FastPixN, a new integrated pixel chip for a future fast version of the IRSN - recoil proton telescope.

A first prototype of recoil proton telescope (RPT) is currently working at the AMANDE facility, being developed as a collaboration between IPHC Strasbourg and the LNE-IRSN. The device, able to measure both energy and fluence of neutron fields in the range of 5-20 MeV, has to be improved further, in order to reduce the considerable inelastic background generated by the neutrons inside the RPT itself. To achieve faster running cycles, the present complementary metal-oxide-semiconductor pixels used for proton tracking are to be replaced by a new integrated chip, specially developed for this application. The authors present a first version of this new element, with individual pixels readout at a 200-MHz frequency, with a fast 4-bit ADC for each column of 64 pixels. The measured performances point to a complete frame treatment in only 12.6 µs. With a readout speed multiplied by a factor 400 over the existing device, the authors expect a considerable improvement of the telescope at AMANDE, with the potential to reach neutron fluence rates up to 10(7) n cm(-2) s(-1) or more.

Fluence measurement of fast neutron fields with a highly efficient recoil proton telescope using active pixel sensors.

The spectrometer ATHENA (Accurate Telescope for High-Energy Neutron metrology Applications) is being developed at the LNE-IRSN and aims at characterising energy and fluence of fast neutron fields. The detector is a recoil proton telescope and measures neutron fields in the range of 5-20 MeV. This telescope is intended to become a primary standard for both energy and fluence measurements. The neutron detection is achieved by a polyethylene radiator for n-p conversion, three 50-µm-thick silicon sensors that use CMOS technology for proton tracking and a 3-mm-thick silicon diode to measure the residual proton energy. The use of CMOS sensors and silicon diode, owing to a large detection solid angle, increases the intrinsic efficiency of the detector by a factor of 10 compared with conventional designs. The ability of the spectrometer to determine the neutron energy was demonstrated and reported elsewhere. This paper focuses on the fluence measurement of monoenergetic neutron fields in the range of 5-20 MeV. Experimental investigations, performed at the AMANDE facility, indicate a good estimation of neutron fluence at various energies. In addition, a complete description of uncertainties budget is presented in this paper and a Monte Carlo propagation of uncertainty sources leads to a fluence measurement with a precision ∼3-5 % depending on the neutron energy.

X-ray diagnostic calibration with the tabletop laser facility EQUINOX.

The broadband x-ray emission of a target irradiated by a laser can be used to check the calibration of detectors. At CEA-DIF we have a tabletop picosecond laser facility called EQUINOX with 0.3 J at 800 nm. The laser is focused inside a target chamber onto a solid target and produces bright radiation in the 100-2000 eV spectral range. The x-ray source is routinely monitored with a pinhole camera for source dimension measurement and with x-ray diodes for flux measurement. In addition an x-ray transmission grating spectrometer, a crystal spectrometer, and a single count charge coupled device camera measure the x-ray spectrum between 100 eV and 15 keV. The absolute calibration of those sets of spectrometers allows us to fully characterize x-ray emission spectra. Typical duration is less than 100 ps. The spectrum can be tuned by changing target material, pulse length, and x-ray filters. An application to checking the calibration of x-ray diodes used in the broad band spectrometer DMX with single shots will be presented.

Paradigms and experimental set-up for the determination of the acceptable delay in telesurgery.

The aim of this work was to develop an experimental set-up and realistic paradigms to study the effect of delay on video flux transmission and surgical performance. Four exercises were performed by 15 surgeons with 5 different simulated transmission delays. Large standard deviation of the duration of an exercise was found. Even with a short transmission delay of 150ms, some surgeon found that the surgical procedure was not possible. Further work has to be done to have a better evaluation of the surgical precision.

Development of a new electronic personal neutron dosemeter using a CMOS active pixel sensor.

A CMOS active pixel sensor, originally designed for the tracking of minimum ionising charged particles in high-energy physics, has been recently used for the detection of fast neutrons. Data were taken at the IRSN Cadarache facility with a (241)Am-Be ISO source and a polyethylene radiator. A high-intrinsic efficiency (1.2 x 10(-3)) has been obtained. It is in good agreement with both calculations and a MCNPX Monte Carlo simulation. This experiment paves the way for a fully electronic personal neutron dosemeter.

Morphometric investigations of sensory vestibular structures in tadpoles (Xenopus laevis) after a spaceflight: implications for microgravity-induced alterations of the vestibuloocular reflex.

In lower vertebrates, gravity deprivation by orbital flights modifies the vestibuloocular reflex. Using the amphibian Xenopus laevis, the experiments should clarify to which extent macular structures of the labyrinth are responsible for these modifications. In particular, the shape of otoconia and number and size of sensory macular cells expressing CalBindin were considered. CalBindin is common in mature sensory cells including vestibular hair cells and is probably involved in otoconia formation. Two developmental stages were used for this study: stage 26/27 embryos, which were unable to perform the roll-induced vestibuloocular reflex (rVOR) at onset of microgravity, and stage 45 tadpoles, which had already developed the reflex. The main observations were that the developmental progress of the animals was not affected by microgravity; that in the young tadpole group with normal body shape the rVOR was not modified by microgravity, while in the older group with microgravity experience, the rVOR was augmented; and that significant effects on the shape of otoconia and on the number and size of CalBindin-expressing cells of the labyrinthine maculae cells were absent. In addition, behavioural data were never significantly correlated with morphological features of macular structures such as size and number of CalBindin-expressing cells. It is postulated that mechanisms of vestibular adaptation to microgravity during early development are probably based on mechanisms located in central structures of the vestibular system.

The long-term adaptation of multicellular model organisms to non-terrestrial and space environments.

The main point in this presentation is the following: It is of crucial importance that the Space Agencies define and support the long-term directions for Space Biology Research. The development and upgrading of Facilities and Carriers should be coordinated with the preparatory activities of scientific groups interested in tackling major questions using the future opportunities in the Space Exploration Programs. The current effort in establishing larger Research Networks may lead the way to a successful Space Program in the XXI Century.

Towards the establishment of a permanent colony of Drosophila in the International Space Station: hardware tests and adaptation of techniques.

Our group has the long-term goal of establishing a permanent colony of Drosophila melanogaster in the International Space Station (ISS) to study its long-term adaptation to this unusual environment. We are currently building an enhanced version of an automatic cultivation unit (ESE1) in which we can grow flies with minimal crew involvement. We are working on a fixation unit as well. We are also adapting current protocols to maintain fixed animals during at least three months, the minimal refurbishment shuttle flight time, with minimal handling and maximal automatization, that can be used for inmuno-cytochemistry, ultrastructure or molecular experiments.

Design of specific hardware to obtain embryos and maintain adult urodele amphibians aboard a space station.

The study of the influence of weightlessness on fertilization and embryonic development of a vertebrate is of importance in the understanding of basic embryogenesis and in the preparation of the future exploration of space. Accordingly, specific hardware was designed to perform experiments on board the MIR space station with an amphibian vertebrate model, taking into account the biological requirements and the multiple constraints of a long-term mission. This paper describes the biological uses and presents the technological specifications of the device developed under CNES management. The hardware was adapted to and is compatible with biological requirements as confirmed by three experiments performed in space on board the orbital MIR station.

All-optical programmable shaping of narrow-band nanosecond pulses with picosecond accuracy by use of adapted chirps and quadratic nonlinearities.

We experimentally demonstrate pure optical pulse picosecond shaping of narrow-bandwidth nanosecond pulses. The method used is based on the manipulation in the spectral domain of strongly chirped femtosecond pulses and on the use of either frequency addition or frequency difference.

Pleurodeles waltl, amphibian, Urodele, is a suitable biological model for embryological and physiological space experiments on a vertebrate.

Pleurodeles waltl (amphibian, Urodele) is an appropriate biological model for space experiments on a vertebrate. One reason for interest in this animal concerns the study of the effects of absence of gravity on embryonic development. First, after mating (on Earth) the females retain live, functional sperm in their cloacum for up to 5 months, allowing normal in vivo fertilisation after hormonal stimulation. Second, their development is slow, which allows analyses of all the key stages of ontogenesis from the oocyte to swimming tailbud embryos or larvae. We have performed detailed studies and analyses of the effects of weightlessness on amphibian Pleurodeles embryos, fertilised and allowed to develop until the swimming larvae stage. These experiments were performed in space during three missions on the MIR-station: FERTILE I, FERTILE II and NEUROGENESIS respectively in 1996, 1998 and 1999. We show that in microgravity abnormalities appeared at specific stages of development compared to 1g-centrifuge control embryos and 1g-ground control embryos. In this report we describe abnormalities occurring in the central nervous system. These modifications occur during the neurulation process (delay in the closure of the neural tube and failure of closure of this tube in the cephalic area) and at the early tailbud stage (microcephaly observed in 40% of the microgravity-embryos). However, if acephalic and microcephalic embryos are not taken into account, these abnormalities did not disturb further morphological, biochemical and functional development and the embryos were able to regulate and a majority of normal hatching and swimming larvae were obtained in weightlessness with a developmental time-course equivalent to that of 1g-centrifuge control embryos (on the MIR station) and 1g-ground control embryos.

Microgravity and hypergravity effects on fertilization of the salamander Pleurodeles waltl (urodele amphibian).

Effects of microgravity (microG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in microG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked enzyme, in progenies obtained in microG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the microG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in microG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on microG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of microG-eggs were observed.

Ultrashort, intense ultraviolet pulse generation by efficient frequency tripling and adapted phase matching.

We demonstrate efficient frequency tripling of 1057-chirped pulses, using adapted chirping and thick KDP crystals. These millijoules broadband pulses at 352 nm have been compressed to 220-fs duration by use of a UV grating-pair compressor. The technique is scalable to kilojoule petatwatt lasers.

Does gravity influence the early stages of the development of the nervous system in an amphibian?

As a result of previous studies using hypergravity (centrifuge) or virtual microgravity (clinostat), it was proposed that gravity was involved in embryonic development, i.e., in the establishment of the embryonic polarities and the body plan pattern which subsequently direct morphogenesis and organogenesis of the central nervous system and of sensory organs. Recent experiments were performed in space using sounding rockets and orbiting space-modules to ascertain whether gravity is indeed required for embryogenesis in Invertebrates and Vertebrates. Eggs fertilised in vivo or in vitro in microgravity showed some abnormalities during embryonic development but were able to regulate and produce nearly normal larvae.

Differentiation in microgravity of neural and muscle cells of a vertebrate (amphibian).

The CELIMENE space experiment (CELulles en Impesanteur: Muscle Et Neurone Embryonnaires) was devoted to the study of the influence of gravity on the differentiation, the organisation and the maintenance of the highly specialised nervous system and muscular system. CELIMENE was carried out during the first flight of the IBIS hardware (Instrument for BIology in Space) with the fully automatic space mission PHOTON 10 in February 1995. Using the amphibian Pleurodeles waltl as a vertebrate model, in vitro experiments involved immunocytochemical detection of glial-, neuronal- and muscle-specific markers, and neurotransmitters in cells developed under conditions of microgravity compared with 1g controls, on-board and on the ground. We observed that the altered gravity did not disturb cell morphogenesis or differentiation.

Efficient generation of narrow-bandwidth picosecond pulses by frequency doubling of femtosecond chirped pulses.

We demonstrate efficient generation of picosecond narrow-bandwidth pulses by frequency mixing of broadband opposite chirped pulses in a type I doubling crystal. This procedure allows us to produce picosecond pulses that are perfectly synchronized with femtosecond pulses. The experiment shows a decrease of the initial bandwidth by a factor of more than 30, while a high conversion efficiency is maintained.

In vitro interleukin-1 and 2 production and interleukin 2 receptor expression in the rhesus monkey.

Anti-human monoclonal antibodies were used to detect and quantify interleukins-1 and 2 and interleukin-2 receptor expression in peripheral blood mononuclear cells from a rhesus monkey. Interleukin-1 production could be induced by phorbol esters (PMA) and was potentiated by phytohemagglutinin (PHA). Interleukin-2 secretion could also be induced by the combination of PHA and PMA, but only weakly with PHA alone. Interleukin-2 receptor expression was present in a subpopulation of unstimulated lymphocytes and could be enhanced by PHA or PMA. These data show once again that the rhesus monkey immune system is cross-reactive with the human one and that rhesus macaque could be a good model to study interleukin therapy.

Neuroendocrine system and immune responses after confinement.

A confinement experiment in a normobaric diving chamber was undertaken to obtain more understanding of the effects of confinement and isolation on human psychology and physiology. Pre- and post-confinement blood samples were obtained from four test subjects and five control subjects for the analysis of plasma proteins, hormone levels and immune responses. The absence of significant changes in the immune responses correlates with the absence of major changes in neurohormones and other hormones such as cortisol, prolactin, growth hormone, insulin-like growth factor 1, triiodothyronin, thyrotrophin and 1,25-dihydroxyvitamin D. It is increasingly recognized that the immune system is not an independent physiological system, but a system that interacts multidirectionally with other organs and body functions. It seems that the conditions of this confinement experiment were not stressful from a psychological point of view. The presence of a female crew member had probably a positive effect on group behavior of the test subjects. In conclusion, the data suggest that confinement for 60 days in a small habitat without particularly stressful situations has no significant impact on a variety of neuroimmunological parameters.

Natural killer cells after ALTAIR mission.

Reduced in vitro NK cytotoxic activity have routinely been observed after both prolonged and short-term space flights. This study investigated the effects of space flight on NK cell functions, NK cell counts and the production of IL-2 and TNF by lymphocytes of French-Russian crew members. In the French cosmonaut, after 21 days space flight, the cytotoxic activity of NK cells, the capacity the NK cells to bind and lyse the individual target cells and the percentage of NK cells were decreased. In this cosmonaut a twofold reduction TNF production in cultures of lymphocytes stimulated with PMA and with the mixture of PHA and PMA was observed on the first day after landing. However, the activity of the production of TNF in 48-hour PHA-cultures of lymphocytes was unchanged and the biological activity of IL-2 was not reduced. The immunological examination did not detect any substantial deviations from the norm in both russian cosmonauts after 197 days space flight. Various explanations for decreased cytotoxicity in cosmonauts after space flight can be proposed, and these include the defective function of NK cells and reduced numbers of circulating effector cells.