Probing the potential of CdZnTe for high-energy high-flux 2D X-ray detection using the XIDer incremental digital integrating readout

The latest synchrotron radiation sources have the capability to produce X-ray beams with a photon flux that can be up to three orders of magnitude higher than previous-generation facilities, and that are not manageable by the currently available 2D photon-counting pixel detectors. The construction of new detectors that exceed the limitations of existing devices is a critical strategic need. Developing such detectors is a challenge in terms of readout electronics as well as sensor material, particularly in the case of devices intended to operate at X-ray energies above 30 keV. The approach adopted at the ESRF to deal with this major difficulty is twofold: the use of a novel semiconductor material with improved electrical properties, high-flux CdZnTe, and the investigation of a specific readout scheme, incremental digital integration, via the XIDer project in collaboration with the University of Heidelberg. Incremental digital integration is a method intended to be less sensitive to variations of the dark current than the conventional charge integration readout. However, this readout scheme requires that the leakage current from the sensor material stays below a certain threshold to reduce the leakage contributions. This paper introduces the ESRF strategy and few examples of the methods employed to evaluate the performance and leakage current behavior of high-flux CdZnTe pixelated sensors. These examples illustrate the first results obtained with this material under moderate to very high X-ray irradiation fluxes of up to 1012 photons/mm2/s

Classification des sauts à partir de l'étude des actions motrices déclenchées pendant la phase aérienne

Michels Carole, Ruat Marie-Hélène. Classification des sauts à partir de l'étude des actions motrices déclenchées pendant la phase aérienne. In: Les Cahiers de l'INSEP, n°18-19, 1997. G.R.S., le sens d’une évolution. pp. 123-129

Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development

International audienceWe have determined the pharmacological characteristics of the rat 5-ht6 receptor stably expressed in CHO cells. Moreover, using RT-PCR experiments the in vivo expression of the gene encoding this receptor was studied in rat at various embryonic days (ED) starting from ED10 to birth (PN0) and at post-natal days (PN) up to PN36. The pharmacological analysis of the [3H]5-HT binding in stably transfected CHO cells expressing rat 5-ht6 receptors revealed the presence of a single class of high affinity saturable binding sites for 5-HT corresponding to an affinity constant: Kd=27.2+/-3.4 nM. This receptor also exhibited a high affinity for a number of typical and atypical antipsychotics, tricyclic antidepressant drugs and ergot alkaloïds. In stably transfected CHO cells, serotonin elicited a potent stimulation of adenylyl cyclase activity which was blocked by antipsychotic and antidepressant drugs. These results confirm the hypothesis that 5-ht6 receptors may correspond to an important target for atypical antipsychotics and reveal an original pharmacological profile for this receptor. The study of the ontogeny of the 5-ht6 mRNA in rat developing brain showed that 5-ht6 mRNA were first detectable with a high level on ED12, slighly decreased up to ED17 and then remained stable at high level until the adult age. The ontogenetic pattern of 5-ht6 mRNA expression appeared to correlate with the occurence of the first cell bodies of serotonergic neurons; the early expression of 5-ht6 mRNA and the fact that this receptor is positively coupled to the production of cAMP may suggest a role for 5-ht6 receptor in the early growth process involving the serotonergic system

An electric lobe suppressor for a yeast choline transport mutation belongs to a new family of transporter-like proteins

Choline is an important metabolite in all cells due to the major contribution of phosphatidylcholine to the production of membranes, but it takes on an added role in cholinergic neurons where it participates in the synthesis of the neurotransmitter acetylcholine. We have cloned a suppressor for a yeast choline transport mutation from a Torpedo electric lobe yeast expression library by functional complementation. The full-length clone encodes a protein with 10 putative transmembrane domains, two of which contain transporter-like motifs, and whose expression increased high-affinity choline uptake in mutant yeast. The gene was called CTL1 for its choline transporter-like properties. The homologous rat gene, rCTL1, was isolated and found to be highly expressed as a 3.5-kb transcript in the spinal cord and brain and as a 5-kb transcript in the colon. In situ hybridization showed strong expression of rCTL1 in motor neurons and oligodendrocytes and to a lesser extent in various neuronal populations throughout the rat brain. High levels of rCTL1 were also identified in the mucosal cell layer of the colon. Although the sequence of the CTL1 gene shows clear homology with a single gene in Caenorhabditis elegans, several homologous genes are found in mammals (CTL2–4). These results establish a new family of genes for transporter-like proteins in eukaryotes and suggest that one of its members, CTL1, is involved in supplying choline to certain cell types, including a specific subset of cholinergic neurons

Calcium sensing receptor-dependent and -independent activation of osteoblast replication and survival by strontium ranelate.

International audienceAbstract Age-related osteopenia is characterized by a negative balance between bone resorption and formation. The anti-osteoporotic drug strontium ranelate was found to reduce bone resorption and to promote bone formation. Here, we investigated the implication of the calcium sensing receptor (CaSR) in the response to strontium ranelate using osteoblasts from CaSR knockout [CaSR(-/-)] and wild-type [CaSR(+/+)] mice. We showed that calcium and strontium ranelate increased cell replication in [CaSR(-/-)] and [CaSR(+/+)] osteoblasts. Strontium ranelate rapidly increased ERK1/2 phosphorylation in [CaSR(+/+)] but not [CaSR(-/-)] osteoblasts, indicating that strontium ranelate can act independently of the CaSR/ERK1/2 cascade to promote osteoblast replication. We also showed that strontium ranelate prevented cell apoptosis induced by serum deprivation or the pro-inflammatory cytokines IL1beta and TNFalpha in [CaSR(-/-)] and [CaSR(+/+)] osteoblasts, indicating that CaSR is not the only receptor involved in the protective effect of strontium ranelate on osteoblast apoptosis. Strontium ranelate activated the Akt pro-survival pathway in [CaSR(-/-)] and [CaSR(+/+)] osteoblasts and pharmacological inhibition of Akt abrogated the anti-apoptotic effect of strontium ranelate. Furthermore, both the proliferative and anti-apoptotic effects of strontium ranelate in [CaSR(-/-)] and [CaSR(+/+)] osteoblasts were abrogated by selective inhibition of COX-2. The results provide genetic and biochemical evidence that the effects of strontium ranelate on osteoblast replication and survival involve ERK1/2 and Akt signalling and PGE2 production, independently of CaSR expression. The finding that CaSR-dependent and -independent pathways mediate the beneficial effects of strontium ranelate on osteoblasts provides novel insight into the mechanism of action of this anti-osteoporotic agent on osteoblastogenesis

Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens.

Hedgehog (Hh) proteins are considered diffusible morphogens that can be membrane anchored, playing an essential role during development. Here we show that Hh morphogens are associated with microvesicles (MVs) shed from the plasma membrane of apoptotic/stimulated T cells. Hh+ MVs induced differentiation of human K562 pluripotent erythroleukemic cells toward megakaryocytic lineage, as testified to by the expression of alpha(IIb)beta3 integrin and CD42b and changes in the cell cycle. Blocking Hh pathway with either cyclopamine, neutralizing antibodies, or inhibitors of the protein kinase A pathway resulted in the inhibition of these effects. Activation of Hh signaling by SAG, a synthetic agonist, mimicked effects of Hh+ MVs on K562 cells. Human Hh+ MVs, circulating in vivo or derived from apoptotic/stimulated lymphocytes from healthy and diabetic individuals, elicited K562 cell differentiation, also inhibited by cyclopamine. In addition, Hh+ MV-treated primary human CD34+ cells presented an increase of CD41+ CD42- and CD41+ CD42+ megakaryocytic populations with an increase of corresponding polyploidy, both being reduced by blockers of the Hh pathway. Because virtually all cell types undergo plasma membrane remodeling when stimulated, derived MVs can therefore be considered true vectors in the transfer of morphogen-borne biologic information to remote responsive cells, and thereby contribute to the maintenance of homeostasis

Re-visiting Acceptance Criteria Calculations for Monolithic Waste Landfill with Reactive Transport Modeling: Application to Total Dissolved Salts (TDS)

International audienceStabilization and solidification of hazardous waste before storage in an engineered landfill has been used at an industrial scale for more than 10 years in several European countries. The European decision 2003/33 specifies a waste acceptance criteria (WAC) for granular waste but there is still no common rules for monolithic waste. One alternative is to define WAC from reverse environmental impact calculations based on compliance of the storage site release with drinkable water criteria at the local water table. However - and contrarily to reactive transport modeling - most published studies do not take into account the physical-chemical processes taking place in the waste and the liners, as well as their long-term evolution with time. Such a simplification can lead to very low acceptance criteria, especially for salts. Chloride and sulfates salts are the major species in air pollution control (APC) residues, which represent the majority of treated waste in France and the Netherlands. A model of the stabilized waste material was set on total element content, mineralogy and physical parameters (diffusion, porosity, density). In a first stage, the model was validated on dynamic leaching tests by modeling element release and mineralogical evolution of leached monoliths. The model was also used to simulate a French compliance leaching test. Modeling is in good agreement with experiment in both cases. These results show that limit values defined by European decision on chloride and total dissolved solid (TDS) are not equivalent. For the studied sample, chloride release is very close to the European limit (25 000 mg/kg) while TDS release is well below the European limit (10%). In a second stage, the model was extended to assess the impact of landfilling stabilized waste on groundwater resources. Modeling hypotheses were similar to the scenario of the European Technical Application Committee (TAC) prescribed for defining acceptance criteria on granular waste, i.e. assuming a complete failure of the geomembranes, a defective drainage system and no effect of the cover slope. The evolution of the waste chemistry and the migration of the pollutant plume were modeled for undamaged monoliths in agreement with recent studies based on the examination of aged site samples. Chloride content in the water table at the point of compliance infinite source term, which is physically impossible as the waste cannot release more chloride than it contains. Chlorides were then assumed to be present in very mobile phases or partly trapped as less soluble Friedel's salts (a chloroaluminate cement phase). Chloride concentrations at POC are below the drinkable water thresholds in both cases, and systematically lower when chlorides are trapped as Friedel's salts. This reactive transport modeling study shows that landfill of monoliths as presently managed should have a negligible impact on the water table. This coupled model is also important for bridging the gap between compliance tests and field conditions. Field modeling is consistent with WAC based on a short monolithic leaching test and the existing TDS limit. Therefore, it is likely that no stricter WAC will need to be defined on salt release for monolithic waste