Applications of the achmatowicz rearrangement in natural product synthesis

The structurally related PM-94128 and Ajudazols A and B exhibit differing biological activities but share the isocoumarin core structure. PM-94128 belongs to a large family of compounds known as the aminodihydroisocoumarins and was isolated in 1997. It has been shown to be an inhibitor of DNA and RNA synthesis and have potent cytotoxic activity in vivo. The Ajudazols A and B were isolated in 2004 and have antifungal activity against several important food spoilers. The work that follows details the design and development of a novel method for the generation of the isocoumarin core from isobenzofuran utilizing the Achmatowicz rearrangement of a-hydroxyisobenzofurans. Spirocyclic pyrans such as Polymaxenolide are structurally complex molecules, containing large amounts of functionality. The biological activity of Polymaxenolide is unknown and there have been no total syntheses reported to date

Animals and anomalies: an analysis of the UK veterinary profession and the relative lack of state reform

The sociology of professions literature would predict that the contemporary state would not allow groups to continue unregulated or unreformed. However, this is indeed the case with the UK veterinary profession, with legislation dating back to 1966. Using an interdisciplinary analysis of published literature and reports, this paper assesses whether wider social, political and ethical dynamics can better explain this intriguing anomaly. We conclude with critical implications for the sociology of the professions. Furthermore, we argue that continuing to ignore the veterinary profession, and animals more generally, in sociological research will result in an impoverished and partial understanding of contemporary healthcare and occupations

Airfoil design utilizing parallel processors. II-Applications

Presented as Paper 95-0126 at the 33rd Aerospace Sciences Meeting and Exhibit January 9-12,1995 / Reno, NVThe article of record as published may be found at https://doi.org/10.2514/6.1995-126One test case and two airfoil design applications were performed utilizing a parallel optimization scheme coupled to different fiow solvers. Parallel processors use computational fluid dynamics to evaluate the aerodynamic performance of multiple geometries simultaneously. The test case designed an airfoil to match the pressure distribution corresponding to an airfoil of a known shape. A transonic design application varied an airfoil's shape to maximize its lift-to-drag ratio

Hyper-efficient model-independent Bayesian method for the analysis of pulsar timing data

A new model independent method is presented for the analysis of pulsar timing data and the estimation of the spectral properties of an isotropic gravitational wave background (GWB). We show that by rephrasing the likelihood we are able to eliminate the most costly aspects of computation normally associated with this type of data analysis. When applied to the International Pulsar Timing Array Mock Data Challenge data sets this results in speedups of approximately 2 to 3 orders of magnitude compared to established methods. We present three applications of the new likelihood. In the low signal to noise regime we sample directly from the power spectrum coefficients of the GWB signal realization. In the high signal to noise regime, where the data can support a large number of coefficients, we sample from the joint probability density of the power spectrum coefficients for the individual pulsars and the GWB signal realization. Critically in both these cases we need make no assumptions about the form of the power spectrum of the GWB, or the individual pulsars. Finally we present a method for characterizing the spatial correlation between pulsars on the sky, making no assumptions about the form of that correlation, and therefore providing the only truly general Bayesian method of confirming a GWB detection from pulsar timing data.Comment: 9 pages, 4 figure

Chemical Leeching of Wood Sealents

Undergraduate Basi

First Observational Tests of Eternal Inflation: Analysis Methods and WMAP 7-Year Results

In the picture of eternal inflation, our observable universe resides inside a single bubble nucleated from an inflating false vacuum. Many of the theories giving rise to eternal inflation predict that we have causal access to collisions with other bubble universes, providing an opportunity to confront these theories with observation. We present the results from the first observational search for the effects of bubble collisions, using cosmic microwave background data from the WMAP satellite. Our search targets a generic set of properties associated with a bubble collision spacetime, which we describe in detail. We use a modular algorithm that is designed to avoid a posteriori selection effects, automatically picking out the most promising signals, performing a search for causal boundaries, and conducting a full Bayesian parameter estimation and model selection analysis. We outline each component of this algorithm, describing its response to simulated CMB skies with and without bubble collisions. Comparing the results for simulated bubble collisions to the results from an analysis of the WMAP 7-year data, we rule out bubble collisions over a range of parameter space. Our model selection results based on WMAP 7-year data do not warrant augmenting LCDM with bubble collisions. Data from the Planck satellite can be used to more definitively test the bubble collision hypothesis.Comment: Companion to arXiv:1012.1995. 41 pages, 23 figures. v2: replaced with version accepted by PRD. Significant extensions to the Bayesian pipeline to do the full-sky non-Gaussian source detection problem (previously restricted to patches). Note that this has changed the normalization of evidence values reported previously, as full-sky priors are now employed, but the conclusions remain unchange

Narrative Bytes : Data-Driven Content Production in Esports

Esports - video games played competitively that are broadcast to large audiences - are a rapidly growing new form of mainstream entertainment. Esports borrow from traditional TV, but are a qualitatively different genre, due to the high flexibility of content capture and availability of detailed gameplay data. Indeed, in esports, there is access to both real-time and historical data about any action taken in the virtual world. This aspect motivates the research presented here, the question asked being: can the information buried deep in such data, unavailable to the human eye, be unlocked and used to improve the live broadcast compilations of the events? In this paper, we present a large-scale case study of a production tool called Echo, which we developed in close collaboration with leading industry stakeholders. Echo uses live and historic match data to detect extraordinary player performances in the popular esport Dota 2, and dynamically translates interesting data points into audience-facing graphics. Echo was deployed at one of the largest yearly Dota 2 tournaments, which was watched by 25 million people. An analysis of 40 hours of video, over 46,000 live chat messages, and feedback of 98 audience members showed that Echo measurably affected the range and quality of storytelling, increased audience engagement, and invoked rich emotional response among viewers

A Rule Chaining Architecture Using a Correlation Matrix Memory

This paper describes an architecture based on superimposed distributed representations and distributed associative memories which is capable of performing rule chaining. The use of a distributed representation allows the system to utilise memory efficiently, and the use of superposition reduces the time complexity of a tree search to O(d), where d is the depth of the tree. Our experimental results show that the architecture is capable of rule chaining effectively, but that further investigation is needed to address capacity considerations

Structure-activity analysis of CJ-15,801 analogues that interact with Plasmodium falciparum pantothenate kinase and inhibit parasite proliferation

Survival of the human malaria parasite Plasmodium falciparum is dependent on pantothenate (vitamin B5), a precursor of the fundamental enzyme cofactor coenzyme A. CJ-15,801, an enamide analogue of pantothenate isolated from the fungus Seimatosporium sp. CL28611, was previously shown to inhibit P. falciparum proliferation in vitro by targeting pantothenate utilization. To inform the design of next generation analogues, we set out to synthesize and test a series of synthetic enamide-bearing pantothenate analogues. We demonstrate that conservation of the R-pantoyl moiety and the trans-substituted double bond of CJ-15,801 is important for the selective, on-target antiplasmodial effect, while replacement of the carboxyl group is permitted, and, in one case, favored. Additionally, we show that the antiplasmodial potency of CJ-15,801 analogues that retain the R-pantoyl and trans-substituted enamide moieties correlates with inhibition of P. falciparum pantothenate kinase (PfPanK)-catalyzed pantothenate phosphorylation, implicating the interaction with PfPanK as a key determinant of antiplasmodial activity.C.S. was funded by an NHMRC Overseas Biomedical Fellowship (1016357). EPSRC and Syngenta provided postgraduate support (MJV) and a Leadership Fellowship (RM). Additional support was provided by Dr. Ian Sword, the EPSRC (grant EP/H005692/1) and the COST Action CM0801

Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach

Structure-guided expansion of a fragment hit for the ATAD2 bromodomain enabled improvement in ATAD2 inhibition and selectivity over BRD4.</p