Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase

Phenolic marine natural product is a kind of new potential aldose reductase inhibitors (ARIs). In order to investigate the binding mode and inhibition mechanism, molecular docking and dynamics studies were performed to explore the interactions of six phenolic inhibitors with human aldose reductase (hALR2). Considering physiological environment, all the neutral and other two ionized states of each phenolic inhibitor were adopted in the simulation. The calculations indicate that all the inhibitors are able to form stable hydrogen bonds with the hALR2 active pocket which is mainly constructed by residues TYR48, HIS110 and TRP111, and they impose the inhibition effect by occupying the active space. In all inhibitors, only La and its two ionized derivatives La_ion1 and La_ion2, in which neither of the ortho-hydrogens of 3-hydroxyl is substituted by Br, bind with hALR2 active residues using the terminal 3-hydroxyl. While, all the other inhibitors, at least one of whose ortho-sites of 3- and 6-hydroxyls are substituted by Br substituent which take much electron-withdrawing effect and steric hindrance, bind with hALR2 through the lactone group. This means that the Br substituent can effectively regulate the binding modes of phenolic inhibitors. Although the lactone bound inhibitors have relatively high RMSD values, our dynamics study shows that both binding modes are of high stability. For each inhibitor molecule, the ionization does not change its original binding mode, but it does gradually increase the binding free energy, which reveals that besides hydrogen bonds, the electrostatic effect is also important to the inhibitor–hALR2 interaction.

Job change and workplace learning in the public sector: the significance of new technology for unskilled work.

Focussing here on local authorities and health services, this paper examines the significance of new technology to unskilled work in the public sector as it is developing and the implications for workplace learning. An argument is developed that new technology is central to a minority of examples of job change, although, significantly, it is more important to staff–initiated change and to workers’ ability to fully participate in life beyond the workplace.

Ethics and Foreign Policy: The Antinomies of New Labour's 'Third Way' in Sub-Saharan Africa

Abrahamsen, Rita, Williams, Paul, 'Ethics and Foreign Policy: The Antinomies of New Labour's 'Third Way' in Sub-Saharan Africa', Political Studies (2002) 49(2) pp.249-264 RAE2008

Health Security in the White Book on National Security of the Republic of Poland - A Review of Provisions

The paper reviews the provisions of the White Book on National Security of the Republic of Poland. It states that the issue of health security is not given adequate significance there. The accessibility of health services is considered, in general, solely in terms of their availability. The assumptions concerning the concept of providing the number of beds required in a state of threat to national security and in time of war do not take into account the current socio-economic conditions and need to be reviewed. The conclusions emphasize the dilemmas that emerge as a result of the unilateral promotion of a single category of national security, that is military security, in the context of ensuring health security.

An account of the life of Mr. David Brainerd : missionary from the Society for Propagating Christian Knowledge, & pastor of a church of Christian Indians in New-Jersey / published by Jonathan Edwards ; with Mr. Brainerd's public journal ; to this edition is added, Mr. Beatty's mission to the westward of the Allegheny Mountains.

http://www.archive.org/details/accountoflifeofm00brairich

Samson Occom and the Christian Indians of New England [electronic resource] / by W. DeLoss Love.

http://www.archive.org/details/samsonoccom00loverich/

An analysis of political efficacy socialisation among threshold voters in the Republic of Ireland

The spread of democracy in the latter part of the twenty first century has been accompanied by an increasing focus on its perceived performance in established western democracies. Recent literature has expressed concern about a critical outlook among younger cohorts which threatens their political support and engagement. Political efficacy, referring to the feeling of political effectiveness, is considered to be a key indicator of the performance of democratic politics; as it refers to the empowerment of citizens, and relates to their willingness to engage in political matters. The aim of this thesis is to analyse the socialisation of political efficacy among those on the threshold of political adulthood; i.e., 'threshold voters'. The long-term significance of attitudes developed by time of entry to adulthood for political engagement during adulthood has been emphasised in recent literature. By capturing the effect of non-political and political learning among threshold voters, the study advances existing research frames which focus on childhood and early adolescent socialisation. The theoretical and methodological framework applied herein recognises the distinction between internal and external political efficacy, which has not been consistently operationalized in existing research on efficacy socialisation. This research involves a case study of 'threshold voters' in the Republic of Ireland, and employs a quantitative methodology. A study on Irish threshold voters is timely as the parliament and government have recently proposed a lowering of the voting age and an expansion of formal political education to this age group. A project-specific survey instrument was developed and administered to a systematic stratified sample of 1,042 post-primary students in the Cork area. Interpretation of the results of statistical analysis leads to findings on the divergent influence of family, school, associational, and political agents/environments on threshold voter internal and external political efficacy.

An exploratory study on the impact of an early years' preschool intervention programme in the Republic of Ireland

Early years’ education has increasingly been identified as a mechanism to alleviate educational disadvantage in areas of social exclusion. Early years’ intervention programmes are now a common government social policy for addressing social problems (Reynolds, Mann, Miedel, and Smokowski, 1997). In particular, state provided early years’ programmes such as Head Start in the United States and Early Start in Ireland have been established to combat educational disadvantage for children experiencing poverty and socio-economic inequality. The focus of this research is on the long-term outcomes of an early years’ intervention programme in Ireland. It aims to assess whether participation in the programme enhances the life course of children at-risk of educational disadvantage. It involves an in-depth analysis of one Early Start project which was included in the original eight projects established by the Department of Education and Science in 1994. The study utilises a multi-group design to provide a detailed analysis of both the academic and social progress of programme participants. It examines programme outcomes from a number of perspectives by collecting the views of the three main stakeholders involved in the education process; students who participated in Early Start in 1994/5, their parents and their teachers. To contribute to understanding the impact of the programme from a community perspective interviews were also conducted with local community educators and other local early years’ services. In general, Early Start was perceived by all participants in this study as making a positive contribution to parent involvement in education and to strengthening educational capital in the local area. The study found that parents and primary school teachers identified aspects of school readiness as the main benefit of participation in Early Start and parents and teachers were very positive about the role of Early Start in preparing children for the transition to formal school. In addition to this, participation in Early Start appears to have made a positive contribution to academic attainment in Maths and Science at Junior Certificate level. Students who had participated in Early Start were also rated more highly by their second level teachers in terms of goal-setting and future orientation which are important factors in educational attainment. Early Start then can be viewed as providing a positive contribution to the long-term social and academic outcomes for its participants.

The impact of new public management on the roles of elected councillors, management and the community sector in Irish local government: a case study of Cork County Council

The fundamental aim of this thesis is to examine the effect of New Public Management (NPM) on the traditional roles of elected representatives, management and community activists in Irish local government. This will be achieved through a case study analysis of one local authority, Cork County Council. NPM promises greater democracy in decision-making. Therefore, one can hypothesise that the roles of the three key groupings identified will become more influenced by principles of participatory decision-making. Thus, a number of related questions will be addressed by this work, such as, have the local elected representatives been empowered by NPM? Has a managerial revolution taken place? Has local democracy been enhanced by more effective community participation? It will be seen in chapter 2 that these questions have not been adequately addressed to date in NPM literature. The three groups identified can be regarded as stakeholders although the researcher is cautious in using this term because of its value-laden nature. Essentially, in terms of Cork County Council, stakeholders can be defined as decision-makers and people within the organization and its environment who are interested in or could be affected directly or indirectly by organizational performance. This is an all-embracing definition and includes all citizens, residents, community groups and client organizations. It is in this context that the term 'stakeholder' should be understood when it is occasionally used in this thesis. In this case, the perceptions of elected councilors, management and community representatives with regard to their changing roles are as significant as the changes themselves. The chapter begins with a brief account of the background to this research. This is followed by an explanation of the methodology which is used and then concludes with short statements about the remaining chapters in the thesis.

The ways in which new public management ideas impact upon the administrative culture of 'street-level' bureaucrats and professionals working within Irish social policy

The conventional meaning of culture is ‘widely shared and strongly held values’ of a particular group or society (Bradley and Parker, 2006: 89). Culture is not a rigid concept; it can be influenced or altered by new ideas or forces. This research examines the ways in which one set of ideas in particular, that is, those associated with New Public Management, have impacted upon the administrative culture of 'street-level' bureaucrats and professionals within Irish social policy. Lipsky (1980: 3) defined 'street-level' bureaucrats as ‘public service workers who interact directly with citizens in the course of their jobs, and who have substantial discretion in the execution of their work’. Utilising the Competing Values Framework (CVF) in the analysis of eighty three semi-structured interviews with 'street-level' bureaucrats and professionals, an evaluation is made as to the impact of NPM ideas on both visible and invisible aspects of administrative culture. Overall, the influence of NPM is confined to superficial aspects of administrative culture such as; increased flexibility in working hours and to some degree job contracts; increased time commitment; and a customer service focus. However, the extent of these changes varies depending on policy sector and occupational group. Aspects of consensual and hierarchical cultures remain firmly in place. These coincide with features of developmental and market cultures. Contrary to the view that members of hierarchical and consensual culture would pose resistance to change, this research clearly illustrates that a very large appetite for change exists in the attitudes of 'street-level' bureaucrats and professionals within Irish social policy, with many of them suggesting changes that correspond to NPM ideas. This study demonstrates the relevance of employing the CVF model as it is clear that administrative culture is very much a dynamic system of competing and co-existing cultures.

The development of new methods for high resolution radio astronomy imaging

Very Long Baseline Interferometry (VLBI) polarisation observations of the relativistic jets from Active Galactic Nuclei (AGN) allow the magnetic field environment around the jet to be probed. In particular, multi-wavelength observations of AGN jets allow the creation of Faraday rotation measure maps which can be used to gain an insight into the magnetic field component of the jet along the line of sight. Recent polarisation and Faraday rotation measure maps of many AGN show possible evidence for the presence of helical magnetic fields. The detection of such evidence is highly dependent both on the resolution of the images and the quality of the error analysis and statistics used in the detection. This thesis focuses on the development of new methods for high resolution radio astronomy imaging in both of these areas. An implementation of the Maximum Entropy Method (MEM) suitable for multi-wavelength VLBI polarisation observations is presented and the advantage in resolution it possesses over the CLEAN algorithm is discussed and demonstrated using Monte Carlo simulations. This new polarisation MEM code has been applied to multi-wavelength imaging of the Active Galactic Nuclei 0716+714, Mrk 501 and 1633+382, in each case providing improved polarisation imaging compared to the case of deconvolution using the standard CLEAN algorithm. The first MEM-based fractional polarisation and Faraday-rotation VLBI images are presented, using these sources as examples. Recent detections of gradients in Faraday rotation measure are presented, including an observation of a reversal in the direction of a gradient further along a jet. Simulated observations confirming the observability of such a phenomenon are conducted, and possible explanations for a reversal in the direction of the Faraday rotation measure gradient are discussed. These results were originally published in Mahmud et al. (2013). Finally, a new error model for the CLEAN algorithm is developed which takes into account correlation between neighbouring pixels. Comparison of error maps calculated using this new model and Monte Carlo maps show striking similarities when the sources considered are well resolved, indicating that the method is correctly reproducing at least some component of the overall uncertainty in the images. The calculation of many useful quantities using this model is demonstrated and the advantages it poses over traditional single pixel calculations is illustrated. The limitations of the model as revealed by Monte Carlo simulations are also discussed; unfortunately, the error model does not work well when applied to compact regions of emission.

Experiences of the foster care process in the Republic of Ireland: retrospective accounts from biological children of foster carers

This thesis examines the experiences of the biological children of foster carers. In particular it explores their experiences in relation to inclusion, consultation and decision-making. The study also examines the support and training needs of birth children in foster families. Using a qualitative methodology in-depth, semi-structured interviews were conducted with fifteen birth children of foster carers aged between 18 and 30 years. The research findings show that for the majority of birth children, fostering was overall a positive experience which helped them develop into individuals who were caring and nonjudgemental. However, from the data collected in this study, it is clear that fostering also brings a range of challenges for birth children in foster families, such as managing feelings of loss, grief, jealousy and guilt when foster children leave. Birth children are reluctant to discuss these issues with their parents and often did not approach fostering social workers as they did not have a meaningful relationship in order to discuss their concerns. The findings also demonstrate that birth children undertake a lot of emotional work in supporting their parents, birth siblings and foster siblings. Despite the important role played by birth children in the fostering process, this contribution often goes unrecognised and unacknowledged by fostering professionals and agencies with birth children not included or consulted about foster care decisions that affect them. It is argued here that birth children are viewed by foster care professionals and agencies from a deficit based perspective. However, this study contends that it is not just foster parents who are involved in the foster care process, but the entire foster family. The findings of this study show that birth children are competent social actors capable of making valuable contributions to foster care decisions that affect their lives and that of their family.

Chemical characterization of oligosaccharides in the milk of six species of New and Old World monkeys.

Human and great ape milks contain a diverse array of milk oligosaccharides, but little is known about the milk oligosaccharides of other primates, and how they differ among taxa. Neutral and acidic oligosaccharides were isolated from the milk of three species of Old World or catarrhine monkeys (Cercopithecidae: rhesus macaque (Macaca mulatta), toque macaque (Macaca sinica) and Hamadryas baboon (Papio hamadryas)) and three of New World or platyrrhine monkeys (Cebidae: tufted capuchin (Cebus apella) and Bolivian squirrel monkey (Saimiri boliviensis); Atelidae: mantled howler (Alouatta palliata)). The milks of these species contained 6-8% total sugar, most of which was lactose: the estimated ratio of oligosaccharides to lactose in Old World monkeys (1:4 to 1:6) was greater than in New World monkeys (1:12 to 1:23). The chemical structures of the oligosaccharides were determined mainly by (1)H-NMR spectroscopy. Oligosaccharides containing the type II unit (Gal(β1-4)GlcNAc) were found in the milk of the rhesus macaque, toque macaque, Hamadryas baboon and tufted capuchin, but oligosaccharides containing the type I unit (Gal(β1-3)GlcNAc), which have been found in human and many great ape milks, were absent from the milk of all species studied. Oligosaccharides containing Lewis x (Gal(β1-4)[Fuc(α1-3)]GlcNAc) and 3-fucosyl lactose (3-FL, Gal(β1-4)[Fuc(α1-3)]Glc) were found in the milk of the three cercopithecid monkey species, while 2-fucosyl lactose (5'-FL, Fuc(α1-2)Gal(β1-4)Glc) was absent from all species studied. All of these milks contained acidic oligosaccharides that had N-acetylneuraminic acid as part of their structures, but did not contain oligosaccharides that had N-glycolylneuraminic acid, in contrast to the milk or colostrum of great apes which contain both types of acidic oligosaccharides. Two GalNAc-containing oligosaccharides, lactose 3'-O-sulfate and lacto-N-novopentaose I (Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc) were found only in the milk of rhesus macaque, hamadryas baboon and tufted capuchin, respectively. Further research is needed to determine the extent to which the milk oligosaccharide patterns observed among these taxa represent wider phylogenetic trends among primates and how much variation occurs among individuals or species.

[In Backpages 18.1] The culture of new writing

The influence of writing workshops on the content of plays is discussed.