (see, for example, Lowenberg [1986 and 2000]; and Morais [2001]). This paper explores how the English-Malay contact has resulted in the incorporation of Malay features into the lexicon of ME. Using a corpus-based approach, the study analysed a comprehensive range of borrowed features extracted from the author’s Malaysian English Newspaper Corpus (MEN Corpus) for the linguistic processes behind the borrowing phenomenon. Haugen’s [1950] groundbreaking work on lexical borrowing provides the theoretical framework of this study. It is proposed that the underlying systematicity of the processes involved is reflected in the linguistic outcomes, and that there is much potential for corpus-based lexicography where ME is concerned. To highlight the non-arbitrariness of the borrowing phenomenon, the social and linguistic factors that motivate ME users to incorporate Malay lexical features into their variety of English are examined

Women of Color Reclaiming Power

The following is the address that was given at the Sixth Annual Women of Color Day Celebration at the University of Massachusetts at Boston on March 5, 1993. In a racist and sexist world, our realities are hardly ever alluded to, let alone affirmed; the way we see ourselves and the way we experience the world is hardly ever reflected in the images we see around us or in the stories we read. We constantly have to translate information in order to make it relevant and applicable to our lives. Our realities, experiences are often discounted, overlooked and ignored. Both racism and sexism make us feel bad about ourselves and about each other. Sexism devalues our humanness, our goodness, abilities and power as females and encourages us to compete to get male attention. Racism devalues our humanness, our goodness, abilities and power as people of color, feeds false information about each other and pits us one against each other. It is no wonder that we have a hard time trying to remember who we really are and our natural deep connections with each other. As a community of women of color, we have all felt the effects of both racism and sexism. But the way racism and sexism work on each community of color is quite specific and different. (The stereotypes and messages put out for and about Hispanic. Afro-American. and Asian women are not quite the same, for example.

The Impact of Network Relationships on Smes' Internationalization Process: A Case Study of Malaysian Firms

Today most business activities are global in scope. A firm that fails to make a global profit may well go out of business. Therefore, more and more Malaysian firms are striving to have an international presence. But when firms decided to explore international market, they begin to face a lot of challenges that require them to take strategic decisions. Therefore, this study intended to look into bow indigenous software firms use their network relationships to facilitate their internationalization process. This research used a multi-site case study methodology to more effectively identify and understand detailed international growth patterns and processes. Three respondent software finns were randomly selected from MSC (Multimedia Super Corridor) status SMEs (Small Medium-sized Enterprises). On top of that, a manufacturing firm was conveniently selected to compare differences on network relationships' influence on its internationalization process with those of manufacturing firms. In each case, upper level managers were interviewed. Information was also collected from printed documents or Internet to increase source validity. In summary, the evidences from the three software firms were found to support the firms' internationalization process in the following: • Network relationships trigger international opportunity. • Network relationships motivate firms to internationalize. • Network relationships influence firms' market selection decision. • Network relationships influence firms' entry mode decision. • Network relationships allow firms' to access additional relationships. • Network relationships allow firms' to access established channel. • Network relationships help lower cost and minimize risk. • Network relationships influence firms' internationalization pace and pattern. Therefore, managers need to have a better understanding of the impact of network relationships on firms' internationalization process as it facilitates their internationalization process through the above. A limitation of this study is that it focused on a single sector, software development firm, with only a manufacturing firm taken for comparison. It would be inappropriate to generalize the results too widely. Although case research provides a richness and depth of understanding, to enhance the qualitative approach, it is suggested that a quantitative research is adopted in future research to enhance or further reinforce the findings

Callous-Unemotional Traits, Negative Parenting Practices and Conduct Problems in Singaporean Families

Research into callous-unemotional traits is largely limited to studies in Western countries (e.g., Waller, Gardner & Hyde, 2013). Three studies were thus conducted to examine CU traits in Asian culture. The first study reviewed existing research on CU traits in Asian countries based on key findings from Western countries: if CU traits in Asia were associated with increased severity of conduct problems, neurodevelopmental/emotion-related correlates, environmental risk factors and treatment outcomes. Findings from 15 samples provided some evidence of similar risk processes between Asian and Western samples, but also indicated some differences, e.g., associations between CU traits and anxiety or peer influence. In the second study, it was predicted that CU traits would moderate the associations between negative parenting and child aggression in a sample of clinic-referred children, based on findings of Yeh, Chen, Raine, Baker and Jacobson (2011) and differences in heritability of conduct problems between children with high and low CU traits (e.g., Dadds et al., 2006). Psychological aggressive parenting was associated with reactive and proactive aggression. Physically aggressive parenting was more strongly associated with proactive aggression among low-CU children than high-CU children. In the third study, it was predicted that there would be moderate stability of CU traits based on findings of genetic influence on CU traits (e.g., Viding et al., 2005) and bidirectional associations between CU traits and negative parenting. Contrary to predictions, our sample of clinic-referred children showed low stability of CU traits over a six-year period, and no bidirectional link between CU traits and negative parenting. Only parental psychological aggression predicted changes in CU traits. These findings raise the need for ongoing research into CU traits in Asian cultures