Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling

In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.     

A guest-induced reversible switching of a self-assembled H-bonded supramolecular framework

A new class of organic crystalline 2,2'-biphenol-based H-bonded material displaying 1D-channels encapsulating solvent molecules is described. A reversible guest-induced crystal-to-crystal conversion between the solvated H-bonded phase and a compact H-bonded non-solvated phase was observed. The energy competition between intramolecular H-bonds formation and solvation of organic pores has been characterized using PACHA calculations.     

On the polymerisation of the epoxidised biodiesel: The importance of the epoxy rings position,the process and the products

Polyesters were prepared using epoxidised methyl esters of oleic acid (EP_OAME) and epoxidised biodiesel (mixture of methyl esters) from sunflower oil (EP_SOME) and linseed oil (EP_LOME) with cis-1,2-cyclohexanedicarboxylic anhydride and triethylamine. The kinetic of partial processes involved in the polymerisation were elucidated and related to epoxy rings position in the fatty acid chain. The activation energies (E_a) for the epoxy ring opening by the catalyst are 298, 216 and 136 kJ/mol for EP_OAME, EP_SOME and EP_LOME respectively. The reactions of the epoxy rings in the positions C9–C10, C12–C13 and C15–C16 with anhydride require average activation energies of 116, 32 and 22 kJ/mol, respectively. The compensation effect between activation energy and pre-exponential factor is observed. The polymerisation enthalpy, molecular weight, glass transition temperature and electrical properties were determined. The polyesters studied show promising properties for use in various technological applications.     

Characterisation of protease activity in extracellular products secreted by Giardia duodenalis trophozoites treated with propolis

Results from our laboratory revealed propolis activity on Giardia trophozoites proliferation. Since therapeutic agents can inhibit the activity of proteases related to relevant biologic and physiologic processes of parasites, this study was undertaken to characterise the proteolytic activity of excretory/secretory products (ESP) of trophozoites treated with propolis. ESP was obtained from culture supernatants of trophozoites exposed to 250 and 500 μg mL(-1) of propolis. ESP were tested in sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the protein profiles and the protease activity was assayed in gelatin-containing gels. Synthetic inhibitors were used to characterise the protease classes. Treated and non-treated ESP showed a similar protein and hydrolysis pattern. A simple pattern of protein composed by five evident bands of approximately 167, 132, 79, 61 and 51 kDa was found, and the zymograms comprised hydrolysis zones distributed from >170 to 23 kDa. No inhibition was seen on protease activity of propolis-treated trophozoites, whose hydrolysis pattern was similar to control. One may conclude that both ESP degraded gelatin and the activity was predominantly due to cysteine proteases. Although propolis had no effect on the proteolytic activity, further studies could identify the active constituents responsible for propolis antigiardial activity and their mechanisms of action.     

Synergies between operations research and data mining: The emerging use of multi-objective approaches

Operations research and data mining already have a long-established common history. Indeed, with the growing size of databases and the amount of data available, data mining has become crucial in modern science and industry. Data mining problems raise interesting challenges for several research domains, and in particular for operations research, as very large search spaces of solutions need to be explored. Hence, many operations research methods have been proposed to deal with such challenging problems. But the relationships between these two domains are not limited to these natural applications of operations research approaches. The counterpart is also important to consider, since data mining approaches have also been applied to improve operations research techniques. The aim of this article is to highlight the interplay between these two research disciplines. A particular emphasis will be placed on the emerging theme of applying multi-objective approaches in this context.     

Relevance of NH4F in acid digestion before ICP-MS analysis

In order to implement a simpler, less expensive and more safe sample dissolution procedure, we have substituted the HF-HClO₄ mixture by NH₄F. By testing three certified reference materials, lichen 336, basalt BE-N, soil 7, it was found that the three-reagents digestion without HF and HClO₄ (HNO₃ + H₂O₂ + NH₄F was used) was very effective for the pretreatment of ICP-MS measurement. The comparison was based on the measurement results and their uncertainties. All are reference material for amount contents of different trace elements. The accuracy and precision of the developed method were tested by replicate analyses of reference samples of established element contents. The accuracy of the data as well as detection limits (LODs) vary among elements but are usually very good (accuracy better than 8%, LODs usually below 1 μg/g in solids). ICP-MS capabilities enable us to determine routinely 13 and 16 minor and trace elements in basalt and soil.     

Electrokinetic capillary chromatography in a polar continuous-phase water-in-oil microemulsion constituted by water, sodium dodecyl sulfate, and n-pentanol

A water-in-oil (w/o) microemulsion (ME) constituted by 15% Tris buffer, pH 8.4, in water and 85% sodium dodecyl sulfate (SDS)/n-pentanol 1:4 mixture, capable of dissolving up to 30% vegetable oils and lard, was used as background electrolyte in reverse microemulsion electrokinetic capillary chromatography (RMEEKC). Owing to the free SDS ions in the continuous phase and some degree of percolation, the ME showed a high conductivity (0.65 mS. cm(-1) at 25 degrees C) and sustained a very stable capillary current. Previous rinsing of the capillary with a quaternary ammonium salt for electroosmotic flow (EOF) reduction, a series of nonionic and anionic solutes dissolved either in the ME or in fat samples diluted with the ME (1:4 ratio), were injected. Using -20 kV, fair separations of the solutes in the migration time order singly charged anions < nonionic solutes < doubly charged anions approximately pyromellitate were obtained, salicylate (I) showing by far the shortest migration time, and phthalate (II) and pyromellitate the longest. Separation was attributed to partition between the aqueous droplets, where pyromellitate and II were assumed to be trapped, and the n-pentanol continuous phase, where the mobilitites could be also modified by association of the solutes with SDS ions. Adequate EOF markers were not found, thus the relative mobility of any solute with respect to the mobility of the droplets, mu(r), was expressed as a fraction of the mobility of I with respect to that of the droplets, being mu(r) = (t(II) - t(R)) t(I) / [(t(II) - t(I)) t(R)], where t(R), t(I), and t(II) are the migration times of the solutes I and II, respectively. The application of RMEEKC to the analysis of both hydrophilic and hydrophobic samples, including edible fats, was demonstrated.     

Quantitative analysis of anabolics on thin-layer chromatographic plates using image analysis techniques

A new detection system is introduced for the quantitative analysis of thin-layer chromatographic plates, which is based on a relatively simple, cheap but advanced image analysis system. Both one- and two-dimensional plates can be analysed. Recording and analysis can also be performed from photographs or even slides. Applications are shown for a number of samples containing anabolic compounds.