The effect of PEO length on the self-assembly of poly(ethylene oxide)−tetrapeptide conjugates prepared by “click” chemistry

Two series of poly(ethylene oxide)-tetrapeptide conjugates have been prepared using a “Click” reaction between an alkyne-modified tetra(phenylalanine) or tetra(valine) and various azide-terminated poly(ethylene oxide) (PEO) oligomers. Three different PEO precursors were used to prepare these conjugates, with number-average molecular weights of 350, 1200, and 1800 Da. Assembly of mPEO-F4-OEt and mPEO-V4-OEt conjugates was achieved by dialysis of a THF solution of the conjugate against water or by direct aqueous rehydration of a thin film. The PEO length has a profound effect on the outcome of the self-assembly, with the F4 conjugates giving rise to nanotubes, fibers, and wormlike micelles, respectively, as the length of the PEO block is increased. For the V4 series, the propensity to form ß-sheets dominates, and hence, the self-assembled structures are reminiscent of those formed by peptides alone, even at the longer PEO lengths. Thus, this systematic study demonstrates that the self-assembly of PEO-peptides depends on both the nature of the peptides and the relative PEO block length.

Developments of the generative topographic mapping

The generative topographic mapping (GTM) model was introduced by Bishop et al. (1998, Neural Comput. 10(1), 215-234) as a probabilistic re- formulation of the self-organizing map (SOM). It offers a number of advantages compared with the standard SOM, and has already been used in a variety of applications. In this paper we report on several extensions of the GTM, including an incremental version of the EM algorithm for estimating the model parameters, the use of local subspace models, extensions to mixed discrete and continuous data, semi-linear models which permit the use of high-dimensional manifolds whilst avoiding computational intractability, Bayesian inference applied to hyper-parameters, and an alternative framework for the GTM based on Gaussian processes. All of these developments directly exploit the probabilistic structure of the GTM, thereby allowing the underlying modelling assumptions to be made explicit. They also highlight the advantages of adopting a consistent probabilistic framework for the formulation of pattern recognition algorithms.

Dynamics and topographic organization of recursive self-organizing maps

Recently there has been an outburst of interest in extending topographic maps of vectorial data to more general data structures, such as sequences or trees. However, there is no general consensus as to how best to process sequences using topographicmaps, and this topic remains an active focus of neurocomputational research. The representational capabilities and internal representations of the models are not well understood. Here, we rigorously analyze a generalization of the self-organizingmap (SOM) for processing sequential data, recursive SOM (RecSOM) (Voegtlin, 2002), as a nonautonomous dynamical system consisting of a set of fixed input maps. We argue that contractive fixed-input maps are likely to produce Markovian organizations of receptive fields on the RecSOM map. We derive bounds on parameter β (weighting the importance of importing past information when processing sequences) under which contractiveness of the fixed-input maps is guaranteed. Some generalizations of SOM contain a dynamic module responsible for processing temporal contexts as an integral part of the model. We show that Markovian topographic maps of sequential data can be produced using a simple fixed (nonadaptable) dynamic module externally feeding a standard topographic model designed to process static vectorial data of fixed dimensionality (e.g., SOM). However, by allowing trainable feedback connections, one can obtain Markovian maps with superior memory depth and topography preservation. We elaborate on the importance of non-Markovian organizations in topographic maps of sequential data. © 2006 Massachusetts Institute of Technology.

A pilot study to evaluate the self-medication system for liver transplant patients at the Queen Elizabeth Hospital in Birmingham

Background and Objective: Medication non-compliance is a considerable obstacle in achievinga therapeutic goal, whichcan result in poorerhealthcare outcomes, increased expenditure, wastage and potential for medication resistance. The UK Government’s Audit Commission’s publication ‘A Spoonful of Sugar’1 addresses these issues and promotes self-medication systems as a possible solution. The self-medication system within the Liver Transplant Unit (LTU) was implemented to induct patients onto new post- transplantation medication regimes ready for discharge. The system involves initial consultations with both the Liver Transplant Pharmacist and Trans- plant Co-ordinator, supported with additional advice as and when necessary. Design: Following ethical approval, evaluation of the self-medication sys- tem for liver transplant patients was conducted between January and March 2004 via two methods: audit and structured post-transplantation interview. The audit enabled any discrepancies between current Hospital guidelines and Liver Transplant Unit (LTU) practices to be highlighted. Patient interviews generated a retrospective insight into patient acceptance of the self-medication system. Setting: LTU, Queen Elizabeth Hospital, Birmingham, England. Main Outcome Measures: LTU compliance with Hospital self-medication guidelines and patient insight into self-medication system. Results: A total of seven patients were audited. Findings illustrated that self- medication by transplant patients is a complex process which was not fully addressed by current Hospital self-medication guidelines. Twenty-three patients were interviewed, showing an overwhelming positive attitude to- wards participating in their own care and a high level of understanding towards their individual medication regimes. Following a drugs counselling session, 100% of patients understood why they were taking their medica- tion, and their doses, 95% understood how to take their medication and 85% were aware of potential side effects. Conclusions: From this pilot evaluation it can be stated that the LTU self-medication system is appreciated by patients and assists them in fully understanding their medication regimes. There appear to be no major defects in the system. However areas such as communication barriers and on-going internet education were illustrated as areas for possible future investigation. References: 1. Audit Commission. A spoonful of sugar – medicines management in NHS hospitals. London: Audit Commission; 2001.