Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein

Natural killer (NK) cells are at the crossroad between innate and adaptive immunity and play a major role in cancer immunosurveillance. NK cell stimulation depends on a balance between inhibitory and activating receptors, such as the stimulatory lectin-like receptor NKG2D. To redirect NK cells against tumor cells, we designed bifunctional proteins able to specifically bind tumor cells and to induce their lysis by NK cells, after NKG2D engagement. To this aim, we used the 'knob into hole' heterodimerization strategy, in which 'knob' and 'hole' variants were generated by directed mutagenesis within the CH3 domain of human IgG1 Fc fragments fused to an anti-CEA or anti-HER2 scFv or to the H60 murine ligand of NKG2D, respectively. We demonstrated the capacity of the bifunctional proteins produced to specifically coat tumor cells surface with H60 ligand. Most importantly, we demonstrated that these bifunctional proteins were able to induce an NKG2D-dependent and antibody-specific tumor cell lysis by murine NK cells. Overall, the results show the possibility to redirect NK cytotoxicity to tumor cells by a new format of recombinant bispecific antibody, opening the way of potential NK cell-based cancer immunotherapies by specific activation of the NKG2D receptor at the tumor site.     

The Effect of Ti on the Early Stages of Oxidation of an Alumina-Forming NiCrAl Alloy

Oxidation of Metals - Model γ-NiCrAl alloys with and without titanium were oxidized for short times up to 32 h at 1000 °C and subsequently characterized by scanning...     

Rhodium complexes containing chiral P-donor ligands as catalysts for asymmetric hydrogenation in non conventional media

Abstract  

Rhodium-catalysed asymmetric hydrogenation using P-donor ligands, such as new fluorinated (R)-BINOL and azadioxaphosphabicyclo[3.3.0]octane derivatives was carried out in different reaction media such as organic solvent (CH₂Cl₂), ionic liquid ([BMI][PF₆]), supercritical carbon dioxide (scCO₂) and [BMI][PF₆]/scCO₂ mixture. The best enantioselectivities were obtained in neat [BMI][PF₆], allowing a recycling up to ten times without activity loss. However, the enantioselectivity was lost due to ligand leaching. The ionic liquid phase containing rhodium molecular species was supported on functionalized multi-walled carbon nanotubes in order to improve the recycling, but unfortunately the asymmetric induction was lost upon catalyst immobilization.     

Moving closer to the fabric of organizing visions: The case of a trade show

This paper examines the fabric of authorized discourses about Information Technology (IT), i.e. of “organizing visions” (OVs), through the investigation of the discourses, practices, and sociomaterial contexts that make up their micro-social underpinnings. The case of a trade show allows us to explore the production of everyday discourses and practices about IT by gathering many of the parties involved in the fabric of organizing visions. Through a combination of direct observations, interviews, pictures, documents and a survey, we identify and analyze a number of micro-social practices related to the fabric of IT discourses. The trade show we studied was not a context in which new IT buzzwords and concepts emerged, but, rather, it was a setting where existing discourses about IT were repeated, refreshed, and materialized. Our three main findings reveal intriguing relationships between practices, discourses, and sociomaterial contexts: (1) practices and artifacts contribute to enclose the production of discourses; (2) practices and discourses aim at refining and updating an existing discourse about IT; and (3) many actors in the trade shows engage in discourses and practices that materialize the IT artifact. This research adds to the conceptualization of the dynamics of OVs through a better understanding of how they are affected by the relationships between the discourses and practices of multiple actors and by the sociomaterial context in which they take place. It draws several strategic implications concerning the dynamics of OVs at the industry level, how actors influence the fabric of OVs, as well as the roles and combination of artifacts, discourses and practices to build OVs.     

Functionalisation of porous hydroxyapatite for bone substitutes

Calcium phosphate ceramics such as hydroxyapatite (HA) have been widely used to repair and reconstruct damaged parts of the human skeleton. This material is currently available as injectable cements, granules or macroporous blocks. The most common materials are granules because of their ability to be implanted in the human body. In this study, a new manufacturing procedure to fabricate either dense or microporous or macroporous hydroxyapatite spherical granules based on a lost wax method and leading to beads with a fully controlled porosity was developed. The as-obtained HA granules porous structure was impregnated by gentamicin and lambda phage and the antibiotic and phage releasing kinetics were studied as a function of time and porosity.     

Uncertainty analysis of the specific absorption rate induced in a phantom using a stochastic spectral collocation method

Uncertainty analysis of human exposure to radio waves is studied with a spectral approach of stochastic collocation methods. This approach allows determining in an efficient way the statistical moments of the output variable, the specific absorption rate, with respect to uncertain input parameters. Polynomial chaos expansions are used for the random output, and the spectral coefficients are determined by projection or regression. These techniques are used with an electromagnetic solver based on a finite difference time domain scheme. The convergence of the statistical moments is analyzed for two case studies. Global sensitivity is also analyzed for the uncertain position of a cellular phone in the close vicinity of a human head model.     

Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson’s disease.

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD) can produce emotional disorders that have been linked to disturbance of the STN’s limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the disease’s natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the disease’s natural progression nor to modifications in DRT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

RTIL-system: a Real-Time Interactive L-system for 3D interactions with virtual plants

The L-system is a rewriting process based on formal grammar and is used to generate 3D, dynamic structures such as virtual plants and fractal graphics. In previous works, we highlighted that existing L-system software applications and programs are limited, either in terms of human interaction or in terms of modelling. In particular, few of them allow the user to interact with virtual plants during their growth. Our own L-system engine was developed and called the real-time interactive L-system (RTIL-system). The RTIL-system covers most important L-system extensions such as parametric and context-sensitive features. Furthermore, real-time interactions with the user and the environment with respect to L-system formalism are available. This paper presents an RTIL-system focusing on human interaction, the Partial Interactive Derivation (PID) concept and further progress by the extension of PID to context-sensitive rules. To illustrate the potential of the RTIL-system, the effect of various interactive tasks such as sub-axis additions, pruning and bending on the subsequent dynamic development of virtual plants is described.     

The WEST programme: Minimizing technology and operational risks of a full actively cooled tungsten divertor on ITER

The WEST programme consists in transforming the Tore Supra tokamak into an X point divertor device, while taking advantage of its long discharge capability. This is obtained by inserting in vessel coils to create the X point while adapting the in-vessel elements to this new geometry. This will allow the full tungsten divertor technology to be used on ITER to be tested in anticipation of its use on ITER under relevant heat loading conditions and pulse duration. The early manufacturing of a significant industrial series of ITER-similar W plasma-facing units will contribute to the ITER divertor manufacturing risk mitigation and to that associated with early W divertor plasma operation on ITER.