Stigmergy refers to indirect communication that was originally found in biological systems. It is used for self-organization by ants, bees, and flocks of birds, by allowing individuals to focus on local information. Through local communication among individuals, larger patterns are formed without centralized communication. This self-organization is just one type of system studied within complex systems. Systems of ants, bees, and flocks of birds are considered complex because they exhibit emergent behavior: the outcome is more than the sum of the individual parts. Emergent behavior can be found in many other systems as well. One example is the Internet, which is a series of computers organized in a self-organized fashion. Complexity can also be defined through properties other than emergent behavior, such as existing on multiple scales. Many biological systems are multi-scale. For instance, cancer exists on many scales, including the sub-cellular and cellular levels. Many computing systems are also multi-scale, as there may be both individual and system-wide controls interacting together to determine the output. Many multi-agent systems would fall into this category, as would many large software systems. In this dissertation I examine complex systems in artificial intelligence and biology: the growth of cancer, population dynamics, emotions, multi-agent fault tolerance, and real-time strategic AI for games. My goal is twofold: a) to develop novel computational models of complex biological systems, and b) to tackle key AI research questions by proposing new algorithms and techniques that are inspired by those complex biological systems. In all of these cases I design variations on stigmergic communication to accomplish the task at hand. My contributions are a new agent-based cancer growth model, a proposed use of location communication for removing cancer, improved multi-agent fault tolerance through localized messaging, a new approach to modeling predator-prey dynamics using computational emotions, and improved strategic game AI through computational emotions.

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<p>The entrapment of biomolecules within TEOS-based sol-gel derived organic/inorganic nanocomposite materials has proven to be a viable platform for the development of biosensors and solid-phase biocatalysts. In this thesis, a series of organically modified silica materials were prepared by a two-step aqueous processing method that was suitable for biomolecule entrapment, and were formed as submicron thick films by dipcasting. Dispersed additives, such as polymers (Class I materials) and covalently bound additives, such as organically modified silanes (Class II materials), were used to modify the internal environment compared to the undoped matrices and to correlate the properties of entrapped enzymes.</p> <p>The morphology of organically modified silica materials could be modified through the use of either separate or co-hydrolysis of the silane precursors, with the later method generating optically transparent materials. Fluorescence microscopy revealed chemical heterogeneity in materials that appeared to be homogeneous by brightfield or SEM.</p> <p>Fluorescence emission studies of a solvatochromic dye entrapped within the film confirmed that the internal chemical environment of the films was strongly affected by doping with polymers and organosilanes. The films showed a rapid initial change in chemical properties owing to solvent evaporation, followed by a much slower evolution over several months owing to continued condensation reactions within the film.</p> <p>A reagentless biosensor was designed based on co-entrapment of an enzyme and a fluorescently labeled polymer. The enzymes urease and lipase were selected for this study as both catalyze reactions that alter the local pH. By co-entrapping pH sensitive fluorophores (SNARF-I and fluorescein) bound to a high molecular weight polymer, it was possible to detect the analytes urea and glyceryl tributyrate using changes in the fluorescence intensity (fluorescein) or emission ratio (SNARF-l). By tuning the polarity of the matrix it was possible to optimize the sensitivity of the sensing film for both the polar and non-polar analyte.</p> / Doctor of Philosophy (PhD)

Published Article / Worldwide, uterine cervical cancer is one of the most frequently occurring cancers in women, with more than 80% of these cases occurring in developing countries. The South African screening policy and screening program, implemented in 2001, attempt to reduce this incidence of cervical cancer in South Africa. It is essential to treat these women with the best modalities available. This retrospective study focused specifically on the curative potential of radiotherapy administered to patients at the Oncology Department, Bloemfontein, since a new modality of high dose-rate intracavitary brachytherapy was implemented in 1994. Late radiation complications were also investigated.

This thesis presents the first investigation of the impact of GPU computing on cognitive robotics by providing a series of novel experiments in the area of action and language acquisition in humanoid robots and computer vision. Cognitive robotics is concerned with endowing robots with high-level cognitive capabilities to enable the achievement of complex goals in complex environments. Reaching the ultimate goal of developing cognitive robots will require tremendous amounts of computational power, which was until recently provided mostly by standard CPU processors. CPU cores are optimised for serial code execution at the expense of parallel execution, which renders them relatively inefficient when it comes to high-performance computing applications. The ever-increasing market demand for high-performance, real-time 3D graphics has evolved the GPU into a highly parallel, multithreaded, many-core processor extraordinary computational power and very high memory bandwidth. These vast computational resources of modern GPUs can now be used by the most of the cognitive robotics models as they tend to be inherently parallel. Various interesting and insightful cognitive models were developed and addressed important scientific questions concerning action-language acquisition and computer vision. While they have provided us with important scientific insights, their complexity and application has not improved much over the last years. The experimental tasks as well as the scale of these models are often minimised to avoid excessive training times that grow exponentially with the number of neurons and the training data. This impedes further progress and development of complex neurocontrollers that would be able to take the cognitive robotics research a step closer to reaching the ultimate goal of creating intelligent machines. This thesis presents several cases where the application of the GPU computing on cognitive robotics algorithms resulted in the development of large-scale neurocontrollers of previously unseen complexity enabling the conducting of the novel experiments described herein.

Rapid prototyping tools exist in many fields of science and engineering, but are rare in biology especially not general tools that can handle the diversity and complexity of the many spatial and temporal scales in nature. In this thesis a general use, cell-based, middle-out biology emulation programming framework (outlining a programming paradigm) is presented, that enables biologists to emulate and use virtual biological systems of previously unimaginable complexity and potentially get results accurate enough to be used in research and ultimately, in clinical practice, such as diagnosis or operations. With this technology, virtual organisms can be created that are viable, fit and can be optimised for any task that arises. The tool, realised with a programming framework created for the C++ language is detailed and demonstrated through several examples of increasing complexity, namely several example organisms and a cancer emulation, showing both viable virtual organisms and usable experimental results.

This thesis describes the studies towards the synthesis of β-amino acids found in the microsclerodermins, a family of complex macrocyclic hexapeptides. These β-amino acids have four or five contiguous stereocentres and an aliphatic side-chain. The synthetic route utilised an aminohydroxylation reaction to install the most challenging moiety in the structure - the 1,2- amino alcohol. The work aimed to construct the core structure (five contiguous stereocentres) of the β-amino acids and install the side-chain later to enable the synthesis of multiple members (A, B, F, G, H and I) of the microsclerodermin family. The synthesis started with Roche ester, which contained the first methyl stereocentre. It was converted to the diene precursor in four high yielding steps. The next two stereocentres were installed via a Sharpless asymmetric dihydroxylation. With the appropriate protecting groups in place, the remaining two stereocentres were to be installed via a Sharpless asymmetric aminohydroxylation. Various reported reagents and conditions were used to effect the transformation, but the attempts were unsuccessful. This forced us to alter our synthetic plans, and the revised synthetic route involved the use of the tethered aminohydroxylation (TA) reaction developed by the Donohoe group. After the development of an efficient protocol to prepare the TA-precursor, the alkene, with three stereocentres already in place, was successfully converted to the desired stereopentad via the TA-reaction (10 steps, 11% overall yield). With the stereopentad in hand, installation of the side-chain of the β-amino acids through an alkenyl or alkyl linkage was investigated. For alkenyl-linked side-chains, the appropriate aldehyde was synthesised, but attempts to effect the transformation via a Horner-Wadsworth- Emmons reaction or a Witting reaction failed. With lessons learnt from those, we then focused our efforts on installing an alkyl-linked side-chain. In this case, we were able to install a side- chain via a copper-mediated displacement reaction, which gave us a protected form of the precursor of the β-amino acid of microsclerodermin B. Finally, various efforts to study the reactivity of the stereopentad and the investigations into finding the most effective set of protecting groups have been used to propose a synthetic route for the incorporation of the β- amino acid into the macrocycle.

<p>S obzirom&nbsp; da su cijanobakterije (modrozelene alge) identifikovane kao jedna od<br />najperspektivnijih grupa organizama za izolaciju novih i biolo&scaron;ki aktivnih prirodnih<br />produkata, cilj ove teze bio&nbsp; je utvrđivanje biotehnolo&scaron;kog potencijala&nbsp; autohtonih<br />filamentoznih sojeva&nbsp; cijanobakterija izolovanih sa područja Vojvodine koji pripadaju<br />azotofiksirajućim rodovima&nbsp;<em> Nostoc</em>&nbsp; i&nbsp; <em>Anabaena</em>&nbsp; i neazotofiksirajućem rodu&nbsp;&nbsp;&nbsp; <em>Spirulina</em>. Biotehnolo&scaron;ki potencijal testiranih sojeva je određen&nbsp; u smislu produkcije biomase, fikobiliproteinskih pigmenata, masnih kiselina, fenolnih jedinjenja, antioksidanata, antibakterijskih i antikancerogenih agenasa. Dobijeni rezultati su pokazali&nbsp; da su produkcija biomase i sadržaj fikobiliproteinskih pigmenata kod svih testiranih sojeva zavisili od primenjenih uslova kultivacije, pri&nbsp; čemu je&nbsp; kod sojeva roda&nbsp; <em>Spirulina</em> produkcija biomase bila jače stimulisana primenom kontinualnog osvetljenja, a kod azotofiksirajućih sojeva rodova&nbsp;<em> Nostoc&nbsp;</em> i&nbsp;<em> Anabaena</em>&nbsp; organskim izvorima ugljenika (glicerolom i glukozom). Kao soj sa najvećim potencijalom za&nbsp; proizvodnju biomase izdvaja se soj&nbsp; <em>Spirulina&nbsp; S1</em>, a za produkciju fikobiliproteina sojevi&nbsp; <em>Spirulina</em>&nbsp; S1,&nbsp;<em> Nostoc</em> 2S1,&nbsp; <em>Anabaena</em>&nbsp; Č2 i&nbsp; <em>Spirulina</em>&nbsp; S2.&nbsp; Određivanjem sadržaja masnih kiselina GC-FID metodom utvrđeno je da su&nbsp; kod svih sojeva&nbsp; najzastupljenije bile palmitinska, palmitoleinska, oleinska i linolna kiselina, pri čemu su&nbsp; sojevi roda <em>Spirulina</em> produkovali i&nbsp; &gamma;-linolensku kiselinu, dok su svi&nbsp; sojevi rodova&nbsp; <em>Nostoc&nbsp;</em> i&nbsp;<em> Anabaena&nbsp;</em> produkovali&nbsp; -linoleinsku kiselinu.&nbsp; Najzastupljenije fenolne komponente testiranih etanolnih ekstrakata određene HPLC-MS/MS metodom&nbsp; bile su hinska kiselina i katehin, pri čemu je najveći sadržaj fenolnih jedinjenja registrovan kod soja&nbsp; <em>Nostoc</em>&nbsp; 2S7B. Hemijskom karakterizacijom ekstrakata kod testiranih sojeva takođe je utvrđen značaj azotnih uslova kultivacije&nbsp; u cilju povećanja produkcije&nbsp; fenolnih jedinjenja,&nbsp; kao i&nbsp; -linoleinske kiseline. Poređenjem rezultata antioksidantne aktivnosti u kori&scaron;ćenim testovima&nbsp; DPPH&nbsp; i FRAP, kao sojevi sa najvećim&nbsp; antioksidantnim potencijalom izdvajaju se&nbsp; <em>Spirulina</em>&nbsp; S1 i<em> Spirulina</em>&nbsp; S2. Antibakterijska aktivnost metanolnih ekstrakata&nbsp; registrovana je kod sojeva<em> Nostoc</em> 2S7B, <em>Nostoc</em> 2S1, <em>Anabaena</em> Č2, <em>Anabaena</em> Č5, <em>Spirulina</em> S1 i&nbsp;<em> Spirulina</em> S2, koji su ispoljili efekat na Gram-pozitivne i Gram-negativne bakterije, pri čemu su&nbsp; sojevi <em>Anabaena</em>&nbsp; Č2,<em> Nostoc&nbsp;</em> 2S7B&nbsp; i&nbsp; <em>Nostoc</em>&nbsp; 2S1&nbsp; delovali na najvi&scaron;e bakterijskih sojeva.&nbsp; Kod svih testiranih sojeva je primenom MTT testa uočena antikancerogena tj. citotoksična aktivnost dimetil sulfoksidnih (DMSO) ekstrakata prema HepG2 ćelijskoj liniji, među kojima su najveću aktivnost&nbsp; ispoljili sojevi&nbsp;<em> Nostoc</em>&nbsp; LC1B i&nbsp; <em>Nostoc&nbsp; </em>2S7B.&nbsp; Primenom bioeseja&nbsp; <em>Artemia salina, Daphnia magna</em>&nbsp; i&nbsp;&nbsp;<em> Danio rerio&nbsp; </em>konstatovan je mali broj sojeva koji su ispoljili toksičnost na test organizme, dok na ćelijsku liniju&nbsp; RTL-W1&nbsp; testirani sojevi nisu ispoljili citotoksičnost&nbsp;<em> in vitro</em>, &scaron;to sa aspekta potencijalne biotehnolo&scaron;ke primene sojeva ima veliki značaj. Kao najtoksičniji izdvojili su se sojevi<em>&nbsp; Nostoc&nbsp; </em>LC1B&nbsp; i <em>Nostoc </em>S8 koji su ispoljili&nbsp; toksičnost u sva tri bioeseja. Ispitivanjem toksičnosti<em> in vitro</em> u enzimskim esejima konstatovano je da je manji broj sojeva inhibirao aktivnost enzimaprotein fosfataze 1 (PP1) u odnosu na aktivnost enzima&nbsp; acetilholinesteraze&nbsp; (AChE). Primenom Analitičkog hijerarhijskog procesa u grupnom kontekstu, najveću težinu su dobili kriterijumi antikancerogena ativnost, produkcija biomase i sadržaj fikocijanina, navedenim redom. Konačno, u vi&scaron;ekriterijumskom kontekstu najbolje rangiran soj je<br /><em>Spirulina</em> S1, na drugom mestu je soj <em>Spirulina</em> S2, dok je na trećem soj&nbsp;<em> Nostoc&nbsp; </em>LC1B.</p> / <p>Cyanobacteria (blue-green algae) have been identified as one&nbsp; of the most promising groups of organisms for the isolation of new and biologically active natural products, therefore, the aim of this thesis was to determine the biotechnological potential of autochthonous filamentous cyanobacterial strains isolated from&nbsp; Vojvodina region,&nbsp; which belong to the N₂-fixing genera&nbsp; <em>Nostoc</em>&nbsp; and&nbsp; Anabaena&nbsp; and non-N₂-fixing genus&nbsp; <em>Spirulina</em>. Biotechnological potential of tested strains was determined using the production of biomass, phycobiliprotein pigments, fatty acids, phenolic co mpounds, antioxidants, antibacterial and anticancer agents. The obtained results showed that the production of biomass and phycobiliprotein pigments, in all tested strains, depended on the cultivationconditions, whereas biomass production was strongly stimulated by continuous light in<em> Spirulina</em>&nbsp; strains, and by organic carbon sources (glycerol and glucose) in N₂-fixingstrains. The highest potential for biomass production was shown in&nbsp;<em> Spirulina</em>&nbsp; S1 strain.On the other hand, the highest potential&nbsp; for the production of phycobiliproteins wasshown in strains&nbsp; <em>Spirulina</em>&nbsp; S1,&nbsp; <em>Nostoc&nbsp;</em> 2S1,&nbsp; <em>Anabaena</em> C2 and&nbsp; <em>Spirulina</em>&nbsp; S2. By determination of the content of fatty acids using GC-FID method it was found that in allthe tested strains the most common fatty acids were palmit ic, palmitoleic, oleic andlinoleic acid, whereby the strains of the genus&nbsp; <em>Spirulina</em> produced &gamma;-linolenic acid as well,while all strains of the<em> Nostoc&nbsp;</em> and <em>Anabaena&nbsp;</em> genera produced y-linolenic acid. The most frequent phenolic compounds of tested strains determined by using the HPLC-MS/MSmethod were quinic acid and catechin, with the highest content of phenolic compounds registered in Nostoc&nbsp; strain 2S7B. By chemical characterization of the extracts in the tested strains it was also stated a significance of&nbsp; the nitrogen cultivation conditions in order toincrease the production of phenolic compounds, as well as&nbsp; y-linolenic acid. Comparing the results of the antioxidant activity in the DPPH and FRAP tests, it&nbsp; was shown that strains&nbsp; <em>Spirulina</em>&nbsp; S1 and&nbsp; <em>Spirulina&nbsp;</em> S2 had the highest antioxidant potential. The antibacterial activity of the intracellular methanolic extracts was registered in strains <em>Nostoc&nbsp;</em> 2S7B,&nbsp; <em>Nostoc&nbsp;</em> 2S1,&nbsp; <em>Anabaena</em>&nbsp; C2,&nbsp; <em>Anabaena</em>&nbsp; C5,&nbsp; Spirulina&nbsp; S1 and&nbsp; Spirulina&nbsp; S2, that&nbsp; inhibited the growth of&nbsp; Gram-positive and Gram&nbsp; -negative bacteria. Using MTT test, anti-cancer ie. cytotoxic activity of&nbsp; dimethyl sulfoxide&nbsp; (DMSO) extracts to the HepG2 cell line was detected in all tested strains, however, the highest activity was exhibited in strains <em>Nostoc</em>&nbsp; LC1B and<em> Nostoc</em> 2S7B . In bioassays <em>Artemia salina,&nbsp; Daphnia magna</em>&nbsp; and <em>Danio rerio</em>&nbsp; a small number of strains exhibited toxicity to the test organisms, while in case of cell line RTL-W1 tested strains did not show&nbsp; in vitro&nbsp; cytotoxicity, which is of great importance from the aspect of the potential biotechnological application of thestrains.&nbsp;<em> Nostoc</em>&nbsp; LC1B and&nbsp; <em>Nostoc</em>&nbsp; S8 strains induced toxicity in all three bioassays, and therefore considered as the most toxic strains. By testing&nbsp; in vitro&nbsp; toxicity in enzyme assays, it was found that few strains inhibited the activity of&nbsp; protein phosphatase (PP1) enzyme in relation to&nbsp; acetylcholinesterase&nbsp; enzyme&nbsp; (AChE) activity. Using the Analytical hierarchical process in the group context, the highest weight was given to the criteria of anticancer&nbsp; activity, biomass production, and the phycocyanin content, respectively. Finally, in the multi-criteria context, the best-ranked strain is&nbsp;<em> Spirulina</em>&nbsp; S1,&nbsp; <em>Spirulina&nbsp;</em> strain S2 is on the second place, while <em>Nostoc</em> strain LC1B is the third one.</p>

The cellular nature of many biological materials, providing them with low density, high strength and high toughness, have fascinated many researchers in the field of botany and structural biology since at least one century. Bamboo, sponges, trabecular bone, tooth and honeybee combs are only few examples of natural materials with cellular architecture. It has been widely recognised that the geometric and mechanical characteristics of the microscopic building blocks play a fundamental role on the behavior observed at the macroscale. Up to date, many efforts have been devoted to the analysis of cellular materials with empty cells to predict the structure-property relations that link the macroscopic properties to the mechanics of their underlying microstructure. Surprisingly, notwithstanding the great advantages of the composite solutions in nature, in the literature a limited number of investigations concern cellular structures having the internal volumes of the cells filled with fluids, fibers or other bulk materials as commonly happens in biology. In particular, a continuum model has not been derived and explicit formulas for the effective elastic constants and constitutive relations are currently not available. To provide a contribution in this limitedly explored research area, this thesis describes the mathematical formulation and modelling technique leading to explicit expressions for the macroscopic elastic constants and stress-strain relations of biologically inspired composite cellular materials. Two examples are included. The first deals with a regular hexagonal architecture inspired by the biological parenchyma tissue. The second concerns a mutable cellular structure, composed by mutable elongated hexagonal cells, inspired by the hygroscopic keel tissue of the ice plant Delosperma nakurense. In both cases, the predicted results are found to be in very good agreement with the available data in the literature. Then, by taking into account the benefits offered by the complex hierarchical organisation of many natural systems, the attention is focused on the potential value of adding structural hierarchy into two-dimensional composite cellular materials having a self-similar hierarchical architecture, in the first case, and different levels with different cell topologies, in the second. In contrast to the traditional cellular materials with empty cells, the analysis reveals that, in the cell-filled configuration, introducing levels of hierarchy leads to an improvement in the specific stiffness. Finally, to offer concrete and relevant tools to engineers for developing future generations of materials with enhanced performance and unusual functionalities, a novel strategy to obtain a honeycomb with mutable cells is proposed. The technique, based on the ancient Japanese art of kirigami, consists in creating a pattern of cuts into a flat sheet of starting material, which is then stretched to give a honeycomb architecture. It emerges a vast range of effective constants that the so-called kirigami honeycomb structures can be designed with, just by changing the value of the applied stretch.

Heteroaryl nitrone spin traps have been suggested to act as free radical scavengers. The geometry optimizations and the single-point energies of the spin trapping reactions of the heteroaryl nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO) and α-phenyl-N-t-butylnitrone (PBN) have been computationally studied using ab initio (Hartree-Fock (HF) and second-order Møller-Plesset (MP2)) methods and Density Functional Theory (DFT) methods. The effects of new heteroaryl substituents on a parent nitrone spin trap have been examined at the HF and MP2 levels with the 6-31G*, and cc-pVnZ (n=D, T, Q) basis sets. The thermodynamics of the spin trapping at the C-site and O-site with •H, •CH3 and •OH radicals were studied at the HF/6-31G* and DFT/m06/6-31G* levels. The addition reactions favor at the C-sites and the double adducts are thermodynamically more stable than the mono adducts. The spin trapping of DMPO, PBN and α(Z)-(3-methylfuroxan-4-yl)-N-tert-butylnitrone (FxBN) with •OH have also been studied.