The Use of Continuous Regularization in the Automated Analysis of MRS Time-Domain Data

In this paper, it is shown how the advantages of continuous regularization (CR) can be exploited to achieve an improved, fully automated LPSVD analysis of MRS time-domain data. The main advantage of CR is its ability to determine the number of spectral components even at low signal-to-noise ratios, which suggested its use forin vivospectroscopy. Estimation of the spectral parameters is possible. Two alternatives of automated data-analysis schemes are thoroughly investigated by means of Monte Carlo studies. The results suggest the combination of CR for model-order estimation with other methods for more-accurate parameter estimation. Several possible combinations, including those with an improved enhancement procedure and a total-least-squares method for quantitation, are discussed. Recommendations are given for spectral analysis, and a new data-analysis protocol which performs significantly better than previously used protocols of the same type is proposed.     

Ein Luftthermometer

Ohne Zusammenfassung     

Quantitative determination of heparinoid mimetics in human and rat plasma by micellar electrokinetic chromatography

The investigated new class of heparinoid mimetics are spaced persulfated carbohydrates designed to increase the success rate of angioplasty and bypass surgery by preventing restenosis without increasing the risk of bleeding. Due to the presence of sulfate groups, these compounds are highly charged and, for preclinical kinetic investigations only small sample volumes of rat plasma were available. Therefore, capillary electrophoresis (CE) was applied. A bioanalytical method based on micellar elektrokinetic chromatography (MEKC) with UV-detection was developed for the selective quantitation of heparinoid mimetics (e.g., Ro 48-0843, Ro 48-3151, Ro 47-6199 and Ro 48-8722) in plasma. Using this method, only small volumes of plasma were required, which could be introduced directly into the separation capillary after 1:1 dilution with 100 mM aqueous sodium dodecyl sulfate (SDS). For increased sample throughput, an additional ultrafiltration step was performed after SDS-dilution of the plasma sample, improving both reproducibility and robustness of the method considerably. The sensitivity of the new method (3 μg/ml) was sufficient to follow plasma levels in pharmacokinetic studies. The practicability of this easy and rapid assay was demonstrated by the analysis of more than 350 plasma samples from pharmacokinetic studies performed in rats.     

N2Broadening in theCO 2–0 Band around 4167 cm

N₂broadening coefficients have been measured for 65 lines of the¹³C¹⁶O 2–0 band using a Fourier transform spectrometer. These lines are located in the spectral range 4011–4252 cm⁻¹. The spectra were recorded with 99% isotopically pure¹³CO in a White-type cell at a resolution of 0.005 cm⁻¹. Voigt profiles convolved with the FTS apparatus function were fitted to the experimental lineshapes using a nonlinear least-squares fit technique. From the fits the Lorentzian HWHM was determined as function of N₂pressure. Pressure broadening coefficients formbetween −33 and +34 were obtained with uncertainties of 5.8%. The results are compared to earlier published N₂broadening coefficients and our measurements in the 2–0 band of¹²C¹⁶O. To our knowledge this is the first investigation of¹³CO pressure broadening.     

Distribution exacte du score local,cas markovien

Given a sequence $\text{X}\text{=(X}{}_{\mathrm{k}}\text{)}{}_{\mathrm{k?1}}$ of random variables taking values in {?v,…,0,…,+u}, let's define the local score of the sequence by H_n=max_1?i?j?n(∑_k=i^jX_k). The local score is used to analyze biological sequences pointing out regions of the sequences with interesting biological properties. In order to separate randomly events from really interesting segments, we establish here the distribution of the local score of H_n when the sequence $\text{X}$ is a Markov chain of order 1. To cite this article: S. Mercier, C. Hassenforder, C. R. Acad. Sci. Paris, Ser. I 336 (2003).     

Electrochemically Induced Modulation of the Catalytic Activity of a Reversible Redoxsensitive Riboswitch

Over the past decade, RNA conformation has been shown to respond to external stimuli. Thus, dependent on the presence of a high affinity ligand, specifically designed ribozymes can be regulated in a classical allosteric way. In this scenario, a binding event in one part of the RNA structure induces conformational changes in a separated part, which constitutes the catalytic centre. As a result activity is switched on (positive regulation) or off (negative regulation). We have developed a hairpin aptazyme responding to flavine mononucleotide (FMN). Ribozyme activity is dependent on binding of FMN and thus is switched on in the presence of FMN in its oxidized form. Under reducing conditions, however, FMN changes its molecular geometry, which is associated with loss of binding and consequently down‐regulation of ribozyme activity. While in previous experiments sodium dithionite was used for reduction of FMN, we now present an assay for electrochemically induced activity switching. We have developed an electrochemical microcell that allows for iterative cycles of reduction/oxidation of FMN in an oxygen free atmosphere and thus for reversible switching of ribozyme activity. The reaction proceeds in droplets of 3 to 10 μL at micro‐ to nanomolar concentrations of the reaction components.