Computer aided approaches against Human African Trypanosomiasis
- Authors: Kimuda, Magambo Phillip
- Date: 2020
- Subjects: African trypanosomiasis , African trypanosomiasis -- Chemotherapy , Genomics , Macrophage migration inhibitory factor , Trypanosoma brucei , Pteridines , Tetrahydrofolate dehydrogenase , Adenylic acid , Molecular dynamics , Principal components analysis , Bioinformatics , Single nucleotide polymorphisms , Single Nucleotide Variants , Candidate Gene Association Study (CGAS)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142542 , vital:38089
- Description: The thesis presented here is divided into two parts under a common theme that is the use of computer based tools, genomics, and in vitro experiments to develop innovative ways of tackling Human African Trypanosomiasis (HAT). Part I of this thesis focused on the human host genetic determinants while Part II focused on the discovery of novel chemotherapeutics against the parasite. Part I is further sub-divided into two parts: The first involves a Candidate Gene Association Study (CGAS) on an African population to identify genetic determinants associated with disease and/or susceptibility to HAT. The second involves studying the effects of missense Single Nucleotide Variants (SNVs) on protein structure, dynamics, and function using Macrophage Migration Inhibitory Factor (MIF) as a case study. Part II is also sub-divided into two parts: The first involves a computer based rational drug discovery of potential inhibitors against the Trypanosoma the folate pathway; particularly by targeting Trypanosoma brucei Pteridine Reductase (TbPTR1) which is an enzyme used by trypanosomes to overcome T. brucei Dihydrofolate Reductase (TbDHFR) inhibition. Lastly the derivation of CHARMM force-field parameters that can be used to accurately model the geometry and dynamics of the T. brucei Phosphodiesterase B1 enzyme (TbrPDEB1) bimetallic active site center. The derived parameters were then used in MD simulations to characterise protein-ligand residue interactions that are important in TbrPDEB1 inhibition with the goal of targeting the cyclic Adenosine Monophosphate (cAMP) signalling pathway. In the CGAS we were unable to detect any genetic associations in the Ugandan cohort analysed that passed correction for multiple testing in spite of the study being sufficiently powered. Additionally, our study found no association of the Apo lipoprotein 1 (APOL1) G2 allele association with protection against acute HAT that has been previously reported. Future investigations for example, Genome Wide Association Studies using larger samples sizes (>3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies
- Full Text:
- Date Issued: 2020
- Authors: Kimuda, Magambo Phillip
- Date: 2020
- Subjects: African trypanosomiasis , African trypanosomiasis -- Chemotherapy , Genomics , Macrophage migration inhibitory factor , Trypanosoma brucei , Pteridines , Tetrahydrofolate dehydrogenase , Adenylic acid , Molecular dynamics , Principal components analysis , Bioinformatics , Single nucleotide polymorphisms , Single Nucleotide Variants , Candidate Gene Association Study (CGAS)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142542 , vital:38089
- Description: The thesis presented here is divided into two parts under a common theme that is the use of computer based tools, genomics, and in vitro experiments to develop innovative ways of tackling Human African Trypanosomiasis (HAT). Part I of this thesis focused on the human host genetic determinants while Part II focused on the discovery of novel chemotherapeutics against the parasite. Part I is further sub-divided into two parts: The first involves a Candidate Gene Association Study (CGAS) on an African population to identify genetic determinants associated with disease and/or susceptibility to HAT. The second involves studying the effects of missense Single Nucleotide Variants (SNVs) on protein structure, dynamics, and function using Macrophage Migration Inhibitory Factor (MIF) as a case study. Part II is also sub-divided into two parts: The first involves a computer based rational drug discovery of potential inhibitors against the Trypanosoma the folate pathway; particularly by targeting Trypanosoma brucei Pteridine Reductase (TbPTR1) which is an enzyme used by trypanosomes to overcome T. brucei Dihydrofolate Reductase (TbDHFR) inhibition. Lastly the derivation of CHARMM force-field parameters that can be used to accurately model the geometry and dynamics of the T. brucei Phosphodiesterase B1 enzyme (TbrPDEB1) bimetallic active site center. The derived parameters were then used in MD simulations to characterise protein-ligand residue interactions that are important in TbrPDEB1 inhibition with the goal of targeting the cyclic Adenosine Monophosphate (cAMP) signalling pathway. In the CGAS we were unable to detect any genetic associations in the Ugandan cohort analysed that passed correction for multiple testing in spite of the study being sufficiently powered. Additionally, our study found no association of the Apo lipoprotein 1 (APOL1) G2 allele association with protection against acute HAT that has been previously reported. Future investigations for example, Genome Wide Association Studies using larger samples sizes (>3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies
- Full Text:
- Date Issued: 2020
Crime and punishment Mzansi style: an exploration of the discursive production of criminality and popular justice in South Africa’s Daily Sun
- Authors: Boshoff, Priscilla A
- Date: 2017
- Subjects: Daily Sun (South Africa) , Tabloid newpapers -- South Africa , Crime in mass media , Justice in mass media , Police in mass media , Newpapers -- South Africa , Newpapers -- Objectivity -- South Africa , Women -- Violence against -- South Africa -- Press coverage , Witchcraft -- South Africa -- Press coverage , Police -- South Africa -- Press coverage
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/44419 , vital:25406
- Description: The highly popular South African tabloid the Daily Sun, established post-apartheid in 2002, is known for its sensationalist and controversial reporting of black township life. Read by over five million black working class readers, much of its reporting concerns the crimes experienced by them and their struggles for justice. The extraordinarily high rate of violent crime in township areas for which South Africa became infamous during the 1980s did not decrease as much as hoped after the political transition in 1994 and crime overshadowed the first decades of the new administration, adding to the frustrations generated by the slow pace of social and economic reform. Part of the Daily Sun’s success can be attributed to how, around these linked concerns, it fashions for its readers a particular discursive world, Sunland. It is the phatic relationship that the tabloid maintains between itself and its readers which forms the foundation upon which this textual study rests. In approaching the tabloid’s representations of crime I draw on cultural criminological understandings of crime as culture and the formative relationship in this regard between crime and the media. As a preeminent site of cultural production in contemporary society, the media contribute to the ongoing definition of what constitutes crime, who is criminal and what counts as justice. This constructivist approach is congruent with Foucault’s notions of discourse and the subject, and I argue that the various competing discourses about crime and justice which appear in the paper establish a set of subjectivities with which its readers may identity. The thesis explores the rhetorical and discursive means by which such subject positions are constructed within the ‘grid of intelligibility’ created by the Daily Sun’s reportage, and using the spatial metaphor of the ‘map’ I trace the contours of the Daily Sun’s domain with regard to crime and popular justice. To this end, the approach taken is a qualitative one which draws eclectically on a variety of interpretive methods, including semiotic, narrative and discourse analysis. Using these, I map the relations between People’s Justice, the police, gender relations and witchcraft crimes, four areas chosen from a broad thematic content analysis of the complete set of editions from 2011. I show how these are not discreet but co-constructed areas within the coverage, drawing their meaning mutually from a range of conflictual relationships derived from the conditions of post-apartheid social life.
- Full Text:
- Date Issued: 2017
- Authors: Boshoff, Priscilla A
- Date: 2017
- Subjects: Daily Sun (South Africa) , Tabloid newpapers -- South Africa , Crime in mass media , Justice in mass media , Police in mass media , Newpapers -- South Africa , Newpapers -- Objectivity -- South Africa , Women -- Violence against -- South Africa -- Press coverage , Witchcraft -- South Africa -- Press coverage , Police -- South Africa -- Press coverage
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/44419 , vital:25406
- Description: The highly popular South African tabloid the Daily Sun, established post-apartheid in 2002, is known for its sensationalist and controversial reporting of black township life. Read by over five million black working class readers, much of its reporting concerns the crimes experienced by them and their struggles for justice. The extraordinarily high rate of violent crime in township areas for which South Africa became infamous during the 1980s did not decrease as much as hoped after the political transition in 1994 and crime overshadowed the first decades of the new administration, adding to the frustrations generated by the slow pace of social and economic reform. Part of the Daily Sun’s success can be attributed to how, around these linked concerns, it fashions for its readers a particular discursive world, Sunland. It is the phatic relationship that the tabloid maintains between itself and its readers which forms the foundation upon which this textual study rests. In approaching the tabloid’s representations of crime I draw on cultural criminological understandings of crime as culture and the formative relationship in this regard between crime and the media. As a preeminent site of cultural production in contemporary society, the media contribute to the ongoing definition of what constitutes crime, who is criminal and what counts as justice. This constructivist approach is congruent with Foucault’s notions of discourse and the subject, and I argue that the various competing discourses about crime and justice which appear in the paper establish a set of subjectivities with which its readers may identity. The thesis explores the rhetorical and discursive means by which such subject positions are constructed within the ‘grid of intelligibility’ created by the Daily Sun’s reportage, and using the spatial metaphor of the ‘map’ I trace the contours of the Daily Sun’s domain with regard to crime and popular justice. To this end, the approach taken is a qualitative one which draws eclectically on a variety of interpretive methods, including semiotic, narrative and discourse analysis. Using these, I map the relations between People’s Justice, the police, gender relations and witchcraft crimes, four areas chosen from a broad thematic content analysis of the complete set of editions from 2011. I show how these are not discreet but co-constructed areas within the coverage, drawing their meaning mutually from a range of conflictual relationships derived from the conditions of post-apartheid social life.
- Full Text:
- Date Issued: 2017
The life and influence of William Shaw, 1820-1856
- Authors: Lyness, Peter Howard
- Date: 1982
- Subjects: Shaw, William, 1798-1872 , South Africa -- History -- Frontier Wars, 1811-1878 , Cape of Good Hope (South Africa) -- History -- 1814-1852 , Missions -- South Africa -- Cape of Good Hope , Methodist Church of Southern Africa -- Missions
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2586 , http://hdl.handle.net/10962/d1006205 , Shaw, William, 1798-1872 , South Africa -- History -- Frontier Wars, 1811-1878 , Cape of Good Hope (South Africa) -- History -- 1814-1852 , Missions -- South Africa -- Cape of Good Hope , Methodist Church of Southern Africa -- Missions
- Description: Preface: William Shaw was undoubtedly one of the greatest of the missionary pioneers to work in southern Africa and it is strange that up until now there has been no major research into his time spent in the Cape Colony and beyond. Apart from his own work, The Story of My Mission, and the Memoir of the Rev. William Shaw by William Boyce, published in 1874, there was nothing devoted exclusively to Shaw until Mrs Celia Sadler published extracts from his letters and journals in Never a Young Man, in 1967. Scholars have examined aspects of Shaw's career in a number of theses, articles and books, but, unlike the attention paid to Dr John Philip, William Shaw has never been the subject of close historical scrutiny. This has, most probably, been attributable to the unfortunate gap in the Shaw correspondence from the late 1830's to the 1850's, but, despite this, I have felt that so important a figure in southern African historiography - both ecclesiastical and secular - should be examined regardless of the lacunae which there might be. When - and if - the missing pieces ever come to light, then the time for the definitive study will have arrived, but until such time there is, most decidedly, a need for what we do have access to, to be sifted and placed in historical context. This is what this thesis has attempted to do with specific reference to his work in the Eastern Cape. As General Superintendent of Wesleyan mission work in "South Eastern Africa", Shaw also had oversight of work in the Bechuana country, but that lies outside the scope of this thesis and requires independent examination. Shaw wrote of the work of the missionary - with his own work firmly in mind, " ... I am fully satisfied ... that wherever there is a British colony in juxtaposition with heathen tribes, or natives, it will be our wisdom to provide for the spiritual wants of the Colonists, while at the same time we ought not to neglect taking earnest measures for the conversion of the heathen."¹ Such an approach made Wesleyan endeavours almost unique in mission history. The proponent of such uniqueness requires a sympathetic yet not hagiographical appraisal. This thesis seeks to accomplish just that. ¹ The Story of My Mission p. 213.
- Full Text:
- Date Issued: 1982
- Authors: Lyness, Peter Howard
- Date: 1982
- Subjects: Shaw, William, 1798-1872 , South Africa -- History -- Frontier Wars, 1811-1878 , Cape of Good Hope (South Africa) -- History -- 1814-1852 , Missions -- South Africa -- Cape of Good Hope , Methodist Church of Southern Africa -- Missions
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2586 , http://hdl.handle.net/10962/d1006205 , Shaw, William, 1798-1872 , South Africa -- History -- Frontier Wars, 1811-1878 , Cape of Good Hope (South Africa) -- History -- 1814-1852 , Missions -- South Africa -- Cape of Good Hope , Methodist Church of Southern Africa -- Missions
- Description: Preface: William Shaw was undoubtedly one of the greatest of the missionary pioneers to work in southern Africa and it is strange that up until now there has been no major research into his time spent in the Cape Colony and beyond. Apart from his own work, The Story of My Mission, and the Memoir of the Rev. William Shaw by William Boyce, published in 1874, there was nothing devoted exclusively to Shaw until Mrs Celia Sadler published extracts from his letters and journals in Never a Young Man, in 1967. Scholars have examined aspects of Shaw's career in a number of theses, articles and books, but, unlike the attention paid to Dr John Philip, William Shaw has never been the subject of close historical scrutiny. This has, most probably, been attributable to the unfortunate gap in the Shaw correspondence from the late 1830's to the 1850's, but, despite this, I have felt that so important a figure in southern African historiography - both ecclesiastical and secular - should be examined regardless of the lacunae which there might be. When - and if - the missing pieces ever come to light, then the time for the definitive study will have arrived, but until such time there is, most decidedly, a need for what we do have access to, to be sifted and placed in historical context. This is what this thesis has attempted to do with specific reference to his work in the Eastern Cape. As General Superintendent of Wesleyan mission work in "South Eastern Africa", Shaw also had oversight of work in the Bechuana country, but that lies outside the scope of this thesis and requires independent examination. Shaw wrote of the work of the missionary - with his own work firmly in mind, " ... I am fully satisfied ... that wherever there is a British colony in juxtaposition with heathen tribes, or natives, it will be our wisdom to provide for the spiritual wants of the Colonists, while at the same time we ought not to neglect taking earnest measures for the conversion of the heathen."¹ Such an approach made Wesleyan endeavours almost unique in mission history. The proponent of such uniqueness requires a sympathetic yet not hagiographical appraisal. This thesis seeks to accomplish just that. ¹ The Story of My Mission p. 213.
- Full Text:
- Date Issued: 1982
The lyric vision of W. H. Davies: pastoral, the unintelligible universe, community
- Authors: Rabinowitz, Ivan Arthur
- Date: 1973
- Subjects: Davies, W. H. (William Henry), 1871-1940 -- Criticism and interpretation , English poetry -- 20th century , Poets, English -- 20th century -- Biography
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2280 , http://hdl.handle.net/10962/d1007579 , Davies, W. H. (William Henry), 1871-1940 -- Criticism and interpretation , English poetry -- 20th century , Poets, English -- 20th century -- Biography
- Description: From Introductory note: The Complete Poems of W.H. Davies (London: Jonathan Cape, 1963; rev. 1968) has been used throughout this study. Accordingly, unless otherwise stated, all citations of poem numbers and pagination refer to this text. Critical literature on the work of W.H. Davies is restricted in quantity and limited in scope. There are few comprehensive assessments of Davies as poet, autobiographer, novelist, or raconteur. Apart from such sources as Richard J. Stonesifer's full-length critical biography (1963), Lawrence Hockey's biographical monograph (1971), and Thomas Moult's anecdotal and historical appreciation (1934), critical material must be drawn from contemporary reviews, isolated articles in magazines such as The Catholic World and Fortnightly Review, and specific chapters in surveys of the poetry of the early twentieth century, although Davies is frequently alluded to passim in literary histories which deal with this period. Many of these studies favour biographical exposition and evaluation rather than descriptive analysis and discursive interpretation. A detailed chronology of Davies's works is included in Stonesifer's discussion. This thesis is not attempting to trace a line of development for two reasons. First, the Complete Poems gives no indication of date of composition or publication of particular poems, and the present writer has access only to the dates of publication of individual volumes as external evidence of a chronology, internal evidence being confined to such infrequent references as "the birds of steel" in Poem no. 236, p. 260. Secondly, the lyrics themselves do not, on the whole, evince much stylistic and thematic development, and the concern of this study is with recurrent themes and techniques dispersed throughout the oeuvre.
- Full Text:
- Date Issued: 1973
- Authors: Rabinowitz, Ivan Arthur
- Date: 1973
- Subjects: Davies, W. H. (William Henry), 1871-1940 -- Criticism and interpretation , English poetry -- 20th century , Poets, English -- 20th century -- Biography
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2280 , http://hdl.handle.net/10962/d1007579 , Davies, W. H. (William Henry), 1871-1940 -- Criticism and interpretation , English poetry -- 20th century , Poets, English -- 20th century -- Biography
- Description: From Introductory note: The Complete Poems of W.H. Davies (London: Jonathan Cape, 1963; rev. 1968) has been used throughout this study. Accordingly, unless otherwise stated, all citations of poem numbers and pagination refer to this text. Critical literature on the work of W.H. Davies is restricted in quantity and limited in scope. There are few comprehensive assessments of Davies as poet, autobiographer, novelist, or raconteur. Apart from such sources as Richard J. Stonesifer's full-length critical biography (1963), Lawrence Hockey's biographical monograph (1971), and Thomas Moult's anecdotal and historical appreciation (1934), critical material must be drawn from contemporary reviews, isolated articles in magazines such as The Catholic World and Fortnightly Review, and specific chapters in surveys of the poetry of the early twentieth century, although Davies is frequently alluded to passim in literary histories which deal with this period. Many of these studies favour biographical exposition and evaluation rather than descriptive analysis and discursive interpretation. A detailed chronology of Davies's works is included in Stonesifer's discussion. This thesis is not attempting to trace a line of development for two reasons. First, the Complete Poems gives no indication of date of composition or publication of particular poems, and the present writer has access only to the dates of publication of individual volumes as external evidence of a chronology, internal evidence being confined to such infrequent references as "the birds of steel" in Poem no. 236, p. 260. Secondly, the lyrics themselves do not, on the whole, evince much stylistic and thematic development, and the concern of this study is with recurrent themes and techniques dispersed throughout the oeuvre.
- Full Text:
- Date Issued: 1973
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