Towards the control of cell states in gene regulatory networks by evolving Boolean networks

Biological cell behaviours emerge from complex patterns of interactions between genes and their products, known as gene regulatory networks (GRNs). More specifically, GRNs are complex dynamical structures that orchestrate the activities of biological cells by governing the expression of mRNA and proteins. Many computational models of these networks have been shown to be able to carry out complex computation in an efficient and robust manner, particularly in the domains of control and signal processing. GRNs play a central role within living organisms and efficient strategies for controlling their dynamics need to be developed. For instance, the ability to push a cell towards or away from certain behaviours, is an important aim in fields such as medicine and synthetic biology. This could, for example, help to find novel approaches in the design of therapeutic drugs. However, current approaches to controlling these networks exhibit poor scalability and limited generality. This thesis proposes a new approach and an alternative method for performing state space targeting in GRNs, by coupling an artificial GRN to an existing GRN. This idea is tested in simulation by coupling together Boolean networks that represent controlled and controller systems. Evolutionary algorithms are used to evolve the controller Boolean networks. Controller Boolean networks are applied to a range of controlled Boolean networks including Boolean models of actual biological circuits, each with different dynamics. The results show that controller Boolean networks can be optimised to control trajectories in the target networks. Also, the approach scales well as the target network size increases. The use of Boolean modelling is potentially advantageous from an implementation perspective, since synthetic biology techniques can be used to refine an optimised controller Boolean network into an in vivo form, which could then control a genetic network directly from within a cell

The historical development of reciprocal pronouns in middle English with selected early modern English comparisons

In Modern English, EACH OTHER and ONE ANOTHER are morphologically fixed as reciprocal compound pronouns. The reciprocal construction has been developed and used in every period of the English language. The main purpose of this study, nevertheless, was to investigate the ways to express the notion of reciprocity in Middle English and Early Modern English.The morphological analyses of the citations demonstrate that Middle English employed a great variety of head words and phrases than does Modern English in reciprocal structures. EACH, EITHER, EVERY, and ONE most frequently appear as head words of Middle English reciprocal construction, and OTHER usually occurs as a subsequent elements. OTHER, however, may also serve as the head word. Middle English also permits EACH MAN, ILLC MANN, EACH ONE, ILLC ONE, EVERY MAN, EVERY ONE, and THE ONE to function as head phrases. In Early Modem English, Malory employs various structures in his writings, but he prefers EITHER, EITHER OF (US, YOU, THEM) as the head of reciprocal patterns. Shakespeare, nevertheless, more frequently uses ONE as the head word.In Middle English, according to the data, the reciprocal sequence (EACH, EITHER, ONE) / OTHER stands in subject position in twenty examples between c. 1200 - c.1450. Rarely, however, do the pronouns function as a compound subject (subject / complement). The underlying structure of the sentence pattern SOV, nevertheless, is SVO. The need to rhyme, therefore, may cause the change of the word order in the period.(EACH, EITHER, EVERY, ONE, OTHER) may be compounded with the pronoun OTHER in forty examples between c. 1285 - c.1513, but the sequence most frequentlyoccur as direct / indirect object. (EACH, EITHER, EVERY, ONE, OTHER) + OTHER functions as object of preposition in four examples between c.1328 - c.1440.The modem usage of EACH OTHER as a compound object is established in Early Modern English learned, imaginative texts, and the use of ONE ANOTHER as the compound direct object and object of preposition are being established in that period.Since the rules for compounding reciprocal pronouns and for their morpho-syntatic features were not restrictly established before the time of Shakespeare, OTHER could function as an uninflected, separable pronoun in Middle English. In position except modification. the development of OTHER as a nominal occured after Middle English except where the head word is ONE. In Modem English, OTHER must be used as a nominal if the reciprocal pronouns are not compounded.Department of EnglishThesis (Ph. D.

The historical development of reciprocal pronouns in middle English with selected early modern English comparisons

In Modern English, EACH OTHER and ONE ANOTHER are morphologically fixed as reciprocal compound pronouns. The reciprocal construction has been developed and used in every period of the English language. The main purpose of this study, nevertheless, was to investigate the ways to express the notion of reciprocity in Middle English and Early Modern English.The morphological analyses of the citations demonstrate that Middle English employed a great variety of head words and phrases than does Modern English in reciprocal structures. EACH, EITHER, EVERY, and ONE most frequently appear as head words of Middle English reciprocal construction, and OTHER usually occurs as a subsequent elements. OTHER, however, may also serve as the head word. Middle English also permits EACH MAN, ILLC MANN, EACH ONE, ILLC ONE, EVERY MAN, EVERY ONE, and THE ONE to function as head phrases. In Early Modem English, Malory employs various structures in his writings, but he prefers EITHER, EITHER OF (US, YOU, THEM) as the head of reciprocal patterns. Shakespeare, nevertheless, more frequently uses ONE as the head word.In Middle English, according to the data, the reciprocal sequence (EACH, EITHER, ONE) / OTHER stands in subject position in twenty examples between c. 1200 - c.1450. Rarely, however, do the pronouns function as a compound subject (subject / complement). The underlying structure of the sentence pattern SOV, nevertheless, is SVO. The need to rhyme, therefore, may cause the change of the word order in the period.(EACH, EITHER, EVERY, ONE, OTHER) may be compounded with the pronoun OTHER in forty examples between c. 1285 - c.1513, but the sequence most frequentlyoccur as direct / indirect object. (EACH, EITHER, EVERY, ONE, OTHER) + OTHER functions as object of preposition in four examples between c.1328 - c.1440.The modem usage of EACH OTHER as a compound object is established in Early Modern English learned, imaginative texts, and the use of ONE ANOTHER as the compound direct object and object of preposition are being established in that period.Since the rules for compounding reciprocal pronouns and for their morpho-syntatic features were not restrictly established before the time of Shakespeare, OTHER could function as an uninflected, separable pronoun in Middle English. In position except modification. the development of OTHER as a nominal occured after Middle English except where the head word is ONE. In Modem English, OTHER must be used as a nominal if the reciprocal pronouns are not compounded.Thesis (Ph. D.)Department of Englis

Optimising Boolean Synthetic Regulatory Networks to Control Cell States

Controlling the dynamics of gene regulatory networks is a challenging problem. In recent years, a number of control methods have been proposed, but most of these approaches do not address the problem of how they could be implemented in practice. In this paper, we consider the idea of using a synthetic regulatory network as a closed-loop controller that can control and respond to the dynamics of a cell's native regulatory network in situ. We explore this idea using a computational model in which both native and synthetic regulatory networks are represented by Boolean networks. We then use an evolutionary algorithm to optimise both the structure and parameters of the synthetic Boolean network. To test this approach, we look at whether controllers can be optimised to target specific steady states in five different Boolean regulatory circuit models. Our results show that in most cases the controllers are able to drive the dynamics of the target system to a specified steady state, often using few interventions, and further experiments using random Boolean networks show that the approach scales well to larger controlled networks

Salinity stress affects growth responses of Cenchrus ciliaris under CO2 enrichment

Salinity stress may affect the response of grass species to atmospheric CO2 enrichment. But the extent and timing of growth responses in hyperarid environments may be different depending on the specific environmental conditions and the type of grass species (C3 vs. C4). The aim of the present study was to assess the extent of Cenchrus ciliaris L. responses to CO2 enrichment and to evaluate the role of salt stress in affecting such response. Three treatments were tested ; namely ambient, alternating and enriched CO 2 concentrations (ACO2 , ALCO2 and ECO2 ; respectively). Shoot length of C. ciliaris was positively affected by atmospheric CO2 enrichment. The number of inflorescence increased with the increase of CO2 level under both salt stress and control conditions. Growth allocation to green blades increased ten times under salinity stress than under control conditions. Allocation to inflorescence parts was almost two times higher under control than under salinity stress. Moreover, root allocation underwent variations between control and salinity stress. In short, CO2 enrichment did influence growth responses of C. ciliaris, especially under salinity tress. Growth allocation was also influenced toward a more reproductive growth pattern. Moreover, plants under salt stress may have responded to the CO2 alternation as an added stress.Le stress salin peut affecter la réponse des espèces fourragères suite à l’enrichissement atmosphérique en CO2 . Mais l’étendue des réponses de croissance dans des environnements hyperarides peut être différente en fonction des conditions environnementales spécifiques et du type d’espèces végétal (C3 vs C4). Le but de la présente étude était d’évaluer l’ampleur des réponses de Cenchrus ciliaris L. à l’enrichissement en CO2 et d’évaluer le rôle du stress salin. Trois traitements ont été testés, à savoir CO 2 ambiant, alternatif et enrichi (ACO2, ALCO2 et ECO2 respectivement). La longueur de C. ciliaris a été influencée positivement par l’enrichissement atmosphérique en CO2 . Le nombre d’inflorescence a augmenté avec l’augmentation du niveau de CO2 dans les individus sous stress salin et les témoins. L’allocation de croissance des feuilles fraîches a augmenté dix fois sous stress salin par rapport aux conditions témoins. La répartition des inflorescences était près de deux fois plus élevée chez les témoins qu’en présence de sel. En outre, l’allocation de ressources à la croissance des racines a connu des variations entre le contrôle et le stress salin. En somme, l’enrichissement en CO2 a affecté la croissance de C. ciliaris, en particulier en milieu salin. L’allocation de croissance a aussi influencé la croissance vers la reproduction. En outre, les plantes sous stress salin ont réagi à l’alternance de CO2 comme étant un stress supplémentaire.Ksiksi Taou Saleh, Alshaygi N.-O. Salinity stress affects growth responses of Cenchrus ciliaris under CO2 enrichment. In: Ecologia mediterranea, tome 38 n°2, 2012. pp. 43-51

Hydrogen freight solutions towards net zero

In realising the global initiative towards a future with net zero emissions, the implementation of cleaner energy sources is critical. The transport sector is a large contributor to the total greenhouse gas emissions and although various innovative solutions, such as hydrogen, biofuels and electricity, are currently being advanced, the adoption towards such a strategy is often challenging. When considering freight transport, hydrogen fuel cell technologies have the advantage of a larger driving range and shorter refuelling time when compared to other green technologies. Prior to the implementation of hydrogen freight solutions, however, it is imperative to gain an understanding of the investment required for hydrogen refuelling and distribution networks. This study considers the methodology towards the analysis of a strategic hydrogen refuelling infrastructure. Data analysis and simulation modelling techniques may be utilised to map the current road freight movement on selected corridors in an attempt to determine the optimal location and capacity of hydrogen infrastructures required to serve the hydrogen needs of the given corridors. From the initial analysis of demand to the development of agent-based models with optimisation capabilities, this methodology aims to provide an economic analysis for deploying hydrogen refuelling infrastructure