Optimisation of a Nacelle Electro-Thermal Ice Protection System for Icing Wind Tunnel Testing

Abstract Aircraft are equipped with ice protection systems (IPS), to avoid, delay or remove ice accretion. Two widely used technologies are the thermo-pneumatic IPS and the electro-thermal IPS (ETIPS). Thermo-pneumatic IPS requires air extraction from the engine negatively affecting its performances. Moreover, in the context of green aviation, aircraft manufacturers are moving towards hybrid or fully electric aircraft requiring all electric on-board systems. In this work, an ETIPS has been designed and optimised to replace the nacelle pneumatic-thermal system. The aim is to minimise the power consumption while assuring limited or null ice formation and that the surface temperature remains between acceptable bounds to avoid material degradation. The design parameters were the length and heat flux of each heater. Runback ice formations and surface temperature were assessed by means of the in-house developed PoliMIce framework. The optimisation was performed using a genetic algorithm, and the constraints were handled through a linear penalty method. The optimal configuration required 33% less power with respect to the previously installed thermo-pneumatic IPS. Furthermore, engine performance is not affected in the case of the ETIPS. This energy saving resulted in an estimated reduction of specific fuel consumption of 3%, when operating the IPS in anti-icing mode

Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating Molecule

Human natural killer (NK) cells express a series of activating receptors and coreceptors that are involved in recognition and killing of target cells. In this study, in an attempt to identify the cellular ligands for such triggering surface molecules, mice were immunized with NK-susceptible target cells. On the basis of a functional screening, four mAbs were selected that induced a partial down-regulation of the NK-mediated cytotoxicity against the immunizing target cells. As revealed by biochemical analysis, three of such mAbs recognized molecules of ∼70 kD. The other mAb reacted with two distinct molecules of ∼65 and 60 kD, respectively. Protein purification followed by tryptic digestion and mass spectra analysis, allowed the identification of the 70 kD and the 65/60 kD molecules as PVR (CD155) and Nectin-2 δ/α (CD112), respectively. PVR-Fc and Nectin-2-Fc soluble hybrid molecules brightly stained COS-7 cells transfected with the DNAM-1 (CD226) construct, thus providing direct evidence that both PVR and Nectin-2 represent specific ligands for the DNAM-1 triggering receptor. Finally, the surface expression of PVR or Nectin-2 in cell transfectants resulted in DNAM-1–dependent enhancement of NK-mediated lysis of these target cells. This lysis was inhibited or even virtually abrogated upon mAb-mediated masking of DNAM-1 (on NK cells) or PVR or Nectin-2 ligands (on cell transfectants)

The ground deformation of the south-eastern flank of Mount Etna monitored by GNSS and SAR interferometry from 2016 to 2019

SUMMARY The south-eastern sector of the Mount Etna, Italy, is characterized by numerous active faults, in particular the Belpasso–Ognina lineament, the Tremestieri–San Gregorio–Acitrezza fault, the Trecastagni fault and the Fiandaca–Nizzeti fault including the Timpe Fault System. Their activity is the result of both volcanism and tectonics. Here, we analyse the ground deformation occurred from 2016 to 2019 across those active faults by using the GNSS data acquired at 22 permanent stations and 35 campaign points observed by the Etna Observatory (INGV) and by the University of Catania. We also use the time-series of line of sight displacement of permanent scatterers SENTINEL-1 A-DInSAR obtained by using the P-SBAS tool of the ESA GEP-TEP (Geohazards Thematic Exploitation Platform) service. We discriminate the contributions of the regional tectonic strain, the inflations, the deflations of the volcano and the gravitational sliding in order to analyse the deformation along the faults of the south-eastern flank of Etna. The shallow and destructive Mw = 4.9 earthquake of 2018 December 26 occurred within the studied area two days after a dyke intrusion, that propagated beneath the centre of the volcano accompanied by a short eruption. Both GNSS and InSAR time-series document well those events and allow to investigate the post-seismic sliding across the faults of south-eastern flank. We analyse the slow slip events (SSE) that are observed in the GNSS and InSAR time-series in the vicinity of the Acitrezza fault. We quantify and discuss the tectonic origin of the Belpasso–Ognina lineament that we interpreted as a tear fault

Tumor Vasculature Targeted TNF\u3b1 Therapy: Reversion of Microenvironment Anergy and Enhancement of the Anti-tumor Efficiency.

Tumor cells and tumor-associated stromal cells such as immune, endothelial and mesenchimal cells create a tumor microenvironment (TME) which allows tumor cell promotion, growth and dissemination while dampening the anti-tumor immune response. Efficient anti-tumor interventions have to keep into consideration the complexity of the TME and take advantage of immunotherapy and chemotherapy combined approaches. Thus, the aim of tumor therapy is to directly hit tumor cells and reverse endothelial and immune cell anergy. Selective targeting of tumor vasculature using TNF\u3b1-associated peptides or antibody fragments in association with chemotherapeutic agents, has been shown to exert a potent stimulatory effect on endothelial cells as well as on innate and adaptive immune responses. These drug combinations reducing the dose of single agents employed have led to minimize the associated side effects. In this review, we will analyze different TNF\u3b1-mediated tumor vesseltargeted therapies in both humans and tumor mouse models, with emphasis on the role played by the cross-talk between natural killer and dendritic cells and on the ability of TNF\u3b1 to trigger tumor vessel activation and normalization. The improvement of the TNF\u3b1-based therapy with anti-angiogenic immunomodulatory drugs that may convert the TME from immunosuppressive to immunostimulant, will be discussed as well

Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel

We report the construction and the use of a phage display human antibody library (>3 x 10(8) clones) based on principles of protein design. A large repertoire of functional antibodies with similar properties was produced by appending short variable complementarity-determining region 3 (CDR3) onto the two antibody germ line segments most frequently found in human antibodies. With this strategy we concentrated sequence diversity in regions of the antibody structure that are centrally located in the antigen binding site, while leaving residues in more peripheral positions available for further mutagenesis aimed at improving the affinity of the selected antibodies. In addition, the library was tested by selecting antibodies against six biologically relevant antigens. Using only 0.3 microg of antigen eluted from a two-dimensional gel spot, we isolated binders specific for the ED-B domain of fibronectin, a marker of angiogenesis. These antibodies recognize the native antigen with affinities in the 10(7)-10(8) M-1 range, and perform well in immunosorbent assays, in two-dimensional Western blotting and in immunohistochemistry. The affinity of one anti-ED-B antibody was improved by 27-fold by combinatorially mutating six strategically selected residues in the heavy chain variable domain. A further 28-fold affinity improvement could be achieved by mutating residues 32 and 50 of the light chain. The resulting antibody, L19, bound to the ED-B domain of fibronectin with very high affinity (Kd = 54 pM), as determined by real-time interaction analysis with surface plasmon resonance detection, band shift analysis, and by competition experiments with electrochemiluminescent detection

GNSS and InSAR study of the ground deformation of the eastern flank of Mount Etna from 2016 to 2019

International audienceThe geodynamic framework of Mount Etna volcano (Italy) is characterised by two superimposed tectonic domains: a compressional one, oriented N-S, and an extensional one, oriented approximately WNW-ESE. The combination of these two domains and the volcano activity, has generated a complex system of faults prevalently on the eastern flank of the volcano. The eastern flank is the most active area of the volcano in terms of deformation and seismicity. The velocities there are at least one order of magnitude greater than in the rest of the volcano flanks due to the eastward sliding of the eastern flank.The monitoring and analysis of the acceleration occurring on the eastern flank of Mount Etna is the keystone to understand the volcano-tectonic dynamics that, apart from the tectonic and magmatic processes, involves the instability of this flank in a densely inhabited area.In order to monitor the deformation, Istituto Nazionale Geofisica e Vulcanologia – Osservatorio Etneo (INGV-OE) and the GeoDynamic & GeoMatic Laboratory of the University of Catania integrate GNSS and InSAR products with twofold objective: to characterize the dynamics of the area and to analyse the deformation transients, this last in view of a possible use in the framework of an alert system.Here, we analyse the ground deformation that occurred between 2016 and 2019 across the faults of the south-eastern flank of Mount Etna. On the south-eastern flank the deformation is accommodated by several faults which have different kinematics and behaviours. We discriminate the deformation transient and the activity of the Belpasso-Ognina lineament, Tremestieri, Trecastagni, San Gregorio-Acitrezza, Linera, Nizzeti and Fiandaca faults. The latter generated the 26 December 2018 earthquake, two days after the eruption of 24 December, which induced a clear post seismic deformation, detected by GNSS and InSAR data. In particular, we discriminate the deformation occurred along the San Gregorio-Acitrezza fault, which is accommodated by the Nizzeti fault, and we analyse the post seismic deformation along the Linera fault. We analyse the Slow Slip Events (SSE) that are observed in the GNSS and InSAR time series in the vicinity of the Acitrezza fault and we quantify and discuss the tectonic origin of the Belpasso-Ognina lineament that we interpreted as a tear fault

Joint GNSS-InSAR analysis of ground deformation on the eastern flank of Mount Etna. 

International audience<p>Mount Etna is located on eastern Sicily on the border of the collision zone between the Eurasia and Nubia plate. The regional geodynamic framework is characterized by two superimposed regional tectonic domains: a compressional one oriented N-S and an extensional one oriented approximately WNW-ESE. These two domains, together with the volcano-tectonic one, generated a tectonic system which is unique in the world. It exhibits a complex system of faults prevalently on the eastern flank of the volcano, which is the most complicated in terms of interaction between the tectonic, volcano and gravitational processes. The eastern flank of Mount Etna is the most active area of the volcano in terms of deformation and seismicity, because the deformation rates are at least one order of magnitude greater than the surrounding area, due to the eastwards sliding of this flank.</p><p>The monitoring and analysis of the high deformation occurring on the eastern flank of Mount Etna is the keystone for understanding the volcano-tectonic dynamics that, apart from the tectonic and volcanic processes, it is paramount relevant because involves the instability of this flank in a densely inhabited area. In this context the Istituto Nazionale di Geofisica e Vulcanologia – Osservatorio Etneo (INGV-OE) created one of the most sophisticated and complete monitoring networks in the world in terms of number of multi-disciplinary station (seismic, geodetic, geochemistry). Since 2014, the GeoDynamic & GeoMatic Laboratory (GD&GM-LAB) of the University of Catania started to create many GNSS sub networks, belonging to the UNICT-Net, in order to determine the offsets occurring on the blocks of each fault of the eastern flank.</p><p>In order to have a complete analysis of deformation, INGV-OE and the GD&GM-LAB started to consider this area as an “open-air laboratory” where integrate GNSS and InSAR data with the twofold objective: to characterize the dynamic of this area for contributing to the volcanic hazard assessment and to identify precursor phenomena on shear structures analysing the relationship between kinematics, dynamics and volcano processes in the frame of the ATTEMPT INGV project.</p&gt

Both CD133(+) and CD133(-) medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity

Adoptive cellular immunotherapy has been proposed as an additional treatment of medulloblastoma, an intracranial tumor characterized by a particularly poor prognosis. However, little is known on the ability of the immune system to effectively attack this tumor. In this study, we show that activated human NK cells efficiently kill medulloblastoma cell lines in vitro. NK-mediated killing involved different activating receptors (including NKp46, NKp30, DNAM-1 and NKG2D) and correlated with the presence of their specific ligands on tumor cells. In contrast, the absence of major adhesion interactions, such as LFA-1/ICAM did not impair the NK-mediated cytotoxicity. Medulloblastoma expressed a number of tumor-associated molecules including CD146 and CD133, considered a marker for cancer stem cells. Remarkably, both CD133-positive and CD133-negative cell lines were susceptible to lysis. Tumor cells also expressed molecules that are currently used as diagnostic tools for neuroblastoma cell identification. In particular, B7 homolog 3 (B7-H3) was expressed by all the medulloblastoma cell lines analyzed, while the presence of GD(2) and NB84 was restricted to given cell lines and/or marked a defined tumor cell subset