Faculty of Science

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Open Access
1,8-Naphthalene Linked Cofacial Binuclear Phthalocyanines
(Wiley-Blackwell, 1987) Lever, A.B.P.; Janda, Pavel; Kobayashi, Nagao; Nevin, Andrew W.; Lam, Herman; Leznoff, Clifford C.
Open Access
1999 Alfred Bader Lecture. From Early Developments in Multi-Step Organic Synthesis on Solid Phase to Multi-Nuclear Phthalocyanines.
(Canadian Journal of Chemistry, NRC Research Press, 2000) Leznoff, Clifford C.
Early developments in solid phase organic synthesis are traced. Particular emphasis is placed on the use of cross-linked polystyrene in the first general method of monoblocking symmetrical difunctional compounds. The monoprotected polymer-bound symmetrical starting materials were then used in multi-step syntheses of a variety of compounds, particularly insect pheromones. Asymmetric synthesis on polymer supports was demonstrated. Diels-Alder and 1,3-dipolar additions on polymer supports proceeded readily as did macrocyclic formation of porphyrins and phthalocyanines. All of these reactions clearly showed that most organic chemical reactions could be performed on solid phases and laid the basis for the development of combinatorial chemistry. The first unsymmetrical phthalocyanine was prepared using the solid phase method and this led eventually to solution phase methods of preparing bi-, tri-, tetra-, and even a dendritic-like pentanuclear phthalocyanine.
Open Access
2,4-Di-O-methylgyrophoric Acid and 2,4,5-Tri-O-methylhiascic Acid. New Tridepsides from Parmelia damaziana
(CSIRO Publishing, 1981) Leznoff, Clifford C.; Jayanthi, Vilas K.; Elix, John A.
Open Access
A 212-nt long RNA structure in the Tobacco necrosis virus-D RNA genome is resistant to Xrn degradation
(Oxford University Press, 2019) White, K. Andrew; Chaminda, Gunawardene D.; Newburn, Laura R.
Plus-strand RNA viruses can accumulate viral RNA degradation products during infections. Some of these decay intermediates are generated by the cytosolic 5′-to-3′ exoribonuclease Xrn1 (mammals and yeast) or Xrn4 (plants) and are formed when the enzyme stalls on substrate RNAs upon encountering inhibitory RNA structures. Many Xrn-generated RNAs correspond to 3′-terminal segments within the 3′-UTR of viral genomes and perform important functions during infections. Here we have investigated a 3′-terminal small viral RNA (svRNA) generated by Xrn during infections with Tobacco necrosis virus-D (family Tombusviridae). Our results indicate that (i) unlike known stalling RNA structures that are compact and modular, the TNV-D structure encompasses the entire 212 nt of the svRNA and is not functionally transposable, (ii) at least two tertiary interactions within the RNA structure are required for effective Xrn blocking and (iii) most of the svRNA generated in infections is derived from viral polymerase-generated subgenomic mRNA1. In vitro and in vivo analyses allowed for inferences on roles for the svRNA. Our findings provide a new and distinct addition to the growing list of Xrn-resistant viral RNAs and stalling structures found associated with different plant and animal RNA viruses.
Open Access
A Derivative Free Optimization Algorithm based on Conditional Moments
(Journal of Mathematical Analysis and Applications, 2006) Wang, Xiaogang; Liang, Dong; Feng, Xingdong; Ye, Lu
In this paper we propose a derivative-free optimization algorithm based on conditional moments for finding the maximizer of an objective function. The proposed algorithm does not require calculation or approximation of any order derivative of the objective function. The step size in iteration is determined adaptively according to the local geometrical feature of the objective function and a pre-specified quantity representing the desired precision. The theoretical properties including convergence of the method are presented. Numerical experiments comparing with the Newton, Quasi-Newton and trust region methods are given to illustrate the effectiveness of the algorithm.
Open Access
A free-standing space elevator structure: a practical alternative to the space tether
(Elsevier, 2009-04-19) Quine, Brendan; Seth, R. K.; Zhu, Z. H.
Space tethers have been investigated widely as a means to provide easy access to space. However, the design and construction of such a device presents significant unsolved technological challenges. We propose an alternative approach to the construction of a space elevator that utilizes a free-standing core structure to provide access to near space regions and to reduce the cost of space launch. The structure is comprised of pneumatically inflated sections that are actively controlled and stabilized to balance external disturbances and support the structure. Such an approach avoids problems associated with a space tether including material strength constraints, the need for in-space construction, the fabrication of a cable at least 50,000 km in length, and the ageing and meteorite-damage effects associated with a thin tether or cable in Low Earth Orbit. An example structure constructed at 5 km altitude and extending to 20 km above sea level is described. The stability and control of the structure, methods for construction and its utility for space launch and other applications are discussed.
Open Access
A Mathematical Model for Assessing Control Strategies Against West Nile Virus
(Bulletin of Mathematical Biology, Society for Mathematical Biology, 2005) Bowman, C.; Gumel, Abba; van den Driessche, P.; Wu, J.; Zhu, Huaiping
Since its incursion into North America in 1999, West Nile virus (WNV) has spread rapidly across the continent resulting in numerous human infections and deaths. Owing to the absence of an effective diagnostic test and therapeutic treatment against WNV, public health officials have focussed on the use of preventive measures in an attempt to halt the spread of WNV in humans. The aim of this paper is to use mathematical modelling and analysis to assess two main anti-WNV preventive strategies, namely: mosquito reduction strategies and personal protection. We propose a single-season ordinary differential equation model for the transmission dynamics of WNV in a mosquito–bird–human community, with birds as reservoir hosts and culicine mosquitoes as vectors. The model exhibits two equilibria; namely the disease-free equilibrium and a unique endemic equilibrium. Stability analysis of the model shows that the disease-free equilibrium is globally asymptotically stable if a certain threshold quantity (R0 ), which depends solely on parameters associated with the mosquito–bird cycle, is less than unity. The public health implication of this is that WNV can be eradicated from the mosquito–bird cycle (and, consequently, from the human population) if the adopted mosquito reduction strategy (or strategies) can make R0 < 1. On the other hand, it is shown, using a novel and robust technique that is based on the theory of monotone dynamical systems coupled with a regular perturbation argument and a Liapunov function, that if R0 > 1, then the unique endemic equilibrium is globally stable for small WNV-induced avian mortality. Thus, in this case, WNV persists in the mosquito–bird population.
Open Access
Ab-initio investigation of Br-3d core-excited electronic structures of HBr and HBr+
(AIP Publishing, 2019-01-30) Kobayashi, Yuki; Zeng, Tao; Neumark, Daniel M.; Leone, Stephen
Ultrafast X-ray absorption spectroscopy is a powerful tool for real-time probing of chemical dynamics. Interpretation of the time-resolved absorption spectra requires knowledge of core-excited potentials, which necessitates assistance from high-level electronic-structure computations. In this study, we investigate Br-3d core-excited electronic structures of hydrogen bromide (HBr) using the spin-orbit general multiconfigurational quasidegenerate perturbation theory (SO-GMC-QDPT). Core-to-valence excitation energies and transition dipole moments are computed as functions of the internuclear distance for five electronic states of HBr (1Σ0+ , 3Π1, 1Π1, 3Π0+ , 3Π1) and two electronic states of HBr+ (2Π3/2, 2Σ1/2). The results illustrate the capabilities of the Br-3d edge probing to capture transitions of electronic-state symmetry as well as nonadiabatic dissociation processes evolving across avoided crossings. Furthermore, core-to-valence absorption spectra are simulated from the neutral and ionic ground states by numerically solving the time-dependent Schrodinger equation, which exhibit an excellent agreement with an experimental spectrum. The calculated comprehensive and quantitative picture of the core-excited potentials allows for transparent analyses of the core-to-valence absorption signals, filling the gap in the theoretical understanding of the Br-3d absorption spectra.
Open Access
Actin and myosin inhibitors block elongation of kinetochore fibre stubs in metaphase crane-fly spermatocytes
(Springer Link, 2007-12) Forer, Arthur; Spurck, Tim; Pickett-Heaps, Jeremy
We used an ultraviolet microbeam to cut individual kinetochore spindle fibres in metaphasecrane-fly spermatocytes; then we followed the growth of the “kinetochore stubs”, the remnants of kinetochore fibres that remain attached to kinetochores. Kinetochore stubs elongate with constant velocity by adding tubulin subunits at the kinetochore, and thus elongation is related to flux of tubulin in the kinetochore microtubules. Stub elongation was blocked by cytochalasin D and latrunculin A, actin inhibitors, and by butanedione monoxime, a myosin inhibitor. We conclude that actin and myosin are involved in generating elongation and thus in producing flux of tubulin in kinetochore microtubules. We suggest that actin and myosin act in concert with a spindle matrix to propel kinetochore fibres poleward thereby causing stub elongation and generating anaphasechromosome movement in non-irradiated cells.
Open Access
An adiponectin-S1P axis protects against lipid induced insulin resistance and cardiomyocyte cell death via reduction of oxidative stress
(Biomed Central, 2019-02-21) Botta, Amy; Liu, Ying; Wannaiampikul, Sivaporn; Tungtrongchitr, Rungsunn; Dadson, Keith; Park, Tae-Sik; Sweeney, Gary
Background: Adiponectin exerts several beneficial cardiovascular effects, however their specific molecular mechanisms require additional understanding. This study investigated the mechanisms of adiponectin action in the heart during high fat diet (HFD) feeding or in palmitate (PA) treated H9c2 cardiomyoblasts. Methods: 6-week-old male adiponectin knock out (Ad-KO) mice were fed chow or 60% HFD for 6 weeks then received saline or recombinant adiponectin (3μg/g body weight) for an additional 2 weeks. After acute insulin stimulation (4 U/kg), tissue and serum samples were collected for analysis. H9c2 cardiomyocytes were treated ±0.1 mM PA, the adiponectin receptor agonist AdipoRon, or the antioxidant MnTBAP then assays to analyze reactive oxygen species (ROS) production and cell death were conducted. To specifically determine the mechanistic role of S1P, gain and loss of function studies were conducted with adding S1P to cells or the inhibitors THI and SKI-II, respectively. Results: HFD feeding induced cardiac insulin resistance in Ad-KO mice, which was reversed following replenishment of normal circulating adiponectin levels. In addition, myocardial total triglyceride was elevated by HFD and lipidomic analysis showed increased levels of ceramides and sphingosine-1 phosphate (S1P), with only the latter being corrected by adiponectin administration. Similarly, treatment of H9C2 cardiomyoblasts with PA led to a significant increase of intracellular S1P but not in conditioned media whereas AdipoRon significantly increased S1P production and secretion from cells. AdipoRon or the antioxidant MnTBAP significantly reduced PA-induced cell death. Gain and loss of function studies suggested S1P secretion and autocrine receptor activation mediated the effect of AdipoRon to attenuate PA-induced ROS production and cell death. Conclusion: Our data establish adiponectin signaling-mediated increase in S1P secretion as a mechanism via which HFD or PA induced cardiomyocyte lipotoxicity, leading to insulin resistance and cell death, is attenuated. Keywords: Adiponectin, Sphingosine-1-phosphate, Ceramide, Cardiomyocyte apoptosis, High fat diet, Palmitate, ROS
Open Access
"Adjacent" Substituted Phthalocyanines
(Georg Thieme Verlag, 1997) Leznoff, C.C.; Hu, M.; Nolan, K.J.M.
Open Access
The Alkaline Decomposition of o-Phthalaldehyde Di-p-toluene Sulfonylhydrazone
(NRC Research Press, 1968) Leznoff, Clifford C.
Open Access
An Iterative Non-parametric Clustering Algorithm Based on Local Shrinking
(Computational Statistics and Data Analysis, 2006) Wang, Xiaogang; Qiu, Weiliang; Zamar, Ruben H.
In this paper, we propose a new non-parametric clustering method based on local shrinking. Each data point is transformed in such a way that it moves a specific distance toward a cluster center. The direction and the associated size of each movement are determined by the median of its K-nearest neighbors. This process is repeated until a pre-defined convergence criterion is satisfied. The optimal value of the K is decided by optimizing index functions that measure the strengths of clusters. The number of clusters and the final partition are determined automatically without any input parameter except the stopping rule for convergence. Our performance studies have shown that this algorithm converges fast and achieves high accuracy.
Open Access
Analysis of the role played by ligand-induced folding of the cocaine-binding aptamer in the photochrome aptamer switch assay
(Elsevier, 2020-04-11) Shoara, Aron A.; Churcher, Zachary R; Steele, Terry W.J.; Johnson, Philip E
The Photochrome Aptamer Switch Assay (PHASA) relies on ligand binding by an aptamer to alter the local environment of a stilbene compound covalently attached to the 5’ end of the aptamer. We used the PHASA with both structure switching and non-structure switching versions of the cocaine-binding aptamer. We show that the largest change in fluorescence intensity and the lowest concentration limit of detection (CLooD) is obtained using the structure-switching cocaine-binding aptamer. Fluorescence anisotropy measurements were used to quantify the affinity of the conjugated aptamer to cocaine. We also used thermal melt analysis and Nuclear Magnetic Resonance (NMR) spectroscopy to show that the addition of the stilbene to the aptamer increases the melt temperature of the cocaine-bound structure-switching aptamer by (6.4 ± 0.3) °C compared to the unconjugated aptamer while the free form of the structure-switching aptamer-stilbene conjugate remains unfolded.
Open Access
Anaphase Chromosomes in Crane-Fly Spermatocytes Treated With Taxol (Paclitaxel) Accelerate When Their Kinetochore Microtubules Are Cut: Evidence for Spindle Matrix Involvement With Spindle Forces
(Frontiers, 2018-07-24) Forer, Arthur; Sheykhani, Rozhan; Berns, Michael
Various experiments have indicated that anaphase chromosomes continue to move after their kinetochore microtubules are severed. The chromosomes move poleward at an accelerated rate after the microtubules are cut but they slow down 1–3 min later and move poleward at near the original speed. There are two published interpretations of chromosome movements with severed kinetochore microtubules. One interpretation is that dynein relocates to the severed microtubule ends and propels them poleward by pushing against non kinetochore microtubules. The other interpretation is that components of a putative “spindle matrix” normally push kinetochore microtubules poleward and continue to do so after the microtubules are severed from the pole. In this study we distinguish between these interpretations by treating cells with taxol. Taxol eliminates microtubule dynamics, alters spindle microtubule arrangements, and inhibits dynein motor activity in vivo. If the dynein interpretation is correct, taxol should interfere with chromosome movements after kinetochore microtubules are severed because it alters the arrangements of spindle microtubules and because it blocks dynein activity. If the “spindle matrix” interpretation is correct, on the other hand, taxol should not interfere with the accelerated movements. Our results support the spindle matrix interpretation: anaphase chromosomes in taxol-treated crane-fly spermatocytes accelerated after their kinetochore microtubules were severed.
Open Access
Antiviral Strategies for Emerging Influenza Viruses in Remote Communities
(PLoS ONE, 2013-04-22) Marek, Laskowski; Amy L., Greer; Moghadas, Seyed
Background: Due to the lack of timely access to resources for critical care, strategic use of antiviral drugs is crucial for mitigating the impact of novel influenza viruses with pandemic potential in remote and isolated communities. We sought to evaluate the effect of antiviral treatment and prophylaxis of close contacts in a Canadian remote northern community. Methods: We used an agent-based, discrete-time simulation model for disease spread in a remote community, which was developed as an in-silico population using population census data. Relative and cumulative age-specific attack rates, and the total number of infections in simulated model scenarios were obtained. Results: We found that early initiation of antiviral treatment is more critical for lowering attack rates in a remote setting with a low population-average age compared to an urban population. Our results show that a significant reduction in the relative, age-specific attack rates due to increasing treatment coverage does not necessarily translate to a significant reduction in the overall arrack rate. When treatment coverage varies from low to moderate, targeted prophylaxis has a very limited impact in reducing attack rates and should be offered at a low level (below 10%) to avoid excessive waste of drugs. Conclusions: In contrast to previous work, for conservative treatment coverages, our results do not provide any convincing evidence for the implementation of targeted prophylaxis. The findings suggest that public health strategies in remote communities should focus on the wider availability (higher coverage) and timely distribution of antiviral drugs for treatment of clinically ill individuals.
Open Access
Approaches Towards the Synthesis of a 2,9,16,23-Tetrasubstituted Phthalocyanine as a Pure Isomer
(NRC Research Press, 1988) Leznoff, Clifford C.; Lever, A.B.P.; Greenberg, Shafrira
Open Access
Aptamers 2017 at Oxford
(2018-02-12) Henri, Justin; McKeague, Maureen; Johnson, Philip E; Suess, Beatrix; Nakamura, Yoshikazu; Nilsen-Hamilton, Marit; Pastor, Fernando; Hahn, Ulrich; Bunka, David; Shigdar, Sarah
The 4th annual symposium of the International Society on Aptamers, Aptamers 2017, was held in Oxford on the 11th and 12th April and was well attended, with presenters from Europe (Spain, Germany, Austria, and UK), North and South America, Asia, and Australasia presenting on a diverse range of topics, from enhancing SELEX, to diagnostic applications such as lateral flow devices or medical imaging, to therapeutic applications such as drug delivery. The conference was split into six sections in total, covering chemical modifications, disease, analysis/diagnostics, tools/selection/design, riboswitches, and computation with over 50 oral and poster presentations. The conference started with a welcome from both the Symposium Chair, Professor Dr Ulrich Hahn (University of Hamburg, Germany) and the President of the International Society on Aptamers, Dr Sarah Shigdar (Deakin University, Australia).
Open Access
Aptamers 2018 – a conference update
(2018-06-29) Tanner, Julian A; Ismail, Said I; Shigdar, Sarah; DeRosa, Maria C; Hahn, Ulrich; Johnson, Philip E; Suess, Beatrix; McKeague, Maureen
The 5th annual symposium of the International Society on Aptamers, Aptamers 2018, was held in Oxford on the 11th and 12th April. We had a very diverse group of attendees and presenters from all over the world with representatives from both academia and industry. This year, the conference included a Lifetime Achievement Award presented to Emeritus Professor Dr Uli Hahn from the University of Hamburg and a very successful “Flash Talks” session.
Open Access
Aptamers 2019 – a conference update
(2019-07-14) Shigdar, Sarah; Johnson, Philip; Pietruschka, Georg; Legen, Tjaša; Mayer, Günter; McKeague, Maureen
The International Society on Aptamers held Aptamers 2019, the sixth successful annual symposium at Oxford in April. The meeting was chaired by Professor Dr Günter Mayer. The participants, representing over 25 countries, included some familiar faces as well as several new ones (~40% PIs/ postdocs, 25% students, and 35% from the industry)! A wide range of topics were covered in in 25+ oral presentations, 15+ flash-talks and 45+ posters. Below, we have briefly discussed some of the highlights of the symposium.