Evolving controllers for a homogeneous system of physical robots: structured cooperation with minimal sensors

We report on recent work in which we employed artificial evolution to design neural network controllers for small, homogeneous teams of mobile autonomous robots. The robots were evolved to perform a formation-movement task from random starting positions, equipped only with infrared sensors. The dual constraints of homogeneity and minimal sensors make this a non-trivial task. We describe the behaviour of a successful system in which robots adopt and maintain functionally distinct roles in order to achieve the task. We believe this to be the first example of the use of artificial evolution to design coordinated, cooperative behaviour for real robots.     

Researching haptics in higher education: The complexity of developing haptics virtual learning systems and evaluating its impact on students’ learning

hapTEL, an interdisciplinary project funded by two UK research councils from 2007 to 2011, involves a large interdisciplinary team (with undergraduate and post-graduate student participants) which has been developing and evaluating a virtual learning system within an HE healthcare education setting, working on three overlapping strands. Strand 1 involves the technical development and evaluation of the hapTEL workstation which simulates clinical conditions for dental training including haptics (sense of touch). Strand 2 involves examining the traditional undergraduate curriculum and how this could benefit from the use of haptics. Strand 3 is concerned with the educational evaluation of the impact of the work carried out within Strands 1 and 2. Two theoretical frameworks (Entwistle, (1987) and Webb and Cox (2004)) have been used to identify as many factors as possible which could affect the impact of Technology Enhanced Learning (TEL) on the quality of the learning achieved. These frameworks have formed a foundation for measuring the impact of TEL on curriculum change, teachers’ pedagogical practices, students’ learning and on institutional practices. A range of quantitative and qualitative methods were designed, piloted and evaluated in order to measure the impact of TEL on teaching and learning; and to have a rich and robust data set which also addresses the variables in the frameworks. The results from using these frameworks show that institutional and departmental factors should be considered when evaluating the impact of TEL in higher education and that these had a major influence on the design and curriculum integration of the hapTEL systems. We have also shown that by involving the end users from the beginning enabled not only an enhancement of the students’ learning experiences but also a modification to the traditional curriculum itself and the successful integration of TEL within a very traditional undergraduate higher education dental curriculum. The conclusions from this paper confirm earlier reviews of researching TEL that technology integration is extremely complex and the related research requires a comprehensive approach of both quantitative and qualitative methods if one is to take account of the range of variables identified by theoretical frameworks. Finally, repeating the range of empirical investigations for a second year enables researchers to validate the effectiveness of the methods used in the initial year and thereby maximise the reliability and generalisability of the research outcomes.     

Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway

We have molecularly analyzed three genes, sqv-3, sqv-7, and sqv-8, that are required for wild-type vulval invagination in Caenorhabditis elegans. The predicted SQV-8 protein is similar in sequence to two mammalian beta(1,3)-glucuronyltransferases, one of which adds glucuronic acid to protein-linked galactose-beta(1, 4)-N-acetylglucosamine. SQV-3 is similar to a family of glycosyltransferases that includes vertebrate beta(1, 4)-galactosyltransferases, which create galactose-beta(1, 4)-N-acetylglucosamine linkages. One model is therefore that SQV-8 uses a SQV-3 product as a substrate. SQV-7 is similar to members of a family of nucleotide-sugar transporters. The sqv genes therefore are likely to encode components of a conserved glycosylation pathway that assembles a C. elegans carbohydrate moiety, the absence of which perturbs vulval invagination.     

Light-dependent changes in outer segment free-Ca2+ concentration in salamander cone photoreceptors

Simultaneous measurements of photocurrent and outer segment Ca2+ were made from isolated salamander cone photoreceptors. While recording the photocurrent from the inner segment, which was drawn into a suction pipette, a laser spot confocal technique was employed to evoke fluorescence from the outer segment of a cone loaded with the Ca2+ indicator fluo-3. When a dark-adapted cone was exposed to the intense illumination of the laser, the circulating current was completely suppressed and fluo-3 fluorescence rapidly declined. In the more numerous red-sensitive cones this light-induced decay in fluo-3 fluorescence was best fitted as the sum of two decaying exponentials with time constants of 43 +/- 2.4 and 640 +/- 55 ms (mean +/- SEM, n = 25) and unequal amplitudes: the faster component was 1.7-fold larger than the slower. In blue-sensitive cones, the decay in fluorescence was slower, with time constants of 140 +/- 30 and 1,400 +/- 300 ms, and nearly equal amplitudes. Calibration of fluo-3 fluorescence in situ from red-sensitive cones allowed the calculation of the free-Ca2+ concentration, yielding values of 410 +/- 37 nM in the dark-adapted outer segment and 5.5 +/- 2.4 nM after saturating illumination (mean +/- SEM, n = 8). Photopigment bleaching by the laser resulted in a considerable reduction in light sensitivity and a maintained decrease in outer segment Ca2+ concentration. When the photopigment was regenerated by applying exogenous 11-cis-retinal, both the light sensitivity and fluo-3 fluorescence recovered rapidly to near dark-adapted levels. Regeneration of the photopigment allowed repeated measurements of fluo-3 fluorescence to be made from a single red-sensitive cone during adaptation to steady light over a range of intensities. These measurements demonstrated that the outer segment Ca2+ concentration declines in a graded manner during adaptation to background light, varying linearly with the magnitude of the circulating current.     

Cysteine-scanning mutagenesis of helix IV and the adjoining loops in the lactose permease of Escherichia coli: Glu126 and Arg144 are essential. off

Cys-scanning mutagenesis has been applied to the remaining 45 residues in lactose permease that have not been mutagenized previously (from Gln100 to Arg144 which comprise helix IV and adjoining loops). Of the 45 single-Cys mutants, 26 accumulate lactose to > 75% of the steady state observed with Cys-less permease, and 14 mutants exhibit lower but significant levels of accumulation (35-65% of Cys-less permease). Permease with Phe140-->Cys or Lys131-->Cys exhibits low activity (15-20% of Cys-less permease), while mutants Gly115-->Cys, Glu126-->Cys and Arg144-->Cys are completely unable to accumulate the dissacharide. However, Cys-less permease with Ala or Pro in place of Gly115 is highly active, and replacement of Lys131 or Phe140 with Cys in wild-type permease has a less deleterious effect on activity. In contrast, mutant Glu126-->Cys or Arg144-->Cys is inactive with respect to both uphill and downhill transport in either Cys-less or wild-type permease. Furthermore, mutants Glu126-->Ala or Gln and Arg144-->Ala or Gln are also inactive in both backgrounds, and activity is not rescued by double neutral replacements or inversion of the charged residues at these positions. Finally, a mutant with Lys in place of Arg144 accumulates lactose to about 25% of the steady state of wild-type, but at a slow rate. Replacement of Glu126 with Asp, in contrast, has relatively little effect on activity. None of the effects can be attributed to decreased expression of the mutants, as judged by immunoblot analysis. Although the activity of most of the single-Cys mutants is unaffected by N-ethylmaleimide, Cys replacement at three positions (Ala127, Val132, or Phe138) renders the permease highly sensitive to alkylation. The results indicate that the cytoplasmic loop between helices IV and V, where insertional mutagenesis has little effect on activity [McKenna, E., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11954-11958], contains residues that play an important role in permease activity and that a carboxyl group at position 126 and a positive charge at position 144 are absolutely required.     

An in vitro tissue culture bilayer model to examine early events in Mycobacterium tuberculosis infection

A tissue culture bilayer system that mimics some aspects of early alveolar infection by Mycobacterium tuberculosis was developed. This model incorporates human lung epithelial type II pneumocyte (A549) (upper chamber) and endothelial cell (lower chamber) layers separated by a microporous membrane. This construction makes it possible to observe and quantify the passage of bacteria through the two layers, to observe the interaction of the bacteria with the various cell types, and to examine the basic mechanisms of immune cell recruitment to the site of infection. After 10(7) organisms were added to the upper chamber we microscopically observed large numbers of bacteria attached to and within the pneumocytes and we determined by viable-cell counting that a small percentage of the inoculum (0.02 to 0.43%) passed through the bilayer into the lower chamber. When peripheral blood mononuclear cells were added to the lower chamber, microscopic examination indicated a migration of the mononuclear cells through the bilayer to the apical surface, where they were seen associated with the mycobacteria on the pneumocytes. The added complexity of the bilayer system offers an opportunity to define more precisely the roles of the various lung cell types in the pathogenesis of early tuberculosis.     

Engineering in Genomics [variable number tandem repeats as agents of functional regulation in the genome]

The explosion of genetic data availability in the last decade has opened up many new avenues for the application of genetics to the improvement of human health, particularly, the common and complex disorders, which previously largely defied researchers seeking to understand their etiology. However, the utilization of this data in healthcare and by the pharmaceutical industry is still in its infancy, with the current focus being almost solely on two forms of genetic variation single nucleotide polymorphisms (SNPs), involving the substitution of one base in DNA for another and copy number variations, involving the deletion and multiplication of regions > 1,000 base pairs (bp). However, there is currently a relative paucity of funding and general interest in a third form of variation called microsatellites and mini- satellites.