Picbreeder: a case study in collaborative evolutionary exploration of design space

For domains in which fitness is subjective or difficult to express formally, interactive evolutionary computation (IEC) is a natural choice. It is possible that a collaborative process combining feedback from multiple users can improve the quality and quantity of generated artifacts. Picbreeder, a large-scale online experiment in collaborative interactive evolution (CIE), explores this potential. Picbreeder is an online community in which users can evolve and share images, and most importantly, continue evolving others' images. Through this process of branching from other images, and through continually increasing image complexity made possible by the underlying neuroevolution of augmenting topologies (NEAT) algorithm, evolved images proliferate unlike in any other current IEC system. This paper discusses not only the strengths of the Picbreeder approach, but its challenges and shortcomings as well, in the hope that lessons learned will inform the design of future CIE systems.     

The IGF-I receptor in mitogenesis and transformation of mouse embryo cells: role of receptor number

The type 1 receptor for insulin-like growth factors (IGF-IR) plays an important role in the growth and transformation of several types of cells. We have investigated the role of IGF-IR number in IGF-I-mediated mitogenesis and transformation of mouse embryo fibroblasts. We have used R- cells (3T3-like cells originating from mouse embryos with a targeted disruption of the IGF-IR genes) transfected with a plasmid expressing the human IGF-IR cDNA to generate clones with receptor numbers ranging from zero to 10(6) receptors per cell. In this model, between 15,000 and 22,000 receptors per cell are sufficient to render mouse embryo cells competent to grow in serum-free medium supplemented solely with IGF-I. For growth in soft agar, 30,000 receptors per cell seem to be the minimum requirement. These experiments indicate that a small increment in the number of receptors per cell, well within the physiological range, can modulate the mitogenic and transforming activities of the IGF-IR in 3T3-like cells.     

Simulator evaluation of drivers' speed, deceleration and lateral position at rural intersections in relation to different perceptual cues

Aim of the study was to investigate, by means of a driving simulator experiment, drivers’ behaviour in terms of speed, deceleration, and lateral position on major approaches of rural intersections in relation to different perceptual cues.In the experiment, ten different design conditions with and without speed-reducing treatments along the approach to the intersection were tested. Twenty-three drivers drove a test route two times and data from the second drive were used for comparison. The order of the ten design conditions was counterbalanced for all the drivers to minimize the presentation order effect. Three different data analysis techniques were used: (a) cluster analysis of speed and lateral position data, (b) statistical tests of speed and lateral position data, and (c) categorical analysis of deceleration behaviour patterns.The most effective treatments were the dragon teeth markings (based on the principle of optical road narrowing), the colored intersection area (based on the principle of intersection highlighting), and the raised median island (based on the principle of physical road narrowing). These measures, in comparison to the base intersection, produced: (1) a significant speed reduction starting from 250 m before the intersection in the range between 13 and 23 km/h, (2) a significant change in the deceleration behaviour with a reduction in the proportion of drivers which did not decelerate, and (3) a shift away from the intersection of the deceleration beginning. Given the significant effects on drivers’ behaviour, the dragon teeth markings, the colored intersection area, and the raised median island are strongly recommended for real world implementation.     

Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.     

Evaluation of the genotoxicity data on caffeine

The potential health effects of caffeine have been investigated for over two decades in a variety of model systems including limited human populations. Thus, it is probably one of the most extensively studied natural occurring dietary chemicals. One area which has received a great deal of attention is the potential genotoxic property of caffeine. To better understand whether caffeine itself or in combination with other agents exhibits genotoxic effects, hundreds of research studies published over the past 5 years have been reviewed. These studies have utilized a number of animal, prokaryotic, eukaryotic, and mammalian cell culture model systems. They have investigated the effects of caffeine alone or in combination with other physical and chemical agents on many aspects of cell division, chromosome stability, toxicity, and mutagenicity. A number of effects have been observed. However, they usually appear after very high doses (> 1 mM) of caffeine in combination with genotoxins, and are usually specific to certain cell types and/or cellular parameters. Humans, on the other hand, consume much less caffeine in the diet, with peak serum levels in the micromolar range 10- and 1000-fold higher compared to levels in animal and cell culture models. Thus, it is difficult to implicate caffeine, even at the highest levels of dietary consumption, as a genotoxin to humans.     

Codesign of architectures for automotive powertrain modules

To guide design decisions in developing an optimized architecture for automotive powertrain modules, we relied upon analysis, a key to hardware-software codesign. Complicating such efforts are ongoing refinements to the underlying algorithms, ever stricter government standards, reusability demands, and late-arriving specifications for the controlled components. In our approach, configuration-level analysis lets us quickly and efficiently explore a large design space. Behavioral-level analysis validates decisions and optimizes hardware and software. Our codesign methodology extends to similar real-time embedded systems     

Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis

Interferon gamma (IFN-gamma) inhibits in vitro the activation of hepatic stellate cells (HSC), the primary extracellular matrix-producing cells in liver fibrosis. This study was undertaken to determine in vivo the effect of IFN-gamma in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an early response to cell injury. Rats were killed after 1 or 3 weeks of treatment with DMN, IFN-gamma, DMN + IFN-gamma, or saline. Immunohistochemistry was used to identify proliferating (desmin-positive/bromodeoxyuridine (BrdU)-positive cells) and activated (alpha-smooth-muscle actin [alpha-SMA]-positive cells) HSCs. Collagen deposition was determined colorimetrically and by morphometry. The parenchymal extension of desmin- and actin-positive cells and of fibrotic tissue was measured by point-counting technique and expressed as a percentage of area. Western blot was used to determine laminin and fibronectin accumulation. The levels of messenger RNA (mRNA) for procollagen type I, fibronectin, and laminin were evaluated by Northern blot. No differences were observed in rats treated with either saline or IFN-gamma alone. IFN-gamma reduced HSC activation induced by liver injury, as shown by the decreased number of proliferating HSC and the reduction of parenchymal area occupied by alpha-SMA-positive cells observed in DMN + IFN-gamma-treated animals compared with the DMN group. This was associated with reduced collagen, laminin, and fibronectin accumulation and lower levels of mRNA for procollagen type I, fibronectin, and laminin in the DMN + IFN-gamma group. Thus, this study indicates that IFN-gamma reduces extracellular matrix deposition in vivo by inhibition of HSC activation.