The C-terminus of c-ABL is required for proliferation and viability signaling in a c-ABL/erythropoietin receptor fusion protein

Activated ABL oncogenes cause B-cell leukemias in mice and chronic myelogenous leukemia in humans. However, the mechanism of transformation is complex and not well understood. A method to rapidly and reversibly activate c-ABL was created by fusing the extra-cytoplasmic and transmembrane domain of the erythropoietin (EPO) receptor with c-ABL (EPO R/ABL). When this chimeric receptor was expressed in Ba/F3 cells, the addition of EPO resulted in a dose-dependent activation of c-ABL tyrosine kinase and was strongly antiapoptotic and weakly mitogenic. To evaluate the contributions of various ABL domains to biochemical signaling and biological effects, chimeric receptors were constructed in which the ABL SH3 domain was deleted (triangle upSH3), the SH2 domain was deleted (triangle upSH2), the C-terminal actin-binding domain was deleted (triangle upABD), or kinase activity was eliminated by a point mutation, K290M (KD). The mutant receptors were stably expressed in Ba/F3 cells and analyzed for signaling defects, proliferation, viability, and EPO-induced leukemia in nude mice. When compared with the ability of the full-length EPO R/ABL receptor to induce proliferation and support viability in vitro, the triangle upSH3 mutant was equivalent, the triangle upSH2 mutant was moderately impaired, and the triangle upABD and KD mutants were profoundly impaired. None of these cell lines caused leukemia in mice in the absence of pharmacological doses of EPO. However, in mice treated with EPO (10 U/d), death from leukemia occurred rapidly with wild-type and triangle upSH3. However, time to death was prolonged by at least twofold for triangle upSH2 and greater than threefold for triangle upABD. This inducible model of ABL transformation provides a method to link specific signaling defects with specific biological defects and has shown an important role for the C-terminal actin-binding domain in proliferation and transformation in the context of this receptor/oncogene.     

On the hot-carrier-induced post-stress interface trap generation inn-channel MOS transistors

A continued fast interface trap generation is observed in n-channel MOS transistors after termination of the hot-carrier stress. The magnitude of this post-stress effect is strongly dependent on the conditions of the preceding stress, on the post-stress conditions and on the process parameters. For measurements at 293 K, a simple model is proposed which is based on the release of hydrogen by the thermal detrapping of holes, and which can explain the observed dependencies. The importance of the post-stress D_it-generation is illustrated for the case of dynamic stress conditions where it can lead to an apparently deviating degradation behavior     

Monitoring the planning quality of health promotion projects in Flanders

The levels of bacterial blood endotoxin, antiendotoxin antibodies and the overall immunity were studied in 48 females with inflammatory genital diseases complicated by pelvioperitonitis. The severest pelvioperitonitis-complicated abnormality was shown to characterized by high concentrations of endotoxin and low levels of antibodies. Endotoxinemia was found to be of diagnostic and prognostic value.     

Quantifying technological aspects of process sustainability: a thermodynamic approach

Thermodynamic analysis has greatly helped to compare and to improve the energy efficiency of all kinds of technological processes, and recently we have also attempted to analyse some important biochemical processes under intracellular conditions. This work has pointed to some key strategies on sustainable process operation, such as the exceptionally high thermodynamic efficiencies of chemical and solar energy conversion in living cells.From this it was expected that the sustainability strategies of specific biochemical processes and those of the ecosphere as a whole could be of guidance to current technological processes, especially now that there is a growing demand from government and industry to effectively deal with sustainability aspects in process analysis. Our focus on this issue has led to methodologies to quantify technological aspects of sustainability by making use of thermodynamic principles. Three indicators were constructed to express three technological aspects of process sustainability. First, an indicator for the sustainability of resource utilization considers the thermodynamic input and the availability the resources used in the process. Secondly, an efficiency indicator focuses on the conversion and loss of thermodynamic quantities in the process itself. Thirdly, an indicator for environmental compatibility takes into account the thermodynamic input required to prevent possible negative side effects of the process, such as global warming or water pollution. The three indicators are used to reflect on (un)sustainable characteristics of current technological processes compared to biochemical processes. Finally, we address the drawbacks of combining indicator values to express overall sustainability.     

Characterisation of inter-particle forces within agglomerated metallurgical powders

The strength of agglomerates of nickel flash furnace concentrate and dust was determined from experimental observations of agglomerates forming under controlled conditions, combined with mathematical equations from the literature. It was found that the agglomerates had a tensile strength ranging from 0.01 Pa to 38.7 Pa, while inter-particle forces ranged from 2.2 × 10^− 12 N to 1.5 × 10^− 10 N. These values were compared to the expected magnitude of van der Waals, electrostatic, magnetic and capillary forces within the agglomerates, and it was found that both electrostatic and van der Waals forces are likely to contribute to the cohesion of agglomerates, although sub-micron particles and the presence of sufficiently large asperities on the surface of particles limit the magnitude of van der Waals forces. Magnetic forces are large enough to contribute to the cohesion of dust agglomerates, which is in keeping with the high magnetite content of the recycle dust. It is postulated that electrostatic forces, acting over a longer range than van der Waals forces, may be responsible for initially bringing particles together. The methodology for determining inter-particle forces can be applied to the computer modelling of flash smelting systems, as well as other gas/particle systems such as fluidized beds.     

A Study of The Moisture-Uptake Kinetics of a Hygroscopic Pharmaceutical Powder

The moisture-uptake kinetics of a hygroscopic powder, sodium heparin contained in a cylindrical container, was determined using a novel moisture-uptake measuring device under a constant convective air flow. The amount of moisture uptake increased with the increase in the relative humidity of the air. The effect of powder-bed height on the total amount of moisture uptake was found to be significant only at the highest relative humidity (75%) evaluated in this study. However, the percent of weight increase of the powder as a result of moisture uptake decreases as the height of the powder bed increases. The results of this study are explained by the dynamic nature of the moisture-uptake process associated with the instrument.     

Digital implementation of bus clamped space vector modulation

Space vector modulation has recently become a popular PWM method of supplying a high performance drive. An adaptation of SVM modulation is presented here. This system is called bus clamped space vector modulation. This method has some practical advantages when compared to normal SVM. These include a reduced average switching frequency, easy digital implementation and asynchronous control and switching frequencies     

Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?)

Pantoprazole is a specific inhibitor of the H+/K(+)-ATPase of the gastric parietal cell. The dose-dependency of a range of pantoprazole pharmacokinetic characteristics was studied. Twelve healthy male subjects were given 10, 20, 40 and 80 mg pantoprazole intravenously according to a randomized, single blind, 4-period change-over scheme. The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with the dose. Apparent volume of distribution (Vd area), clearance (Cl) and terminal half-life (t1/2) were independent of the dose. The dose-independent elimination of pantoprazole was attributed to the lack of interaction of the drug with cytochrome P450. In clinical practice, a good predictable response, as well as a low potential for interaction with other drugs might be expected.