Synthetic Studies in the Santonin Series

Part I. A study of some synthetic routes to santonin. Mukherjee's preparation of ethyl alpha-(4-methyl-3-oxo-cyclohexyl)propionate has been shortened and the overall yield raised considerably. The preparation of the hitherto unknown 1-chloro- and l-diethylaminopent-1-en-3-one is described. Attempts to condense these compounds with 2-methylcyclohexanone and with ethyl alpha-(4-methyl-3-oxo-cyclohexyl)propionate were unsuccessful. Condensation of the latter with l-diethylaminopentan-3-one affords ethyl alpha-(2:3:4:5:6:7:8:10-octahydro-1:10-dimethyl-2-oxo-7-naphthyl)propionate: the best conditions for the reaction have been determined. The bromination-dehydrobromination of ethyl alpha-(2:3:4:5:6:7:8:10-octahydro-1:10-dimethyl-2-oxo-7-naphthyl)-propionate has been studied - ethyl alpha-(2:3:4:5:6:10-hexa-hydro-1:10-dimethyl-2-oxo-7-naphthyl)propionate is the product in all cases. An attempt to convert the latter to dihydrosantonin was not successful. Several other approaches to the santonin structure have been studied, but a satisfactory synthesis has not been found. Part II. The synthesis of some compounds analogous to santonin. Methyl 4-methyl-3-oxocyclohexyl acetate has been prepared for the first time by a modification of Mukherjee's procedure. Condensation with 1-diethylamino-pentan-3-one followed by hydrolysis gives 2:3:4:5:6:7:8 :10-octahydro-1:10-dimethyl-2-oxo-7-naphthylacetic acid which yields 3:8-dibromo-2:3:4:5:6:7:8:10-octahydro-1:10-di-methyl-2-oxo-7-naphthylacetic acid on bromination. Dehydrobromination and lactonisation then give the gamma lactone of 2:5:6:7:8:10-hexahydro-8-hydroxy-1:10-dimethyl-2-oxo-7-naphthylacetic acid which is similar in structure to santonin, but lacks the methyl group at C11. Chemical and spectrographic evidence for this structure are provided. In the hope of preparing a second analogue, the gamma lactone of 2:5:6:7:8:10-hexahydro-8-hydroxy-10-methyl-2-oxo-7-naphthylacetic acid, 2:3:4:5:6:7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid has been prepared. 3 :8-Dibromo-2:3 :4:5:6:7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid and the gamma lactone of 2:3:4:5:6:-7:8:10-octahydro-8-hydroxy-10-methyl-2-oxo-7-naphthyl-acetic acid have been obtained from this acid, but could not be converted to the second analogue. The second isomer of 2:3:4:5:6 :7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid has also been prepared by a shorter route from 2-methylcyclohexanone

Stereospecific hydroxylation of long chain compounds by a species of Torulopsis.

Abstract A species of yeast of the genus Torulopsis hydroxylates long chain C18 compounds and then converts them to glycosides of 17-l-hydroxy C18 fatty acids. Incubation of methyl [17-18O]hydroxyoleate with whole cells and of methyl oleate in the presence of 18O2 or H218O showed that the oxygen atom, introduced on hydroxylation, is not lost on glycoside formation and that it is derived from molecular oxygen and not from water. Esters of [18-2H3], [16,18-2H5], [17-2H2], [17-d-2H], and [17-l-2H]octadecanoates have been synthesized. On incubation of these compounds no deuterium atoms at C-16 and C-18 are removed but the 17-l-deuterium atom is lost. Unsaturated intermediates are, therefore, most probably not involved and 17-l-hydroxy acid is produced by displacement of an l-hydrogen atom (retention of configuration). The rate of formation of glycoside from l-deuterostearate was less than half of that from d-deuterostearate or from unlabeled stearate, suggesting the operation of a primary isotope effect

Bayesian photon counting with electron-multiplying charge coupled devices (EMCCDs)

The EMCCD is a CCD type that delivers fast readout and negligible detector noise, making it an ideal detector for high frame rate applications. Because of the very low detector noise, this detector can potentially count single photons. Considering that an EMCCD has a limited dynamical range and negligible detector noise, one would typically apply an EMCCD in such a way that multiple images of the same object are available, for instance, in so called lucky imaging. The problem of counting photons can then conveniently be viewed as statistical inference of flux or photon rates, based on a stack of images. A simple probabilistic model for the output of an EMCCD is developed. Based on this model and the prior knowledge that photons are Poisson distributed, we derive two methods for estimating the most probable flux per pixel, one based on thresholding, and another based on full Bayesian inference. We find that it is indeed possible to derive such expressions, and tests of these methods show that estimating fluxes with only shot noise is possible, up to fluxes of about one photon per pixel per readout.Comment: Fixed a few typos compared to the published versio

Opioid prescribing for acute postoperative pain : an overview of systematic reviews related to two consensus statements relevant at patient, prescriber, system and public health levels

Peer reviewedPublisher PD

Did the Student Engage in Academic Dishonesty on their Exam? Yes, No, and Shades of Grey in Decision Making

In academia, there are guidelines as to what constitutes academic dishonesty, and how to report it. This leads to the assumption that when instances arise, there are clear yes or no answers to the questions: (a) did the student engage in academic dishonesty, and (b) how should the student be disciplined? Previous research has been conducted examining the behaviours students engage in and the repercussions, but less research has examined the cognitions and actions of the people who discover the instances of academic dishonesty. Therefore, the purpose of this study was to examine how participants make sense of potential academic dishonesty scenarios and the resulting actions they would take. We presented 201 preservice teachers with three scenarios: (a) sneaking answers into an exam, (b) having someone tell you the answers and (c) peeking at someone else’s answers. For each scenario, they had to respond to the items (1) to what extent do you consider the student’s behaviour as academic dishonesty, (2) What in the story helped you decide on your response? and (3) What do you think is an appropriate form of discipline? Overall, participants strongly agreed the behaviours were academically dishonest, however, when asked to indicate what in the story helped them decide, the majority made embellishments to the story, and close to half of the participants provided their opinions related to academic dishonesty more broadly. Moreover, participants indicated a wide range of disciplines for the same scenarios. The results will be utilized to create discussion around decision-making and academic dishonesty

Informed actions: Where to cost effectively manage multiple threats to species to maximize return on investment

Conservation practitioners, faced with managing multiple threats to biodiversity and limited funding, must prioritize investment in different management actions. From an economic perspective, it is routine practice to invest where the highest rate of return is expected. This return-on-investment (ROI) thinking can also benefit species conservation, and researchers are developing sophisticated approaches to support decision-making for cost-effective conservation. However, applied use of these approaches is limited. Managers may be wary of "black-box'' algorithms or complex methods that are difficult to explain to funding agencies. As an alternative, we demonstrate the use of a basic ROI analysis for determining where to invest in cost-effective management to address threats to species. This method can be applied using basic geographic information system and spreadsheet calculations. We illustrate the approach in a management action prioritization for a biodiverse region of eastern Australia. We use ROI to prioritize management actions for two threats to a suite of threatened species: habitat degradation by cattle grazing, and predation by invasive red foxes (Vulpes vulpes). We show how decisions based on cost-effective threat management depend upon how expected benefits to species are defined and how benefits and costs co-vary. By considering a combination of species richness, restricted habitats, species vulnerability, and costs of management actions, small investments can result in greater expected benefit compared with management decisions that consider only species richness. Furthermore, a landscape management strategy that implements multiple actions is more efficient than managing only for one threat, or more traditional approaches that don't consider ROI. Our approach provides transparent and logical decision support for prioritizing different actions intended to abate threats associated with multiple species; it is of use when managers need a justifiable and repeatable approach to investment

Tight constraints on the existence of additional planets around HD 189733

We report a transit timing study of the transiting exoplanetary system HD 189733. In total we observed ten transits in 2006 and 2008 with the 2.6-m Nordic Optical Telescope, and two transits in 2007 with the 4.2-m William Herschel Telescope. We used Markov-Chain Monte Carlo simulations to derive the system parameters and their uncertainties, and our results are in a good agreement with previously published values. We performed two independent analyses of transit timing residuals to place upper mass limits on putative perturbing planets. The results show no evidence for the presence of planets down to 1 Earth mass near the 1:2 and 2:1 resonance orbits, and planets down to 2.2 Earth masses near the 3:5 and 5:3 resonance orbits with HD 189733b. These are the strongest limits to date on the presence of other planets in this system.Comment: 10 pages, 4 figures, accepted by MNRA

Factoring attitudes towards conflict risk into selection of protected areas for conservation

The high incidence of armed conflicts in biodiverse regions poses significant challenges in achieving international conservation targets. Because attitudes towards risk vary, we assessed different strategies for protected area planning that reflected alternative attitudes towards the risk of armed conflicts. We find that ignoring conflict risk will deliver the lowest return on investment. Opting to completely avoid conflict-prone areas offers limited improvements and could lead to species receiving no protection. Accounting for conflict by protecting additional areas to offset the impacts of armed conflicts would not only increase the return on investment (an effect that is enhanced when high-risk areas are excluded) but also increase upfront conservation costs. Our results also demonstrate that fine-scale estimations of conflict risk could enhance the cost-effectiveness of investments. We conclude that achieving biodiversity targets in volatile regions will require greater initial investment and benefit from fine-resolution estimates of conflict risk

Diversionary feeding: an effective management strategy for conservation conflict?

Human population growth has led to increased contact between people and wildlife, with adverse impacts for both, such as damage to economic crops and wildlife persecution. Diversionary feeding, where food is used to draw animals away from problem activities or locations, is sometimes proposed as a socially acceptable conservation action, but little information exists on its success or what influences its efficacy. Here, we review literature on diversionary feeding and evaluate factors contributing to its success or failure. Success varied greatly among studies and successful uptake of diversionary food did not consistently produce outcomes that met stakeholder objectives. Studies often failed to report results in sufficient detail to allow a quantitative evaluation of efficiency. Of 30 trials presented in 21 studies, 13 enabled assessment of outcomes related to the ultimate objective of reducing conflict (related to threatened prey density, crop yield or nuisance reports) and only five of these were considered successful by the researchers conducting the study. A grand mean increase of 15% in respective measures of success at the outcome stage was found across all studies. Although diversionary feeding is considered expensive, cost-effectiveness analyses were rarely conducted. Only a third of studies reported information on costs and benefits that could be used to inform future management actions. We propose a decision-making framework that incorporates ecological knowledge, financial costs and evidence from previous studies to aid the planning and implementation of diversionary feeding in an adaptive format. Future studies of diversionary feeding should clearly report objectives, results, costsand effort to allow the return-on-investment to be calculated for different levels of management effort