TOWARDS USABILITY INTEGRATION INTO E-LEARNING DESIGN

While e-learning use has sharply increased, the drop-out rate is high. This paper addresses some of the aspects that cause users to reject e-learning and not finish. It focuses on the concept of “usability”, especially pedagogical usability that is currently central to usability design. While the term is nebulous, it is identified by attributes such as learnability, efficiency and (subjective) satisfaction. Attributes can be measured and designers add new ones as the need arises. Satisfaction has become the focus of pedagogical usability experts who claim the term includes motivational and emotive factors and may be measured by psychometric testing. Currently, efforts are underway to integrate pedagogical usability into e-learning design and create attractive, flexible features that are easy to handle and available on demand. Efforts are also underway to design mobile learning that incorporates usability principles. Usability improvements have been incremental because the e-learning process is not clear to designers, but it is expected that awareness and innovations will correct this problem in the future

El Infinito es quien te coge de la mano

Abstract not availabl

Binding of hydrophobic ligands to plant lectins: Titration with arylaminonaphthalenesulfonates

Binding of the Hydrophobic ligands 1,8-anilinonaphthalenesulfonic acid (ANS) and 2,6-toluidinylnaphthalenesulfonic acid (TNS) to a variety of plant lectins was studied by lectin-induced alteration of the fluorescence spectra of the two ligands. With one exception, all legume lectins examined bound ANS, with affinity constants ranging from 103 to 104 M-1. Similar ANS binding was noted for some nonlegume lectins. Titration of the five isolectins from Phaseolus vulgaris with ANS indicated positive cooperative binding of ANS to the two isolectins E4 and E3L1. Titrations with TNS revealed high-affinity sites for this ligand in a number of lectins. Addition of haptenic sugars did not inhibit binding of ANS, suggesting that the hydrophobic binding sites of lectins are independent of the carbohydrate binding sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25163/1/0000599.pd

Synthesis and evaluation of an agrocin 84 toxic moiety (TM84) analogue as a malarial threonyl tRNA synthetase inhibitor

An analogue of a toxic moiety (TM84) of natural product agrocin 84 containing threonine amide instead of 2,3-dihydroxy-4-methylpentanamide was prepared and evaluated as a putative Plasmodium falciparum threonyl t-RNA synthetase (PfThrRS) inhibitor. This TM84 analogue features submicromolar inhibitory potency (IC50 = 440 nM) comparable to that of borrelidin (IC50 = 43 nM) and therefore complements chemotypes known to inhibit malarial PfThrRS, which are currently limited to borrelidin and its analogues. The crystal structure of the inhibitor in complex with the E. coli homologue enzyme (EcThrRS) was obtained, revealing crucial ligand-protein interactions that will pave the way for the design of novel ThrRS inhibitors

Plasmodium subtilisin-like protease 1 (SUB1): insights into the active-site structure, specificity and function of a pan-malaria drug target.

Release of the malaria merozoite from its host erythrocyte (egress) and invasion of a fresh cell are crucial steps in the life cycle of the malaria pathogen. Subtilisin-like protease 1 (SUB1) is a parasite serine protease implicated in both processes. In the most dangerous human malarial species, Plasmodium falciparum, SUB1 has previously been shown to have several parasite-derived substrates, proteolytic cleavage of which is important both for egress and maturation of the merozoite surface to enable invasion. Here we have used molecular modelling, existing knowledge of SUB1 substrates, and recombinant expression and characterisation of additional Plasmodium SUB1 orthologues, to examine the active site architecture and substrate specificity of P. falciparum SUB1 and its orthologues from the two other major human malaria pathogens Plasmodium vivax and Plasmodium knowlesi, as well as from the rodent malaria species, Plasmodium berghei. Our results reveal a number of unusual features of the SUB1 substrate binding cleft, including a requirement to interact with both prime and non-prime side residues of the substrate recognition motif. Cleavage of conserved parasite substrates is mediated by SUB1 in all parasite species examined, and the importance of this is supported by evidence for species-specific co-evolution of protease and substrates. Two peptidyl alpha-ketoamides based on an authentic PfSUB1 substrate inhibit all SUB1 orthologues examined, with inhibitory potency enhanced by the presence of a carboxyl moiety designed to introduce prime side interactions with the protease. Our findings demonstrate that it should be possible to develop 'pan-reactive' drug-like compounds that inhibit SUB1 in all three major human malaria pathogens, enabling production of broad-spectrum antimalarial drugs targeting SUB1

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand-based drug design.

Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure-Activity Relationship investigation was carried out

Concept of Learner Behaviour Data Based Learning Support

AbstractIn this article we present our developing progress with the multi-screen e-learning system initially developed and named as eBig3 system that gives users learning access by the means of computers, mobiles and TV, depending on their choice. In the new project JAUZI we build on our previous experience. We identified that insufficient learning support in traditional eLearning settings is the key obstacle to the broad deployment of eLearning and a cause for the high drop-out rate from these programs. As a remedy for this problem, we developed an algorithm to track user trajectories and to identify problem areas. Here, we present the analysis of the data we gathered and used to assign further user support provisions. The particular support provisions we designed were based on a multiple messaging system: SMSs to users, to teachers and also emails to users and teachers. The JAUZI support system is designed respond to potential critical actions in learners’ behaviour and to quickly provide a remedy

Amino Acids in Comets and Meteorites: Stability under Gamma Radiation and Preservation of Chirality

Amino acids in solar system bodies may have played a key role in the chemistry that led to the origin of life on Earth. We present laboratory studies testing the stability of amino acids against gamma radiation photolysis. All the 20 chiral amino acids in the levo form used in the proteins of the current terrestrial biochemistry have been irradiated in the solid state with gamma radiation to a dose of 3.2 MGy which is the dose equivalent to that derived by radionuclide decay in comets and asteroids in 1.05x109 years. For each amino acid the radiolysis degree and the radioracemization degree was measured by differential scanning calorimetry (DSC) and by optical rotatory dispersion (ORD) spectroscopy. From these measurements a radiolysis rate constant kdsc and a radioracemization rate constant krac have been determined for each amino acid and extrapolated to a dose of 14 MGy which corresponds to the expected total dose delivered by the natural radionuclides decay to all the organic molecules present in comets and asteroids in 4.6x109 years, the age of the Solar System. It is shown that all the amino acids studied can survive a radiation dose of 14 MGy in significant quantity although part of them are lost in radiolytic processes. Similarly, also the radioracemization process accompanying the radiolysis does not extinguish the chirality. The knowledge of the radiolysis and radioracemization rate constants may permit the calculation of the original concentration of the amino acids at the times of the formation of the Solar System starting from the concentration found today in carbonaceous chondrites. For some amino acids the concentration in the presolar nebula could have been up to 6 times higher than currently observed in meteorites.Comment: 20 pages, 5 figures, submitted to MNRA

Peptidic boronic acids are potent cell-permeable inhibitors of the malaria parasite egress serine protease SUB1.

Malaria is a devastating infectious disease, which causes over 400,000 deaths per annum and impacts the lives of nearly half the world's population. The causative agent, a protozoan parasite, replicates within red blood cells (RBCs), eventually destroying the cells in a lytic process called egress to release a new generation of parasites. These invade fresh RBCs to repeat the cycle. Egress is regulated by an essential parasite subtilisin-like serine protease called SUB1. Here, we describe the development and optimization of substrate-based peptidic boronic acids that inhibit Plasmodium falciparum SUB1 with low nanomolar potency. Structural optimization generated membrane-permeable, slow off-rate inhibitors that prevent P falciparum egress through direct inhibition of SUB1 activity and block parasite replication in vitro at submicromolar concentrations. Our results validate SUB1 as a potential target for a new class of antimalarial drugs designed to prevent parasite replication and disease progression

Peptidomimetic plasmepsin inhibitors with potent anti-malarial activity and selectivity against cathepsin D.

Following up the open initiative of anti-malarial drug discovery, a GlaxoSmithKline (GSK) phenotypic screening hit was developed to generate hydroxyethylamine based plasmepsin (Plm) inhibitors exhibiting growth inhibition of the malaria parasite Plasmodium falciparum at nanomolar concentrations. Lead optimization studies were performed with the aim of improving Plm inhibition selectivity versus the related human aspartic protease cathepsin D (Cat D). Optimization studies were performed using Plm IV as a readily accessible model protein, the inhibition of which correlates with anti-malarial activity. Guided by sequence alignment of Plms and Cat D, selectivity-inducing structural motifs were modified in the S3 and S4 sub-pocket occupying substituents of the hydroxyethylamine inhibitors. This resulted in potent anti-malarials with an up to 50-fold Plm IV/Cat D selectivity factor. More detailed investigation of the mechanism of action of the selected compounds revealed that they inhibit maturation of the P. falciparum subtilisin-like protease SUB1, and also inhibit parasite egress from erythrocytes. Our results indicate that the anti-malarial activity of the compounds is linked to inhibition of the SUB1 maturase plasmepsin subtype Plm X