On the persistence of computer dreams: an application framework for robust adaptive deployment

The anticipated rewards of adaptive approaches will only be fully realised when autonomic algorithms can take configuration and deployment decisions that match and exceed those of human engineers. Such decisions are typically characterised as being based on a foundation of experience and knowledge. In humans, these underpinnings are themselves founded on the ashes of failure, the exuberance of courage and (sometimes) the outrageousness of fortune. In this paper we describe an application framework that will allow the incorporation of similarly risky, error prone and downright dangerous software artefacts into live systems – without undermining the certainty of correctness at application level. We achieve this by introducing the notion of application dreaming.

Capturing teachers' experience of learning design through case studies

This article distinguishes three dimensions to learning design: a technological infrastructure, a conceptual framework for practice that focuses on the creation of structured sequences of learning activities, and a way to represent and share practice through the use of mediating artefacts. Focusing initially on the second of these dimensions, the article reports the key findings from an exploratory study, eLIDA CAMEL. This project examined a hitherto under-researched aspect of learning design: what teachers who are new to the domain perceive to be its value as a framework for practice in the design of both flexible and classroom-based learning. Data collection comprised 13 case studies constructed from participants' self-reports. These suggest that providing students with a structured sequence of learning activities was the major value to teachers. The article additionally discusses the potential of such case studies to function as mediating artefacts for practitioners who are considering experimenting with learning design.

The use of fluorescence microscopy to define polymer localisation to the late endocytic compartments in cells that are targets for drug delivery

Macromolecular therapeutics and nano-sized drug delivery systems often require localisation to specific intracellular compartments. In particular, efficient endosomal escape, retrograde trafficking, or late endocytic/lysosomal activation are often prerequisites for pharmacological activity. The aim of this study was to define a fluorescence microscopy technique able to confirm the localisation of water-soluble polymeric carriers to late endocytic intracellular compartments. Three polymeric carriers of different molecular weight and character were studied: dextrin (Mw~50,000 g/mol), a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer (Mw approximately 35,000 g/mol) and polyethylene glycol (PEG) (Mw 5000 g/mol). They were labelled with Oregon Green (OG) (0.3-3 wt.%; <3% free OG in respect of total). A panel of relevant target cells were used: THP-1, ARPE-19, and MCF-7 cells, and primary bovine chondrocytes (currently being used to evaluate novel polymer therapeutics) as well as NRK and Vero cells as reference controls. Specific intracellular compartments were marked using either endocytosed physiological standards, Marine Blue (MB) or Texas-red (TxR)-Wheat germ agglutinin (WGA), TxR-Bovine Serum Albumin (BSA), TxR-dextran, ricin holotoxin, C6-7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)-labelled ceramide and TxR-shiga toxin B chain, or post-fixation immuno-staining for early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins (LAMP-1, Lgp-120 or CD63) or the Golgi marker GM130. Co-localisation with polymer-OG conjugates confirmed transfer to discreet, late endocytic (including lysosomal) compartments in all cells types. The technique described here is a particularly powerful tool as it circumvents fixation artefacts ensuring the retention of water-soluble polymers within the vesicles they occupy.