Studies on the biosynthesis of penicillins

A high yielding synthesis of the acyclic precursor of the penicillins, δ— (L—α—aminoadipyl)—L—cysteinyl—D— valine (LLD-ACV) was developed. Using this synthesis the isotopically enriched ACV peptides, δ-(DL-α—aminoadipyl)—L—cysteinyl—D— (3R)— [4-¹ ³C]—valine and δ—(L—α - aminoadipyl)—L— [3-¹ ³c]—cysteinyl-D— [¹ ³N]—valine were prepared. In an extension to this work the tetrapeptide, δ— (L—α—aminoadipyl)— L— cysteinyl—D— valylglycine (LLD-ACVG) was prepared.A putative intermediate in the biosynthesis of isopenicillin N, N— [δ— (L—α—aminoadipyl)—L—cysteinyl ]—N—hydroxy—D—valine (LLD-AC( N-OH) V), was synthesised from N—hydroxy—D—valine benzyl ester.A cell-free system capable of converting δ— (L—α—aminoadipyl )—L— cysteinyl—D—valine to isopenicillin N was obtained from cultures of the cephalosporin producing fungus Cephalosporium acremonium CW19. The cell-free system was used to test the importance of the above synthesised compounds in penicillin biosynthesis. N— [ δ— (L—α—aminoadipyl )—L—cysteinyl ]-N—hydroxy—D—valine was shown not to be a substrate for the enzyme "isopenicillin N synthetase" but to be a potent inhibitor of the LLD-ACV to isopenicillin N conversion. The tetrapeptide, δ— (L—α—aminoadipyl )—L—cysteinyl—D—valylglycine, was found to be a weak inhibitor of this conversion.The isotopically enriched ACV peptides were used to confirm the stereochemistry of the valine C3 centre in biosynthesised δ— (L—α— aminoadipyl)—L—cysteinyl—D—valine and to allow preliminary ¹ ³C n.m.r. studies on the biosynthesis of isopenicillin N

Ultrafast laser inscription of mid-IR directional couplers for stellar interferometry

We report the ultrafast laser fabrication and mid-IR characterization (3.39 microns) of four-port evanescent field directional couplers. The couplers were fabricated in a commercial gallium lanthanum sulphide glass substrate using sub-picosecond laser pulses of 1030 nm light. Straight waveguides inscribed using optimal fabrication parameters were found to exhibit propagation losses of 0.8 dB/cm. A series of couplers were inscribed with different interaction lengths, and we demonstrate power splitting ratios of between 8% and 99% for mid-IR light with a wavelength of 3.39 microns. These results clearly demonstrate that ultrafast laser inscription can be used to fabricate high quality evanescent field couplers for future applications in astronomical interferometry.Comment: 4 pages, 4 figure

Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

Funding: This work was funded by the Scottish Government Rural and Environment Science and Analytical Services Division. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Motion of buoyant particles and coarsening of solid-liquid mixtures in a random acceleration field

Flow induced by a random acceleration field (g-jitter) is considered in two related situations that are of interest for microgravity fluid experiments: the random motion of an isolated buoyant particle and coarsening of a solid-liquid mixture. We start by analyzing in detail actual accelerometer data gathered during a recent microgravity mission, and obtain the values of the parameters defining a previously introduced stochastic model of this acceleration field. We then study the motion of a solid particle suspended in an incompressible fluid that is subjected to such random accelerations. The displacement of the particle is shown to have a diffusive component if the correlation time of the stochastic acceleration is finite or zero, and mean squared velocities and effective diffusion coefficients are obtained explicitly. Finally, the effect of g-jitter on coarsening of a solid-liquid mixture is considered. Corrections due to the induced fluid motion are calculated, and estimates are given for coarsening of Sn-rich particles in a Sn-Pb eutectic fluid, experiment to be conducted in microgravity in the near future.Comment: 25 pages, 4 figures (included). Also at http://www.scri.fsu.edu/~vinals/ross2.p

Raeburn, life and art

This thesis gives the biography of the Scottish portrait painter Sir Henry Raeburn R.A. (1756-1823), an outline of his training, a description of his stylistic development and a catalogue of his works.The problem of his activities as a miniaturist is addressed: only two are known but he is reported to have produced many. It is proposed that mourning jewels, made when he was an apprentice goldsmith, may have constituted part of this lost body of work. Raeburn was given some training by David Deuchar (1743-1808), Alexander Runciman (1736- 1785) and David Martin (1737-1798). New evidence relating to Raeburn's time with Martin is given. Raeburn's portrait George Chalmers of Pittencrieff is not accepted as dating from before the trip to Rome. Only one independent portrait commission is dated in the thesis to that period. It is suggested that as an artist Raeburn was a probationer when he left Scotland and that he rapidly matured in Italy. He studied in Rome from 1784 - c. 1787 in the circle of James Byres (1734-1817). An important portrait from his Roman years has been uncovered. He returned to Scotland in about 1787 and spent his entire career in Edinburgh. It is argued that it was his time in Italy which formed his early style, rather than some presumed contact with the work of Reynolds.Raeburn's painting of c. 1800 responded to new concerns. He is also recorded as working as an underwriter shortly after that date. For an unknown reason the artist went bankrupt in 1808. New documents pn this matter are presented.An examination is made of the widely held view that Raeburn's late style was due to a trip he made to London in 1810. Proof is given dating from before 1810 of a move in this new artistic direction.Those with closed minds on Raeburn, holding views formulated ninety years ago, will not read these sections with pleasure.The catalogue contains slightly more than eight hundred entries dealing with almost one thousand works. Dating Raeburn's portraits is difficult and consequently the catalogue is arranged alphabetically. The catalogue contains entries on the copies Raeburn made after the works of other artists and entries on works known only from archival sources. Rejected works are not listed. The thesis does not deal with Raeburn's influence on other painters

HARMLESS DISCRIMINATION

ABSTRACTIn Born Free and Equal: A Philosophical Inquiry into the Nature of Discrimination, Kasper Lippert-Rasmussen defends the harm-based account of the wrongness of discrimination, which explains the wrongness of discrimination with reference to the harmfulness of discriminatory acts. Against this view, we offer two objections. The conditions objection states that the harm-based account implausibly fails to recognize that harmless discrimination can be wrong. The explanation objection states that the harm-based account fails adequately to identify all of the wrong-making properties of discriminatory acts. We argue that the structure of a satisfactory view cannot be outcome-focused. A more promising family of views focuses on the deliberation of the discriminator and in particular on the reasons that motivate or fail to motivate her action.</jats:p

Understanding inclusive design education

There is a need for responsible engineering design to accommodate the diverse user requirements that come with the global phenomenon of population ageing. Inclusive design is a design philosophy that considers the needs of a wide diversity of users within the design process, therefore is an approach that can address these diverse user requirements. However, uptake of inclusive design in industry has been limited, with designer awareness of the approach and its associated methods and tools noted as barriers to the uptake of the approach. This research aims to understand the current approach to ID education within UK Higher Education Institutions, utilising interviews with design educators and a student survey. The study concluded that the teaching of inclusive design varied between institutions with some conflicting responses from academics and students relating to methods, tools and processes taught. This study recommends that greater transparency should be encouraged between universities to encourage the development of a cohesive ID education strategy, in addition to the development of a framework to aid the implementation of appropriate ID methods and tools within the design process