The Synthesis of Oxazole-containing Natural Products

The first section describes the synthesis of the C1' to C11' side chain of leucascandrolide A. The key step of the synthesis is a modified Robinson-Gabriel synthesis of the oxazole. The C1' to C11' side chain was constructed in 9 steps and 7% overall yield.The second section describes the synthesis of 2-alkynyl oxazoles and subsequent transformations into a variety of useful motifs. The conjugate addition of nucleophiles to 2-alkynyl oxazoles under basic conditions affords vinyl ethers, vinyl thioethers and enamines. The addition of ethanedithiol affords dithiolanes that can be transformed into ethyl thioesters and ketones. Nucleophilic additions of thiols to 2-alkynyl oxazolines affords oxazoline thioethers. Additions of halides under acidic conditions stereoselectively affords vinyl halides that can be further transformed by Sonogashira cross-coupling reactions.The third section describes the synthesis of (-)-disorazole C1 and analogs. The macrocycle was constructed with minimal protecting group manipulations, using mild esterification and Sonogashira cross-coupling reactions. The convergent synthesis of disorazole C1 allowed for the synthesis of additional analogs. These analogs include the C14-t-butyl and C17-18-cyclopropane derivatives. Results from preliminary biological evaluations of synthetic intermediates, analogs and derivatives are also discussed

Energy-level pinning and the 0.7 spin state in one dimension: GaAs quantum wires studied using finite-bias spectroscopy

We study the effects of electron-electron interactions on the energy levels of GaAs quantum wires (QWs) using finite-bias spectroscopy. We probe the energy spectrum at zero magnetic field, and at crossings of opposite-spin-levels in high in-plane magnetic field B. Our results constitute direct evidence that spin-up (higher energy) levels pin to the chemical potential as they populate. We also show that spin-up and spin-down levels abruptly rearrange at the crossing in a manner resembling the magnetic phase transitions predicted to occur at crossings of Landau levels. This rearranging and pinning of subbands provides a phenomenological explanation for the 0.7 structure, a one-dimensional (1D) nanomagnetic state, and its high-B variants.Comment: 6 pages, 4 figure

Ultrasonic Evaluation of Low Density Powder Compacts

Ultrasonic evaluation of powder compacts provides valuable information about the density of the powder and incipient defects in the compact. Since the specimens would be contaminated if they were inspected with traditional immersion or contact techniques, procedures to dry couple or vacuum bag and immerse the powder samples were implemented. With these methods ultrasonic energy was propagated through the powder compacts and the acoustic velocity and attenuation were measured. The ability to immerse the powder samples not only provides consistent coupling but allows scanning which is a valuable tool to image variations and defects in the compacts

Multigrid preconditioners for the hybridised discontinuous Galerkin discretisation of the shallow water equations

17 USC 105 interim-entered record; under review.The article of record as published may be found at https://doi.org/10.1016/j.jcp.2020.109948Numerical climate- and weather-prediction models require the fast solution of the equations of fluid dynamics. Discontinuous Galerkin (DG) discretisations have several advantageous properties. They can be used for arbitrary domains and support a structured data layout, which is particularly important on modern chip architectures. For smooth solutions, higher order approximations can be particularly efficient since errors decrease exponentially in the polynomial degree. Due to the wide separation of timescales in atmospheric dynamics, semi-implicit time integrators are highly efficient, since the implicit treatment of fast waves avoids tight constraints on the time step size, and can therefore improve overall efficiency. However, if implicit-explicit (IMEX) integrators are used, a large linear system of equations has to be solved in every time step. A particular problem for DG discretisations of velocity-pressure systems is that the normal Schur-complement reduction to an elliptic system for the pressure is not possible since the numerical fluxes introduce artificial diffusion terms. For the shallow water equations, which form an important model system, hybridised DG methods have been shown to overcome this issue. However, no attention has been paid to the efficient solution of the resulting linear system of equations. In this paper we address this issue and show that the elliptic system for the flux unknowns can be solved efficiently by using a non-nested multigrid algorithm. The method is implemented in the Firedrake library and we demonstrate the excellent performance of the algorithm both for an idealised stationary flow problem in a flat domain and for nonstationary setups in spherical geometry from the well-known testsuite in Williamson et al. (1992) [23]. In the latter case the performance of our bespoke multigrid preconditioner (although itself not highly optimised) is comparable to that of a highly optimised direct solver.EPSRCEPSRCEP/L015684/1UK-Fluids network (EPSRC grant EP/N032861/1

Towards a membrane proteome in Drosophila: a method for the isolation of plasma membrane

<p>Abstract</p> <p>Background</p> <p>The plasma membrane (PM) is a compartment of significant interest because cell surface proteins influence the way in which a cell interacts with its neighbours and its extracellular environment. However, PM is hard to isolate because of its low abundance. Aqueous two-phase affinity purification (2PAP), based on PEG/Dextran two-phase fractionation and lectin affinity for PM-derived microsomes, is an emerging method for the isolation of high purity plasma membranes from several vertebrate sources. In contrast, PM isolation techniques in important invertebrate genetic model systems, such as <it>Drosophila melanogaster</it>, have relied upon enrichment by density gradient centrifugation. To facilitate genetic investigation of activities contributing to the content of the PM sub-proteome, we sought to adapt 2PAP to this invertebrate model to provide a robust PM isolation technique for <it>Drosophila</it>.</p> <p>Results</p> <p>We show that 2PAP alone does not completely remove contaminating endoplasmic reticulum and mitochondrial membrane. However, a novel combination of density gradient centrifugation plus 2PAP results in a robust PM preparation. To demonstrate the utility of this technique we isolated PM from fly heads and successfully identified 432 proteins using MudPIT, of which 37% are integral membrane proteins from all compartments. Of the 432 proteins, 22% have been previously assigned to the PM compartment, and a further 34% are currently unassigned to any compartment and represent candidates for assignment to the PM. The remainder have previous assignments to other compartments.</p> <p>Conclusion</p> <p>A combination of density gradient centrifugation and 2PAP results in a robust, high purity PM preparation from <it>Drosophila</it>, something neither technique can achieve on its own. This novel preparation should lay the groundwork for the proteomic investigation of the PM in different genetic backgrounds in <it>Drosophila</it>. Our results also identify two key steps in this procedure: The optimization of membrane partitioning in the PEG/Dextran mixture, and careful choice of the correct lectin for the affinity purification step in light of variations in bulk membrane lipid composition and glycosylation patterns respectively. This points the way for further adaptations into other systems.</p

Lasing and cooling in a hot cavity

We present a microscopic laser model for many atoms coupled to a single cavity mode, including the light forces resulting from atom-field momentum exchange. Within a semiclassical description, we solve the equations for atomic motion and internal dynamics to obtain analytic expressions for the optical potential and friction force seen by each atom. When optical gain is maximum at frequencies where the light field extracts kinetic energy from the atomic motion, the dynamics combines optical lasing and motional cooling. From the corresponding momentum diffusion coefficient we predict sub-Doppler temperatures in the stationary state. This generalizes the theory of cavity enhanced laser cooling to active cavity systems. We identify the gain induced reduction of the effective resonator linewidth as key origin for the faster cooling and lower temperatures, which implys that a bad cavity with a gain medium can replace a high-Q cavity. In addition, this shows the importance of light forces for gas lasers in the low-temperature limit, where atoms can arrange in a periodic pattern maximizing gain and counteracting spatial hole burning. Ultimately, in the low temperature limit, such a setup should allow to combine optical lasing and atom lasing in single device.Comment: 11 pages, 6 figure

Characterization of a supercoil-dependent S1 sensitive site 5\u27 to the Drosophila melanogaster hsp 26 gene

We have analyzed the prominent supercoil-dependent S1 nuclease cleavage site 5\u27 to hsp 26 in the plasmid 88B13, which contains 11.7 kilobases from the Drosophila locus 67B1. The double stranded cleavage product is generated by initial nicking on the purine strand, six preferred sites occurring between positions -96 and -90 (relative to the start of transcription) with weaker ones extending to position -84, followed by cleavage on the pyrimidine strand at positions -86 and -84. A derivative of 88B13, 88B13-X, was generated by insertion of an Xho I linker at position -84; this does not affect the positions or strand specificity of the S1 cleavage in that region. A small deletion, delta 41.1, removes the homopurine/homopyrimidine stretch from positions -86 to -132 and is no longer sensitive to cleavage by S1 nuclease 5\u27 to hsp 26. Mung bean and P1 nucleases recognize the same site 5\u27 to hsp 26 and give the same general pattern of cleavage. All three nucleases show an initial cleavage of 88B13 DNA at this site at pH 5.5 but not at pH 6.5, indicating that the DNA structure there may be pH dependent in vitro

Conceptualisations of children’s wellbeing at school: the contribution of recognition theory

A large study in Australian schools aimed to elucidate understandings of ‘wellbeing’ and of factors in school life that contribute to it. Students and teachers understood wellbeing primarily, and holistically, in terms of interpersonal relationships, in contrast to policy documents which mainly focused on ‘problem areas’ such as mental health. The study also drew on recognition theory as developed by the social philosopher Axel Honneth. Results indicate that recognition theory may be useful in understanding wellbeing in schools, and that empirical research in schools may give rise to further questions regarding theory