Comparative mutagenicity of N-nitrosamines in a semi-solid and in a liquid incubation system in the presence of rat or human tissue fractions

The rat liver microsome-mediated mutagenicities of a series of N-nitrosodialkylamines and heterocyclic N-nitrosamines were determined in a liquid incubation system using Salmonella typhimurium TA1530. The influence on mutation frequency of the concentration of co-factors for mixed-function oxidase and composition and molarity of the buffer was investigated, using N-nitrosomorpholine as substrate. The mutagenicity of the N-nitroso compounds in the liquid incubation system under optimal reaction conditions at equimolar concentration was compared quantitatively with that obtained in a soft-agar incorporation assay. N-Nitrosodi-n-pentylamine and N-nitrosodi-n-butylamine showed no enzyme-mediated mutagenicity in the liquid incubation system, and metabolically activated N-nitroso-dimethylamine and N-nitroso-diethylamine showed negligible mutagenic activity in the soft-agar assays. In contrast with these results with the N-nitrosodialkylamines, the mutagenic effects of heterocyclic N-nitrosamines were similar in the liquid incubation system and in soft-agar incorporation assays. The heterocyclic N-nitrosamines showed rat-liver microsome-mediated mutagenicity in the following descending order: N-nitrosomorpholine greater than N-nitrosopyrrolidine greater than N-nitrosopiperidine greater than N-nitroso-N'-methylpiperazine. Seven human liver specimens converted all heterocyclic N-nitrosamines into mutagens; this activity was similar to that of rat liver, except that for N-nitroso-N'-methylpiperazine, fractions from three human liver biopsies were three to 30 times more active than those from untreated rats. The specific reversion of S. typhimurium TA1530 to histidine prototrophy provides experimental evidence that all the N-nitrosamines studied were converted by liver microsomal enzymes into monofunctional alkylating agents.     

T-cell recognition of a cross-reactive antigen(s) in erythrocyte stages of Plasmodium falciparum and Plasmodium yoelii: inhibition of parasitemia by this antigen(s)

In the current study, we investigated the presence of a cross-reactive antigen(s) in the erythrocyte stage from Plasmodium yoelii (265 BY strain) and Plasmodium falciparum through recognition by T cells primed in vivo with antigens from each of these parasites. BALB/c mice are naturally resistant to P. falciparum but are susceptible to P. yoelii infection. Mice that had recovered from P. yoelii primary infection became resistant to a second infection. A higher in vitro proliferative response to a soluble blood stage preparation of P. falciparum was observed in splenic cells from immune animals than in those from mice with a patent P. yoelii infection. The antigen-induced proliferative response was enhanced when animals were exposed to a secondary infection. Animals exposed to a challenge infection were treated with anti-CD4 or anti-CD8 monoclonal antibodies to deplete the corresponding subset of T cells. There was a marked diminution in P. falciparum antigen-induced proliferative response in the total splenic cell populations from CD8-depleted but not from CD4-depleted mice. In CD8-depleted and nondepleted animals, the antigen-induced proliferation in the total cell populations was markedly lower than in the T-cell-rich populations, indicating inhibitory activities of B cells and/or macrophages. There was no such difference in the stimulation between total and T-enriched cell populations from CD4-depleted animals. Flow cytometry analysis demonstrated the presence of an almost equal percentage of CD8+ (59.6%) and CD4+ (64%) T cells in the spleen preparations following in vivo depletion of CD4- and CD8-bearing T cells, respectively. When cultured with P. yoelii blood stage antigen, splenocytes from animals immunized with P. falciparum antigen displayed a significant proliferative response which was markedly diminished by treatment with anti-Thy-1.2 antibody plus complement. Animals immunized with P. falciparum antigen and then challenged with P. yoelii blood stage parasites displayed about a 50% lower level of parasitemia. These results demonstrated the existence of a cross-reactive antigen(s) between a murine and a human Plasmodium species, as determined from both in vivo and in vitro biological assays, and indicated the reactivity of mainly CD8+ T cells with this antigen.     

Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.     

Modified technique for efficient detection of microsporidia

Changes in temperature (from room temperature to 50 degrees C) and staining time (from 90 to 10 min) were evaluated as a means of improving the detection of microsporidia from stool specimens. A blinded and independent comparison of 50 known positive matched-specimen pairs by three technologists resulted in consistently easier microscopic detection. The background is clearer, and spores stain more intensely. Staining time is reduced by 80 min.     

Electron-Phonon Decoupling NbSi CMB Bolometers

Precise measurements of the cosmic microwave background (CMB) is crucial to cosmology, since any proposed model of the Universe must account for the features of this radiation. E_cient very large bolometer arrays (>10,000?pixels) constitute an important challenge for CMB observations and are actually developed by many groups worldwide. We present here an explorative new bolometer design based on a structure that simplifies the fabrication process and exhibits high sensitivity. This innovative device replaces delicate membrane-based structures and eliminates the mediation of phonons: the incoming energy is directly captured and measured in the electron bath of an appropriate sensor and the thermal decoupling is achieved via the intrinsic electron-phonon decoupling of the sensor at very low temperature. Reported results come from a 204-pixel matrix of Nb _x Si_1?x transition edge sensors with a meander structure fabricated on a 2-inch silicon wafer using electron-beam co-evaporation and standard lithography process. To validate the application to CMB measurements, we have realized an optical calibration of our sample in the focal plane of a dilution cryostat test bench.     

A spray pyrolysis route to the undoped ZnO layer of Cu(In,Ga)(S,Se)2 solar cells

The undoped ZnO in the window layer of Cu(In,Ga)(S,Se)₂ solar cells is deposited here by a non-vacuum spray pyrolysis method yielding solar cells of similar efficiencies to cells prepared with the standard sputtered layer. The spray pyrolysis method allows the undoped ZnO to be deposited in sequence on the same apparatus or in-line directly after deposition of the spray-‘ILGAR’ (ion layer gas reaction) In₂S₃ buffer layer. Thus it is highly suitable for manufacturing, not only is spray pyrolysis economical, avoiding the need for two target sputtering systems, but for monolithic integrated modules the second ‘P2’ scribe, carried out to interconnect cells, can be undertaken before sputtering permitting the highly doped ZnO:Al front contact to directly connect to the rear Mo back contact.     

50 mK cooling solution with an ADR precooled by a sorption cooler

CEA/SBT is currently developing a 2.5 K-50 mK cooling solution composed of a small demagnetization refrigerator (ADR) precooled by a sorption cooler, equivalent to the high temperature stage of a two-stage ADR system. Thanks to the use of this dual technology, a low weight cooler able to reach 50 mK with a heat sink up to 2.5 K can be designed. Because the sorption cooler is probably the lightest solution to produce sub-Kelvin temperatures, these developments allow us to propose a solution to face the drastic reduction in the mass budget of space missions like SPICA or IXO. The European Space Agency (ESA) is funding the development of an engineering model able to produce 1 μW net heat lift at 50 mK. It is sized so that the sorption cooler provides an additional 10 μW at 300 mK. The ESA main requirements are an autonomy of more than 24 h and a recycling time smaller than 8 h. We present the design of the system able to meet these requirements as well as the expected performances and preliminary measurements.     

Development of damage in a 2D woven C/SiC composite under mechanical loading: I. Mechanical characterization

An investigation has been undertaken to determine the damage mechanisms and the associated mechanical response of a 2D reinforced composite of carbon fibers in an SiC CVI-processed matrix subjected to uniaxial tensile and compressive loadings at room temperature. Under tension loading, an extended non-linear stress/strain response was evidenced and related to a multi-stage development of damage involving transverse matrix microcracking, bundle/matrix and inter-bundle debonding as well as thermal residual stress release. This tensile behavior proved to be damageable-elastic with respect to a fictitious thermalstress-free origin of the stress/strain axis lying in the compression domain. In compression, after an initial stage involving closure of the thermal microcracks present from processing, the composite displayed a linear-elastic behavior until failure. The extent of damage over the material was characterized quantitatively at the microscale by the decrease of the average transverse microcrack spacing and at the macroscale by the decrease of both the longitudinal Young's modulus and the in-plane Poisson's ratio.     

Patients with absolutely immotile spermatozoa and intracytoplasmic sperm injection

The microinjection of completely immotile spermatozoa may impair the outcome of intracytoplasmic sperm injection (ICSI). Eleven couples underwent an initial ICSI cycle with 100% immotile freshly ejaculated spermatozoa. Two-pronuclear fertilization ensued in 18 of 145 (12.4%) successfully injected oocytes. None of these cycles resulted in a pregnancy. Nine couples underwent ICSI in subsequent cycles (n = 16). Ejaculated spermatozoa were injected in 15 cycles and testicular spermatozoa in one cycle. In 10 of the 15 cycles, motile spermatozoa were available at the time of injection. Motile testicular spermatozoa could also be injected. In the subsequent cycles, 91 of 176 (51.7%) successfully injected oocytes fertilized normally and four patients became pregnant. In the subsequent cycles where again immotile spermatozoa had to be injected no pregnancies occurred. In four subsequent cycles embryo cryopreservation was carried out. After replacement of two frozen-thawed embryos one additional pregnancy was obtained. In all, five healthy infants were born. It has been ascertained that motile spermatozoa can be detected either in repeated ejaculates or after testicular biopsy. The causes of total asthenozoospermia are variable and the problem is a sporadic rather than a permanent condition.