High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximate to 20,000 microbial extracts, 12 hits were identified with broadspectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.

Effects of temperature, hypoxia, ammonia and nitrate on the bleaching among three coral species

Coral bleaching, which is defined as the loss of colour in corals due to the loss of their symbiotic algae (commonly called zooxanthellae) or pigments or both, is occurring globally at increasing rates, and its harm becomes more and more serious during these two decades. The significance of these bleaching events to the health of coral reef ecosystems is extreme, as bleached corals exhibited high mortality, reduced fecundity and productivity and increased susceptibility to diseases. This decreased coral fitness is easily to lead to reef degradation and ultimately to the breakdown of the coral reef ecosystems. Recently, the reasons leading to coral bleaching are thought to be as follows: too high or too low temperature, excess ultraviolet exposure, heavy metal pollution, cyanide poison and seasonal cycle. To date there has been little knowledge of whether mariculture can result in coral bleaching and which substance has the worst effect on corals. And no research was conducted on the effect of hypoxia on corals. To address these questions, effects of temperature, hypoxia, ammonia and nitrate on bleaching of three coral species were studied through examination of morphology and the measurement of the number of symbiotic algae of three coral species Acropora nobilis, Palythoa sp. and Alveopora verrilliana. Results showed that increase in temperature and decrease in dissolved oxygen could lead to increasing number of symbiotic algae and more serious bleaching. In addition, the concentration of 0.001 mmol/L ammonia or nitrate could increase significantly the expulsion of the symbiotic algae of the three coral species. Except for Acropora nobilis, the numbers of symbiotic algae of other two corals did not significantly increase with the increasing concentration of ammonia and nitrate. Furthermore, different hosts have different stress susceptibilities on coral bleaching.

Synthesis and QSAR studies of novel triazole compounds containing thioamide as potential antifungal agents

Eighteen novel triazole compounds containing thioamide were designed and synthesized. Their structures were confirmed by elemental analysis, H-1 NMR, IR, and MS. The title compounds exhibited certain antifungal activity. And the geometry structures of the title compounds were optimized by means of the density functional theory (DFT) method at B3LYP/6-31G* level. The quantitative structure-activity relationship (QSAR) of the title compounds was systematically investigated. A correlative equation between FA and DELH, V was well established by using the multiple linear regression (MLR). (c) 2006 Elsevier Ltd. All rights reserved.

A novel method to synthesize amorphous silica-alumina materials with mesoporous distribution without using templates and pore-regulating agents

In this study, a novel sol-gel method is used to synthesize amorphous silica-alumina materials with a narrow mesoporous distribution and various Si/Al molar ratios without using any templates and pore-regulating agents. During the preparation procedure, only inexpensive inorganic salts were used as raw materials, instead of expensive and harmful alkoxides. The precursor sol was dried at room temperature in a vacuum box kept at 60 mmHg until it began to form the gel. The results of a nitrogen sorption experiment indicate that the synthesized materials with different Si/Al molar ratios have similar mesoporous distributions (within 2-12 nm). Moreover, it was found that the material's pore size distribution remains at a similar value during the heat treatment from room temperature to 550 degreesC. On the basis of the nitrogen sorption, TEM, and AFM characterization results, a formation mechanism of mesopores which accounts for the experimental data is also suggested. This suggested mechanism involves rearrangement of the primary particles during the drying process to form the precursors of the similarly sized mesopores. The synthesized materials were characterized by XRD, thermal analysis (TG/DTA), Al-27 and Si-29 MAS NMR spectroscopy, SEM, TEM, and AFM. The results of Al-27 and 29Si MAS NMR indicate that the distribution of silicon and aluminum in the synthesized materials is more uniform and homogeneous than that in the mixed oxides prepared via the traditional sol-gel method even at high alumina contents. The type and density of the acid sites were studied using pyridine adsorption-desorption FTIR spectroscopy. It was shown that the acidity of the synthesized materials is higher than that of the silica-alumina materials prepared by conventional methods.

The Epistemological Foundations of Artificial Agents

Lacey, N. J., Lee, M. H. (2003). The Epistemological Foundations of Artificial Agents. Minds and Machines, 13, 339-365.

The Influence of Epistemology on the Design of Artificial Agents

Lee, M. H., Lacey, N. J. (2003). The Influence of Epistemology on the Design of Artificial Agents. Minds and Machines, 13 (3), 367-395

The Implications of Philosophical Foundations for Knowledge Representation and Learning in Agents

N.J. Lacey and M.H. Lee, ?The Implications of Philosophical Foundations for Knowledge Representation and Learning in Agents?, Springer-Verlag Lecture Notes on Artificial Intelligence, Vol 2636 on Adaptive Agents and Multi-Agent Systems, 2002.

The Implications of Philosophical Foundations for Knowledge Representation and Learning in Agents

Lacey N and Lee M.H., The Implications of Philosophical Foundations for Knowledge Representation and Learning in Agents, in Proc. AISB?01 Symposium on Adaptive Agents and Multi-agent Systems, York, March 2001, pp13-24.

Volcanoes as agents of past environmental change

Sadler, J. Grattan, J. Volcanoes as agents of past environmental change. Global and Planetary Change. 1999. 21 pp 181-196

Animated virtual agents to cue user attention: comparison of static and dynamic deictic cues on gaze and touch responses

This paper describes an experiment developed to study the performance of virtual agent animated cues within digital interfaces. Increasingly, agents are used in virtual environments as part of the branding process and to guide user interaction. However, the level of agent detail required to establish and enhance efficient allocation of attention remains unclear. Although complex agent motion is now possible, it is costly to implement and so should only be routinely implemented if a clear benefit can be shown. Pevious methods of assessing the effect of gaze-cueing as a solution to scene complexity have relied principally on two-dimensional static scenes and manual peripheral inputs. Two experiments were run to address the question of agent cues on human-computer interfaces. Both experiments measured the efficiency of agent cues analyzing participant responses either by gaze or by touch respectively. In the first experiment, an eye-movement recorder was used to directly assess the immediate overt allocation of attention by capturing the participant’s eyefixations following presentation of a cueing stimulus. We found that a fully animated agent could speed up user interaction with the interface. When user attention was directed using a fully animated agent cue, users responded 35% faster when compared with stepped 2-image agent cues, and 42% faster when compared with a static 1-image cue. The second experiment recorded participant responses on a touch screen using same agent cues. Analysis of touch inputs confirmed the results of gaze-experiment, where fully animated agent made shortest time response with a slight decrease on the time difference comparisons. Responses to fully animated agent were 17% and 20% faster when compared with 2-image and 1-image cue severally. These results inform techniques aimed at engaging users’ attention in complex scenes such as computer games and digital transactions within public or social interaction contexts by demonstrating the benefits of dynamic gaze and head cueing directly on the users’ eye movements and touch responses.

Application of flow cytometry for the determination of minimal inhibitory concentration of several antibacterial agents on Mycoplasma hyopneumoniae

P. Assun??o, N.T. Antunes, R.S. Rosales, C. Poveda, C. de la Fe, J.B. Poveda and H.M. Davey (2007). Application of flow cytometry for the determination of minimal inhibitory concentration of several antibacterial agents on Mycoplasma hyopneumoniae. Journal of Applied Microbiology, 102(4), 1132-1137. Sponsorship: Gobierno de Canarias (IDT-LP-04/016) RAE2008

Christian missions ; their agents, and their results / by T.W.M. Marshall.

http://www.archive.org/details/a592254601marsuoft

Christian missions : their agents and their results (vol. 1) / by T.W.M. Marshall.

http://books.google.com/books?vid=ISBN0665456816&id=sipohllLjKQC&dq=protestant+missions&a_sbrr=1 View book via Google

Christian missions : their agents and their results (vol. 2) / by T.W.M. Marshall.

http://books.google.com/books?vid=ISBN0665456816&id=sipohllLjKQC&dq=protestant+missions&a_sbrr=1 View book via Google