Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity

Anovel one-pot synthesis of tri-substituted purines and the discovery of purine analogues with trypanocidal activity are reported. The reaction is initiated by a metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with Schiff base formation and subsequent annulation in the presence of large N,N-dimethylamides (e.g.N,N-dimethylpropanamide or larger). This synthetic route is in competition with a reaction previously-reported by our group1, allowing the generation of a combinatorial library of tri-substituted purines by the simple modification of the amide and the alkoxide employed. Among the variety of structures generated, two purine analogues displayed trypanocidal activity against the protozoan parasite Trypanosoma brucei with IC50 , 5 mM, being each of those compounds obtained through each of the synthetic pathways.J.J.D.M. thanks Spanish Ministerio de Economı´a y Competitividad for a Ramon y Cajal Fellowship. A.U.B. thanks MRC IGMM for an academic fellowship. This work was partially supported by Grant SAF2011-30528 to J.A.G.S.

Critical thinking perspectives on work integrated learning in information systems education

World Academy of Science, Engineering and Technology 64, Paris, France, 28-29 November 2012Students with high level skills are in demand, especially in scare skill environments. If universities wish to be successful and competitive, its students need to be adequately equipped with the necessary tools. Work Integrated Learning (WIL) is an essential component of the education of a student. The relevance of higher education should be assessed in terms of how it meets the needs of society and the world of work in a global economy. This paper demonstrates how to use Habermas's theory of communicative action to reflect on students- perceptions on their integration in the work environment to achieve social integration and financial justification. Interpretive questionnaires are used to determine the students- view of how they are integrated into society, and contributing to the economy. This paper explores the use of Habermas-s theory of communicative action to give theoretical and methodological guidance for the practice of social findings obtained in this inquiry.http://www.waset.org/Publications/?path=Publication

Towards a conceptual UML model for tracking a learner's progress in an outcomes-based environment

The arrival of outcomes-based education (OBE) in South African means that we have to change the way in which we assess our learners. Coupled with this change comes a move to larger classes where individual assessment has become difficult. This has led to frustration on the part of educators as well as learners. This paper investigates the needs of the OBE system with regards to assessment and then proposes an object-oriented model for storing all the information needs. It is suggested that the model can meet the needs of both the human educator and the learner and with more detailed information, even the needs of a computer system

Automatic detection and diagnosis of problems in drilling geothermal wells

Sandia National Laboratories and Tracor Applied Sciences have developed a proof-of-concept Expert System for the automatic detection and diagnosis of several important problems in geothermal drilling. The system is designed to detect loss of circulation, influx, loss of pump efficiency, and sensor problems. Data from flow sensors (including the rolling float meter), the pump stroke counter and other sensors are processed and examined for deviations from expected patterns. The deviations from expected patterns. The deviations are transformed into evidence for a Bayesian Network (a probabilistic reasoning tool), which estimates the probability of each fault. The results are displayed by a Graphical User Interface, which also allows the user to see data related to a specific fault. The prototype was tested on real data, and successfully detected and diagnosed faults

Merkel cells in the human oesophagus

Merkel cells (MCs) are well recognized in the basal layers of the skin and oral mucosa, but this paper describes for the first time the presence of MCs in the human oesophagus. These cells are not identified in neonatal oesophagus, but are seen singly and in clusters in adult specimens. Application of stereological techniques shows that MCs are more numerous in the mid-oesophageal region. Cells expressing established markers of MCs have also been demonstrated in two out of six primary small cell carcinomas of the oesophagus. Further investigation of the role of MCs in oesophageal innervation and epithelial biology will be of interest

Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum

The development of novel chemotherapeutic agents has become an urgent task due to the development and rapid spread of drug resistance in Plasmodium falciparum, the protozoan parasite responsible for cerebral malaria. Cyclin-dependent kinases (CDKs) are essential for the regulation of the eukaryotic cell cycle, and several enzymes of this family have been identified in P. falciparum. In recent years, a number of purine-derived kinase inhibitors have been synthesised, some of which display selective activity against CDKs. This report describes a study in which various purine derivatives were screened for in vitro antimalarial activity. The erythrocytic asexual stages of the chloroquine-resistant P. falciparum strain (FCR-3) were cultivated in vitro in the presence of the various purines, and their effect on parasite proliferation was determined by the [3H]hypoxanthine incorporation assay. Our results show considerable variation in the sensitivity of P. falciparum to the different purines, as well as a general independence from their effect on purified starfish CDK1/cyclin B activity, which has been the standard assay used to identify CDK-specific inhibitors. Two subfamilies of purines with moderate to poor activity against CDK1/cyclin B activity showed submicromolar activity against P. falciparum. Structure-activity analysis indicates that certain structural features are associated with increased activity against P. falciparum. These features can be exploited to synthesise compounds with higher activity and specificity towards P. falciparum