Strong optical nonlinearities of self-assembled polymorphic microstructures of phenylethynyl functionalized fluorenones

The polymorphs of a phenylethynyl functionalized fluorenone derivative, and their controlled self-assembly for microstructures with different morphologies have been studied. These polymorphic microcrystals exhibit very distinctive NLO properties, which are highly correlated to their electronic and supramolecular structures.     

Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition

A procedure is presented for copper(I)-catalyzed [3+2] cycloaddition of nucleosides and nucleotides in near-quantitative yield. Azido-alkyne cycloaddition was applied for the preparation of a range of adenosine dimers and derivatives with versatile functionality, as well as for the smooth condensation of two oligonucleotide strands. The described technology may find valuable application in the synthesis of oligonucleotide dimers and conjugates.     

Solubility of phosphonium ionic liquid in alcohols, benzene, and alkylbenzenes

The (solid + liquid) phase equilibria and (liquid + liquid) phase equilibria of binary mixtures containing quaternary phosphonium salt-tetrabutylphosphonium methanesulfonate and alcohols or alkylbenzenes were investigated. The systems {[(CH(3)CH(2)CH(2)CH(2))4P][CH(3)SO(3)] + 1-butanol, or 1-hexanol, 1-octanol, 1-decanol, or 1-dodecanol} and {[(CH(3)CH(2)CH(2)CH(2))4P][CH(3)SO(3)] + benzene, or toluene, ethylbenzene, or propylbenzene} have been measured by a dynamic method at a wide range of temperatures from 220 to 386 K. Solid-liquid equilibria with immiscibility in the liquid phase were detected with the aromatic hydrocarbons ethylbenzene and propylbenzene. The basic thermodynamic properties of pure ionic liquid--the melting point, enthalpy of fusion, enthalpy of solid-solid-phase transition, and glass transition--have been determined by differential scanning calorimetry. The experimental data of systems with alcohols were correlated by means of the UNIQUAC ASM and NRTL1 equations and of systems with alkylbenzenes with Wilson and NRTL equations utilizing parameters derived from the (solid + liquid) equilibrium. The root-mean-square deviations of the solubility temperatures for all calculated data are dependent upon the particular system and the particular equation used.     

Development of a multiplex non-radioactive receptor assay: the benzodiazepine receptor, the serotonin transporter and the beta-adrenergic receptor

Binding assays still form a fundamental part of modern drug development. Receptor binding assays are mostly based on radioactivity because of their speed, ease of use and reproducibility. Disadvantages, such as health hazards and production of radioactive waste, have prompted the development of non-radioactive receptor binding assays. This application therefore focuses on measuring receptor-ligand interactions using mass spectrometry. Moreover, the novelty of this approach originates in determining multiple analytes in a single assay (multiplexing). The proof of principle of a non-radioactive multiplex receptor assay is demonstrated using a pool of receptors from rat cortical tissue with flunitrazepam, MADAM and pindolol in one vial with or without their respective displacers. Flunitrazepam, MADAM and pindolol bound specifically at 73%, 30% and 40% to their respective receptors. This corresponds to specific binding sites of 0.61 pmol/mg protein, 0.07 pmol/mg protein and 0.06 pmol/mg protein, respectively. We propose to measure the bound fraction instead of the free fraction in order to reach a significant difference in measured signals (total binding versus non-specific binding). The bound fraction can be obtained after dissociating the ligand from the receptor-ligand complex using 50% methanol in water. The current setup of the assay calls for further improvement with respect to the measurement of binding constants for a multitude of receptors in one assay with sufficient accuracy and precision.     

Criteria to define the standard deviation for proficiency assessment for the determination of essential trace elements in serum: comparison of Z-scores based on the Horwitz function or on biological variability

A critical issue in the organisation of Proficiency Testing/External Quality Assessment Schemes is the definition of the criteria against which the performance of individual laboratories should be evaluated. Organisers of EQAS in Occupational and Environmental Laboratory Medicine (http://www.occupational-environmental-laboratory.com) collaborate to define common acceptable levels of performance. The aim of this study was to compare the Horwitz function to the Fraser’s approach. Sets of results obtained from the distribution of test materials in the Network schemes (for the measurands: copper, selenium or zinc in serum) were used to calculate Z-scores according to both approaches. Quality specifications derived from both approaches were also compared to the standard deviations obtained. Except for selenium, Horwitz criteria suggests a more stringent evaluation than Fraser criteria, the latter being very stringent as regard the participant analytical variability.     

Statistical shape priors for level set segmentation

Starting in the early 1990's level set methods have become a popular mathematical framework for variational image segmentation. In many applications of segmentation, however, cost functionals which merely take into account the intensity information of the input image will not give rise to the desired segmentation results. To cope with missing or misleading image information, researchers have proposed to impose statistical shape priors into the segmentation process. Such shape priors favor the evolving embedding function to remain similar to embedding functions associated with a collection of training shapes. As a consequence, one can obtain shape-consistent segmentation despite large amounts of noise, background clutter and partial occlusion of the object of interest. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Uncertainty calculation for calibrators of the IFCC HbA1c standardization network

Within the last decade, the IFCC HbA1c standardization network has established the metrologically highest reference measurement procedure for HbA1c testing. Based on this procedure, reference calibrators are produced which in turn provide the starting point for the standardization of the manufactures routine HbA1c assays. According to the IVD directive, the uncertainty of the reference calibrators must be calculated and reported together with their assigned values. Within this article, we elaborate the uncertainty calculation according to GUM (guide to the expression of uncertainty in measurement) in detail. Finally, the results are validated by a simulation study.     

Efficient preparation of an N-aryl β-amino acid via asymmetric hydrogenation and direct asymmetric reductive amination en route to Ezetimibe

Two routes for the preparation of an N-aryl β-amino acid, an important precursor for the cholesterol-lowering drug Ezetimibe, were investigated. The first pathway proceeds via an Rh- or Ir-catalyzed asymmetric hydrogenation of N-aryl enamine giving the desired product with up to 82% ee. The other pathway involves a direct asymmetric reductive amination (DARA) of the β-keto ester which yielded the β-amino ester in high yield and 97% ee. Subsequent copper-catalyzed N-arylation gave the target compound.     

Proficiency testing in analytical chemistry,microbiology and laboratory medicine – working group discussions on current status,problems and future directions

Working group (WG) discussions on proficiency testing and external quality assessment held at the Eurachem workshop, Portorož, Slovenia 26–27 Sept 2005 are summarised. The discussions focused on performance criteria (WG 1), different aspects of accreditation (WGs 2–3), the revised international harmonised protocol (WG 4), pre- and post-analytical schemes (WG 5), Internet applications (WG 6), experience from the CoEPT project (WG 7), and future aspects (WG 8). Current status, problems and future directions were identified. The WG contained a mix of participants with different expertise. This was done to promote cross-fertilisation of ideas between sectors. The WG issues reflected the content of the keynote lectures and some issues were covered from different perspectives by more than one WG.Presented at the Eurachem PT Workshop September 2005, Portorož, Slovenia.     

Measurements and calculations on the simple up-down adaptive procedure for speech-in-noise tests

The simple up-down adaptive procedure is a common method for measuring speech reception thresholds. It is used by the Dutch speech-in-noise telephone screening test [National Hearing test; Smits and Houtgast Ear Hear. 26, 89-95 (2005)]. The test uses digit triplets to measure the speech reception threshold in noise by telephone (SRTT(n)). About 66 000 people took this test within four months of its introduction and details were stored of all individual measurements. Analyses of this large volume of data have revealed that the standard deviation of SRTT(n) estimates increases with hearing loss. This paper presents a calculation model which--using an intelligibility function as input--can determine the standard deviation of SRTT(n) estimates and the bias for the simple up-down procedure. The effects of variations in the slope of the intelligibility function, the guess rate, the starting level, the heterogeneity of the speech material, and the possibilities of optimizing SRTT(n) measurements were all explored with this model. The predicted decrease in the standard deviation of SRTT(n) estimates as a result of optimizing the speech material was confirmed by measurements in 244 listeners. The paper concludes by discussing possibilities for optimizing the development of comparable tests.