Nucleoside and nucleotide analogues containing fluorine

The work contained in this thesis is divided into four sections detailing the formation of (diethoxyphosphinyl)difluoromethylene substituted cycloalkanes and alkenes and their chemistry, as well as the syntheses of purine and pyrimidine substituted polyfluoroethers:(i) The methodology for the introduction of the (diethoxyphosphinyl)difluoromethylene group was studied and extended, with specific reference to cyclic systems. The group was successfully introduced into cyclic alkenes with (diethoxyphosphinyl)difluoro- methylene zinc bromide and saturated systems with (diethoxyphosphinyl)difluoromethyl lithium. The organolithium reagent was also shown to be capable of ring opening epoxides to yield alcohols ;(ii) The (diethoxyphosphinyl)difluoromethylene substituted cyclohexene derivative was further functionalised in a four step process to a new class of adenine and guanine based nucleotide analogues. Model studies were carried out on the (diethoxyphosphinyl)- difluoromethylene substituted cyclohexene derivative with a variety of reagents to introduce functionality at the double bond;(iii) The radical addition of (diethoxyphosphinyl)bromodifluoromethane and (diethoxyphosphinyl)difluoroiodomethane to cycloalkenes using ultraviolet photolysis and gamma-ray initiation were successfully carried out, thus opening up a new route into (diethoxyphosphinyl)difluoromethylene substituted cycloalkanes;(iv) The synthesis of purine and pyrimidine nucleoside analogues is described via the coupling of 2-amino-6-chloropurine, 6-chloropurine, silylated 5-fluorouracil and silylated uracil to various α-haloethers. The α-haloethers having previously been synthesised by radical chlorination of both cyclic and acyclic polyfluoroethers

On the Insignificance of Photochemical Hydrocarbon Aerosols in the Atmospheres of Close-in Extrasolar Giant Planets

The close-in extrasolar giant planets (CEGPs) reside in irradiated environments much more intense than that of the giant planets in our solar system. The high UV irradiance strongly influences their photochemistry and the general current view believed that this high UV flux will greatly enhance photochemical production of hydrocarbon aerosols. In this letter, we investigate hydrocarbon aerosol formation in the atmospheres of CEGPs. We find that the abundances of hydrocarbons in the atmospheres of CEGPs are significantly less than that of Jupiter except for models in which the CH$_4$ abundance is unreasonably high (as high as CO) for the hot (effective temperatures $\gtrsim 1000$ K) atmospheres. Moreover, the hydrocarbons will be condensed out to form aerosols only when the temperature-pressure profiles of the species intersect with the saturation profiles--a case almost certainly not realized in the hot CEGPs atmospheres. Hence our models show that photochemical hydrocarbon aerosols are insignificant in the atmospheres of CEGPs. In contrast, Jupiter and Saturn have a much higher abundance of hydrocarbon aerosols in their atmospheres which are responsible for strong absorption shortward of 600 nm. Thus the insignificance of photochemical hydrocarbon aerosols in the atmospheres of CEGPs rules out one class of models with low albedos and featureless spectra shortward of 600 nm.Comment: ApJL accepte

Vegetation Structure of Mangrove Ecosystems in Panama

Mangroves provide important habitat for terrestrial and marine wildlife. They buffer shorelines from flooding and sequester excess nutrients and pollutants in runoff before reaching rivers and oceans. Mangroves provide a wintering habitat for migratory bird species. These habitats are being rapidly lost to coastal development. This research focused on assessing the vegetation structure of mangrove ecosystems in Panama

Multigene analyses identify the three earliest lineages of extant flowering plants

AbstractFlowering plants (angiosperms) are by far the largest, most diverse, and most important group of land plants, with over 250,000 species and a dominating presence in most terrestrial ecosystems. Understanding the origin and early diversification of angiosperms has posed a long-standing botanical challenge [1]. Numerous morphological and molecular systematic studies have attempted to reconstruct the early history of this group, including identifying the root of the angiosperm tree. There is considerable disagreement among these studies, with various groups of putatively basal angiosperms from the subclass Magnoliidae having been placed at the root of the angiosperm tree (reviewed in [2–4]). We investigated the early evolution of angiosperms by conducting combined phylogenetic analyses of five genes that represent all three plant genomes from a broad sampling of angiosperms. Amborella, a monotypic, vesselless dioecious shrub from New Caledonia, was clearly identified as the first branch of angiosperm evolution, followed by the Nymphaeales (water lilies), and then a clade of woody vines comprising Schisandraceae and Austrobaileyaceae. These findings are remarkably congruent with those from several concurrent molecular studies [5–7] and have important implications for whether or not the first angiosperms were woody and contained vessels, for interpreting the evolution of other key characteristics of basal angiosperms, and for understanding the timing and pattern of angiosperm origin and diversification

The WiggleZ Dark Energy Survey: Final data release and cosmological results

This paper presents cosmological results from the final data release of the WiggleZ Dark Energy Survey. We perform full analyses of different cosmological models using the WiggleZ power spectra measured at z=0.22, 0.41, 0.60, and 0.78, combined with other cosmological data sets. The limiting factor in this analysis is the theoretical modeling of the galaxy power spectrum, including nonlinearities, galaxy bias, and redshift-space distortions. In this paper we assess several different methods for modeling the theoretical power spectrum, testing them against the Gigaparsec WiggleZ simulations (GiggleZ). We fit for a base set of six cosmological parameters, {Ω_(b)h^2,Ω_(CDM)h^2,H_0,τ,A_s,n_s}, and five supplementary parameters {n_(run),r,w,Ω_k,∑m_ν}. In combination with the cosmic microwave background, our results are consistent with the ΛCDM concordance cosmology, with a measurement of the matter density of Ωm=0.29±0.016 and amplitude of fluctuations σ_8=0.825±0.017. Using WiggleZ data with cosmic microwave background and other distance and matter power spectra data, we find no evidence for any of the extension parameters being inconsistent with their ΛCDM model values. The power spectra data and theoretical modeling tools are available for use as a module for CosmoMC, which we here make publicly available at http://smp.uq.edu.au/wigglez-data. We also release the data and random catalogs used to construct the baryon acoustic oscillation correlation function

Impact of 18F-Choline PET scan acquisition time on delineation of GTV in prostate cancer [Poster Abstract]

Background: Dose painting radiotherapy requires accurate outlining of primary tumour volumes in the prostate. T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) is the best imaging method for defining the gross tumour volume (GTV). Choline positron emission tomography (PET) is currently a controversial tracer. The image acquisition differs significantly in published studies. Many used early static imaging. One study found that 18F-choline PET/CT with late image acquisition has superior accuracy to T2W MR and functional MR alone1. We investigate whether increasing 18F-Choline PET scan acquisition time from 60 (PET-60) to 90 (PET-90) minutes improves GTV TVD. Methods. Analysis was performed on 9 18F-Choline PET scans. Patients were injected with 370MBq of activity. Three clinicians (C1, C2 and C3) independently and without reference to each other contoured GTVs on each of the T2W-MRI, PET-60 and PET-90 scans at differing times. Scans were registered by a clinician using rigid co-registration. The treating clinicians MRI contour was used as a reference contour. The resulting PET and MRI GTVs were transferred to the PET-60 and PET-90 scans after image registration. The Dice Similarity Coefficient (DSC), Specificity (Sp) and Sensitivity (S) were calculated from contour mask voxel analysis. Results. Table 1 shows the mean and range DSC, S and Sp scores on MRI, PET-60 and PET-90 for C1, C2 and C3 in comparison to the treating clinicians contour on MRI (C1). A 2 sampled T-test (P < 0.01) showed, no significant difference in the Sp, S and DSC between GTVs on PET-60 and PET-90 scans. Further to this, as shown in Figure 1, variability in GTV delineation is significant between observers in a singular case as well as across imaging modalities. Conclusion. Compared to MRI delineated GTVs, 18F-Choline PET GTVs are significantly different. This study found however that increasing the PET scan acquisition time from 60 to 90 minutes did not improve the performance of GTV TVD in comparison to MRI delineated GTV

The accuracy of intramedullary femoral alignment in total knee replacement in the prescence of ipsilateral hip replacement

Objectives: During total knee replacement (TKR) surgery, the most commonly used method for aligning the distal femur appropriately is via an intramedullary (IM) distal femoral alignment rod. The alignment of the rod itself is reliant on the isthmus which is used to most accurately place the rod in the correct anatomical axis. In the instance of something preventing the rod from entering the isthmus correctly, such as a hip replacement, then the degree of accuracy could be assumed to be even less. Mechanical-anatomical malalignment has been shown to decrease the implant (TKR) survival and so methods of increasing accuracy of alignment relative to the mechanical axis have been developed. At present the most accurate method intraoperatively is computer navigation and several studies have demonstrated improved alignment. An increasing number of patients year on year are having both knee and hip replacements and as the population ages the likelihood of having both a knee and hip replacement will also increase. We propose that the presence of a hip replacement within the isthmus of the femur may further decrease the accuracy of the IM alignment of the femur leading to incorrect implant positioning. Methods: The study was conducted on 10 cadaveric specimens (20 femurs). Computational navigation instrumentation was attached in turn to each femur and the ideal alignment data recorded in a standard fashion by a single operator (principal investigator). A standard entry port was then be made in the femur for the introduction of the IM rod. An IM rod was then inserted with the distal femoral cutting block in the accepted position recorded blindly on the computer navigation (both in terms of varus/valgus alignment to the mechanical axis and the degree of flexion). The process was then repeated at 3 levels to represent primary and revision hip lengths from the greater trochanter (replicating the changes that would occur in the presence of a hip replacement) The process was recorded three times at each level. Results: The resection angles between the cutting surface and the mechanical axis were measured and collected by means of computer navigation system. The results show that the IM alignment had mean Valgus of 0 degrees +/- 0.8 but with a hip replacement in situ this increased to 0.46 degrees +/- 1.49 (range 2.5 varus to 4.5 valgus), with a revision stem 0.825 +/- 1.68 (range 2.5 varus to 4.5 valgus)and long stemmed revision 1.325 +/- 2.09 (range 5 varus to 6.5 valgus). In terms of Flexion IM alignment had a mean flexion of 0.92 +/- 1.7 (range 3 extension to 4 flexion) but with a hip replacement in situ this increased to 1.88 degrees +/- 2.03 (range 2.5 extension to 8.5 flexion), with a revision stem 2.35 +/- 2.2 (range 2.5 extension to 8 flexion) and long stemmed revision 2.75 +/- 2.16(range 3.5 extension to 7 flexion). Conclusion: This Study concludes that the prescence of a hip replacement, in particular long stemmed prosthesis, further reduces the accuracy of IM alignment in the Femur for Total Knee Replacement. Consideration of an alternative method, such as navigation, should be considered insuch situations

Phylogeography of the Central American lancehead Bothrops asper (SERPENTES: VIPERIDAE)

The uplift and final connection of the Central American land bridge is considered the major event that allowed biotic exchange between vertebrate lineages of northern and southern origin in the New World. However, given the complex tectonics that shaped Middle America, there is still substantial controversy over details of this geographical reconnection, and its role in determining biogeographic patterns in the region. Here, we examine the phylogeography of Bothrops asper, a widely distributed pitviper in Middle America and northwestern South America, in an attempt to evaluate how the final Isthmian uplift and other biogeographical boundaries in the region influenced genealogical lineage divergence in this species. We examined sequence data from two mitochondrial genes (MT-CYB and MT-ND4) from 111 specimens of B. asper, representing 70 localities throughout the species' distribution. We reconstructed phylogeographic patterns using maximum likelihood and Bayesian methods and estimated divergence time using the Bayesian relaxed clock method. Within the nominal species, an early split led to two divergent lineages of B. asper: one includes five phylogroups distributed in Caribbean Middle America and southwestern Ecuador, and the other comprises five other groups scattered in the Pacific slope of Isthmian Central America and northwestern South America. Our results provide evidence of a complex transition that involves at least two dispersal events into Middle America during the final closure of the Isthmus

Bayesian Calibrated Significance Levels Applied to the Spectral Tilt and Hemispherical Asymmetry

Bayesian model selection provides a formal method of determining the level of support for new parameters in a model. However, if there is not a specific enough underlying physical motivation for the new parameters it can be hard to assign them meaningful priors, an essential ingredient of Bayesian model selection. Here we look at methods maximizing the prior so as to work out what is the maximum support the data could give for the new parameters. If the maximum support is not high enough then one can confidently conclude that the new parameters are unnecessary without needing to worry that some other prior may make them significant. We discuss a computationally efficient means of doing this which involves mapping p-values onto upper bounds of the Bayes factor (or odds) for the new parameters. A p-value of 0.05 ($1.96\sigma$) corresponds to odds less than or equal to 5:2 which is below the `weak' support at best threshold. A p-value of 0.0003 ($3.6\sigma$) corresponds to odds of less than or equal to 150:1 which is the `strong' support at best threshold. Applying this method we find that the odds on the scalar spectral index being different from one are 49:1 at best. We also find that the odds that there is primordial hemispherical asymmetry in the cosmic microwave background are 9:1 at best.Comment: 5 pages. V2: clarifying comments added in response to referee report. Matches version to appear in MNRA

Chromophores in molecular nanorings : when is a ring a ring?

The topology of a conjugated molecule plays a significant role in controlling both the electronic properties and the conformational manifold that the molecule may explore. Fully π-conjugated molecular nanorings are of particular interest, as their lowest electronic transition may be strongly suppressed as a result of symmetry constraints. In contrast, the simple Kasha model predicts an enhancement in the radiative rate for corresponding linear oligomers. Here we investigate such effects in linear and cyclic conjugated molecules containing between 6 and 42 butadiyne-linked porphyrin units (corresponding to 600 C–C bonds) as pure monodisperse oligomers. We demonstrate that as the diameter of the nanorings increases beyond ∼10 nm, its electronic properties tend toward those of a similarly sized linear molecule as a result of excitation localization on a subsegment of the ring. However, significant differences persist in the nature of the emitting dipole polarization even beyond this limit, arising from variations in molecular curvature and conformation