5,144 research outputs found
Planning to fail? A critique of current project definitions as a basis for benefit realisation
This paper explores the notion that current project definitions provide a singular view: that of project managers and this perspective leads to limited boundaries which are prejudicial to good project delivery. Thus, it takes a radically different view of project failure from that which is generally accepted.
We will contend that viewing projects through this limiting lens often results in failure being attributed to reasons that are only symptomatic, and that root causes are not uncovered. The paper establishes that project failure is endemic and has existed for over 25 years. Attempts to apply control and prescriptive methodologies have made the position worse.
We go on to describe an appreciative research project that uses a definition of projects emphasising the realisation of benefits, rather than production of outputs. We then give an overview of the success this has achieved so far. We conclude by making some proposals for further research
Multiscale benchmarking of drug delivery vectors
Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose–response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo
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Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure–response characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle–cell interaction dynamics and accurately predicts the population exposure–response curves from individual cell heterogeneity distributions
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