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Distribution by Scientific Domains

Chemistry	42%
Medical Sciences	28%

Selected Abstracts

Development of Pharmaceutical Drugs, Drug Intermediates and Ingredients by Using Direct Organo-Click Reactions

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2008
Dhevalapally B. Ramachary
Abstract Here we report on our studies of the use of combinations of amino acids, amines, K2CO3 or Cs2CO3 and CuSO4/Cu for catalysing green cascade reactions. We aimed to prepare the highly reactive and substituted olefin species 7 and 8, under very mild and environmentally friendly conditions, thus giving the hydrogenated products 10 and 12 through the action of Hantzsch ester (4) by self-catalysis through decreasing the HOMO,LUMO energy gaps between olefins 7/8 and Hantzsch ester (4) through biomimetic reductions. Highly useful compounds 10 to 14 were assembled from simple substrates such as aldehydes 1, ketones 2, CH acids 3, Hantzsch ester (4) and alkyl halides 5 by diversity-oriented green synthesis involving cascade olefination/hydrogenation (O/H), olefination/hydrogenation/alkylation (O/H/A) and hydrogenation/olefination/hydrogenation (H/O/H) reaction sequences in one-pot fashion with stereospecific organo- and organo-/metal-carbonate catalysis. Highly functionalized diverse compounds such as 10 to 14 are biologically active products and have found wide applications as pharmaceutical drugs, drug intermediates and drug ingredients. For the first time in organocatalysis, we report the O/H/A/TE reaction to furnish high yields of transesterification products 11 by simply mixing the reactants under proline/K2CO3 catalysis conditions. Additionally, a novel organocatalytic H/O/H reaction sequence for the synthesis of alkyl-substituted aromatics has been developed. Furthermore, for the first time we have developed organocatalysed cascade olefination/hydrogenation/hydrolysis (O/H/H) reactions to furnish highly useful materials such as 2-oxochroman-3-carboxylic acid (14kc) and 2-amino-4H -chromene-3-carbonitrile (14kj) in good yields. Experimentally simple and environmentally friendly organocatalytic two-carbon homologation through cascade O/H/H reactions of aldehydes 1, Meldrum's acid (3c), Hantzsch ester (4) and acetic acid/triethylamine in ethanol has been demonstrated. Additionally, we have developed a green synthesis of the highly substituted 1,2,3-triazole 17 from simple substrates through a two-step combination of olefination/hydrogenation/alkylation and Huisgen cycloaddition reaction sequences under stereospecific organocopper catalysis conditions. In this paper we have found strong support for our hypothesis that, "decreasing the HOMO,LUMO energy gap between olefins 7/8 and Hantzsch ester (4) will drive the biomimetic hydrogenation reaction by self-catalysis". This self-catalysis was further confirmed with many varieties of examples.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

Teaching & Learning Guide for: Victorian Life Writing

LITERATURE COMPASS (ELECTRONIC), Issue 5 2007
Valerie Sanders
Author's Introduction The Victorian period was one of the great ages for life-writing. Though traditionally renowned for its monumental ,lives and letters', mainly of great men, this was also a time of self-conscious anxiety about the genre. Critics and practitioners alike were unsure who should be writing autobiography, and whether its inherent assertiveness ruled out all but public men as appropriate subjects. It was also a period of experimentation in the different genres of life-writing , whether autobiography, journals, letters, autobiographical novels, and narratives of lives combined with extracts from correspondence and diaries. Victorian life-writing therefore provides rich and complex insights into the relationship between narrative, identity, and the definition of the self. Recent advances in criticism have highlighted the more radical and non-canonical aspects of life-writing. Already a latecomer to the literary-critical tradition (life-writing was for a long time the ,poor relation' of critical theory), auto/biography stresses the hidden and silent as much as the mainstream and vocal. For that reason, study of Victorian life-writing appeals to those with an interest in gender issues, postcolonialism, ethnicity, working-class culture, the history of religion, and family and childhood studies , to name but a few of the fields with which the genre has a natural connection. Author Recommends A good place to start is the two canonical texts for Victorian life-writing: George P. Landow's edited collection, Approaches to Victorian Autobiography (Athens, OH: Ohio University Press, 1979) and Avrom Fleishman's Figures of Autobiography: The Language of Self-Writing in Victorian and Modern England (Berkeley and Los Angeles, CA: University of California Press, 1983). These two re-ignited interest in Victorian life-writing and in effect opened the debate about extending the canon, though both focus on the firmly canonical Ruskin and Newman, among others. By contrast, David Amigoni's recently edited collection of essays, Life-Writing and Victorian Culture (Aldershot: Ashgate 2006) shows how far the canon has exploded and expanded: it begins with a useful overview of the relationship between lives, life-writing, and literary genres, while subsequent chapters by different authors focus on a particular individual or family and their cultural interaction with the tensions of life-writing. As this volume is fairly male-dominated, readers with an interest in women's life-writing might prefer to start with Linda Peterson's chapter, ,Women Writers and Self-Writing' in Women and Literature in Britain 1800,1900, ed. Joanne Shattock (Cambridge: Cambridge University Press, 2001), 209,230. This examines the shift from the eighteenth-century tradition of the chroniques scandaleuses to the professional artist's life, domestic memoir, and spiritual autobiography. Mary Jean Corbett's Representing Femininity: Middle-Class Subjectivity in Victorian and Edwardian Women's Autobiographies (New York, NY: Oxford University Press, 1992) begins with material on Wordsworth and Carlyle, but ,aims to contest the boundaries of genre, gender, and the autobiographical tradition by piecing together a partial history of middle-class women's subjectivities in the nineteenth and early twentieth centuries' (3). Corbett is particularly interested in the life-writing of actresses and suffragettes as well as Martineau and Oliphant, the first two women autobiographers to be welcomed into the canon in the 1980s and 90s. Laura Marcus's Auto/biographical Discourses, Theory, Criticism, Practice (Manchester and New York, NY: Manchester University Press, 1994) revises and updates the theoretical approaches to the study of life-writing, stressing both the genre's hybrid qualities, and its inherent instability: in her view, it ,comes into being as a category to be questioned' (37). Another of her fruitful suggestions is that autobiography functions as a ,site of struggle' (9), an idea that can be applied to aesthetic or ideological issues. Her book is divided between specific textual examples (such as the debate about autobiography in Victorian periodicals), and an overview of developments in critical approaches to life-writing. Her second chapter includes material on Leslie Stephen, who is also the first subject of Trev Lynn Broughton's Men of Letters, Writing Lives: Masculinity and Literary Auto/biography in the Late Victorian Period (London: Routledge, 1999) , her other being Froude's controversial Life of Carlyle. With the advent of gender studies and masculinities, there is now a return to male forms of life-writing, of which Martin A. Danahay's A Community of One: Masculine Autobiography and Autonomy in Nineteenth-Century Britain (Albany, NY: State University of New York Press, 1993) is a good example. Danahay argues that nineteenth-century male autobiographers present themselves as ,autonomous individuals' free of the constraints of social and familial contexts, thus emphasizing the autonomy of the self at the expense of family and community. Online Materials My impression is that Victorian life-writing is currently better served by books than by online resources. There seem to be few general Web sites other than University module outlines and reading lists; for specific authors, on the other hand, there are too many to list here. So the only site I'd recommend is The Victorian Web: http://.victorianweb.org/genre/autobioov.html This Web site has a section called ,Autobiography Overview', which begins with an essay, ,Autobiography, Autobiographicality and Self-Representation', by George P. Landow. There are sections on other aspects of Victorian autobiography, including ,Childhood as a Personal Myth', autobiography in Dickens and Elizabeth Barrett Browning, and a list of ,Suggested Readings'. Each section is quite short, but summarizes the core issues succinctly. Sample Syllabus This sample syllabus takes students through the landmarks of Victorian life-writing, and demonstrates the development of a counter-culture away from the mainstream ,classic male life' (if there ever was such a thing) , culminating in the paired diaries of Arthur Munby (civil servant) and Hannah Cullwick (servant). Numerous other examples could have been chosen, but for those new to the genre, this is a fairly classic syllabus. One week only could be spent on the ,classic male texts' if students are more interested in pursuing other areas. Opening Session Open debate about the definition of Victorian ,life-writing' and its many varieties; differences between autobiography, autobiographical fiction, diary, letters, biography, collective biography, and memoir; the class could discuss samples of selected types, such as David Copperfield, Father and Son, Ruskin's Praeterita, and Gaskell's Life of Charlotte Brontë. Alternatively, why not just begin with Stave Two of Dickens's A Christmas Carol (1843), in which the First Spirit takes Scrooge back through his childhood and youth? This is a pretty unique type of life-writing, with Scrooge ,laughing and crying' as his childhood and youth are revealed to him in a series of flashbacks (a Victorian version of ,This is Your Life?'). The dual emotions are important to note at this stage and will prompt subsequent discussions of sentimentality and writing for comic effect later in the course. Week 2 Critical landmarks: discussion of important stages in the evolution of critical approaches to life-writing, including classics such as Georges Gusdorf's ,Conditions and Limits of Autobiography', in Autobiography: Essays Theoretical and Critical, ed. James Olney (Princeton, NJ: Princeton University Press, 1980), 28,47; Philippe Lejeune's ,The Autobiographical Pact', in On Autobiography, ed. Paul John Eakin, trans. Katherine Leary (original essay 1973; Minneapolis: University of Minnesota Press, 1989), 3,30; and Paul De Man's ,Autobiography as De-Facement', Modern Language Notes 94 (1979): 919,30. This will provide a critical framework for the rest of the course. Weeks 3,4 Extracts from the ,male classics' of Victorian life-writing: J. S. Mill's Autobiography (1873), Ruskin's Praeterita (1885,89), and Newman's Apologia pro Vita Sua (1864). What do they think is important and what do they miss out? How open or otherwise are they about their family and personal lives? Are these essentially ,lives of the mind'? How self-aware are they of autobiographical structures? Are there already signs that the ,classic male life' is fissured and unconventional? An option here would be to spend the first week focusing on male childhoods, and the second on career trajectories. Perhaps use Martin Danahay's theory of the ,autonomous individual' (see above) to provide a critical framework here: how is the ,Other' (parents, Harriet Taylor) treated in these texts? Weeks 5,6 Victorian women's autobiography: Harriet Martineau's Autobiography (1877) and Margaret Oliphant's Autobiography (1899): in many ways these are completely unalike, Martineau's being ordered around the idea of steady mental growth and public recognition, while Oliphant's is deeply emotional and disordered. Can we therefore generalize about ,women's autobiography'? What impact did they have on Victorian theories of life-writing? Students might like to reconsider Jane Eyre as an ,autobiography' alongside these and compare scenes of outright rebellion. The way each text handles time and chronology is also fascinating: Martineau's arranged to highlight stages of philosophical development, while Oliphant's switches back and forth in a series of ,flashbacks' to her happier youth as her surviving two sons die ,in the text', interrupting her story. Week 7 Black women's autobiography: how does Wonderful Adventures of Mrs Seacole in Many Lands (1857) differ from the Martineau and Oliphant autobiographies? What new issues and genre influences are introduced by a Caribbean/travelogue perspective? Another key text would be Harriet Jacobs's Incidents in the Life of a Slave-Girl (1861). How representative and how individual are these texts? Do these authors see themselves as representing their race as well as their class and sex? Week 8 Working-class autobiography: Possible texts here could be John Burnett's Useful Toil (Allen Lane, 1974, Penguin reprint); Carolyn Steedman's edition of John Pearman's The Radical Soldier's Tale (Routledge, 1988) and the mini oral biographies in Henry Mayhew's London Labour and the London Poor (1861,62) (e.g., the Water-Cress Seller). There is also a new Broadview edition of Factory Lives (2007) edited by James R. Simmons, with an introduction by Janice Carlisle. This contains four substantial autobiographical texts (three male, one female) from the mid-nineteenth century, with supportive materials. Samuel Bamford's Passages in the Life of a Radical (1839,42; 1844) and Early Days (1847,48) are further options. Students should also read Regenia Gagnier's Subjectivities: A History of Self-Representation in Britain 1832,1910 (Oxford University Press, 1991). Week 9 Biography: Victorian Scandal: focus on two scandals emerging from Victorian life-writing: Gaskell's Life of Charlotte Brontë (1857) (the Branwell Brontë/Lady Scott adultery scandal), and Froude's allegations of impotence in his Life of Carlyle (1884). See Trev Broughton's ,Impotence, Biography, and the Froude-Carlyle Controversy: ,Revelations on Ticklish Topics', Journal of the History of Sexuality, 7.4 (Apr. 1997): 502,36 (in addition to her Men of Letters cited above). The biographies of the Benson family written about and by each other, especially E. F. Benson's Our Family Affairs 1867,1896 (London: Cassell, 1920) reveal the domestic unhappiness of the family of Gladstone's Archbishop of Canterbury, Edward White Benson, whose children and wife were all to some extent homosexual or lesbian. Another option would be Edmund Gosse's Father and Son (1907) in which the son's critical stance towards his father is uneasy and complex in its mixture of comedy, pity, shame, and resentment. Week 10 Diaries: Arthur Munby's and Hannah Cullwick's relationship (they were secretly married, but lived as master and servant) and diaries, Munby: Man of Two Worlds: The Life and Diaries of Arthur Munby, ed. Derek Hudson (John Murray, 1972), and The Diaries of Hannah Cullwick: Victorian Maidservant, ed. Liz Stanley (New Brunswick, NJ: Rutgers University Press, 1984): issues of gender and class identity; the idealization of the working woman; the two diaries compared. Half the class could read one diary and half the other and engage in a debate about the social and sexual fantasies adopted by each diarist. It would also be sensible to leave time for an overview debate about the key issues of Victorian life-writing which have emerged from this module, future directions for research, and current critical developments. Focus Questions 1To what extent does Victorian autobiography tell an individual success story? Discuss with reference to two or three contrasting examples. 2,All life writing is time writing' (Jens Brockmeier). Examine the way in which Victorian life-writers handle the interplay of narrative, memory, and time. 3To what extent do you agree with the view that Victorian life-writing was ,a form of communication that appeared intimate and confessional, but which was in fact distant and controlled' (Donna Loftus)? 4,Bamford was an autobiographer who did not write an autobiography' (Martin Hewitt). If autobiography is unshaped and uninterpreted, what alternative purposes does it have in narrating a life to the reader? 5,Victorian life-writing is essentially experimental, unstable, and unpredictable.' How helpful is this comment in helping you to understand the genre? [source]

Chloroquine resistance in the malarial parasite, Plasmodium falciparum

MEDICINAL RESEARCH REVIEWS, Issue 5 2002
Lyann M.B. Ursos
Abstract Malarial parasites remain a health problem of staggering proportions. Worldwide, they infect about 500 million, incapacitate tens of millions, and kill approximately 2.5 million (mostly children) annually. Four species infect humans, but most deaths are caused by one particular species, Plasmodium falciparum. The rising number of malarial deaths is due in part to increased drug resistance in P. falciparum. There are many varieties of antimalarial drug resistance, and there may very well be several molecular level contributions to each variety. This is because there are a number of different drugs with different mechanisms of action in use, and more than one molecular event may sometimes be relevant for resistance to any one class of drugs. Thus, "multidrug" resistance in a clinical setting likely entails complex combinations of overlapping resistance pathways, each specific for one class of drug, that then add together to confer the particular multidrug resistance phenotype. Nonetheless, rapid progress has been made in recent years in elucidating mechanisms of resistance to specific classes of antimalarial drugs. As one example, resistance to the antimalarial drug chloroquine, which has been the mainstay therapy for decades, is becoming well understood. This article focuses on recent advances in determining the molecular mechanism of chloroquine resistance, with particular attention to the biochemistry and biophysics of the P. falciparum digestive vacuole, wherein changes in pH have recently been found to be associated with chloroquine resistance. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 465,491, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10016 [source]

Observing the approaches to weaning of the long-term ventilated patients

NURSING IN CRITICAL CARE, Issue 2 2010
Kalliopi Kydonaki
Background: The weaning process from mechanical ventilation is a complicated issue for patients with respiratory failure who require long-term respiratory support. Although the application of weaning protocols reduces weaning time, and enhances patient outcome, little is known about the actual approaches that clinicians use for the weaning of these patients. Aim: The purpose of this paper is to explore approaches to weaning of long-term ventilated patients in a Scottish Intensive Care Unit. The findings are part of a larger study on decision-making during the weaning of long-term ventilated patients. Method: Data were collected through participant observation and follow-up interviews with the nursing staff. Twenty-four-hour chart and medical notes review and informal conversation with the bedside nurse were also used to collect information on the weaning process. Findings: Nine patients were recruited to the study. Two patients were extubated and three patients were extubated but then required a tracheostomy. A further four patients had a tracheostomy performed. Thematic analysis of the data showed that weaning was individualized, and physician led, regardless of the existence of the weaning protocol. Six different weaning approaches were identified. Nurses followed a conservative approach to weaning in comparison to doctors who appeared more aggressive. Conclusion: There are many varieties in the approaches clinicians use when weaning long-term ventilated patients, which acts on the continuity of their care. A shift of focus to identify ways of maintaining continuity of care and a combined ,wake and wean' approach needs to be considered. [source]

MIXED INDUSTRIAL STRUCTURE AND SHORT-RUN FISCAL MULTIPLIER

AUSTRALIAN ECONOMIC PAPERS, Issue 2 2008
ROBERTO CENSOLO
Existing studies on the fiscal multiplier under imperfect competition assume a symmetric market structure with identical firms. This paper examines the fiscal policy implications of introducing a multisectoral economy, where a composite commodity is offered in many varieties within a market of monopolistic competition and a homogeneous good is produced in a perfectly competitive environment. Within the context of this mixed industrial structure we show that the size of the short-run multiplier crucially depends on the composition of public expenditure chosen by the government. [source]

Classification of reproductive performance of ten winegrape varieties

AUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 2010
P.R. DRY
Abstract Background and Aims:, Flowering and fruitset are principal determinants of grapevine yield. Poor fruitset is said to limit the yield of many varieties in most regions in Australia; however, there is a lack of knowledge of the reproductive performance of most varieties under Australian conditions. Methods and Results:, The reproductive performance of Vitis vinifera winegrape varieties , Cabernet Sauvignon, Chardonnay, Merlot, Nebbiolo, Pinot Noir, Sangiovese, Sauvignon Blanc, Shiraz, Tempranillo, and Zinfandel , was studied in four consecutive growing seasons (commencing in 2004/05) across a range of climatic regions from cool (Adelaide Hills) to warm (Adelaide Plains). Measures of reproductive performance included flower number per inflorescence, fruitset (%), berry number per bunch, coulure index (CI), and millerandage index (MI). Principal component analysis and agglomerative hierarchical classification were used to group the varieties into three classes of reproductive performance. Conclusions:, Certain varieties have a reputation of having ,poor fruitset' that has been inferred from relatively low berry number per bunch; however, for some of these varieties, it is ,low flower number per inflorescence' rather than ,poor fruitset' that is the cause of low berry number. Significance of the Study:, An improved understanding of the reproductive performance of winegrape varieties has been achieved. [source]

Tapetoretinal degenerations: Experiences, experiments and expectations

ACTA OPHTHALMOLOGICA, Issue 3 2000
Berndt Ehinger
ABSTRACT. Tapetoretinal degenerations are a common cause for vision problems, but have until recently not been amenable to rational treatment. With rapidly increasing insights into basic neurobiology and pathobiology this has now begun to change. From having been a relatively small group of largely unknown yet fairly prevalent disorders, they are rapidly forming a large set of well defined diseases, and it is easy to predict that our knowledge about them will continue to increase for many years to come. Vitamin A (15 ,000 IU daily) is currently the only rational treatment available. However, in experimental animals, therapy strategies are now actively being developed along several different lines. Apoptotic photoreceptor cell death can be delayed with different drugs, and at least one of them, diltiazem, is approved for human use in cardiovascular diseases. It remains to be seen if it has any clinically significant effect in human tapetoretinal degenerations. Other strategies aim at counteracting the production of harmful protein variants, acting either on DNA or mRNA levels. Transgenes can also be used to induce the production of important but missing metabolic components. Finally, cells or retina sheets can be transplanted, either to replace failing cells or as a source for missing trophic factors. Neither of these strategies has yet been transferred to humans, but trials are under way. With the high increase in the flow of new information on tapetoretinal disorders, much more precise diagnoses and much improved treatments are soon to be expected, augmenting considerably the possibilities for ophthalmologists to help patients with such diseases. It is not likely that there will be a single treatment for all the many varieties. Instead, we are most likely going to see pharmacological treatments for some of them, DNA transfers for some, and transplantations for others. [source]