Self-adaptability and man-in-the-loop: a dilemma in autonomic computing systems

This paper addresses some controversial issues relating to two main questions. Firstly, we discuss 'man-in-the loop' issues in SAACS. Some people advocate this must always be so that man's decisions can override autonomic components. In this case, the system has two subsystems - man and machine. Can we, however, have a fully autonomic machine - with no man in sight; even for short periods of time? What kinds of systems require man to always be in the loop? What is the optimum balance in self-to-human control? How do we determine the optimum? How far can we go in describing self-behaviour? How does a SAACS system handle unexpected behaviour? Secondly, what are the challenges/obstacles in testing SAACS in the context of self/human dilemma? Are there any lesson to be learned from other programmes e.g. Star-wars, aviation and space explorations? What role human factors and behavioural models play whilst in interacting with SAACS?.

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pH-dependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of (125)I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3h) and ISA1 dose (0.04-100mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed approximately 60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10mg/kg to 100mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.