Modeling and simulation of a synthetic genetic circuit that implements a multicelled behavior in a growing microcolony of E. coli

Synthetic Biology is a relatively new discipline, born at the beginning of the New Millennium, that brings the typical engineering approach (abstraction, modularity and standardization) to biotechnology. These principles aim to tame the extreme complexity of the various components and aid the construction of artificial biological systems with specific functions, usually by means of synthetic genetic circuits implemented in bacteria or simple eukaryotes like yeast. The cell becomes a programmable machine and its low-level programming language is made of strings of DNA. This work was performed in collaboration with researchers of the Department of Electrical Engineering of the University of Washington in Seattle and also with a student of the Corso di Laurea Magistrale in Ingegneria Biomedica at the University of Bologna: Marilisa Cortesi. During the collaboration I contributed to a Synthetic Biology project already started in the Klavins Laboratory. In particular, I modeled and subsequently simulated a synthetic genetic circuit that was ideated for the implementation of a multicelled behavior in a growing bacterial microcolony. In the first chapter the foundations of molecular biology are introduced: structure of the nucleic acids, transcription, translation and methods to regulate gene expression. An introduction to Synthetic Biology completes the section. In the second chapter is described the synthetic genetic circuit that was conceived to make spontaneously emerge, from an isogenic microcolony of bacteria, two different groups of cells, termed leaders and followers. The circuit exploits the intrinsic stochasticity of gene expression and intercellular communication via small molecules to break the symmetry in the phenotype of the microcolony. The four modules of the circuit (coin flipper, sender, receiver and follower) and their interactions are then illustrated. In the third chapter is derived the mathematical representation of the various components of the circuit and the several simplifying assumptions are made explicit. Transcription and translation are modeled as a single step and gene expression is function of the intracellular concentration of the various transcription factors that act on the different promoters of the circuit. A list of the various parameters and a justification for their value closes the chapter. In the fourth chapter are described the main characteristics of the gro simulation environment, developed by the Self Organizing Systems Laboratory of the University of Washington. Then, a sensitivity analysis performed to pinpoint the desirable characteristics of the various genetic components is detailed. The sensitivity analysis makes use of a cost function that is based on the fraction of cells in each one of the different possible states at the end of the simulation and the wanted outcome. Thanks to a particular kind of scatter plot, the parameters are ranked. Starting from an initial condition in which all the parameters assume their nominal value, the ranking suggest which parameter to tune in order to reach the goal. Obtaining a microcolony in which almost all the cells are in the follower state and only a few in the leader state seems to be the most difficult task. A small number of leader cells struggle to produce enough signal to turn the rest of the microcolony in the follower state. It is possible to obtain a microcolony in which the majority of cells are followers by increasing as much as possible the production of signal. Reaching the goal of a microcolony that is split in half between leaders and followers is comparatively easy. The best strategy seems to be increasing slightly the production of the enzyme. To end up with a majority of leaders, instead, it is advisable to increase the basal expression of the coin flipper module. At the end of the chapter, a possible future application of the leader election circuit, the spontaneous formation of spatial patterns in a microcolony, is modeled with the finite state machine formalism. The gro simulations provide insights into the genetic components that are needed to implement the behavior. In particular, since both the examples of pattern formation rely on a local version of Leader Election, a short-range communication system is essential. Moreover, new synthetic components that allow to reliably downregulate the growth rate in specific cells without side effects need to be developed. In the appendix are listed the gro code utilized to simulate the model of the circuit, a script in the Python programming language that was used to split the simulations on a Linux cluster and the Matlab code developed to analyze the data.

Le collocazioni in traduzione e interpretazione tra italiano e francese: Uno studio su eptic_01_2011

This dissertation aims at investigating differences in phraseological patterns in translated and interpreted language, on the basis of the intermodal corpus EPTIC_01_2011 and focusing on Italian and French. First of all, an overview is offered of the main studies and theories about corpus linguistics and collocations: the notion of corpus is defined and a typology (focusing on intermodal corpora) is presented, before moving on to the linguistic phenomenon of collocation and its investigation through corpus linguistics methods. Second, the general structure of EPTIC_01_2011 is presented, including the ways in which its texts have been assembled, edited through ad hoc conventions and enriched with metadata. The methodology proposed by Durrant and Schmitt (2009), slightly edited to fit the present study, has been used to extract and compare noun+adjective/adjective+noun bigrams from a quantitative point of view. A subset of these data have then been extracted and analysed manually. The results of the study are presented through graphs and examples, with an in-depth discussion of the bigrams considered. Lastly, the data collected are analysed and categorised in terms of shifts occurring in translation and in interpreting, potential causes are discussed and ideas for further research and for the development of the EPTIC corpus are sketched.

No(i)rthern Ireland: Crime fiction and the northern-irish scene. Proposed translation into italian of two short stories from "belfast noir"

The present thesis aims at proving the importance of cultural and literary contexts in the practice of translation: I shall show that, in the case of Northern Irish crime fiction, knowledge of both Northern Irish history and culture as well as of the genre of crime fiction are essential prerequisites for the production of a “responsible” translation. I will therefore offer a brief overview of the history of crime and detective fiction and its main subgenres; some of the most important authors and works will be presented as well, in an analysis that goes from the early years of the genre to the second half of the 20th century. I will then move the focus to Northern Ireland, its culture and its history, and particular attention will be paid to fiction writing in Ireland and Northern Ireland, with a focus on the peculiar phenomenon of “Troubles Trash”. I will tackle the topic of Northern Irish literature and present the contemporary scene of Northern Irish crime fiction; the volume from which the texts for the translation have been taken will be presented, namely Belfast Noir. Subsequently the focus will move on the theoretical framework within which the translations were produced: I will present a literary review of the most significative developments in Translation Studies, with particular attention to the “cultural turn” that has characterised this subject since the 1960s. I will then highlight the phenomenon of “realia” in translation and analyse the approaches of different scholars to the translation of culture-bound references. The final part represents the culmination and practical application of all that was presented in the previous sections: I will discuss the translation of culture-bound references according to the strategies presented in Chapter 4, referring to the proposed translations of two stories. Such analysis aims to show that not only expert linguistic knowledge, but also cultural awareness and a wide literary background are needed in order to make conscious choices in translation.

Una scossa all'economia: le conseguenze del sisma dell'Aquilano. Traduzione dall'inglese in italiano di un articolo di ricerca economica ed esperienza di collaborazione con gli autori.

The aim of this dissertation is to provide a translation from English into Italian of a specialised scientific article published in the Cambridge Working Papers in Economics series. In this text, the authors estimate the economic consequences of the earthquake that hit the Abruzzo region in 2009. An extract of this translation will be published as part of conference proceedings. The main reason behind this choice is a personal interest in specialised translation in the economic domain. Moreover, the subject of the article is of particular interest to the Italian readership. The aim of this study is to show how a non-specialised translator can tackle with such a highly specialised translation with the use of appropriate terminology resources and the collaboration of field experts. The translation could be of help to other Italian linguists looking for translated material in this particular domain where English seems to be the dominant language. In order to ensure consistent terminology and adequate style, the document has been translated with the use of different resources, such as dictionaries, glossaries and specialised corpora. I also contacted field experts and the authors of text. The collaboration with the authors proved to be an invaluable resource yet one to be carefully managed. This work is divided into 5 chapters. The first deals with domain-specific sublanguages. The second gives an overview of corpus linguistics and describes the corpora designed for the translation. The third provides an analysis of the article, focusing on syntactical, lexical and structural features while the fourth presents the translation, side-by-side with the source text. The fifth comments on the main difficulties encountered in the translation and the strategies used, as well as the relationship with the authors and their review of the published text. Appendix I contains the econometric glossary English – Italian.

Pontypool, traduci e muori. Traduzione di pontypool changes everything di tony burgess.

This work is focused on the translation of the first half of the novel Pontypool Changes Everything, written by Canadian author and screenplay writer Tony Burgess in 1998 and – quite surprisingly – still unpublished in Italy. Although the book disguises itself as a product for general consumption – more precisely as a tale of zombies – it is clear from the very beginning that the author is not interested in conforming to the conventions of the genre to which his work belongs. On the contrary, he seems to exploit the recent success of zombiea-pocalypse inspired stories to build up a more complex type of narrative. Nonetheless, he writes a story that introduces certain innovative elements in the rather repetitive and seemingly outworn genre, like the idea of a language-borne virus. Burgess, who has a graduate degree in semiotics, was by his own admission “insufferably preoccupied with literary malformations” when he wrote the book. As a matter of fact his narrative tackles issues – albeit superficially and always entertainingly – that seem to stem from the theories which originated in the field of linguistics around the second half of the twentieth century. It goes without saying that translating – as much as reading – such a book is both a difficult and compelling operation. As a translator you are required to constantly shift from one strategy to another, paying great attention to the semantic nuances of the written words whilst keeping in mind what the actual intention of the text is. Together with the book translation, this dissertation offers a brief introduction to the fundamental principles of translation and a detailed analysis of some of the translation problems posed by the novel.