40 research outputs found
Theoretical studies of interactions of transition metal anticancer complexes with DNA
No full textDensity functional theory (DFT) and combined quantum mechanics/molecular mechanics (QM/MM) calculations have been used to model inter- and intra-molecular non-covalent interactions of transition metal complexes and where applicable their interactions with DNA. Two DFT functionals, BHandH and B97-D, which have shown
to be efficient in modelling systems containing non-covalent interactions, have been tested against high level ab initio calculations on test transition metal complexes, designed to represent the intermolecular interactions present in the benzene dimer and
methane benzene systems. The DFT functionals above show good agreement with the benchmark calculations and have been used to study ruthenium arene 'piano stool' type
complexes, of the general form [6(arene)Ru(en)Cl]+, which have shown potential as anticancer agents. The intramolecular interactions of these ruthenium complexes
through coordination to guanine and adenine through the N7 nitrogen, has been explored using a selection of pure DFT, hybrid DFT, and post Hartree-Fock approaches
against benchmark correlated wavefunction methods, where the best methods were found to be BHandH, B97-D2, and MP2(0.25). The B97-D2 functional was used to
model these ruthenium complexes, with a selection of extended aromatic ligands with potential to act as intercalators, interacting with base pair steps. Calculated binding energies show a sensitivity to the nature of the arenes, where the more flexible ligands
form more non-covalent interactions with DNA, as demonstrated by QTAIM analysis.
Conformations and binding energies of a relatively new platinum anticancer drug, kiteplatin, with small single strand fragments of DNA, have been studied using B97-D
and semi-empirical methods and compared to established drugs cisplatin and oxaliplatin. Isotropic shielding values and J coupling constants have also been
calculated for these systems to relate these values to conformational data. Extended dual strand kiteplatin-DNA adducts have been studied using the QM/MM method ONIOM,
combining BHandH with AMBER, to calculate binding energies and optimised structures. These results show that as the DNA adduct increases in size the values of the
kiteplatin energies start to converge and comparison of base pair parameters show that around the site of coordination all fragments show comparable geometrical distortions
Modulation of stacking interactions by transition-metal coordination: ab initio benchmark studies
No full textA series of ab initio calculations are used to determine the CHπ and ππ-stacking interactions of aromatic rings coordinated to transition-metal centres. Two model complexes have been employed, namely, ferrocene and chromium benzene tricarbonyl. Benchmark data obtained from extrapolation of MP2 energies to the basis set limit, coupled with CCSD(T) correction, indicate that coordinated aromatic rings are slightly weaker hydrogen-bond acceptors but are significantly stronger hydrogen-bond donors than uncomplexed rings. It is found that ππ stacking to a second benzene is stronger than in the free benzene dimer, especially in the chromium case. This is assigned, by use of energy partitioning in the local correlation method, to dispersion interactions between metal d and benzene π orbitals. The benchmark data is also used to test the performance of more efficient theoretical methods, indicating that spin-component scaling of MP2 energies performs well in all cases, whereas various density functionals describe some complexes well, but others with errors of more than 1 kcal mol−1
Density functional theory studies of interactions of ruthenium arene complexes with base pair steps
No full textDensity functional theory (DFT) calculations have been performed to determine the strength and geometry of intermolecular interactions of “piano-stool” ruthenium arene complexes, which show potential as anticancer treatments. Model complexes with methane and benzene indicate that the coordinated arene has C–H···π acceptor ability similar to that of free benzene, whereas this arene acts as a much stronger C–H donor or partner in π-stacking than free benzene. The source of these enhanced interactions is identified as a combination of electrostatic and dispersion effects. Complexes of Ru-arene complexes with base-pair step fragments of DNA, in which the arene has the potential to act as an intercalator, have also been investigated. Binding energies are found to be sensitive to the size and nature of the arene, with larger and more flexible arenes having stronger binding. π-stacking and C–H···π interactions between arene and DNA bases and hydrogen bonds from coordinated N–H to DNA oxygen atoms, as well as covalent Ru–N bonding, contribute to the overall binding. The effect of complexation on DNA structure is also examined, with larger rise and more negative slide values than canonical B-DNA observed in all case
Molecular Dynamics Simulation on the Effect of Transition Metal Binding to the N-Terminal Fragment of Amyloid-β
No full textMolecular dynamics trajectories in PDB format for 3x Cu-Aβ, 3x Zn-Aβ and 9x Fe-Aβ simulations.</p
Piloting the PREVIEW-ED Tool in Fraser Health Authority
No full textIn 2016, Fraser Health (FH) partnered with the Langara School of Nursing and senior nurse consultant, Marilyn El Bestawiand to pilot the PREVIEW-ED© tool.
Two (2) term 8 Bachelor of Science in Nursing (BSN) students facilitated implementation of the tool with Fraser Health’s first cohort of 176 residents across 4 Fraser Health Care Homes.
Students worked with Care Aides who completed the PREVIEW-ED© tool to prevent transfers to the Emergency Department for: pneumonia, congestive heart failure, urinary tract infections and dehydration.
A noted 71% reduction in Emergency Departments (ED) transfers for tool sensitive conditions.
This is now a best practice for Fraser Health Residential Care Homes
The press reception of Austrian works of Vergangenheitsbewältigung
No full textThis thesis explores the relationship between literature and historical memory in Austria through five case studies of literary press reception, examining the validity of common conceptions of Austrian Vergangenheitsbewättigung. The introduction provides an overview and explanation of the historico-political context of the thesis, considering cultural narratives on Vergangenheitsbewaltigung, the position of the Austrian press and its relationship with contemporary, socially critical literature. Chapters One and Two compare 'the press reception of Hans Lebert'ร Die Wolfshaut and Gerhard Fritsch's Fasching to the widely held view of a failed Vergangenheitsbewältigung in 1960ร Austria. Chapter Three considers the reception of Elfriede Jelinek's Die Ausgesperrten in the context of the Sozialpartnerschaft and the politics of memory associated with this period of forced political harmony. Chapter Four deals with the most extreme case, Thomas Bemhard's Heldenplatz, questioning the common assumption that the late 1980s marked a turning point in Austria's troubled relationship with its past. This is developed in Chapter Five, which examines the reception of Robert Schindel’s Gebürtig and considers the extent to which Austrian Vergangenheitsbewältigung can be viewed as a completed process. In the Conclusion the findings of the previous five chapters are brought together and compared with the grand cultural narrative on Austrian historical memory in a consideration of the validity of a linear conceptualisation of Vergangenheitsbewältigung
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Rural life in English poetry of the mid-eighteenth century
No full textThis thesis examines several mid-eighteenth century poems, assessing their portrayal of rural life, its literary and historical significance, and the aesthetic and ideological issues it presents. An introductory essay on developments in rural poetry sets the scene for two extended essays. The first essay is a comparative reading of the subject of rural labour in three poems: James Thomson’s The Seasons (1726-44), Stephen Duck’s The Thresher’s Labour (1730, 1736) and Mary Collier’s The Woman’s Labour (1739). The viewpoints of a professional poet (Thomson), a farm labourer (Duck), and a working woman (Collier) are compared in relation to kinds of work all three address as well as to individual labouring subjects. The responses of the three poets to such related issues as folk traditions, forms of charity and other ‘compensations’, are also compared. Some surprising similarities as well as instructive differences are located; and an interesting picture of idealistic and realistic, male-oriented and female-oriented attitudes to labour and labour-related themes emerges
The Rhetoric of Sensibility: Argument, Sentiment, and Slavery in the Late Eighteenth Century.
No full textPhDThis dissertation argues that by adapting the style and techniques of
sentimental novels, poetry, and drama to persuasive writing a significant
number of late-eighteenth century political writers were able to develop a
distinct and recognisable rhetoric of sensibility. It develops this argument by
examining eighteenth-century views on the use and purpose of rhetoric, and by
looking at writing in one of the most wide-ranging debates of the lateeighteenth
century, the debate over abolition of the slave trade. Chapter One
looks at traditional ('neo-classical') rhetoric and contrasts this with some of the
many varieties of the eighteenth-century 'new rhetoric'. Chapter Two looks at
particular rhetorical strategies employed during the sentimental period and
identifies the main tropes of the rhetoric of sensibility. Chapter Three examines
the relationship between slavery and literary sentimentalism, looking at the way
in which imaginative writers used sentimental rhetoric to advance the idea of
anti-slavery. It also considers the extent to which abolitionist poems, plays,
and novels themselves contributed to the development of a sentimental
rhetoric. Chapter Four examines the use of sentimental rhetoric in nonfictional
slavery-related tracts and pamphlets. It explores the ways in which
the sentimental rhetorical strategies outlined in Chapter Two were adopted by
both pro and anti-slavery writers of the 1780s. Chapter Five discusses how
William Wilberforce, the main parliamentary advocate for abolition, used
sentimental rhetoric in his early parliamentary speeches. The conclusion
examines anti-slavery writing after the collapse of the first abolition campaign
in 1792. In particular, it examines the use of sentimental rhetoric in responses
to the revolutions in France and Haiti and suggests that after this date
sentimental rhetoric, though never entirely disappearing, was progressively
supplanted by other forms of rhetoric
Matthew’s Emmanuel Messiah: a paradigm of presence for god's people
No full textThe motif of divine presence is a clear phenomenon within the Gospel of Matthew. The modern critical means for assessing the ancient biblical text have multiplied to the point, some claim, of disparity. This study employs both narrative and redaction criticism in an attempt to respond authentically to the structural, historical and theological dimensions of Matthew's Gospel. This study begins with the presumption of the wholeness and integrity of Matthew's narrative, and assumes the gospel story to have an inherently dramatic structure which invites readers to inhabit imaginatively its narrative world and respond to its call. But since we are concerned with the role of both reader and author, this study also assumes a text with an historical author and context. The introduction focuses on the meta-critical dilemma facing New Testament students - what is the text and how do we read it? - and seeks some balance in terms of Krieger's analogy of the text as both window and mirror. Proposed is a narrative reading of Matthew's presence motif alongside a redaction critical assessment of it. In Chapter 2 the elements of narrative theory are introduced and relevant terms defined: the structure of narrative, the function of the narrator, points of view. Chapter 3 becomes an exercise in narrative reading, with Matthew's presence motif providing the focus, and the implied reader’s interaction with the story being predominant in interpretation. Characters, rhetorical devices, and points of view are discussed, to understand the motif's development throughout the story's progress. The thrust of Chapter 4 is thereafter to examine divine presence as a dominant motif within Matthew's most important literary context: the Jewish scriptures. Here the primary paradigms of divine presence provided by the Patriarchs, the Sinai experience, and the Davidic-Zion traditions are assessed. Chapter 5 follows with a more detailed examination of the OT "I am with you/God is with us" formula and its µeo' vµwv/ηuwv language, so strongly connected to Matthew's presence motif. Chapters 6-8 build on these investigations with a closer analysis of the three critical "presence passages" of Mt 1:23. 18:20 and 28:20. The passages and their contexts are probed from a redaction critical perspective, guided by the narrative investigation of Chapter 3, and the background from Chapters 4 and 5.The three major "presence passages" examined in Chapters 6-8 are also complimented by a number of secondary issues: worship, wisdom, the Spirit and the poor in Matthew, and their relation to Jesus' divine presence. These are discussed in Chapter 9. Chapter 10 summarizes and looks briefly at some implications. Matthew' presence motif proves to be an important element of the Gospel’s rhetorical design, redactional strategy and Christology. The presence of Jesus, the Emmanuel Messiah, exhibited in his risen authority, becomes the focus of his people's hopes and experiences in the post-Easter world. What the presence of Yahweh was to his people. Jesus now provides in a new paradigm for his people - his followers, the little ones, the poor and the marginalized, from all nations
