Producing 'Human Elements Based Medical Technologies' in Biotech Companies: Some Ethical and Organisational Ingredients for Innovative Cooking

This article is based on the findings of an EU-funded qualitative research project, entitled 'From GMP to GBP: Fostering good bioethics practices [GBP] among the European biotechnology industry', which seeks to improve the understanding of bioethical issues through the observation of the daily practices in European biotechnology companies and proposes a methodology approaching ethical issues. The comparative study was carried out in biotech companies in France, Italy, Sweden, Hungary and Belgium which develop a wide range of new technologies, all of them involving human materials or where human subjects participate (in clinical trials). Based on our findings in these local settings, we suggest that the notion of bioethics and the way its production is theorised need to be re-conceptualised. We argue that material practices and moral statements are intermingled in inextricable ways that render the formation of bioethical concerns fully dependent on the organisational landscape in which it is embedded. More precisely, the here presented co-production model of moral statements and organisational practices presents a set of common factors that influence how bioethical discourses are shaped, despite the heterogeneity of their epistemic cultures. For example, the procedural design of cell-based-products, the modes of collecting and storing biological specimen, the relationship between patients and companies and technological transfers to emerging countries are defining components that contribute to the shaping process of bioethical concerns. Thus, the path dependency of bioethical concerns relies on an already existing, specific infrastructure and existing relationships within and outside a company rather than on external judgement subsequently applied to its objects, or a collection of processes of reasoning coming from external institutions

Mass spectrometry-based ligand binding assays on adenosine A(1) and A(2A) receptors

Conventional methods to measure ligand-receptor binding parameters typically require radiolabeled ligands as probes. Despite the robustness of radioligand binding assays, they carry inherent disadvantages in terms of safety precautions, expensive synthesis, special lab requirements, and waste disposal. Mass spectrometry (MS) is a method that can selectively detect ligands without the need of a label. The sensitivity of MS equipment increases progressively, and currently, it is possible to detect low ligand quantities that are usually found in ligand binding assays. We developed a label-free MS ligand binding (MS binding) assay on the adenosine A(1) and A(2A) receptors (A(1)AR and A(2A)AR), which are well-characterized members of the class A G protein-coupled receptor (GPCR) family. Radioligand binding assays for both receptors are well established, and ample data is available to compare and evaluate the performance of an MS binding assay. 1,3-Dipropyl-8-cyclopentyl-xanthine (DPCPX) and 4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol (ZM-241,385) are high-affinity ligands selective for the A(1)AR and A(2A)AR, respectively. To proof the feasibility of MS binding on the A(1)AR and A(2A)AR, we first developed an MS detection method for unlabeled DPCPX and ZM-241,385. To serve as internal standards, both compounds were also deuterium-labeled. Subsequently, we investigated whether the two unlabeled compounds could substitute for their radiolabeled counterparts as marker ligands in binding experiments, including saturation, displacement, dissociation, and competition association assays. Furthermore, we investigated the accuracy of these assays if the use of internal standards was excluded. The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11302-015-9477-0) contains supplementary material, which is available to authorized users

Incertitudes de mesure: Applications concrètes pour les étalonnages

Les besoins de la société moderne, basée sur la technologie, nécessitent toutes sortes de mesures. Tout résultat de mesure n\u27est en général qu\u27une estimation de la valeur de la "vraie" valeur reste inconnue. L\u27estimation des incertitudes de mesure dans l\u27industrie ou dans les laboratoires est loin d\u27être maîtrisée de façon complète. Ce premier tome présente concrètement les procédures adaptées pour la thermométrie, le pesage et la mesure dimensionnelle. Les auteurs ont souhaité être pragmatiques et utiles dans leurs approches. Ainsi, chaque application peut servir de guide pour estimer l\u27incertitude de mesure d\u27un capteur thermométrique, d\u27un poids, d\u27une balance ou d\u27un interféromètre laser. Les parties sont suffisamment détaillées et justifiées de façon à ce que tous les lecteurs (enseignants, chercheurs, ingénieurs, techniciens, étudiants...) puissent s\u27en inspirer pour déterminer une incertitude de mesure quel que soit le domaine de mesure. Le deuxième tome complète ce premier en montrant qu\u27il est possible également d\u27estimer une incertitude de mesure même pour des mesures "difficiles" pratiquées par exemple dans les analyses médicales et agroalimentaires, et dans les essais électromagnétiques ou acoustiques, etc

Deep carbon cycle constrained by carbonate solubility.

Earth's deep carbon cycle affects atmospheric CO2, climate, and habitability. Owing to the extreme solubility of CaCO3, aqueous fluids released from the subducting slab could extract all carbon from the slab. However, recycling efficiency is estimated at only around 40%. Data from carbonate inclusions, petrology, and Mg isotope systematics indicate Ca2+ in carbonates is replaced by Mg2+ and other cations during subduction. Here we determined the solubility of dolomite [CaMg(CO3)2] and rhodochrosite (MnCO3), and put an upper limit on that of magnesite (MgCO3) under subduction zone conditions. Solubility decreases at least two orders of magnitude as carbonates become Mg-rich. This decreased solubility, coupled with heterogeneity of carbon and water subduction, may explain discrepancies in carbon recycling estimates. Over a range of slab settings, we find aqueous dissolution responsible for mobilizing 10 to 92% of slab carbon. Globally, aqueous fluids mobilise [Formula: see text]% ([Formula: see text] Mt/yr) of subducted carbon from subducting slabs

Signals for a Transition from Surface to Bulk Emission in Thermal Multifragmentation

Excitation-energy-gated two-fragment correlation functions have been studied between 2 to 9A MeV of excitation energy for equilibrium-like sources formed in $\pi^-$ and p + $^{197}$Au reactions at beam momenta of 8,9.2 and 10.2 GeV/c. Comparison of the data to an N-body Coulomb-trajectory code shows a decrease of one order of magnitude in the fragment emission time in the excitation energy interval 2-5A MeV, followed by a nearly constant breakup time at higher excitation energy. The observed decrease in emission time is shown to be strongly correlated with the increase of the fragment emission probability, and the onset of thermally-induced radial expansion. This result is interpreted as evidence consistent with a transition from surface-dominated to bulk emission expected for spinodal decomposition.Comment: 11 pages including 3 postscript figures (1 color

Response of CsI(Tl) scintillators over a large range in energy and atomic number of ions (Part I): recombination and delta -- electrons

A simple formalism describing the light response of CsI(Tl) to heavy ions, which quantifies the luminescence and the quenching in terms of the competition between radiative transitions following the carrier trapping at the Tl activator sites and the electron-hole recombination, is proposed. The effect of the delta rays on the scintillation efficiency is for the first time quantitatively included in a fully consistent way. The light output expression depends on four parameters determined by a procedure of global fit to experimental data.Comment: 28 pages, 6 figures, submitted to Nucl. Inst. Meth.

Spallation Neutron Production by 0.8, 1.2 and 1.6 GeV Protons on various Targets

Spallation neutron production in proton induced reactions on Al, Fe, Zr, W, Pb and Th targets at 1.2 GeV and on Fe and Pb at 0.8, and 1.6 GeV measured at the SATURNE accelerator in Saclay is reported. The experimental double-differential cross-sections are compared with calculations performed with different intra-nuclear cascade models implemented in high energy transport codes. The broad angular coverage also allowed the determination of average neutron multiplicities above 2 MeV. Deficiencies in some of the models commonly used for applications are pointed out.Comment: 20 pages, 32 figures, revised version, accepted fpr publication in Phys. Rev.

Measurements of sideward flow around the balance energy

Sideward flow values have been determined with the INDRA multidetector for Ar+Ni, Ni+Ni and Xe+Sn systems studied at GANIL in the 30 to 100 A.MeV incident energy range. The balance energies found for Ar+Ni and Ni+Ni systems are in agreement with previous experimental results and theoretical calculations. Negative sideward flow values have been measured. The possible origins of such negative values are discussed. They could result from a more important contribution of evaporated particles with respect to the contribution of promptly emitted particles at mid-rapidity. But effects induced by the methods used to reconstruct the reaction plane cannot be totally excluded. Complete tests of these methods are presented and the origins of the ``auto-correlation'' effect have been traced back. For heavy fragments, the observed negative flow values seem to be mainly due to the reaction plane reconstruction methods. For light charged particles, these negative values could result from the dynamics of the collisions and from the reaction plane reconstruction methods as well. These effects have to be taken into account when comparisons with theoretical calculations are done.Comment: 27 pages, 15 figure

Effect of the intermediate velocity emissions on the quasi-projectile properties for the Ar+Ni system at 95 A.MeV

The quasi-projectile (QP) properties are investigated in the Ar+Ni collisions at 95 A.MeV taking into account the intermediate velocity emission. Indeed, in this reaction, between 52 and 95 A.MeV bombarding energies, the number of particles emitted in the intermediate velocity region is related to the overlap volume between projectile and target. Mean transverse energies of these particles are found particularly high. In this context, the mass of the QP decreases linearly with the impact parameter from peripheral to central collisions whereas its excitation energy increases up to 8 A.MeV. These results are compared to previous analyses assuming a pure binary scenario