2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Combined differentiating therapy for myelodysplastic syndromes: a phase II study

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.     

Low temperature delamination of plastic encapsulated microcircuits

Plastic encapsulated microcircuits (PEMs) are increasingly being used in applications requiring operation at temperatures lower than the manufacturer’s recommended minimum temperature, which is 0°C for commercial grade components and −40°C for industrial and automotive grade components. To characterize the susceptibility of PEMs to delamination at these extreme low temperatures, packages with different geometries, encapsulated in both biphenyl and novolac molding compounds, were subjected to up to 500 thermal cycles with minimum temperatures in the range −40 to −65°C in both the moisture saturated and baked conditions. Scanning acoustic microscopy revealed there was a negligible increase in delamination at the die-to-encapsulant interface after thermal cycling for the 84 lead PQFPs encapsulated in novolac and for both 84 lead PQFPs and 14 lead PDIPs encapsulated in biphenyl molding compound. Only the 14 lead novolac PDIPs exhibited increased delamination. Moisture exposure had a significant effect on the creation of additional delamination.     

A Constraint-based Approach for Annotating Music Scores with Gestural Information

The physical gestures that operate music instruments are responsible for the qualities of the sound being produced in a performance. Gestural information is thereby crucial for a model of music performance, paired with a model of sound synthesis where this information is applied. The highly constrained nature of performers gestures makes this task suitable to be modeled via a constraint-based approach, coupled with a strategy aimed at maximizing the gestural comfort of performers. We illustrate the problem representation, the search strategy and a validation of the model against human performance.     

Electrocatalysis of chlorine evolution on different materials and its influence on the performance of an electrochemical reactor for indirect oxidation of pollutants

Two different Ti/Pt–Ir materials (commercial and home made) and Ti/PdO + Co₃O₄ were investigated for their electrocatalytic properties versus Cl₂ evolution reaction. The materials were used in a batch electrochemical reactor to treat biologically recalcitrant di-azo compound. An electrochemically driven oxidation, mediated by a Cl₂/Cl⁻ couple, proved efficient for destruction of this complex organic molecule, causing cleavage of the conjugated double bonds and destruction of unsatured bonds. Both Ti/Pt–Ir materials performed well; lower kinetics obtained with the Ti/PdO + Co₃O₄ anode was caused by adsorption of the model compound, evidenced in preliminary voltammetric measurements. The dye oxidation reaction followed the second order kinetics with partial orders in the model compound and (time varying) chlorine concentrations equal to one. Specific energy consumption of 3.12 kWh m⁻³ proved the process more economic than the homogeneous phase oxidation.     

Use of the polymerase chain reaction in the diagnosis of leprosy

A case is described in which a pericardial branch of a nongrafted left internal mammary artery communicated directly with the distal left anterior descending artery, following saphenous vein bypass grafting. This type of collateralization following coronary artery bypass surgery seems to be very rare, and perhaps could protect the myocardium from severe ischemia.     

CO2 abatement by co-firing of natural gas and biomass-derived gas in a gas turbine

In this work, a possible way for partial CO₂ emissions reduction from gas turbine exhausts by co-firing with biomass is investigated. The basic principle is the recirculation of a fraction of the exhausts (still rich in oxygen) to a gasifier, in order to produce syngas to mix with natural gas fuel. As biomass is a CO₂ neutral fuel, the fraction of replaced natural gas is a measure of CO₂ removal potential of the powerplant.     

Specific heat of thin helium films in a cylindrical geometry

We report measurements of the specific heat of thin helium films adsorbed in the 0.2 µm pores of Anopore membranes. Over the temperature range of these studies, two specific heat anomalies, strongly dependent on helium film thickness, were found.