http://hdl.handle.net/2292/2879 2017-07-14T11:21:39Z 2017-07-14T11:21:39Z Bujalance, E Cirre, FJ Conder, MDE http://hdl.handle.net/2292/34238 2017-07-14T04:32:52Z 2017-02-01T00:00:00Z

On automorphism groups of Riemann double covers of Klein surfaces Bujalance, E; Cirre, FJ; Conder, MDE If G is a group of automorphisms of a compact Klein surface X, then the direct product G × C2 is a group of automorphisms of the Riemann double cover X+ of X. In this paper we analyse the relationship between G and the full groups of automorphisms Aut(X) and Aut(X+) of X and X+ respectively, in the special case where the group G is uniformised by a non-Euclidean crystallographic group with quadrangular signature (2, 2, 2, n). There is a difference in what happens between bordered surfaces and unbordered non-orientable surfaces, and so we consider those cases separately (including the special situation for n = 4 in the unbordered case).

2017-02-01T00:00:00Z Conder, M Širáň, J http://hdl.handle.net/2292/34236 2017-07-14T04:18:59Z 2016-12-01T00:00:00Z

Orientably-regular maps with given exponent group Conder, M; Širáň, J We prove that for every integer d ≥ 3 and every group U of units mod d, there exists an orientably regular map of valency d with exponent group U.

2016-12-01T00:00:00Z Conder, MDE Zhang, W-J http://hdl.handle.net/2292/34234 2017-07-14T03:47:10Z 2017-05-01T00:00:00Z

Abelian covers of chiral polytopes Conder, MDE; Zhang, W-J Abstract polytopes are combinatorial structures with certain properties drawn from the study of geometric structures, like the Platonic solids, and of maps on surfaces. Of particular interest are the polytopes with maximal possible symmetry (subject to certain natural constraints). Symmetry can be measured by the effect of automorphisms on the ‘flags’ of the polytope, which are maximal chains of elements of increasing rank (dimension). An abstract polytope of rank n is said to be chiral if its automorphism group has precisely two orbits on the flags, such that two flags that differ in one element always lie in different orbits. Examples of chiral polytopes have been difficult to find and construct. In this paper, we introduce a new covering method that allows the construction of some infinite families of chiral polytopes, with each member of a family having the same rank as the original, but with the size of the members of the family growing linearly with one (or more) of the parameters making up its ‘type’ (Schläfli symbol). In particular, we use this method to construct several new infinite families of chiral polytopes of ranks 3, 4, 5 and 6.

2017-05-01T00:00:00Z Hannah, Katherine http://hdl.handle.net/2292/34227 2017-07-14T00:29:18Z 2017-01-01T00:00:00Z

Finding Matilda: deconstructing women's invisibility in Finding New Zealand's Scientific Heritage Hannah, Katherine Formal narratives of New Zealand science have largely focused on the development of science infrastructure in New Zealand since the appointment of James Hector to head the New Zealand Geological Survey in 1865. This short communication uses the discourses of the 2015 conference, Finding New Zealand’s Scientific Heritage to explore the impact of institutional history, and the high number of participants (for example, retired scientists), on New Zealand historiography of science. I suggest this approach has resulted in the absenting or camouflaging of the contribution of women. The short communication then explores approaches that might mitigate against these effects, suggesting ‘starting thought from women's lives’ (Harding S. 1991. Whose science? Whose knowledge? Thinking from women’s lives. Ithaca, NY: Cornell University Press, p. 150) as a primary mode for novel revisions of history of science in New Zealand.

2017-01-01T00:00:00Z Jamieson, Stephen Brooke, Darby Heinrich, D Atwell, GJ Silva, S Hamilton, EJ Turnbull, AP Rigoreau, LJ Trivier, E Soudy, C Samlal, SS Owen, PJ Schroeder, E Raynham, T Flanagan, Jack Denny, William http://hdl.handle.net/2292/34225 2017-07-14T00:18:27Z 2012-01-01T00:00:00Z

3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3 Jamieson, Stephen; Brooke, Darby; Heinrich, D; Atwell, GJ; Silva, S; Hamilton, EJ; Turnbull, AP; Rigoreau, LJ; Trivier, E; Soudy, C; Samlal, SS; Owen, PJ; Schroeder, E; Raynham, T; Flanagan, Jack; Denny, William A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.

2012-01-01T00:00:00Z Rewcastle, GW Gamage, SA Flanagan, JU Kendall, JD Denny, WA Baguley, BC Buchanan, CM Chao, M Kestell, P Kolekar, S Lee, W-J Lill, CL Malik, A Singh, R Jamieson, SMF Shepherd, PR http://hdl.handle.net/2292/34223 2017-07-14T00:10:12Z 2013-06-01T00:00:00Z

Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: Solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) Rewcastle, GW; Gamage, SA; Flanagan, JU; Kendall, JD; Denny, WA; Baguley, BC; Buchanan, CM; Chao, M; Kestell, P; Kolekar, S; Lee, W-J; Lill, CL; Malik, A; Singh, R; Jamieson, SMF; Shepherd, PR A range of 4-substituted derivatives of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) were prepared in a search for more soluble analogs. 4-Aminoalkoxy substituents provided the most potent derivatives, with the 4-O(CH2)3NMe2 analog (compound 14) being identified as displaying the best overall activity in combination with good aqueous solubility (25 mg/mL for the hydrochloride salt). This compound was tested in a U87MG xenograft model, but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile.

2013-06-01T00:00:00Z Talekar, M Ganta, S Amiji, M Jamieson, S Kendall, J Denny, WA Garg, S http://hdl.handle.net/2292/34222 2017-07-13T23:55:37Z 2013-06-01T00:00:00Z

Development of PIK-75 nanosuspension formulation with enhanced delivery efficiency and cytotoxicity for targeted anti-cancer therapy Talekar, M; Ganta, S; Amiji, M; Jamieson, S; Kendall, J; Denny, WA; Garg, S PIK-75 is a phosphatidylinositol 3-kinase (PI3K) inhibitor that shows selectivity toward p110-α over the other PI3K class Ia isoforms p110-β and p110-δ, but it lacks solubility, stability and other kinase selectivity. The purpose of this study was to develop folate-targeted PIK-75 nanosuspension for tumor targeted delivery and to improve therapeutic efficacy in human ovarian cancer model. High pressure homogenization was used to prepare the non-targeted and targeted PIK-75 nanosuspensions which were characterized for size, zeta potential, entrapment efficiency, morphology, saturation solubility and dissolution velocity. In vitro analysis of drug uptake, cell viability and cell survival was conducted in SKOV-3 cells. Drug pharmacokinetics and pAkt expression were determined in SKOV-3 tumor bearing mice. PIK-75 nanosuspensions showed an improvement in dissolution velocity and an 11-fold increase in saturation solubility over pre-milled PIK-75. In vitro studies in SKOV-3 cells indicated a 2-fold improvement in drug uptake and 0.4-fold decrease in IC50 value of PIK-75 following treatment with targeted nanosuspension compared to non-targeted nanosuspension. The improvement in cytotoxicity was attributed to an increase in caspase 3/7 and hROS activity. In vivo studies indicated a 5-10-fold increased PIK-75 accumulation in the tumor with both the nanosuspension formulations compared to PIK-75 suspension. The targeted nanosuspension showed an enhanced downregulation of pAkt compared to non-targeted formulation system. These results illustrate the opportunity to formulate PIK-75 as a targeted nanosuspension to enhance uptake and cytotoxicity of the drug in tumor.

2013-06-01T00:00:00Z Talekar, M Kendall, J Denny, W Jamieson, S Garg, S http://hdl.handle.net/2292/34221 2017-07-13T23:43:12Z 2012-12-18T00:00:00Z

Development and evaluation of PIK75 nanosuspension, a phosphatidylinositol-3-kinase inhibitor Talekar, M; Kendall, J; Denny, W; Jamieson, S; Garg, S PURPOSE: PIK75 is a specific inhibitor of the p110 α isoform of phosphatidylinositol-3-kinase, an enzyme which is upregulated in several human cancers. However its poor water solubility and stability has limited its pre-clinical development. METHOD: In our current work we developed and evaluated PIK75 nanosuspension prepared using high pressure homogenization technique. The nanosuspension was characterized for various properties such as size, surface charge and saturation solubility. The saturation solubility processing techniques were critically evaluated to optimize sample processing conditions. In vitro studies were conducted to determine the stability of the formulation and in vivo studies were carried out to understand the pharmacokinetic and tissue distribution properties of the nanosuspension. RESULTS: The nanosuspension exhibited an 11-fold improvement in saturation solubility with drug recovery greater than 90% for 6h in the nanosuspension system and in human plasma. In vivo studies indicated that both PIK75 suspension and nanosuspension showed a similar plasma pharmacokinetic profile however tissue distribution studies indicated lower PIK75 levels in the kidney post nanosuspension administration. CONCLUSION: The results of this study showed that PIK75 could be formulated as a nanosuspension to improve saturation solubility, enhance stability in plasma and minimize exposure to drug metabolizing tissues.

2012-12-18T00:00:00Z Schillewaert, J Maldeghem, HV http://hdl.handle.net/2292/34219 2017-07-13T23:17:40Z 2016-12-20T00:00:00Z

On the varieties of the second row of the split Freudenthal-Tits Magic Square Schillewaert, J; Maldeghem, HV Our main aim is to provide a uniform geometric characterization of the analogues over arbitrary fields of the four complex Severi varieties, i.e.~the quadric Veronese varieties in 5-dimensional projective spaces, the Segre varieties in 8-di\-men\-sional projective spaces, the line Grassmannians in 14-dimensional projective spaces, and the exceptional varieties of type $\mathsf{E}_{6}$ in 26-dimensional projective space. Our theorem can be regarded as a far-reaching generalization of Mazzocca and Melone's approach to finite quadric Veronesean varieties. This approach takes projective properties of complex Severi varieties as smooth varieties as axioms.

2016-12-20T00:00:00Z Berka, AL Harnmeijer, J Roberts, D Phimister, E Msika, J http://hdl.handle.net/2292/34213 2017-07-13T06:06:45Z 2017-07-01T00:00:00Z

A comparative analysis of the costs of onshore wind energy: Is there a case for community-specific policy support? Berka, AL; Harnmeijer, J; Roberts, D; Phimister, E; Msika, J There is growing policy interest in increasing the share of community-owned renewable energy generation. This study explores why and how the costs of community-owned projects differ from commercially-owned projects by examining the case of onshore wind in the UK. Based on cross-sectoral literature on the challenges of community ownership, cost differences are attributed to six facets of an organisation or project: internal processes, internal knowledge and skills, perceived local legitimacy of the project, perceived external legitimacy of the organisation, investor motivation and expectations, and finally, project scale. These facets impact not only development costs but also project development times and the probability that projects pass certain critical stages in the development process. Using survey-based and secondary cost data on community and commercial projects in the UK, a model is developed to show the overall impact of cost, time and risk differences on the value of a hypothetical 500 kW onshore wind project. The results show that the main factors accounting for differences are higher pre-planning costs and additional risks born by community projects, and suggest that policy interventions may be required to place community- owned projects on a level playing field with commercial projects.

2017-07-01T00:00:00Z