4-metalated condensed pyrimidines: their preparation and reaction with aldehydes under Barbier-type conditions

[reaction: see text] The organometallic intermediate obtained from halogen-metal exchanges of 4-iodo-6-phenylthieno[2,3-d]pyrimidine under Barbier-type conditions was reacted with aldehydes to form the corresponding alcohols in moderate yields. The reaction involving an organolithium intermediate proceeded only at low temperature, whereas the reaction involving a magnesium ate intermediate also proceeded at room temperature. A crystal structure confirms that the expected constitutional alcohol isomer is formed, where no migration has taken place. The conditions were also suitable for 9-benzyl-6-iodopurine.     

The dual spectral set conjecture

Suppose that where are real numbers such that and The union is not assumed to be disjoint. It is shown that the translates , , tile the real line for some bounded measurable set if and only if the exponentials , , form an orthogonal basis for some bounded measurable set

     

Optical waveguide sensor for on-line monitoring of bacteria

A grating-coupled planar optical waveguide sensor is presented for sensing of bacteria by evanescent waves. The waveguide design results in increased depth of penetration into the sample volume, which makes it suitable for detecting micrometer-sized biological objects. We tested the sensor's performance by monitoring the adhesion of Escherichia coli K12 cells to the sensor surface.     

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.     

Synthesis and evaluation of new potential HIV-1 non-nucleoside reverse transcriptase inhibitors. New analogues of MKC-442 containing Michael acceptors in the C-6 position

Analogues of MKC-442 capable of undergoing Michael addition reactions were synthesised in order to investigate the activity against the HIV-1 mutant (Y181C). An improved activity was postulated on the basis of a possible covalent binding to the mercapto group of Cys181. Lithiation of the C-6 position of 1-ethoxymethyl-5-ethyl-1H-pyrimidine-2,4-dione (5) was followed by reaction with alpha,beta-unsaturated aldehydes and oxidation of the alcohols formed to give the alkenoyl analogues 1a-3a. Analogues 1b-3b containing an allyloxymethyl group in the N-1 position instead of the ethoxymethyl group could not be synthesised due to isomerisation of the allylic group during the metallation reaction. The NMR data for compounds 1a-3a showed a hindered rotation, which was more pronounced for the 6-cyclohexenylcarbonyl derivative 3a than for the propenyl derivatives 1a and 2a. Moderate activity against wild type HIV-1 was observed for the alcohol 8 and the ketones 2a-3a. However, no activity was observed against the Y181C mutant.     

Structural diversity of small molecule libraries

A novel method for assessing structural diversity is presented. Maximum common subgraph identity is used as the measure of similarity between two chemical structures. A conditional probability treatment of similarity distributions for libraries of chemical structures is used to define diversity. This evaluation method together with the evaluation of traditional physicochemical properties is used to assess a large number of chemical libraries and to understand structural differences between these.     

A continuous parametric shape model

In this paper we propose a flexible continuous parametric shape model for star-shaped planar objects. The model is based on a polar Fourier expansion of the normalized radius-vector function. The expected phase amplitudes are modelled by a simple regression with parameters having nice geometric interpretations. The suggestedgeneralized p-order model is an extension of first- and second-order Gaussian shape models, and in particular the Gaussian assumption is relaxed. The statistical analysis is straightforward, as demonstrated by an application concerning shape discrimination of two cell nuclei populations.     

Estimates of Entire Functions of Exponential Type Less than π in Terms of Logarithmic Sums over Real Duffin and Schaeffer Sequences

We give uniform estimates of entire functions of exponential type less than having sufficiently small logarithmic sums over real sequences { _n } satisfying | _n –n|L and _n+1– _n for fixed positive constants L and . We thereby generalize results about logarithmic sums over the set of integers and so-called relatively h-dense sequences.     

Observation of a 1/t decay law for hot clusters and molecules in a storage ring

The exponential law is valid both for decay from a single quantum state into a continuum and for an ensemble maintained in thermal equilibrium. For statistical decay of an ensemble of isolated systems with a broad energy distribution, the exponential decay is replaced by a 1/t distribution. We present confirmation of this decay law by experiments with cluster anions in a small electrostatic storage ring. Deviations from the 1/t law for such an ensemble give important information on the dynamics of the systems. As examples, we present measurements revealing strong radiative cooling of anions of both metal clusters and fullerenes.     

Experimental implementation of a low-frequency global sound equalization method based on free field propagation

An experimental implementation of a global sound equalization method in a rectangular room using active control is described in this paper. The main purpose of the work has been to provide experimental evidence that sound can be equalized in a continuous three-dimensional region, the listening zone, which occupies a considerable part of the complete volume of the room. The equalization method, based on the simulation of a progressive plane wave, was implemented in a room with inner dimensions of 2.70 m × 2.74 m × 2.40 m. With this method, the sound was reproduced by a matrix of 4 × 5 loudspeakers in one of the walls. After traveling through the room, the sound wave was absorbed on the opposite wall, which had a similar arrangement of loudspeakers, by means of active control. A set of 40 digital FIR filters was used to modify the original input signal before it was fed to the loudspeakers, one filter for each transducer. The optimal arrangement of the loudspeakers and the maximum frequency that can be equalized is analyzed theoretically in this paper. The presented experimental results show that sound equalization was possible from 10 Hz to approximately 425 Hz in the listening zone. A flat frequency response with deviations within ±5 decibels from the desired value was achieved. A higher demanding performance with deviations within ±1.5 decibels from a flat frequency response was attained in the interval between 20 Hz and 280 Hz. At the same time, the impulse response was quite well approximated to a delayed delta function in the listening zone. Examples of the spatial distribution of the sound field are also shown.