Genetic Manipulation, Gene Silencing and Biomarker Development in Multiple Experimental Models.

The thesis is set in three different parts, according to the relative experimental models. First, the domestic pig (Sus scrofa) is part of the study on reproductive biotechnologies: the transgenesis technique of Sperm Mediated Gene Transfer is widely studied starting from the quality of the semen, through the study of multiple uptakes of exogenous DNA and lastly used in the production of multi-transgenic blastocysts. Finally we managed to couple the transgenesis pipeline with sperm sorting and therefore produced transgenic embryos of predetermined sex. In the second part of the thesis the attention is on the fruit fly (Drosophila melanogaster) and on its derived cell line: the S2 cells. The in vitro and in vivo models are used to develop and validate an efficient way to knock down the myc gene. First an efficient in vitro protocol is described, than we demonstrate how the decrease in myc transcript remarkably affects the ribosome biogenesis through the study of Polysome gradients, rRNA content and qPCR. In vivo we identified two optimal drivers for the conditional silencing of myc, once the flies are fed with RU486: the first one is throughout the whole body (Tubulin), while the second is a head fat body driver (S32). With these results we present a very efficient model to study the role of myc in multiple aspects of translation. In the third and last part, the focus is on human derived lung fibroblasts (hLF-1), mouse tail fibroblasts and mouse tissues. We developed an efficient assay to quantify the total protein content of the nucleus on a single cell level via fluorescence. We coupled the protocol with classical immunofluorescence so to have at the same time general and particular information, demonstrating that during senescence nuclear proteins increase by 1.8 fold either in human cells, mouse cells and mouse tissues.

Robotic Sensing and Manipulation of Deformable Linear Objects with Learning-based methods

Nowadays robotic applications are widespread and most of the manipulation tasks are efficiently solved. However, Deformable-Objects (DOs) still represent a huge limitation for robots. The main difficulty in DOs manipulation is dealing with the shape and dynamics uncertainties, which prevents the use of model-based approaches (since they are excessively computationally complex) and makes sensory data difficult to interpret. This thesis reports the research activities aimed to address some applications in robotic manipulation and sensing of Deformable-Linear-Objects (DLOs), with particular focus to electric wires. In all the works, a significant effort was made in the study of an effective strategy for analyzing sensory signals with various machine learning algorithms. In the former part of the document, the main focus concerns the wire terminals, i.e. detection, grasping, and insertion. First, a pipeline that integrates vision and tactile sensing is developed, then further improvements are proposed for each module. A novel procedure is proposed to gather and label massive amounts of training images for object detection with minimal human intervention. Together with this strategy, we extend a generic object detector based on Convolutional-Neural-Networks for orientation prediction. The insertion task is also extended by developing a closed-loop control capable to guide the insertion of a longer and curved segment of wire through a hole, where the contact forces are estimated by means of a Recurrent-Neural-Network. In the latter part of the thesis, the interest shifts to the DLO shape. Robotic reshaping of a DLO is addressed by means of a sequence of pick-and-place primitives, while a decision making process driven by visual data learns the optimal grasping locations exploiting Deep Q-learning and finds the best releasing point. The success of the solution leverages on a reliable interpretation of the DLO shape. For this reason, further developments are made on the visual segmentation.

Affordances and Language: How the Level of Object Familiarity modulates the Manipulation and Categorization of Objects across Development

According to much evidence, observing objects activates two types of information: structural properties, i.e., the visual information about the structural features of objects, and function knowledge, i.e., the conceptual information about their skilful use. Many studies so far have focused on the role played by these two kinds of information during object recognition and on their neural underpinnings. However, to the best of our knowledge no study so far has focused on the different activation of this information (structural vs. function) during object manipulation and conceptualization, depending on the age of participants and on the level of object familiarity (familiar vs. non-familiar). Therefore, the main aim of this dissertation was to investigate how actions and concepts related to familiar and non-familiar objects may vary across development. To pursue this aim, four studies were carried out. A first study led to the creation of the Familiar and Non-Familiar Stimuli Database, a set of everyday objects classified by Italian pre-schoolers, schoolers, and adults, useful to verify how object knowledge is modulated by age and frequency of use. A parallel study demonstrated that factors such as sociocultural dynamics may affect the perception of objects. Specifically, data for familiarity, naming, function, using and frequency of use of the objects used to create the Familiar And Non-Familiar Stimuli Database were collected with Dutch and Croatian children and adults. The last two studies on object interaction and language provide further evidence in support of the literature on affordances and on the link between affordances and the cognitive process of language from a developmental point of view, supporting the perspective of a situated cognition and emphasizing the crucial role of human experience.

Price manipulation: theoretical models and empirical investigation

Understanding why market manipulation is conducted, under which conditions it is the most profitable and investigating the magnitude of these practices are crucial questions for financial regulators. Closing price manipulation induced by derivatives’ expiration is the primary subject of this thesis. The first chapter provides a mathematical framework in continuous time to study the incentive to manipulate a set of securities induced by a derivative position. An agent holding a European-type contingent claim, depending on the price of a basket of underlying securities, is considered. The agent can affect the price of the underlying securities by trading on each of them before expiration. The elements of novelty are at least twofold: (1) a multi-asset market is considered; (2) the problem is solved by means of both classic optimisation and stochastic control techniques. Both linear and option payoffs are considered. In the second chapter an empirical investigation is conducted on the existence of expiration day effects on the UK equity market. Intraday data on FTSE 350 stocks over a six-year period from 2015-2020 are used. The results show that the expiration of index derivatives is associated with a rise in both trading activity and volatility, together with significant price distortions. The expiration of single stock options appears to have little to no impact on the underlying securities. The last chapter examines the existence of patterns in line with closing price manipulation of UK stocks on option expiration days. The main contributions are threefold: (1) this is one of the few empirical studies on manipulation induced by the options market; (2) proprietary equity orderbook and transaction data sets are used to define manipulation proxies, providing a more detailed analysis; (3) the behaviour of proprietary trading firms is studied. Despite the industry concerns, no evidence is found of this type of manipulative behaviour.