Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes

Recent reports have demonstrated fusion of the TEL gene on 12p13 to the JAK2 gene on 9p24 in human leukemias. Three variants have been identified that fuse the TEL pointed (PNT) domain to (i) the JAK2 JH1-kinase domain, (ii) part of and (iii) all of the JH2 pseudokinase domain. We report that all of the human TEL/JAK2 variants, and a human/mouse chimeric hTEL/mJAK2(JH1) fusion gene, transform the interleukin-3 (IL-3)-dependent murine hematopoietic cell line Ba/F3 to IL-3-independent growth. Transformation requires both the TEL PNT domain and JAK2 kinase activity. Furthermore, all TEL/JAK2 variants strongly activated STAT 5 by phosphotyrosine Western blots and by electrophoretic mobility shift assays (EMSA). Mice (n = 40) transplanted with bone marrow infected with the MSCV retrovirus containing either the hTEL/mJAK2(JH1) fusion or its human counterpart developed a fatal mixed myeloproliferative and T-cell lymphoproliferative disorder with a latency of 2-10 weeks. In contrast, mice transplanted with a TEL/JAK2 mutant lacking the TEL PNT domain (n = 10) or a kinase-inactive TEL/JAK2(JH1) mutant (n = 10) did not develop the disease. We conclude that all human TEL/JAK2 fusion variants are oncoproteins in vitro that strongly activate STAT 5, and cause lethal myelo- and lymphoproliferative syndromes in murine bone marrow transplant models of leukemia.     

The robustness of series-connected high power IGBT modules

The behaviour in terms of robustness of series-connected high power IGBT modules is presented, arranged in a topology which ensures voltage balance on IGBT’s and diodes by means of a simple auxiliary circuit applied directly on the high power devices, which are used in hard switching mode. Analyses in terms of IGBT and diode SOA (safe operating area), collector to emitter voltage gradient and short circuit condition are reported as well as an extended experimental characterisation. Both analyses confirm superior switching rating and system reliability, by using two series-connected IGBT in substitution of a single module, same current and double voltage rated. Moreover, thanks the auxiliary circuit presence, the robustness of total system is maintained also in extreme operating conditions.     

Evaluation of ageing in asphalt cores using low-field nuclear magnetic resonance

This paper introduces an innovative methodology for estimating the ageing of asphalt concrete cores without extracting the binder. Asphalt concrete samples at different ageing stages (unaged, 3-month and 6-month aged) and with different percent air voids (4%, 7% and 10%) were analysed with low-field nuclear magnetic resonance (NMR). The transverse relaxation time T₂ and relative hydrogen index (RHI) obtained from NMR measurements were related to the viscosity of the asphalt binder. The samples were analysed during cooling from 70°C to room temperature, showing increase in viscosity with decreasing temperature. There was a clear trend indicating higher viscosities in samples that were aged for a longer period and samples with higher percent air voids. The RHI and T₂ values obtained from low-field NMR measurements and the viscosity data calculated from measurements using a dynamic shear rheometer were correlated to develop a model that relates viscosity with RHI.     

Snap-back Analysis of Fracture Evolution in Multi-Cracked Solids Using Boundary Element Method

According to the Linear Elastic Fracture Mechanics criteria, a numerical model is developed to simulate the failure evolution of multi-cracked finite plates by means of an incremental loading procedure. A modified crack length control scheme is used in order to analyse such problems depending on one or more independent parameters. The aim is to provide information about a discontinuous response, such as the snap-back instability, which can be highlighted only by a deformation controlled process. The load vs. displacement curve, included possible snap-back branches, is numerically traced by means of a procedure based on the Displacement Discontinuity Boundary Element Method. With reference to finite plates with ordered crack distributions in plane strain loading conditions, the model is applied in order to analyse the effects of the crack interaction on the fracture evolution. This revised version was published online in July 2006 with corrections to the Cover Date.     

Complex Price Dynamics in a Financial Market with Imitation

In this work a simple financial model with fundamentalists and imitators is being considered. In order to describe the price dynamics of the heterogeneous stock market, a synergetic approach is used and some global bifurcations arising in the model are being studied. It is shown that the fundamental equilibrium point P* may be destabilized through a subcritical Neimark–Sacker bifurcation and that two invariant closed curves, one attracting and one repelling, appear when P* is still stable. This particular bifurcation scenario allows us to show some noticeable features of the market that emerge when the imitation effect is emphasized. Among these features are, for instance, the volatility clusters associated with the presence of multistability (i.e. coexistence of attractors) and the hysteresis phenomenon.     

Ionic liquids as diathermic fluids for solar trough collectors’ technology: A corrosion study

The AISI 304 and AISI 1018 steels (frequently used in solar collectors’ plants) in contact with four different ionic liquids (ILs) suitable as diathermic fluids, were studied. Immersion tests were performed at 220 °C (the working temperature in such plants) for 10 days. The corrosion morphologies of the steels were investigated by scanning electron microscopy coupled with energy dispersive X-ray (EDX) microanalysis and the content of metals in the solution were detected via ICP-OES. The tests showed that the most performing IL is the ethyl-dimethyl-propyl-ammonium-bis(trifluoromethylsulphonyl)imide. The corrosion properties of the two alloys in contact with such IL were investigated by means of Tafel plots and resistance polarization at room temperature in open-to-air vessels.     

Understanding the Selectivity Mechanism of the Human Asialoglycoprotein Receptor (ASGP-R) toward Gal- and Man-type Ligands for Predicting Interactions with Exogenous Sugars

A practical approach for addressing the computer simulation of protein-carbohydrate interactions is described here. An articulated computational protocol was set up and validated by checking its ability to predict experimental data, available in the literature, and concerning the selectivity shown by the Carbohydrate Recognition Domain (CRD) of the human asialoglycoprotein receptor (ASGP-R) toward Gal-type ligands. Some required features responsible for the interactions were identified. Subsequently the same protocol was applied to monomer sugar molecules that constitute the building blocks for alginates and ulvans. Such sugar polymers may supply a low-cost source of rare sugars with a potential impact on several industrial applications, from pharmaceutical to fine chemical industry. An example of their applicative exploitation could be given by their use in developing biomaterial with adhesion properties toward hepatocytes, through interaction with the ASGP-R. Such a receptor has been already proposed as a target for exogenous molecules, specifically in the case of hepatocytes, for diagnostic and therapeutic purposes. The DOCK5.2 program was used to search optimal locations of the above ligands of interest into CRD binding site and to roughly estimate interaction energies. Finally, the binding ΔG of theoretical protein-ligand complexes was estimated by using the DelPhi program in which the solvation free energy is accounted for with a continuum solvent model, by solving the Poisson-Boltzmann equation. The structure analysis of the obtained complexes and their ΔG values suggest that one of the sugar monomers of interest shows the desired characteristics.     

Functional Properties of Plasticized Bio-Based Poly(Lactic Acid)_Poly(Hydroxybutyrate) (PLA_PHB) Films for Active Food Packaging

Fully bio-based and biodegradable active films based on poly(lactic acid) (PLA) blended with poly(3-hydroxybutyrate) (PHB) and incorporating lactic acid oligomers (OLA) as plasticizers and carvacrol as active agent were extruded and fully characterized in their functional properties for antimicrobial active packaging. PLA_PHB films showed good barrier to water vapor, while the resistance to oxygen diffusion decreased with the addition of OLA and carvacrol. Their overall migration in aqueous food simulant was determined and no significant changes were observed by the addition of carvacrol and OLA to the PLA_PHB formulations. However, the effect of both additives in fatty food simulant can be considered a positive feature for the potential protection of foodstuff with high fat content. Moreover, the antioxidant and antimicrobial activities of the proposed formulations increased by the presence of carvacrol, with enhanced activity against Staphylococcus aureus if compared to Escherichia coli at short and long incubation times. These results underlined the specific antimicrobial properties of these bio-films suggesting their applicability in active food packaging.