Development of Signal Amplification By Reversible Exchange (SABRE) towards biological and forensic applications

Work presented in this thesis focuses on the application of signal amplification by reversible exchange (SABRE) to the hyperpolarisation of small molecules. The aim of this work was to develop the technique towards future biologically relevant applications through resolution of barriers currently preventing clinical relevance. Furthermore, applications to forensics were also investigated. SABRE currently almost exclusively utilises iridium-based catalysts, however, there are reports of the utilisation of cobalt and one mixed iridium/rhodium system. A range of rhodium based complexes, [Rh(IMes)(COD)Cl] (6), [Rh(ImNPri2)(COD)Cl] (7), [Rh(ItBu)(COD)Cl] (8) and [Rh(ICy)(COD)Cl] (9), were synthesised and evaluated for SABRE activity. Testing demonstrated that these species were unable to form stable dihydride species at room temperature and therefore the iridium complex [Ir(IMes)(COD)Cl] (4) was utilised for the remainder of the work. 19F SABRE provides a versatile route for measurements in vivo due to the low background present within the body. This work assessed the hyperpolarisation of 2-, 3-, 4-, 3,5- and pentafluoropyridine (L2 – L6), that have been interrogated by SABRE to establish a theoretical understanding of their efficacy with respect to polarisation transfer. However, hyperpolarisation of L3, which yielded the highest enhancement, resulted in an antiphase signal which may lead to internal cancelation within a biological imaging context. Thus, Signal Amplification By Reversible Exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) was employed to generate an in-phase absorptive hyperpolarised signal. Recent studies have demonstrated 4 is cytotoxic, therefore the mounting of the catalyst on silica or polymer derived supports was evaluated for the generation of a HET-SABRE catalyst and hyperpolarisation reported for a heterogeneous system. The solids proved effective at scavenging the metal from solution, therefore, an evaluation of their potential efficacy for production of a biocompatible bolus following homogenous SABRE is presented. 2-(2-pyridyl)ethyl - functionalised silica gel (S5) is reported to be the most effective 4 metal scavenger utilised, with results suggesting ~1g of S5 is capable of reducing the iridium content of a bolus from ~1005ppm to below background levels within 2 minutes. The hyperpolarisation of a range of fentanyl derivatives is F1-F5, including Mirfentanil (F5), a derivative with known biological activity. Both F2 and F5 have been detected within an excess of heroin. F5 was detected at a concentration of 81 μM in ~5 seconds when ~145 mM of heroin was present. Further to this, the 19F SABRE of a world health organisation essential medicine, voriconazole, is reported at a concentration ~4 times below current dosing guidelines

A study of beryllium and beryllium-lithium complexes in single crystal silicon

When beryllium is thermally diffused into silicon, it gives rise to acceptor levels 191 MeV and 145 meV above the valence band. Quenching and annealing studies indicate that the 145-MeV level is due to a more complex beryllium configuration than the 191-MeV level. When lithium is thermally diffused into a beryllium-doped silicon sample, it produces two acceptor levels at 106 MeV and 81 MeV. Quenching and annealing studies indicate that these levels are due to lithium forming a complex with the defects responsible for the 191-MeV and 145-MeV beryllium levels, respectively. Electrical measurements imply that the lithium impurity ions are physically close to the beryllium impurity atoms. The ground state of the 106-MeV beryllium level is split into two levels, presumably by internal strains. Tentative models are proposed

Are there any good digraph width measures?

Several different measures for digraph width have appeared in the last few years. However, none of them shares all the "nice" properties of treewidth: First, being \emph{algorithmically useful} i.e. admitting polynomial-time algorithms for all \MS1-definable problems on digraphs of bounded width. And, second, having nice \emph{structural properties} i.e. being monotone under taking subdigraphs and some form of arc contractions. As for the former, (undirected) \MS1 seems to be the least common denominator of all reasonably expressive logical languages on digraphs that can speak about the edge/arc relation on the vertex set.The latter property is a necessary condition for a width measure to be characterizable by some version of the cops-and-robber game characterizing the ordinary treewidth. Our main result is that \emph{any reasonable} algorithmically useful and structurally nice digraph measure cannot be substantially different from the treewidth of the underlying undirected graph. Moreover, we introduce \emph{directed topological minors} and argue that they are the weakest useful notion of minors for digraphs

Orbit-resolved photometry and echelle spectroscopy of the cataclysmic variable ST LMi during a 2007 high state

We present high-resolution echelle spectra and contemporaneous photometry of the polar ST LMi during a high state in 2007 March. Emission lines at Hα, He I λ5876, and He I λ7065 show similar line profiles over orbital phase and have narrow and broad components. These profile changes with phase are very similar to those reported in earlier high-state studies of ST LMi. The radial velocity curves from double Gaussian fits to the line profiles are interpreted as two crossing curves, neither of which is coincident with the orbital motion of the secondary star. We attribute one component to infall motions near the white dwarf and the other to a gas streaming along magnetic field lines connecting the two stars

Multi-wavelength visibility measurements of the red giant R Doradus

We present visibility measurements of the nearby Mira-like star R Doradus taken over a wide range of wavelengths (650--990 nm). The observations were made using MAPPIT (Masked APerture-Plane Interference Telescope), an interferometer operating at the 3.9-m Anglo-Australian Telescope. We used a slit to mask the telescope aperture and prism to disperse the interference pattern in wavelength. We observed in R Dor strong decreases in visibility within the TiO absorption bands. The results are in general agreement with theory but differ in detail, suggesting that further work is needed to refine the theoretical models.Comment: 8 pages; SPIE Conf. 4006 "Interferometry in Optical Astronomy

An FPT 2-Approximation for Tree-Cut Decomposition

The tree-cut width of a graph is a graph parameter defined by Wollan [J. Comb. Theory, Ser. B, 110:47-66, 2015] with the help of tree-cut decompositions. In certain cases, tree-cut width appears to be more adequate than treewidth as an invariant that, when bounded, can accelerate the resolution of intractable problems. While designing algorithms for problems with bounded tree-cut width, it is important to have a parametrically tractable way to compute the exact value of this parameter or, at least, some constant approximation of it. In this paper we give a parameterized 2-approximation algorithm for the computation of tree-cut width; for an input $n$-vertex graph $G$ and an integer $w$, our algorithm either confirms that the tree-cut width of $G$ is more than $w$ or returns a tree-cut decomposition of $G$ certifying that its tree-cut width is at most $2w$, in time $2^{O(w^2\log w)} \cdot n^2$. Prior to this work, no constructive parameterized algorithms, even approximated ones, existed for computing the tree-cut width of a graph. As a consequence of the Graph Minors series by Robertson and Seymour, only the existence of a decision algorithm was known.Comment: 17 pages, 3 figure