New evidence of broader diets for archaic Homo populations in the northwestern Mediterranean.

Investigating diet breadth is critical for understanding how archaic Homo populations, including Neanderthals, competed for seasonally scarce resources. The current consensus in Western Europe is that ungulates formed the bulk of the human diet during the Lower and Middle Paleolithic, while small fast prey taxa were virtually ignored. Here, we present a multisite taphonomic study of leporid assemblages from Southern France that supports frequent exploitation of small fast game during marine isotope stages 11 to 3. Along with recent evidence from Iberia, our results indicate that the consumption of small fast game was more common prior to the Upper Paleolithic than previously thought and that archaic hominins from the northwestern Mediterranean had broader diets than those from adjacent regions. Although likely of secondary importance relative to ungulates, the frequent exploitation of leporids documented here implies that human diet breadths were substantially more variable within Europe than assumed by current evolutionary models.

Evidence that the Great Pacific Garbage Patch is rapidly accumulating plastic.

Ocean plastic can persist in sea surface waters, eventually accumulating in remote areas of the world's oceans. Here we characterise and quantify a major ocean plastic accumulation zone formed in subtropical waters between California and Hawaii: The Great Pacific Garbage Patch (GPGP). Our model, calibrated with data from multi-vessel and aircraft surveys, predicted at least 79 (45-129) thousand tonnes of ocean plastic are floating inside an area of 1.6 million km2; a figure four to sixteen times higher than previously reported. We explain this difference through the use of more robust methods to quantify larger debris. Over three-quarters of the GPGP mass was carried by debris larger than 5 cm and at least 46% was comprised of fishing nets. Microplastics accounted for 8% of the total mass but 94% of the estimated 1.8 (1.1-3.6) trillion pieces floating in the area. Plastic collected during our study has specific characteristics such as small surface-to-volume ratio, indicating that only certain types of debris have the capacity to persist and accumulate at the surface of the GPGP. Finally, our results suggest that ocean plastic pollution within the GPGP is increasing exponentially and at a faster rate than in surrounding waters.

Development of a µ-TPC detector as a standard instrument for low-energy neutron field characterisation.

In order to measure the energy and fluence of neutron fields, in the energy range of 8 to 1 MeV, a new primary standard is being developed at the Institute for Radioprotection and Nuclear Safety (IRSN). This project, Micro Time Projection Chamber (µ-TPC), carried out in collaboration with the Laboratoire de Physqique Subatomique et de Cosmologie (LPSC), is based on the nucleus recoil detector principle. The measurement strategy requires track reconstruction of recoiling nuclei down to a few kiloelectronvolts, which can be achieved using a micro-pattern gaseous detector. A gas mixture, mainly isobutane, is used as an n-p converter to detect neutrons within the detection volume. Then electrons, coming from the ionisation of the gas by the proton recoil, are collected by the pixelised anode (2D projection). A self-triggered electronics system is able to perform the anode readout at a 50-MHz frequency in order to give the third dimension of the track. Then, the scattering angle is deduced from this track using algorithms. The charge collection leads to the proton energy, taking into account the ionisation quenching factor. This article emphasises the neutron energy measurements of a monoenergetic neutron field produced at 127 keV. The fluence measurement is not shown in this article. The measurements are compared with Monte Carlo simulations using realistic neutron fields and simulations of the detector response. The discrepancy between experiments and simulations is 5 keV mainly due to the calibration uncertainties of 10 %.

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.

Diversity of Ralstonia solanacearum in French Guiana expands knowledge of the "emerging ecotype".

Although bacterial wilt remains a major plant disease throughout South America and the Caribbean, the diversity of prevalent Ralstonia solanacearum populations is largely unknown. The genetic and phenotypic diversity of R. solanacearum strains in French Guiana was assessed using diagnostic polymerase chain reactions and sequence-based (egl and mutS) genotyping on a 239-strain collection sampled on the families Solanaceae and Cucurbitaceae, revealing an unexpectedly high diversity. Strains were distributed within phylotypes I (46.9%), IIA (26.8%), and IIB (26.3%), with one new endoglucanase sequence type (egl ST) found within each group. Phylotype IIB strains consisted mostly (97%) of strains with the emerging ecotype (IIB/sequevar 4NPB). Host range of IIB/4NPB strains from French Guiana matched the original emerging reference strain from Martinique. They were virulent on cucumber; virulent and highly aggressive on tomato, including the resistant reference Hawaii 7996; and only controlled by eggplant SM6 and Surya accessions. The emerging ecotype IIB/4NPB is fully established in French Guiana in both cultivated fields and uncultivated forest, rendering the hypothesis of introduction via ornamental or banana cuttings unlikely. Thus, this ecotype may have originated from the Amazonian region and spread throughout the Caribbean region.

Numerical modelling of floating debris in the world's oceans.

A global ocean circulation model is coupled to a Lagrangian particle tracking model to simulate 30 years of input, transport and accumulation of floating debris in the world ocean. Using both terrestrial and maritime inputs, the modelling results clearly show the formation of five accumulation zones in the subtropical latitudes of the major ocean basins. The relative size and concentration of each clearly illustrate the dominance of the accumulation zones in the northern hemisphere, while smaller seas surrounded by densely populated areas are also shown to have a high concentration of floating debris. We also determine the relative contribution of different source regions to the total amount of material in a particular accumulation zone. This study provides a framework for describing the transport, distribution and accumulation of floating marine debris and can be continuously updated and adapted to assess scenarios reflecting changes in the production and disposal of plastic worldwide.

Experimental comparison of 241Am-Be neutron fluence energy distributions.

(241)Am-Be(alpha,n) neutron sources provide one of the most commonly used neutron fields for routine calibration of neutron sensitive devices. The neutron energy distribution of the IRSN standard (241)Am-Be source was measured in the energy region above 1.65 MeV using a BC501A proton-recoil liquid scintillator. The experimental data were compared to the ISO-recommended neutron energy distribution for an (241)Am-Be source. Some differences in shape were observed, with large variations mainly within the energy interval 3-6 MeV and around 8 MeV. Within the framework of a collaboration between three national metrological institutes (PTB, Germany; NPL, UK and LNE-IRSN, France), the neutron energy distributions of (241)Am-Be sources at each laboratory have been compared. The IRSN-BC501A proton-recoil scintillator was used to measure all the sources. The results show different energy distributions a priori influenced by the origin of the source, i.e. the manufacturing process. The maximum deviation observed for the integral dose equivalent, in the measured BC501A energy range, is within the 4% uncertainty recommended by ISO standard 8529-2 to allow for variations of the neutron spectrum among different (241)Am-Be sources. However, knowledge of the energy distribution of an (241)Am-Be source provides a way to reduce the uncertainty in the dose equivalent rate delivered by such a source.

Photon contribution to ambient dose equivalent H(10) in the wide-spectrum neutron reference fields of the IRSN.

The photon contribution to ambient dose equivalent in several wide-spectrum reference neutrons fields of the Institute for Radiological Protection and Nuclear Safety were measured using a Geiger-Müller counter. For the investigated fields, the ratio of photon to neutron ambient dose equivalent ranged between 0.03 and 0.20. The results show that the Geiger-Müller tube is a versatile instrument for dosimetry in mixed photon-neutron fields if sufficient information for the calculation of corrections is available.

Investigation of the neutron energy distribution of the IRSN 241Am-Be(alpha,n) source.

The neutron energy distribution of the IRSN standard 241Am-Be(alpha,n) source was measured using a proton recoil liquid scintillator, BC501A, >1.65 MeV. The experimental data were compared with the ISO recommended neutron energy distribution for an Am-Be source and some significant discrepancies were observed. Monte Carlo simulations were then performed to investigate on the neutron source term in order to consider the different parameters between the IRSN Am-Be source and the one used to establish the neutron emission spectrum recommended by the ISO standard. The variation of the parameters of the source did not explain the remaining discrepancies. A good agreement with the experimental results was observed when the theoretical neutron energy distribution from Geiger and Van der Zwan was introduced in the study as new source term. These investigations showed that the ISO recommended Am-Be distribution might not be well suited to represent the neutron energy distribution of all Am-Be sources, and that the manufacturing of the sources might play a major role in the neutron fluence energy distribution.

AMANDE: a new facility for monoenergetic neutron fields production between 2 keV and 20 MeV.

The variation of the response of the instruments with the neutron energy has to be determined in well-characterized monoenergetic neutron fields. The AMANDE facility will deliver such neutron fields between 2 keV and 20 MeV in an experimental hall designed with metallic walls for neutron scattering minimisation. The neutrons will be produced by nuclear interaction of accelerated protons or deuterons on thin targets of selected materials. The measuring devices to be characterised will be accurately placed with a fully automated detector transport system. The energy of the neutron field will be validated by time-of-flight experiments and a large set of standard detectors and fluence monitors will be used to determine the neutron fluence references. The scattered neutron fluence and dose equivalent were calculated by the MCNP Monte Carlo code at several measuring points in order to determine their contribution to the neutron field.

Characterisation of the IRSN graphite moderated Americium-Beryllium neutron field.

The SIGMA facility was set up at IRSN to provide thermal neutrons for metrology and dosimetry purposes. SIGMA consists of six Am-Be radioactive sources located in a 1.5 x 1.5 x 1.5 m3 graphite moderator block. The neutron field at the calibration position, situated at 50 cm from the west surface of the assembly was characterised experimentally and by Monte Carlo calculations. The thermal neutron fluence was determined by the activation of gold foils; the neutron fluence energy distribution above 240 keV was measured with proton recoil spectrometers and the neutron fluence energy distribution from thermal energies to 20 MeV was measured with a Bonner spheres spectrometer. A Monte Carlo simulation of the SIGMA assembly was undertaken using the MCNP4C code, and the calculated neutron fluence energy distribution was compared with the measurements. As a whole, the experimental data and the MCNP calculation are in a good agreement.

Characterisation of the IRSN CANEL/T400 facility producing realistic neutron fields for calibration and test purposes.

The new CANEL/T400 facility has been set-up at the Institute for Radiological Protection and Nuclear Safety (IRSN) to produce a realistic neutron field. The accurate characterisation of this neutron field is mandatory since this facility will be used as a reference neutron source. For this reason an international measuring campaign, involving four laboratories with extensive expertise in neutron metrology and spectrometry, was organised through a concerted EUROMET project. Measurements were performed with Bonner sphere (BS) systems to determine the energy distribution of the emitted neutrons over the whole energy range (from thermal energy up to a few MeV). Additional measurements were performed with proton recoil detectors to provide detailed information in the energy region above 90 keV. The results obtained by the four laboratories are in agreement with each other and are compared with a calculation performed with the MCNP4C Monte-Carlo code. As a conclusion of this exercise, a reliable characterisation of the CANEL/T400 neutron field is obtained.

Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety.

A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine "D" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene alpha to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60e which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.

Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety.

A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

Aggressiveness and Competitive Fitness of Phytophthora infestans Isolates Collected from Potato and Tomato in France.

ABSTRACT To test the hypothesis that host-related differences in the genotypic composition of populations of the late blight pathogen Phytophthora infestans can be explained by differential pathogenicity, the aggressiveness of isolates of the pathogen collected in France from potato and tomato was measured on detached leaflets of potato (cv. Bintje) and tomato (cv. Marmande). A preliminary trial with four isolates (two each from potato and tomato) showed that lesion appearance and development were similar for each isolate in detached leaflets and in whole plant tests in growth cabinets. Isolates collected from tomato were more pathogenic to tomato than isolates collected from potato. This was particularly the case for isolates belonging to the A2 mating type. Isolates originating from potato had a higher infection efficiency and a higher sporulation capacity on this host, but they induced lesions that generally spread more slowly than those caused by isolates from tomato. Extensive variation for components of aggressiveness on potato, and to a lesser extent on tomato, was observed in collections of isolates from each of the two hosts. Competition experiments between one potato isolate and one tomato isolate in field plots of the susceptible potato cv. Bintje clearly demonstrated the higher competitive fitness of the potato isolate on its host of origin. Therefore, differential pathogenicity to potato and tomato certainly contributes to the differentiation between P. infestans populations present on potato and tomato in France; however, additional factors, possibly related to survival ability or random genetic drift, are probably also involved and may explain the persistence of weakly pathogenic isolates in these populations.

Selective and potent monoamine oxidase type B inhibitors: 2-substituted 5-aryltetrazole derivatives.

Twenty new 2-(cyanoalkyl)tetrazoles (15 and 16) and twenty new 2-(hydroxyalkyl)tetrazoles (17 and 18) were synthesized and investigated in vitro for their abilities to inhibit selectively rat brain monoamine oxidase (MAO) B over MAO A. Most of them were MAO B inhibitors and those bearing a substituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 microM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37,000 for 16a. The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests. The 5-[4-(phenylmethoxy)phenyl]-2-(2-cyanoethyl)tetrazole (16a) its derivative 16h and the 5-[4-(phenylmethoxy)phenyl]-2-(2-hydroxyethyl)tetrazole (18a) and its derivative 18h were found to be potent, in vitro selective, and competitive MAO B inhibitors. Tetrazole 16a can be considered one of the most active and selective competitive MAO B inhibitors known up to now. This compound was selected for ex vivo experiments and was shown to be a strong and reversible MAO B inhibitor with a short duration of action after oral administration at 5 mg/kg. The structure-activity approach gives rise to the great importance of lipophilicity over electronic effects of the compounds in these series.

[The Sauvé-Kapandji operation. Analysis and results of 69 cases]. / L'intervention de Sauvé-Kapandji. Analyse et résultats de 69 cas.

The authors present the results of 69 cases operated between 1983 and 1989. The indications were dominated by two aetiologies: degenerative lesions of the inferior radio-ulnar joint in rheumatoid arthritis: 58% of cases, and traumatic sequelae, predominantly secondary to fractures of the distal radius: 34% of cases. The authors stress the effects of distant lesions: skeletal lesions of the two bones of the forearm or the superior radio-ulnar joint. A third group of rarer indications consisted of painful dislocations of the inferior radio-ulnar joint in Madelung's disease (indication only applied to adults). There were two types of complications: complications due to excessively long or intra-articular screws, which were treated by removal of the screws and, more severe, ossifications of the zone of diaphyseal resection (5 cases) which interfered with the functional result in terms of mobility. Three cases required extensive diaphyseal resection. The results are analysed for each aetiological group in terms of pain, mobility prehensile strength after more than one year of follow-up. Good results were obtained in 80% of cases of post-traumatic lesions (16 cases). The insufficient results were related to associated lesions of the elbow or the 2 bones of the forearm. A good result was obtained in 3 out of 4 cases of Madelung's disease and one case, operated elsewhere and revised by pseudoarthrodesis, obtained a moderate result. Lastly, in rheumatoid arthritis, the results in terms of pain, mobility and prehensile strength were good, apart from 2 failures due to progression of rheumatoid disease (cases unsuitable for this treatment). Radiographic analysis according to Youm and Mac Murtry's criteria showed minimal regression in the carpoulnar translation index (pre-op: 0.28; post-op: 0.22). Overall, the Sauvé-Kapandji operation provided good quality clinical results when the indications and technique were rigorously applied.