Beta spectrometry with metallic magnetic calorimeters in the framework of the European EMPIR project MetroBeta.

The aim of the European Metrology Research Project MetroBeta is to improve the knowledge of the shapes of beta spectra, both in terms of theoretical calculation and measurement. The precise knowledge of beta spectra is required for the activity standardisation of pure beta emitters. Metallic magnetic calorimeters (MMCs), a type of cryogenic detectors, with the beta emitter embedded in the absorber have proven to be among the best beta spectrometers, in particular for low-energy beta transitions. Within this project, new designs of MMCs optimized for five different beta energy ranges were developed and a new detector module was constructed. The beta spectra of 151Sm, 14C and 99Tc have been measured so far; additional measurements with 36Cl are under preparation. Improved theoretical calculation methods and complementary measurement techniques complete the project.

Measurement of the electron capture probabilities of 55Fe with a metallic magnetic calorimeter.

The ratios of the electron capture probabilities PK, PL and PM of 55Fe have been measured with a metallic magnetic calorimeter, a specific type of cryogenic detector. The 55Fe source was enclosed in the detector absorber, whose dimensions were chosen such that the detection efficiency for Mn K X-rays was larger than 99.99%. Since all electrons and photons emitted by the source are absorbed in the detector, the detection efficiency is virtually 100% for K, L and M captures. The energy threshold was low enough to allow for clear separation of the M captures (~ 80eV) from noise. The capture probability ratios were translated to capture probabilities using the recommended value for the probability of the undetected N captures. The resulting values are in agreement both with the recommended values of PK, PL and PM and with the experimental data of Pengra and coworkers.

L X-ray satellite effects on the determination of photon emission intensities of radionuclides.

L X-ray satellites are usually not considered during the fitting procedure of L X-ray spectra obtained with semiconductor detectors. Based on a high energy resolution spectrum of X-rays of (241)Am obtained with a metallic magnetic calorimeter, it has been demonstrated that satellites are intense with respect to their parent diagram line. In addition, it has been shown that the presence of satellites involves significant systematic errors on the determined photon intensities when they are ignored in the spectrum processing.

Beta spectrometry with metallic magnetic calorimeters.

Metallic magnetic calorimeters are a specific type of cryogenic detectors that have been shown to enable precise measurement of the shape of low energy beta spectra. The aim of their use at LNHB is the determination of the shape factors of beta spectra. The beta source is enclosed in the detector absorber, allowing for very high detection efficiency. It has turned out that the type of source is of crucial importance for the correctness of the measured spectrum. Spectra of (63)Ni measured with several sources prepared by drying a NiCl2 solution differ from one another and from theory, whereas spectra measured with electroplated sources are reproducible and agree with theory. With these latter measurements we could confirm the atomic exchange effect down to very low energy (200 eV).

Alpha-particle emission probabilities in the decay of 240Pu.

Sources of enriched (240)Pu were prepared by vacuum evaporation on quartz substrates. High-resolution alpha-particle spectrometry of (240)Pu was performed with high statistical accuracy using silicon detectors and with low statistical accuracy using a bolometer. The alpha-particle emission probabilities of six transitions were derived from the spectra and compared with literature values. Additionally, some alpha-particle emission probabilities were derived from gamma-ray intensity measurements with a high-purity germanium detector. The alpha-particle emission probabilities of the three main transitions at 5168.1, 5123.6 and 5021.2 keV were derived from seven aggregate spectra analysed with five different fit functions and the results were compatible with evaluated data. Two additional weak peaks at 4863.5 and 4492.0 keV were fitted separately, using the exponential of a polynomial function to represent the underlying tailing of the larger peaks. The peak at 4655 keV could not be detected by alpha-particle spectrometry, while gamma-ray spectrometry confirms that its intensity is much lower than expected from literature.

On the variation of the 210Po half-life at low temperature.

Experiments were performed to verify the possible influence of the temperature and source matrix on the half-life of (210)Po. Since the precise measurement of the activity of an alpha-emitting source at cryogenic temperature is far from trivial, a simpler approach was used: the activity of a (210)Po source was measured at ambient temperature, but in between the measurements, the source was cooled down during a few weeks in a liquid helium Dewar. A (210)Po solid source was prepared by electro-deposition on a silver plate. The activity of this source was first measured at room temperature, using the defined solid angle alpha measurement method. The source was then placed in a specific gastight container inside a liquid helium bath at 4 K during 28 days. Then the source was heated up and measured again using the same instrument in the same geometric conditions. The same experiment was repeated with the source coated with a thin layer of silver, in order to be sure that the radioactive material was fully embedded inside the metallic matrix. Our experiments showed no evidence of (210)Po half-life change at low temperature. A reduction of the half-life of (210)Po by 6.3% at low temperature, as claimed by Raiola et al. (2007), would have lead to a decay-corrected activity reduction of about 1% after 29 days, which would have been easily detectable. The paper describes the steps of this experiment and gives a detailed uncertainty budget for the measurements. The half-life of (210)Po obtained in each measurement is compared with the evaluated value of (138.3763+/-0.0017) d.

First measurement of the beta spectrum of 241Pu with a cryogenic detector.

The LNE-LNHB is developing metallic magnetic calorimeters, a specific type of cryogenic detectors, for beta spectrometry. The aim is the determination of the shape factors of beta spectra. Our latest detector has been designed to measure the spectrum of (241)Pu, a pure beta emitter with an endpoint energy of 20.8 keV. In this paper, the detection principle of metallic magnetic calorimeters is explained and a detailed description is given of the realization of the detector enclosing a (241)Pu source inside the detector absorber. A spectrum resulting from our first measurement is shown and compared with a theoretical spectrum.

Validation study of a new technique for absolute activity measurement with 4pi solid angle metallic magnetic calorimeters.

In this paper we present a prototype of a new class of detectors, metallic magnetic calorimeters operating at cryogenic temperatures, which we are developing for absolute activity measurement of low-energy-emitting radionuclides. We explain the detection principle and give a detailed description of the realisation of the prototype, containing an (55)Fe source inside the detector absorber. The analysis of first data taken with this detector is presented and the result of activity measurement compared with liquid scintillation counting. Some ways for reducing the uncertainty that can be achieved with this new technique are proposed.

High-energy resolution X-ray, gamma and electron spectroscopy with cryogenic detectors.

Cryogenic detectors offer remarkably better energy resolutions than those achievable with conventional semiconductor or scintillation detectors. With the additional asset of a detection efficiency close to unity for low-energy X-ray photons and electrons, these detectors have the potential to perform X-ray, gamma and electron spectroscopy of a hitherto unknown quality, in particular at low energies. Two types of cryogenic detectors are described and the results of prototype detectors are presented.

A new absolute method for the standardization of radionuclides emitting low-energy radiation.

Microcalorimeters (or bolometers) operated at temperatures below 100 mK allow individual counting of photons and electrons with a very low energy detection threshold. The physics is based on the pulse temperature increase of the target (or absorber) of the detector due to the complete absorption of both electrons and photons. Since this target can be constructed with a perfect 4-pi geometry, a bolometer offers potentially a new method for absolute activity measurements of radionuclides emitting low-energy radiation. In this paper we present our first results of a feasibility study of activity standardization of a 55Fe solution with a prototype 4-pi bolometer.

Isolation and continuous growth of Chlamydia pneumoniae from arterectomy specimens.

For the purpose of collecting Chlamydia pneumoniae strains of vascular origin that could be grown continuously in vitro, a cell culture system has been established. Using different types of vascular specimens obtained from 38 patients, Chlamydia pneumoniae could be isolated in three (7.9%) cases. The strains were obtained from specimens of the carotid artery, the femoral artery and an infrarenal aneurysm of the abdominal aorta of three male atherosclerosis patients. Thus, viable Chlamydia pneumoniae strains are also present in vascular regions other than those hitherto described.

Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin.

Concentrations of total (R) + (S) and of the enantiomers (R) and (S) of thioridazine and metabolites were measured in 21 patients who were receiving 100 mg thioridazine for 14 days and who were comedicated with moclobemide (450 mg/day). Two patients were poor metabolizers of dextromethorphan and one was a poor metabolizer of mephenytoin. Cytochrome P450IID6 (CYP2D6) is involved in the formation of thioridazine 2-sulfoxide (2-SO) from thioridazine and also probably partially in the formation of thioridazine 5-sulfoxide (5-SO), but not in the formation of thioridazine 2-sulfone (2-SO2) from thioridazine 2-SO. Significant correlations between the mephenytoin enantiomeric ratio and concentrations of thioridazine and metabolites suggest that cytochrome P450IIC19 could contribute to the biotransformation of thioridazine into yet-unknown metabolites, other than thioridazine 2-SO, thioridazine 2-SO2, or thioridazine 5-SO. An enantioselectivity and a large interindividual variability in the metabolism of thioridazine have been shown: measured (R)/(S) ratios of thioridazine, thioridazine 2-SO fast eluting (FE), thioridazine 2-SO slow eluting (SE), thioridazine 2-SO (FE+SE), thioridazine 2-SO2, thioridazine 5-SO(FE), and thioridazine 5-SO(SE) were (mean +/- SD) 3.48 +/- 0 .93 (range, 2.30 to 5.80), 0.45 +/- 0.22 (range, 0.21 to 1.20), 2.27 +/- 8.1 (range, 6.1 to 40.1), 4.64 +/- 0.68 (range, 2.85 to 5.70), 3.26 +/- 0.58 (range, 2.30 to 4.30), 0.049 +/- 0.019 (range, (0.021 to 0.087), and 67.2 +/- 66.2 (range, 16.8 to 248), respectively. CYP2D6 is apparently involved in the formation of (S)-thioridazine 2-SO(FE), (R)-thioridazine 2-SO(SE), and also probably (S)-thioridazine 5-SO(FE) and (R)-thioridazine 5-SO(SE).

A double-blind comparison of moclobemide and thioridazine versus moclobemide and placebo in the treatment of refractory, severe depression.

In a multicenter study of 78 severely depressed inpatients (44 women and 34 men; age range, 23 to 70 years), the efficacy, onset of efficacy, and tolerability of the reversible monoamine oxidase-A inhibitor moclobemide (450 mg/day) in combination with thioridazine (100 mg/day) were compared with those of moclobemide (450 mg/day) plus placebo. Patients enrolled met the DSM-III-R criteria for severe depression and had a severity score of at least 20 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Additionally, these patients had not responded to at least two standard antidepressants during the 2 years preceding screening and the mean duration of the current episode was 6 months. After a washout period of 3 to 5 days, patients were randomized to one of the two treatment groups, which at the outset had similar characteristics. Efficacy was assessed by the HAM-D, a depression observation rating for nurses, and a Clinical Global Impression (CGI) scale. Tolerability assessments included an overall rating, a description of adverse events, vital signs, electrocardiogram, and laboratory tests. After 4 weeks of therapy, both groups of patients showed significant improvements in HAM-D and CGI scores. The response rates (based on HAM-D > or = 50% decrease) were 74% for moclobemide/thioridazine and 77% for moclobemide/placebo, and according to CGI scores, 76 and 72% were "very much improved" or "much improved," respectively. Onset of effect was noted after 9.2 and 9.8 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudomonas acidovorans: a bacterium capable of mineralizing 2-chloroaniline.

Prolonged adaptation of Ca-alginate immobilized cells of Pseudomonas acidovorans CA28 to a mixture of 3-chloroaniline (3-CA)1) and 2-CA and subsequently to 2-CA as sole substrate led to the isolation of another strain, termed CA50 with the additional capability of utilizing 2-CA as sole source of carbon, nitrogen, and energy. Batch-degradation of 190 mg/l of 2-CA at pH 6.1 by this newly isolated strain was achieved within 3 days, at higher concentrations up to 0.6 g/l increasing lag-phases and degradation periods were observed. Except chloride and ammonium no further metabolites were detectable in the medium. Mineralization of 2-CA proceeds via the modified ortho-cleavage pathway as demonstrated by the presence of catechol 1,2-dioxygenase (C120) activity, which is characterized by its substrate specificity and elution behaviour on DEAE-cellulose.

Characterization of isofunctional ring-cleaving enzymes in aniline and 3-chloroaniline degradation by Pseudomonas acidovorans CA28.

During degradation of aniline and 3-chloroaniline, respectively, by Pseudomonas acidovorans CA28, selective induction of two catechol 1,2-dioxygenases (C12O) was observed. C12O I activity was the sole ring-cleaving enzyme detectable in cell-free extracts after growth on aniline, while C12O II was exclusively found after growth on 3-chloroaniline. Both enzymes were clearly differentiated by their elution behaviour on DEAE-cellulose and their substrate specificities. For C12O I high activity was demonstrable only with unsubstituted catechol, while C12O II showed preference for and high affinity towards chlorinated catechols. Therefore, evidence of different ortho-cleavage enzymes in Pseudomonas acidovorans CA28 involved in aniline and 3-chloroaniline metabolism, respectively, is indicated.

Degradation of phenol and phenolic compounds by Pseudomonas putida EKII.

The phenol-degrading strain Pseudomonas putida EKII was isolated from a soil enrichment culture and utilized phenol up to 10.6 mM (1.0 g.l-1) as the sole source of carbon and energy. Furthermore, cresols, chlorophenols, 3,4-dimethylphenol, and 4-chloro-m-cresol were metabolized as sole substrates by phenol-grown resting cells of strain EKII. Under conditions of cell growth, degradation of these xenobiotics was achieved only in co-metabolism with phenol. Phenol hydroxylase activity was detectable in whole cells but not in cell-free extracts. The specificity of the hydroxylating enzyme was found during transformation of cresols and chlorophenols: ortho- and meta-substituted phenols were degraded via 3-substituted catechols, while degradation of para-substituted phenols proceeded via 4-substituted catechols. In cell-free extracts of phenol-grown cells a high level of catechol 2,3-dioxygenase as well as smaller amounts of 2-hydroxymuconic semialdehyde hydrolyase and catechol 1,2-dioxygenase were detected. The ring-cleaving enzymes were characterized after partial purification by DEAE-cellulose chromatography.

Isolation and characterization of a 2-(2,4-dichlorophenoxy) propionic acid-degrading soil bacterium.

The 2-(2,4-dichlorphenoxy)propionic acid (2,4-DP)-degrading bacterial strain MH was isolated after numerous subcultivations of a mixed culture obtained by soil-column enrichment and finally identified as Flavobacterium sp. Growth of this strain was supported by 2,4-DP (maximum specific growth rate 0.2 h-1) as well as by 2,4-dichlorophenoxyacetic acid (2,4-D), 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB), and 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) as sole sources of carbon and energy under aerobic conditions. 2,4-DP-Grown cells (10(8] of strain MH degraded 2,4-dichlorophenoxyalkanoic acids, 2,4-dichlorophenol (2,4-DCP), and 4-chlorophenol at rates in the range of 30 nmol/h. Preliminary investigations indicate that cleavage of 2,4-DP results in 2,4-DCP, which is further mineralized via ortho-hydroxylation and ortho-cleavage of the resulting 3,5-dichlorocatechol.

Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double-blind multicenter study, Austria.

In a double-blind, 4-week, prospective, randomized multicenter (17 centers) study we checked on the efficacy, tolerability and safety of moclobemide (300-600 mg/d) compared to imipramine (100-200 mg/d) in parallel groups of patients with a Major Depressive Episode (DSM III). The mean % reduction of the HAMD at the end of treatment was 51.7 in the moclobemide group and 52.1 in the imipramine group. The percentage of patients in whom efficacy was globally judged as "good" or "very good" was 62% in the moclobemide group and 60% in the imipramine group. There was no statistically significant difference in the efficacy in both groups but in some factors there was a trend for a better amelioration favoring moclobemide. The final overall physician's judgement of tolerability was "good" or "very good" in 83% of moclobemide patients and in 74% of imipramine patients. Adverse events were reported or observed in 56% of moclobemide patients and in 69% of imipramine patients. The number of mild, moderate and severe adverse events was higher in the imipramine group with a total of 286 versus 189. There was a statistically high significant difference considering the tolerability favoring moclobemide again. In this project the basic goal to find a substance with at least the same efficacy but a much better tolerability for sure got fulfilled.