Synthesis of conformationally constrained adamantane imidazolines with trypanocidal activity

Aiming at the development of new adamantano building blocks for treating African trypanosomiasis, we report on the synthesis of spiro adamantane 2‐imidazolines 8a‐f and 9a‐c , and their congeneric 5‐(1‐adamantyl)imidazolines 14 and 15 . The potency of these compounds against Trypanosoma brucei was compared to that of rimantadine and found, in the case of compound 14e , to be three fold higher. Together with the other active compounds, 14b and 15b , which were equipotent to rimantadine, the new molecules illustrate the synergistic effect of the lipophilic character of adamantane and the C1 amidine functionality on trypanocidal activity.     

The use of novel water-in-oil microemulsions in microemulsion electrokinetic chromatography

We describe the novel use of water-in-oil (W/O) microemulsions to achieve unique separations in microemulsion electrokinetic chromatography (MEEKC). The choice and concentration of the buffer type, surfactant and co-surfactant were all examined and optimized. Separations of a range of neutral and acidic analytes was shown to be markedly different to that obtained by (oil-in-water) O/W MEEKC. Neutral solutes are separated by virtue of their solubility (log P) values in O/W MEEKC with the more water-insoluble solutes migrating last. This separation process does not occur in W/O, as neutral solutes are not separated in order of log P.     

Expression and Characterization of the Intracellular Part of Receptor Protein Tyrosine Phosphatase PTPRU

PTPRU is an MAM domain-containing receptor-like protein tyrosine phosphatase. Previous studies have demonstrated an important role of the enzyme in the maintenance of epithelial integrity and in the regulation of the Wnt/β-catenin signaling pathway. To better understand the function of PTPRU, we cloned and expressed the intracellular portion of PTPRU as a GST fusion protein in E. coli cells. We purified the protein to homogeneity and used it to immunize mice for antibody production. The resultant antibody s...     

New and efficient routes for the synthesis of murrayaquinone A and murrayanine

Three new routes were established for the synthesis of biologically active murrayaquinone A and a new method was developed for synthesis of murrayanine from the same starting material as 4-hydroxy carbazole. During the synthetic course a few novel observation were recorded, which include two one pot reaction sequences and C–N bond cleavage by sodium cyanoborohydride.     

Quantile regression for modelling distributions of profit and loss

Quantile regression is applied in two retail credit risk assessment exercises exemplifying the power of the technique to account for the diverse distributions that arise in the financial service industry. The first application is to predict loss given default for secured loans, in particular retail mortgages. This is an asymmetric process since where the security (such as a property) value exceeds the loan balance the banks cannot retain the profit, whereas when the security does not cover the value of the defaulting loan then the bank realises a loss. In the light of this asymmetry it becomes apparent that estimating the low tail of the house value is much more relevant for estimating likely losses than estimates of the average value where in most cases no loss is realised. In our application quantile regression is used to estimate the distribution of property values realised on repossession that is then used to calculate loss given default estimates. An illustration is given for a mortgage portfolio from a European mortgage lender. A second application is to revenue modelling. While credit issuing organisations have access to large databases, they also build models to assess the likely effects of new strategies for which, by definition, there is no existing data. Certain strategies are aimed at increasing the revenue stream or decreasing the risk in specific market segments. Using a simple artificial revenue model, quantile regression is applied to elucidate the details of subsets of accounts, such as the least profitable, as predicted from their covariates. The application uses standard linear and kernel smoothed quantile regression.     

Finite element and implicit Runge–Kutta implementation of an acoustics–convection upstream resolution algorithm for the time‐dependent two‐dimensional Euler equations

The second of a two‐paper series, this paper details a solver for the characteristics‐bias system from the acoustics–convection upstream resolution algorithm for the Euler and Navier–Stokes equations. An integral formulation leads to several surface integrals that allow effective enforcement of boundary conditions. Also presented is a new multi‐dimensional procedure to enforce a pressure boundary condition at a subsonic outlet, a procedure that remains accurate and stable. A classical finite element Galerkin discretization of the integral formulation on any prescribed grid directly yields an optimal discretely conservative upstream approximation for the Euler and Navier–Stokes equations, an approximation that remains multi‐dimensional independently of the orientation of the reference axes and computational cells. The time‐dependent discrete equations are then integrated in time via an implicit Runge–Kutta procedure that in this paper is proven to remain absolutely non‐linearly stable for the spatially‐discrete Euler and Navier–Stokes equations and shown to converge rapidly to steady states, with maximum Courant number exceeding 100 for the linearized version. Even on relatively coarse grids, the acoustics–convection upstream resolution algorithm generates essentially non‐oscillatory solutions for subsonic, transonic and supersonic flows, encompassing oblique‐ and interacting‐shock fields that converge within 40 time steps and reflect reference exact solutions. Copyright © 2005 John Wiley & Sons, Ltd.     

An empirical study of PLAD regression using the bootstrap

Partial LAD regression uses the L ₁ norm associated with least absolute deviations (LAD) regression while retaining the same algorithmic structure of univariate partial least squares (PLS) regression. We use the bootstrap in order to assess the partial LAD regression model performance and to make comparisons to PLS regression. We use a variety of examples coming from NIR experiments as well as two sets of experimental data.     

Benchmarking with quality-adjusted DEA (Q-DEA) to seek lower-cost high-quality service: Evidence from a U.S.bank application

Benchmarking is a widely cited method to identify and adopt best-practices as a means to improve performance. Data envelopment analysis (DEA) has been demonstrated to be a powerful benchmarking methodology for situations where multiple inputs and outputs need to be assessed to identify best-practices and improve productivity in organizations. Most DEA benchmarking studies have excluded quality, even in service-sector applications such as health care where quality is a key element of performance. This limits the practical value of DEA in organizations where maintaining and improving service quality is critical to achieving performance objectives. In this paper, alternative methods incorporating quality in DEA benchmarking are demonstrated and evaluated. It is shown that simply treating the quality measures as DEA outputs does not help in discriminating the performance. Thus, the current study presents a new, more sensitive, quality-adjusted DEA (Q-DEA), which effectively deals with quality measures in benchmarking. We report the results of applying Q-DEA to a U.S. bank's 200-branch network that required a method for benchmarking to help manage operating costs and service quality. Q-DEA findings helped the bank achieve cost savings and improved operations while preserving service quality, a dimension critical to its mission. New insights about ways to improve branch operations based on the best-practice (high-quality low-cost) benchmarks identified with Q-DEA are also described in the paper. This demonstrates the practical need and potential benefits of Q-DEA and its efficacy in one application, and also suggests the need for further research on measuring and incorporating quality into DEA benchmarking. The review process of this paper was handled by the Edit-in-Chief Peter Hammer.     

Selective reagent ionisation‐time of flight‐mass spectrometry: a rapid technology for the novel analysis of blends of new psychoactive substances

In this study we demonstrate the potential of selective reagent ionisation‐time of flight‐mass spectrometry for the rapid and selective identification of a popular new psychoactive substance blend called ‘synthacaine’, a mixture that is supposed to imitate the sensory and intoxicating effects of cocaine. Reactions with H₃O⁺ result in protonated parent molecules which can be tentatively assigned to benzocaine and methiopropamine. However, by comparing the product ion branching ratios obtained at two reduced electric field values (90 and 170 Td) for two reagent ions (H₃O⁺ and NO⁺) to those of the pure chemicals, we show that identification is possible with a much higher level of confidence then when relying solely on the m/z of protonated parent molecules. A rapid and highly selective analytical identification of the constituents of a recreational drug is particularly crucial to medical personnel for the prompt medical treatment of overdoses, toxic effects or allergic reactions. Copyright © 2015 John Wiley & Sons, Ltd.