The plasticity of NBS resistance genes in sorghum is driven by multiple evolutionary processes

Background Increased disease resistance is a key target of cereal breeding programs, with disease outbreaks continuing to threaten global food production, particularly in Africa. Of the disease resistance gene families, the nucleotide-binding site plus leucine-rich repeat (NBS-LRR) family is the most prevalent and ancient and is also one of the largest gene families known in plants. The sequence diversity in NBS-encoding genes was explored in sorghum, a critical food staple in Africa, with comparisons to rice and maize and with comparisons to fungal pathogen resistance QTL. Results In sorghum, NBS-encoding genes had significantly higher diversity in comparison to non NBS-encoding genes and were significantly enriched in regions of the genome under purifying and balancing selection, both through domestication and improvement. Ancestral genes, pre-dating species divergence, were more abundant in regions with signatures of selection than in regions not under selection. Sorghum NBS-encoding genes were also significantly enriched in the regions of the genome containing fungal pathogen disease resistance QTL; with the diversity of the NBS-encoding genes influenced by the type of co-locating biotic stress resistance QTL. Conclusions NBS-encoding genes are under strong selection pressure in sorghum, through the contrasting evolutionary processes of purifying and balancing selection. Such contrasting evolutionary processes have impacted ancestral genes more than species-specific genes. Fungal disease resistance hot-spots in the genome, with resistance against multiple pathogens, provides further insight into the mechanisms that cereals use in the “arms race” with rapidly evolving pathogens in addition to providing plant breeders with selection targets for fast-tracking the development of high performing varieties with more durable pathogen resistance.

An evaluation of current and future botnet defenses

Botnets are large networks of compromised machines under the control of a bot master. These botnets constantly evolve their defences to allow the continuation of their malicious activities. The constant development of new botnet mitigation strategies and their subsequent defensive countermeasures has lead to a technological arms race, one which the bot masters have significant incentives to win. This dissertation analyzes the current and future states of the botnet arms race by introducing a taxonomy of botnet defences and a simulation framework for evaluating botnet techniques. The taxonomy covers current botnet techniques and highlights possible future techniques for further analysis under the simulation framework. This framework allows the evaluation of the effect techniques such as reputation systems and proof of work schemes have on the resources required to disable a peer-to-peer botnet. Given the increase in the resources required, our results suggest that the prospects of eliminating the botnet threat are limited.

Perpetuating Racism: Legal Education, Race and Social Justice

By presenting the results of a content analysis of Australian undergraduate legal education, this paper examines the extent to which issues of race, ethnicity, discrimination, and multiculturalism feature within this component of the moral, ethical, and professional development of legal professionals. It will demonstrate that instead of encouraging a deep, critical and contextual understanding of such issues, legal education provides a relatively superficial one, which has important implications for the role that legal professionals play in overcoming injustices such as institutional racism, and the kinds of social reform that they are likely to undertake.

A generative design system based on evolutionary and mathematical functions

Previous work by Professor John Frazer on Evolutionary Architecture provides a basis for the development of a system evolving architectural envelopes in a generic and abstract manner. Recent research by the authors has focused on the implementation of a virtual environment for the automatic generation and exploration of complex forms and architectural envelopes based on solid modelling techniques and the integration of evolutionary algorithms, enhanced computational and mathematical models. Abstract data types are introduced for genotypes in a genetic algorithm order to develop complex models using generative and evolutionary computing techniques. Multi-objective optimisation techniques are employed for defining the fitness function in the evaluation process.

An evolutionary framework for enhancing design

A computational framework for enhancing design in an evolutionary approach with a dynamic hierarchical structure is presented in this paper. This framework can be used as an evolutionary kernel for building computer-supported design systems. It provides computational components for generating, adapting and exploring alternative design solutions at multiple levels of abstraction with hierarchically structured design representations. In this paper, preliminary experimental results of using this framework in several design applications are presented.

A natural model for architecture : the nature of the evolutionary model 1995

John Frazer's architectural work is inspired by living and generative processes. Both evolutionary and revolutionary, it explores informatin ecologies and the dynamics of the spaces between objects. Fuelled by an interest in the cybernetic work of Gordon Pask and Norbert Wiener, and the possibilities of the computer and the "new science" it has facilitated, Frazer and his team of collaborators have conducted a series of experiments that utilize genetic algorithms, cellular automata, emergent behaviour, complexity and feedback loops to create a truly dynamic architecture. Frazer studied at the Architectural Association (AA) in London from 1963 to 1969, and later became unit master of Diploma Unit 11 there. He was subsequently Director of Computer-Aided Design at the University of Ulter - a post he held while writing An Evolutionary Architecture in 1995 - and a lecturer at the University of Cambridge. In 1983 he co-founded Autographics Software Ltd, which pioneered microprocessor graphics. Frazer was awarded a person chair at the University of Ulster in 1984. In Frazer's hands, architecture becomes machine-readable, formally open-ended and responsive. His work as computer consultant to Cedric Price's Generator Project of 1976 (see P84)led to the development of a series of tools and processes; these have resulted in projects such as the Calbuild Kit (1985) and the Universal Constructor (1990). These subsequent computer-orientated architectural machines are makers of architectural form beyond the full control of the architect-programmer. Frazer makes much reference to the multi-celled relationships found in nature, and their ongoing morphosis in response to continually changing contextual criteria. He defines the elements that describe his evolutionary architectural model thus: "A genetic code script, rules for the development of the code, mapping of the code to a virtual model, the nature of the environment for the development of the model and, most importantly, the criteria for selection. In setting out these parameters for designing evolutionary architectures, Frazer goes beyond the usual notions of architectural beauty and aesthetics. Nevertheless his work is not without an aesthetic: some pieces are a frenzy of mad wire, while others have a modularity that is reminiscent of biological form. Algorithms form the basis of Frazer's designs. These algorithms determine a variety of formal results dependent on the nature of the information they are given. His work, therefore, is always dynamic, always evolving and always different. Designing with algorithms is also critical to other architects featured in this book, such as Marcos Novak (see p150). Frazer has made an unparalleled contribution to defining architectural possibilities for the twenty-first century, and remains an inspiration to architects seeking to create responsive environments. Architects were initially slow to pick up on the opportunities that the computer provides. These opportunities are both representational and spatial: computers can help architects draw buildings and, more importantly, they can help architects create varied spaces, both virtual and actual. Frazer's work was groundbreaking in this respect, and well before its time.

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Creative design and the generative evolutionary paradigm

Design as seen from the designer's perspective is a series of amazing imaginative jumps or creative leaps. But design as seen by the design historian is a smooth progression or evolution of ideas that they seem self-evident and inevitable after the event. But the next step is anything but obvious for the artist/creator/inventor/designer stuck at that point just before the creative leap. They know where they have come from and have a general sense of where they are going, but often do not have a precise target or goal. This is why it is misleading to talk of design as a problem-solving activity - it is better defined as a problem-finding activity. This has been very frustrating for those trying to assist the design process with computer-based, problem-solving techniques. By the time the problem has been defined, it has been solved. Indeed the solution is often the very definition of the problem. Design must be creative-or it is mere imitation. But since this crucial creative leap seem inevitable after the event, the question must arise, can we find some way of searching the space ahead? Of course there are serious problems of knowing what we are looking for and the vastness of the search space. It may be better to discard altogether the term "searching" in the context of the design process: Conceptual analogies such as search, search spaces and fitness landscapes aim to elucidate the design process. However, the vastness of the multidimensional spaces involved make these analogies misguided and they thereby actually result in further confounding the issue. The term search becomes a misnomer since it has connotations that imply that it is possible to find what you are looking for. In such vast spaces the term search must be discarded. Thus, any attempt at searching for the highest peak in the fitness landscape as an optimal solution is also meaningless. Futhermore, even the very existence of a fitness landscape is fallacious. Although alternatives in the same region of the vast space can be compared to one another, distant alternatives will stem from radically different roots and will therefore not be comparable in any straightforward manner (Janssen 2000). Nevertheless we still have this tantalizing possibility that if a creative idea seems inevitable after the event, then somehow might the process be rserved? This may be as improbable as attempting to reverse time. A more helpful analogy is from nature, where it is generally assumed that the process of evolution is not long-term goal directed or teleological. Dennett points out a common minsunderstanding of Darwinism: the idea that evolution by natural selection is a procedure for producing human beings. Evolution can have produced humankind by an algorithmic process, without its being true that evolution is an algorithm for producing us. If we were to wind the tape of life back and run this algorithm again, the likelihood of "us" being created again is infinitesimally small (Gould 1989; Dennett 1995). But nevertheless Mother Nature has proved a remarkably successful, resourceful, and imaginative inventor generating a constant flow of incredible new design ideas to fire our imagination. Hence the current interest in the potential of the evolutionary paradigm in design. These evolutionary methods are frequently based on techniques such as the application of evolutionary algorithms that are usually thought of as search algorithms. It is necessary to abandon such connections with searching and see the evolutionary algorithm as a direct analogy with the evolutionary processes of nature. The process of natural selection can generate a wealth of alternative experiements, and the better ones survive. There is no one solution, there is no optimal solution, but there is continuous experiment. Nature is profligate with her prototyping and ruthless in her elimination of less successful experiments. Most importantly, nature has all the time in the world. As designers we cannot afford prototyping and ruthless experiment, nor can we operate on the time scale of the natural design process. Instead we can use the computer to compress space and time and to perform virtual prototyping and evaluation before committing ourselves to actual prototypes. This is the hypothesis underlying the evolutionary paradigm in design (1992, 1995).

Co-creating games: A co-evolutionary analysis

ABSTRACT. The phenomenon of consumer co-creation is often framed in terms of whether either economic market forces or socio-cultural non-market forces ultimately dominate. We propose an alternate model of consumer co-creation in terms of co-evolution between markets and non-markets. Our model is based on a recent ethnographic study of a massively multiplayer online game through its development, release and ultimate failure, and cast in terms of two explanatory models: multiple games and social network markets. We conclude that consumer co-creation is indeed complex, but in ways that relate to both emergent market expectations and the evolution of markets, not to the transcendence of markets.