Collaborative eLearning Assistant Network: caring agents are conscious agents

Would a research assistant - who can search for ideas related to those you are working on, network with others (but only share the things you have chosen to share), doesn’t need coffee and who might even, one day, appear to be conscious - help you get your work done? Would it help your students learn? There is a body of work showing that digital learning assistants can be a benefit to learners. It has been suggested that adaptive, caring, agents are more beneficial. Would a conscious agent be more caring, more adaptive, and better able to deal with changes in its learning partner’s life? Allow the system to try to dynamically model the user, so that it can make predictions about what is needed next, and how effective a particular intervention will be. Now, given that the system is essentially doing the same things as the user, why don’t we design the system so that it can try to model itself in the same way? This should mimic a primitive self-awareness. People develop their personalities, their identities, through interacting with others. It takes years for a human to develop a full sense of self. Nobody should expect a prototypical conscious computer system to be able to develop any faster than that. How can we provide a computer system with enough social contact to enable it to learn about itself and others? We can make it part of a network. Not just chatting with other computers about computer ‘stuff’, but involved in real human activity. Exposed to ‘raw meaning’ – the developing folksonomies coming out of the learning activities of humans, whether they are traditional students or lifelong learners (a term which should encompass everyone). Humans have complex psyches, comprised of multiple strands of identity which reflect as different roles in the communities of which they are part – so why not design our system the same way? With multiple internal modes of operation, each capable of being reflected onto the outside world in the form of roles – as a mentor, a research assistant, maybe even as a friend. But in order to be able to work with a human for long enough to be able to have a chance of developing the sort of rich behaviours we associate with people, the system needs to be able to function in a practical and helpful role. Unfortunately, it is unlikely to get a free ride from many people (other than its developer!) – so it needs to be able to perform a useful role, and do so securely, respecting the privacy of its partner. Can we create a system which learns to be more human whilst helping people learn?

Soilborne fungi and bacteria symbiotically associated with Steinernema spp. acting as biological agents against Fusarium wilt of tomato

An isolate of Gliocladium virens from disease affected soil in a commercial tomato greenhouse proved highly antagonistic to Fusarium oxysporum f.sp. lycopersici, used together with an isolate of the nematophagus fungus Verticillium chlamydosporium. Significant disease control was obtained when young mycelial preparation (on a food-base culture) of the G. virens together with V. chlamydosporium was applied in potting medium. Similar results were observed when a Trichoderma harzianum isolate was treated in combination with the V. chlamydosporium isolate. Most promising, in terms of minimizing the Fusarium wilt of tomato incidence, was also the effect of the bacteria associated with entomopathogenic nematodes (Steinernema spp.), Pseudomonas oryzihabitans and Xenorhabdus nematophilus.

Macrocyclic amines as structure-directing agents for the synthesis of three-dimensional antimony-sulfide frameworks

A new family of antimony sulfides, incorporating the macrocyclic tetramine 1,4,8,11-tetraazacyclotetradecane ( cyclam), has been prepared by a hydrothermal method. [C10N4H26][Sb4S7] (1), [Ni(C10N4H24)][Sb4S7] (2), and [Co(C10N4H24)](x)[C10N4H26](1-x)[Sb4S7] (0.08 <= x <= 0.74) (3) have been characterized by single-crystal X-ray diffraction, elemental analysis, thermogravimetry, and analytical electron microscopy. All three materials possess the same novel three-dimensional Sb4S72- framework, constructed from layers of parallel arrays of Sb4S84- chains stacked at 90 to one another. In 1, doubly protonated macrocyclic cations reside in the channel structure of the antimonysulfide framework. In 2 and 3, the cyclam acts as a ligand, chelating the divalent transition- metal cation. Analytical and X-ray diffraction data indicate that the level of metal incorporation in 2 is effectively complete, whereas in 3, both metalated and nonmetalated forms of the macrocycle coexist within the structure.

Flavonoids: antioxidants or signalling molecules?

Many studies are accumulating that report the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids, and their in vivo metabolites, do not act as conventional hydrogen-donating antioxidants but may exert modulatory actions in cells through actions at protein kinase and lipid kinase signalling pathways. Flavonoids, and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), tyrosine kinases, protein kinase C (PKC), and mitogen activated protein kinase (MAP kinase) signalling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as antioxidants or modulators of cell signalling, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anticancer agents, cardioprotectants, and inhibitors of neurodegeneration (C) 2004 Elsevier Inc. All rights reserved.

The neuroprotective potential of flavonoids: a multiplicity of effects

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

Neuroinflammation and its modulation by flavonoids

There is increasing evidence to suggest that neuroinflammatory processes contribute to the cascade of events that lead to the progressive neuronal damage observed in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Therefore, treatment regimes aimed at modulating neuroinflammatory processes may act to slow the progression of these debilitating brain disorders. Recently, a group of dietary polyphenols known as flavonoids have been shown to exert neuroprotective effects in vivo and in neuronal cell models. In this review we discuss the evidence relating to the modulation of neuroinflammation by flavonoids. We highlight the evidence which suggests their mechanism of action involves: 1) attenuation of the release of cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α); 2) an inhibitory action against inducible nitric oxide synthase (iNOS) induction and subsequent nitric oxide (NO•) production; 3) inhibition of the activation of NADPH oxidase and subsequent reactive oxygen species generation; 4) a capacity to down-regulate the activity of pro-inflammatory transcription factors such as nuclear factor-κB (NF-κB); and 5) the potential to modulate signalling pathways such as mitogen-activated protein kinase (MAPK) cascade. We also consider the potential of these dietary compounds to represent novel therapeutic agents by considering their metabolism in the body and their ability to access the brain via the blood brain barrier. Finally, we discuss future areas of study which are necessary before dietary flavonoids can be established as therapeutic agents against neuroinflammation.

Dietary vitamin E modulates differential gene expression in the rat hippocampus: potential implications for its neuroprotective properties

A wide range of cell culture, animal and human epidemiological studies are suggestive of a role of vitamin E (VE) in brain function and in the prevention of neurodegeneration. However, the underlying molecular mechanisms remain largely unknown. In the current investigation Affymetrix gene chip technology was utilised to establish the impact of chronic VE deficiency on hippocampal genes expression. Male albino rats were fed either a VE deficient or standard diet (60 mg/kg feed) for a period of 9 months. Rats were sacrificed, the hippocampus removed and genes expression established in individual animals. VE deficiency showed to have a strong impact on genes expression in the hippocampus. An important number of genes found to be regulated by VE was associated with hormones and hormone metabolism, nerve growth factor, apoptosis, dopaminergic neurotransmission, and clearance of amyloid-beta and advanced glycated endproducts. In particular, VE strongly affected the expression of an array of genes encoding for proteins directly or indirectly involved in the clearance of amyloid beta, changes which are consistent with a protective effect of VE on Alzheimer's disease progression.

Effects of calcium-chelating agents and pasteurisation on certain properties of calcium-fortified soy milk

Addition of 25 mM calcium chloride to soy milk reduced pH, increased ionic calcium and caused it to coagulate. The effects of different chelating agents were investigated on selected physicochemical properties of soy milk and on preventing coagulation. The soy milks were then pasteurised to examine how heat treatment changed some of these properties as well as to evaluate their effects on heat stability. Sediment formation and susceptibility to coagulation could be reduced by decreasing ionic calcium and increasing pH. To achieve this, the most effective chelating agents were tri-sodium citrate and disodium hydrogen phosphate. These chelating agents also reduce absolute viscosity and particle size. Sodium hexa meta phosphate was also effective, but less so; it reduced ionic calcium but had a less noticeable effect on pH. The disodium salt of ethylenediamine tetraacetic acid was not effective, as it decreased the pH of soy milk. Ionic calcium and pH are useful indicators of heat stability of calcium-fortified soy beverages. (C) 2009 Elsevier Ltd. All rights reserved.

Challenge testing the lactoperoxidase system against a range of bacteria using different activation agents

Lactoperoxidase (LP) exerts antimicrobial effects in combination with H2O2 and either thiocyanate (SCN-) or a halide (e. g., I-). Garlic extract in the presence of ethanol has also been used to activate the LP system. This study aimed to determine the effects of 3 LP activation systems (LP+SCN-+H2O2; LP+I-+H2O2; LP + garlic extract + ethanol) on the growth and activity of 3 test organisms (Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus cereus). Sterilized milk was used as the reaction medium, and the growth pattern of the organisms and a range of keeping quality (KQ) indicators (pH, titratable acidity, ethanol stability, clot on boiling) were monitored during storage at the respective optimum growth temperature for each organism. The LP+I-+H2O2 system reduced bacterial counts below the detection limit shortly after treatment for all 3 organisms, and no bacteria could be detected for the duration of the experiment (35 to 55 h). The KQ data confirmed that the milk remained unspoiled at the end of the experiments. The LP + garlic extract + ethanol system, on the other hand, had no effect on the growth or KQ with P. aeruginosa, but showed a small retardation of growth of the other 2 organisms, accompanied by small increases (5 to 10 h) in KQ. The effects of the LP+SCN-+H2O2 system were intermediate between those of the other 2 systems and differed between organisms. With P. aeruginosa, the system exerted total inhibition within 10 h of incubation, but the bacteria regained viability after a further 5 h, following a logarithmic growth curve. This was reflected in the KQ indicators, which implied an extension of 15 h. With the other 2 bacterial species, LP+SCN-+H2O2 exerted an obvious inhibitory effect, giving a lag phase in the growth curve of 5 to 10 h and KQ extension of 10 to 15 h. When used in combination, I- and SCN- displayed negative synergy.

Growth inhibition of mammalian cells by synthetic and natural photosensitising agents

A mammalian cell line, J774, was susceptible to both synthetic and natural photosensitising agents after irradiation with long-wave ultraviolet light. Both UV-A light and psoralen did not affect cell growth individually; a reduction in visual confluency was achieved only when psoralen and UV-A light were used in combination. The maximum visual confluency decreased by 55% when 50 ppm psoralen was added to a growing culture and irradiated with UV light for 3 min. Decreasing the UV-A exposure times from 3 min to 3 s did not greatly affect the maximum total visual confluence reached using different synthetic psoralen concentrations, but did affect the rate at which cell death occurred. The 3 min exposure time resulted in a rapid decrease in cell numbers in comparison to 3 s exposure time. Synthetic psoralen was found to have an increasing photosensitising activity with increasing concentration using a logarithmic shift between 0.5 ppm and 50 ppm. A visual confluency of 45% was achieved using concentrations of 50 ppm psoralen, and 70% visual confluency using 0.5 ppm. Natural mixtures of furanocoumarins containing psoralens, obtained from two separate parsley sources, were found to have greater efficacy at inhibiting the growth cycle of the cells when compared to the synthetic psoralen.

Glycol methyl ether and glycol amine substituted titanocenes as antitumor agents

6-[4-(2-Methoxyethoxy)phenyl]fulvene (3a) and 6-(4-[2-(di-methylamino)ethoxy]phenyl)fulvene (3b) were prepared as starting materials for the synthesis of three dofferent classes of titanocenes, which are ansa-titanocenes, diarylmethyl-substituted titanicenes and benzyl-substituted titanocenes and benyzyl-subtituted titanocenes. Because the synthetic possibilities seem to be limited, only ansa-titanocene {1,2-bis(cyclopentadienyl)-1,2-bis[4-(2-methoxyethoxy)phenyl]ethanediyl}titanium dichloride (4a) and benzyl-substituted titanocene bis-{[4-(2-methoxyethoxy)benzyl]cyclopentadienyl}titantium(IV) dichloride (6a) were obtained and characterised. The change in the substitution pattern f the phenyl moiety from an oxygen atom to a nitrogen atom had such a big influence on the reaction that not one compound of the threee titanocene classes could be synthesised, and it was also not possible to obtain diarylmethyl-substituted titanocenes with the use of either of the fulvenes. When benzyl-substituted titanocene 6a was tested agianst pig kidney cells (LLC-PK), an antiproliferative effect that result in an IC50 value of 43 mu m, was observed. This IC50 value is in the lower range of the cytotoxicities evaluated for titanocenes up to now. ansa-Titanocene 4a surprisingly showed, when tested on the same cell line, a proliferative effect together with a fast rate of hydrolysis.

Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation

Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory, effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300 nM, 15 min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18 h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300 nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.