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AbstractIntegrated modeling (IM) of present experiments and future tokamak reactors requires the provision of computational resources and numerical tools capable of simulating multiscale spatial phenomena as well as fast transient events and relatively slow plasma evolution within a reasonably short computational time. Recent progress in the implementation of the new computational resources for fusion applications in Europe based on modern supercomputer technologies (supercomputer MARCONI-FUSION), in the optimization and speedup of the EU fusion-related first-principle codes, and in the development of a basis for physics codes/modules integration into a centrally maintained suite of IM tools achieved within the EUROfusion Consortium is presented. Physics phenomena that can now be reasonably modelled in various areas (core turbulence and magnetic reconnection, edge and scrape-off layer physics, radio-frequency heating and current drive, magnetohydrodynamic model, reflectometry simulations) following successful code optimizations and parallelization are briefly described. Development activities in support to IM are summarized. They include support to (1) the local deployment of the IM infrastructure and access to experimental data at various host sites, (2) the management of releases for sophisticated IM workflows involving a large number of components, and (3) the performance optimization of complex IM workflows.

The aim of this paper is to give a new insight into some fundamental concepts of the IEC 61508 standard. First, low and high or continuous demand modes of operation of safety instrumented systems are examined by analysing their official definitions given in the IEC 61508 and IEC 61511 standards. In this context, the paper proposes a new criterion for distinguishing these two modes of operation. A study allowing the determination of accident frequency is also presented, where the system under study consists of one element under control and its associated safety instrumented system. Second, the relationship between the average probabilities of failure on demand and the risk reduction factor is studied. It is shown that the commonly used approach (the standard approach) may lead to an optimistic value for the risk reduction factor. Finally, the paper clarifies the nature of the probability of failure per hour of a safety instrumented system and proposes different ways to compute this in the general case, based on fault tree, Markov model, and Petri nets approaches.

In the oil industry, high-integrity protection systems tend to replace traditional safety systems. In this paper, a snapshot is provided of the methods and tools designed by the authors to evaluate efficiently safety integrity levels of high-integrity protection systems, as required by IEC 61508 and 61511 standards. These standards provide rigorous processes to build the safety of safety-instrumented systems. They are very efficient from an organizational point of view. However, difficulties arise with definitions and probabilistic calculations. To overcome these difficulties, the existing methods and tools were extended. These extensions are presented by means of simple examples. The focus is on the treatment of high-integrity protection systems working in low-demand mode (that is, with less than one demand per year according to the standards), e.g. systems such as high-integrity pressure protection systems. Some indications for safety systems working in continuous mode are given. Some practical conclusions are drawn from the various experiments performed. First, fault trees, when properly used, are very efficient for low-demand safety systems. Second, multi-phase Markov processes provide accurate results, even if only very small systems are tractable with this approach. Finally, behavioural modelling coupled with Monte Carlo simulation on Petri nets is both efficient and accurate. From the authors’ point of view, these approaches are simpler to handle than the informative formulae proposed in the present issue of IEC 61508 and 61511 standards.

The aim of this paper is to show how the stochastic Petri nets, commonly used in reliability field to model the functional and dysfunctional behaviour of industrial systems and to assess their dependability, are also able to give some interesting information on their global performance, which can be exploited from a technical and economical point of view. By this way the Petri nets can be used, in some cases, to identify the best configuration of system being under design and to determine the right number of spares to be kept in store. Thus, this engineering approach could be an alternative to optimization methods.

The process of spontaneous learning in an automatic food dispenser by a group of domestic female pigs was studied when one of the animals of the group had an aversive experience. Restraining a gilt in the dispenser without access to food resulted in later avoidance of the system by other gilts, especially when the reactions of the restrained animal had been especially violent and associated with urination. The hypothesis of a delayed transmission of an unpleasant experience was tested. The food dispenser was sprayed with urine collected from either a control gilt or from an animal undergoing stress. In half of the cases, the presence of urine of a stressed animal resulted in a long-lasting avoidance of the food dispenser, suggesting the existence of some kind of alarm pheromone produced in the urine of a sow during an unpleasant experience.

We have used the axolotl oocyte (Ambystoma mexicanum Shaw) to study the stability of exogenously injected Xenopus RNAs. Three different cellular developmental stages have been analysed: (1) the growing oocyte (stage III–IV of vitellogenesis), (2) the full-grown oocyte at the end of vitellogenesis (stage VI) and (3) the progesterone-matured stage VI oocyte. Three exogenous RNAs have been synthesized in vitro from a c-myc Xenopus cDNA clone. One transcript is 2.3 kb long (full length), the second is 1.5 kb long, with most of the 3' untranslated region (3'UTR) removed, and the third corresponds to the 3'UTR (0.8 kb). After injection or coinjection of these exogenous Xenopus RNAs into axolotl oocytes, the stability of the molecules was studied after 5 min, 6 h and 21 h by extraction of total RNA and Northern blot analysis.

We have previously described an in vivo heterologous system which has allowed us to study the stability of different Xenopus c-myc RNA constructs injected into axolotl oocytes. In full-grown oocytes, degradation of c-myc RNA does not occur. In mature oocytes treated with progesterone, transcripts containing the coding sequence of the gene are degraded, whereas those corresponding to the 3'UTR (untranslated region) alone are stable. In order to study the role of nuclear or cytoplasmic components in this process, degradation of injected c-myc transcripts was analysed (i) after inhibition of germinal vesicle breakdown (GVBD) in progesterone treated oocytes (ii) after induced maturation of enucleated oocytes, (iii) injection of nuclear contents into immature oocytes and (iv) after direct injection into the germinal vesicle of full-grown oocytes. Our results demonstrate the role of a nuclear factor stockpiled in the germinal vesicle of full-grown oocytes and specifically involved in the degradation of c-myc transcripts containing the coding region. Further biochemical characterization of this new nuclear component should lead to a better understanding of the post-transcriptional control of c-myc expression during oogenesis and early development.

Summary: During animal development and gametogenesis two DNA ligases are found and successively expressed. In this study the two DNA ligases present in the axolotl egg and the two ligases present during ram sperm cell maturation were distinguished by biochemical and immunological methods. The expression of the genes for the heavy and light ram DNA ligases has been studied using transplantation of spermatid and sperm nuclei in axolotl eggs. We found that ram DNA ligases were expressed in axolotl egg cytoplasm. The exclusion phenomenon between the heavy and light form of DNA ligase is species-specific and involves a cytoplasmic mediator. In the transplanted ram germ cell nuclei the heavy ram DNA ligase expression was found to be sensitive to inhibitors of transcription while the light one was not. When mRNA was used, no exclusion process was observed and both the heavy and light enzyme expression were sensitive to cycloheximide and not to aamanitin. These results are discussed in terms of the possible stability of the gene-regulated state following nuclear transfer.

A light form of DNA ligase (EC 6.5.1.2), the only form present in oocytes of the axolotl (Ambystoma mexicanum), has been shown to be replaced by a heavy form of the enzyme when the egg enters cleavage. This early biochemical event has been assumed to rely on direct nuclear input. Sucrose gradient analysis permits discrimination between enzymes from axolotl and the sharp-ribbed salamander (Pleurodeles waltlii) for both heavy and light enzymatic forms of DNA ligase. Genetic activity of blastula nuclei transplanted in activated cytoplasm has been tested by determination of the enzymatic forms and specific types of DNA ligases when the implanted egg enters cleavage. A blastula nucleus of Pleurodeles in axolotl cytoplasm determines a heavy ligase of the Pleurodeles type. Conversely, a haploid androgenetic nucleus of Pleurodeles in axolotl cytoplasm controls a light ligase of the Pleurodeles type. Reciprocal experiments give homologous results. To our knowledge, this is the earliest nucleus-dependent synthesis revealed in development for any system. The heavy ligase of one species may coexist with the light form of the other species but not with the light form of its own specific type. Inhibition of the production of the heavy form for one genome results in the expression of the light form. We conclude that genetic control of DNA ligase in very early development involves structural genes for heavy and light forms of enzyme, with an exclusion process operating an alternative expression of corresponding genes. This exclusion relationship between nonallelic genes is species specific.

Summary.In anoestrous ewes, male chemosignals elicit rapid increases in luteinizing hormone (LH) secretion that can ultimately lead to ovulation. To assess the possible involvement of the accessory (vomeronasal) olfactory system in the mediation of those chemical cues, we destroyed this pathway by vomeronasal organ electrocauterization (Exp. I) and vomeronasal nerve section (Exp. II). Neither of these lesions inhibited the LH response of ewes to the odour of the male. These results suggest that the vomeronasal system is not necessary to mediate the neuroendocrine response of the ewe to the male odour. As both surgical methods spared the main olfactory system but destroyed the vomeronasal system, it is likely that the main olfactory system is involved in the LH response to chemical stimulation in sexually experienced ewes.Keywords:sheep; male effect; chemosignals; vomeronasal system

Summary.The response of sexually experienced Ile-de-France rams to the presentation of oestrous females in October at sunrise (Subgroup S) or at 11:00 h (Subgroup N) was studied and compared with unstimulated controls (Subgroup C). Animals (12 per group) were bled for 7 h at 20-min intervals, starting 3 h before stimulation by oestrous females (3 per group). Eight rams from Subgroup S showed an increase of LH pulse frequency and only 3 in Subgroup N (P< 0·03). In Subgroup S the introduction of females led to 2- and 3-fold increases in LH pulse frequency during the stimulation period compared with values in Subgroup C or before the stimulation period (3, 1·6 and 1 peaks/rams/6 h respectively; P< 0·05). The presence of females also led to an increase in mean testosterone concentrations, and small increases in basal and mean LH values. No differences were found in LH peak amplitudes. In Subgroup N only inconsistent evidence of increases in mean LH and testosterone values was found. No differences between Subgroups S and N in behavioural patterns during stimulation were detected. We conclude that the presence of females affects LH pulse frequency at sunrise but not at noon during the breeding season and this effect is at least partly independent of sexual behaviour. These results suggest a possible circadian variation in CNS sensitivity involving the hypothalamic regulation of LH secretion in response to the presence of oestrous females.Keywords:temporal variations; LH; testosterone; ram; female effect; teasing

DNA-ligase activity in eukaryotic cells is carried out by two different molecular forms of the enzyme. This molecular duality, first described in mammals (So¨derha¨ll & Lindhal, 1973), has been reported in chicken (David, 1977), amphibians (Carre´, Signoret, Lefresne & David, 1981), fish, sea urchin and crab (Signoret & David, 1986). Depending on the developmental stage and the tissue considered, types of cell are available that express exclusively either one or the other of the two DNA-ligases with a defined level of activity. DNA-ligase I and DNA-ligase II, encoded by distinct structural genes (Thiebaud et al. 1985), can be unambiguously characterized and the advantages offered by the early amphibian embryo have made possible the identification of some basic features of their regulation. The Gene for DNA-ligase I exists in two Regulated States The heavy molecular form of the enzyme, referred to as DNA-ligase I, is generally present in proliferating tissues.

Summary.Reproductive events were recorded in two groups of female wild boars kept in semi natural conditions. The first group had been kept for 2 consecutive years with a male. Most farrowing took place within 4–5 days: 6/7 in the first year and 8/9 for the second. A second group of 5 females was kept for 13 months in the absence of a male, and oestrous cycles were monitored by weekly measurement of plasma progesterone concentrations. All the females experienced summer–autumn anoestrus and resumed cycling in the same week of December. This accurate synchronization of reproduction may result from stimulation amongst females belonging to the same social unit.Keywords:reproduction; synchronization of oestrus; social group; wild boar

I.N.R.A.-Laboratoire de Physiologie de la Reproduction, Nouzilly, 37380 Monnaie, France(Received 29th May 1974)The concentrations of a number of reproductive hormones found in the peripheral plasma of the cow around the time of oestrus have been measured by numerous authors: plasma concentrations of progesterone throughout the oestrous cycle (Stabenfeldt, Ewing & McDonald, 1969), LH (Schams & Karg, 1969), oestrogen and progesterone (Henricks, Dickey & Hill, 1971) and LH and progesterone (Henricks, Dickey & Niswender, 1970). These and other reports have paid little attention to the precise onset and duration of oestrus, behaviour being checked at various intervals (usually two or three times a day) before the expected onset.To obtain a more precise pattern of hormone concentrations around oestrus, we have measured simultaneously LH, oestradiol-17β and progesterone in samples of plasma taken at 2-hr intervals from cows over a period of 5 days. The cows were maintained with a

Une technique est décrite permettant d'obtenir des images chromosomiques particulièrement favorables fournies par des blastulas d'Axolotl. A partir de ce matériel le caryotype de cette espèce est analysé.

It seems that the sexual activity in mammals is primarily controlled by the day-light ratio, and under certain experimental conditions sexual activity is entirely dependent on the daily light ratio.

Mating has been shown to have effects on ovulation in a number of species which ovulate spontaneously, such as rats (Aron, Asch & Asch, 1961; Aron, Asch & Ross, 1966; Zarrow & Clark, 1968) and sheep (Parsons, Hunter & Rayner, 1967; Van der Westhuysen, Van Niekerk & Hunter, 1970). In the sow, the results obtained by Pitkjanen (1955) and Lebedev (1957) suggest that mating hastens ovulations and shortens the time during which ova are liberated. Direct inspection of the ovaries by coelioscopy (Locatelli, 1971) allows rapid and accurate determination of the time of ovulation and causes minimal trauma. By this technique, the earlier results have been confirmed in a preliminary experiment (Signoret, 1970).The present experiment was designed to show by how many hours mating advances ovulation and shortens its total duration.Fifty-nine Large

I.N.R.A., Station de Physiologie de la Reproduction, 37380 Nouzilly, France(Received13 September1974)The continuous presence of rams reduces the duration of the sexual receptivity both in intact ewes during spontaneous oestrus (Parsons & Hunter, 1967) and in ovariectomized ewes after progesterone-oestrogen treatment (Fletcher & Lindsay, 1971). Moreover, the exposure of intact ewes to rams accelerates the surge of luteinizing hormone (LH) resulting in earlier ovulation (Lindsay, Cognié, Pelletier & Signoret, 1975). Oestrogens appear to provide the primary stimulus for the LH surge in the ovariectomized ewe (Pelletier & Signoret, 1970; Scaramuzzi, Tillson, Thorneycroft & Caldwell, 1971). This present experiment was designed to investigate a possible 'male effect' on the timing of the pituitary release of LH after progesterone-oestrogen treatment of the ovariectomized ewe.Thirty-seven mature Ile-de-France ewes, ovariectomized at least 1 month before the hormone injections, were used in the experiment. They were primed by five

A new DNA ligase activity is expressed when the Axolotl eggs enter cleavage. The messenger RNA can be labelled by [3H] uridine thereby indicating its de novo synthesis. This new genetic expression is occuring just before cleavage and is the earliest found during Amphibian development. The newly synthesized [3H] mRNA can be translated in vitro in the rabbit reticulocyte lysate system. The resulting product is a 160 K protein specifically iramuno-precipitated with the antiserum directed against 8S DNA ligase. This in vitro translated polypeptide exhibits 8S DNA ligase activity specific of activated or fertilized eggs but does not display 6S DNA ligase activity of non activated eggs.