Data-driven approaches to modelling collective cell migration

Collective cell migration is the defining characteristic of many biological events involved in morphogenesis, regeneration, and pathology. This abundance, together with the immense clinical and therapeutic advances that would arise from the ability to control collective migration in specific applications in regenerative medicine and oncology, has led to an enormous increase in the number of studies on collective cell migration. Yet, the integration of large biological data sets with modelling has proven challenging. In this thesis, we address three main challenges: connecting mathematical models with high-dimensional data, leveraging biological data to learn new mathematical models, and controlling biological systems using mathematical models. In our first case study, we combine individual-based models with computational Bayesian statistics to identify links between genetic perturbations and cellular phenotypes in a large siRNA screen. We propose a new approach to approximate Bayesian computation (ABC) and show that it is possible to identify the functional impact of a range of different genetic perturbations. Second, in the context of Madin-Darby canine kidney (MDCK) epithelial monolayers, we use a continuum mechanics model to characterise the role of mechanical power expenditure in regulating active cellular forces. We then utilise this knowledge in a continuum model for collective electrotaxis which takes into account energy expenditure during migration, and develop an optimal control framework to achieve experimentally desirable outcomes. By deriving a Keller-Segel type model of collective electrotaxis, we propose design of optimal electric fields that vary in space and in time. Finally, by combining single-cell tracking with deep attention networks, we discover a set of genes critical for the invasion of c8161 melanoma cells: failure to express these genes leads to abnormal leader-follower dynamics. Together, the contributions of this thesis are towards developing new approaches to data-driven mathematical modelling, using the derived models to control biological systems, and understanding the underlying mechanisms

Efficient Bayesian inference for mechanistic modelling with high-throughput data

Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing

Efficient Bayesian inference for mechanistic modelling with high-throughput data

Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing

Bayesian uncertainty quantification for data-driven equation learning

Equation learning aims to infer differential equation models from data. While a number of studies have shown that differential equation models can be successfully identified when the data are sufficiently detailed and corrupted with relatively small amounts of noise, the relationship between observation noise and uncertainty in the learned differential equation models remains unexplored. We demonstrate that for noisy data sets there exists great variation in both the structure of the learned differential equation models as well as the parameter values. We explore how to combine data sets to quantify uncertainty in the learned models, and at the same time draw mechanistic conclusions about the target differential equations. We generate noisy data using a stochastic agent-based model and combine equation learning methods with approximate Bayesian computation (ABC) to show that the correct differential equation model can be successfully learned from data, while a quantification of uncertainty is given by a posterior distribution in parameter space

A study of factors that influence growth performance and carcass and meat quality of iberian pigs reared under intensive management systems : Estudio de los factores que influyen sobre la productividad y la calidad de la canal y la carne de cerdo Ibérico en intensivo

The general aim of this Doctoral Thesis has been to study the influence of factors that influence growth performance and carcass and meat quality of Iberian (IB) pigs reared under intensive management systems. The influence of gender and castration of females, slaughter weight, feed restriction and terminal sire line were studied. To reach these goals, four trials were carried out. In the first trial a total of 360 IB dam x Spanish Duroc sire pigs was used to study the influence of gender and castration (intact females, IF vs. castrated females, CF vs. castrated males, CM) and slaughter weight (SW; 145 vs. 156 kg body weight, BW) on performance and carcass and meat quality. Pigs that were slaughtered with 145 kg BW (251 d of age) began the trial with 20 kg BW (80 d of age) and pigs that were slaughtered with 156 kg BW (268 d of age) began the trial with 30 kg BW (97 d of age). Meat samples were taken at m. Longissimus dorsi at the level of the last rib and backfat (BF) samples were taken at the tail insertion. Fatty acid profile of BF was not analysed in the pigs slaughtered at 156 kg BW and therefore only the fatty acid profile of each gender from pigs slaughtered at 145 kg BW were compared. There were six treatments with four replicates each. The experimental unit was a pen (15 pigs for productive performance and carcass quality, four pigs for meat quality and two pigs for fatty acid profile of BF). For the entire experiment, IF ate less feed (2.72 vs. 2.85 and 2.92 kg/d; P0,10). For the entire experiment (from 20 to 145 and from 30 to 156 kg BW, respectively), pigs slaughtered at 145 kg BW ate less feed (2.74 vs. 2.92 kg/d; P0.10). It is concluded that intact females are an alternative to castrated females for intensive production of Iberian pigs. Also, the reduction in slaughter weight from 156 to 145 kg body weight is recommended for this type of production. In the second trial, IB × Duroc pigs (n=168), with an average age of 152 d (42 ± 2 kg) were used to investigate the influence of feeding regimen (ad libitum access to feed, AL vs. 82% of AL from 152 to 201 d of age and 72% from 202 to 263 d of age, FR) and gender (intact females, IF vs. castrated females, CF vs. castrated males, CM) on growth performance and carcass and meat quality. For the last 54 d before slaughter at 317 d of age, all pigs had AL access to feed. Meat samples were taken at m. Longissimus dorsi at the level of the last rib. Between 152 and 263 d of age, pigs consuming AL had greater (P0.10) affect pork quality. Intact females tended (P0.10). Duroc sired pigs grew faster (689 vs. 549 g/d; P0.10). It is concluded that productive performance and primal cuts yield are higher for intact females than for castrated males. Danish Duroc sires are a good alternative to Spanish Duroc and Retinto Iberian sires for production of Iberian pigs under intensive systems

The sense of taste and the act of eating as metaphorical thinking

The Sense of Taste and the Act of Eating as Metaphorical Thinking investigates how the sense of taste and the act of eating can be used as tools of representation, exemplification and symbolism and are able to communicate meanings through something else than images. The aim of this work is to show the variety of contexts and situations where flavour has communicated history, culture in different contexts, artistic practice, poetry, fiction, non-fiction and everything in between. In the same way, it explores the act of eating as an exercise for extraction and digestion of values and virtues. My work specifically emphasizes the communication of meaning in the context of Contemporary Art and reveals how eating and tasting can transmit metaphors, tropes and ideas in a uniquely direct and intimate manner. This Master Thesis is constituted by three different parts: (1) An academic research -the present manuscript-, (2) the Memory Popsicles Exhibition and (3) the Cooking from Memory cookbook. 1. The present academic research explains the role of the sense of taste and of the act of eating in the production and communication of meaning and metaphors. The concept of metaphor in this investigation is framed as a transposition of ideas and exchange of meanings between different objects and subjects. This paper is built around the statement: Food has no meaning, but it acquires it through a specific historical period, specific location, and function. It explores how, from the beginning of time, different cultures, communities, religions, art movements and sub-cultures have attributed meaning to food in order to communicate or fix aspects of their identity. This meaning is not always articulated as images or as words but expressed metaphorically through flavours and textures. Through this research, I wish to portray the act of eating and the sense of taste as grounds where new forms of metaphorical thinking can take place and investigate why are these important in the construction of our identities. This investigation starts by exploring how food has been used as a metaphorical tool to represent our human condition, its temporality and mortality; that is, the unavoidable passing of time. The act of eating is portrayed here as an act of consumption of values, virtues and defects. This leads us to the relationship between food, cannibalism and meaning. Specific cultural practices, such as the Christian Eucharist or the rituals of the Wari and Tupi communities in the Brazilian Amazon, have framed the practice of cannibalism as a tool for the absorption of qualities, essences and symbols. We will then analyze how different disciplines such as biology, anthropology, philosophy, literature and the visual arts have approached and studied the act of eating and the sense of taste, in different cultures around the world. Further on, we will review the relationship between the performativity of eating and the performativity of writing and how these two types of languages support each other. A complete chapter will frame cookbooks as a common ground for the dialogue, among these different performativities. Similarly, the next section will present references to food and eating that exist outside the literary genre of cookbooks, such as comic books, artistic manifestoes and poems. Finally, we will take a look at how gustative metaphors have been increasingly used in Contemporary Art as tools for communication through textual and gustatory symbolism. In this context, I will present the concept of my final M.A. exhibition, Memory Popsicles. The variety of examples and points of view discussed in this thesis can teach us about the way different ways cultures have approached their own history through taste and how has the act of eating been a powerful and intimate tool, for the interpretation of reality. 2. The second part of my thesis project is the Exhibition Memory Popsicles, a participatory installation of edible art. This exhibition materializes memories into flavours and explores the relationship between fiction, memory, subjectivity and taste. It wishes to exemplify how different palates and combinations of flavours can represent the multilayered nature of memory and communicate its narratives. This exhibition is based on interviews with different people about a particular memory they had regarding taste. This exhibition took place at two venues: as a Flavor Laboratory at Third Space Gallery in May 2018 and as a participatory installation during Helsinki Design Week in September 2018, at Flavor Studio A21. 3. The final part of this project is materialized in the form of a cookbook. This book is a compilation of the memories that were transformed into popsicles for the Exhibition Memory Popsicles side by side with their correspondent recipes. At its final version, it will also include interviews with the donors of memories about their experience at the happening and documentation of the cooking sessions of the popsicles. Keywords: Taste, Food, Metaphor, Poetics, Language, Symbolism, Philosophy, Art, Subjectivity, Edibility, Interpretation

Accesibilidad del espacio público y políticas públicas de personas con discapacidad en el distrito de San Martin de Porres, 2021

El presente trabajo investigativo se propuso como objetivo general determinar en qué medida se relaciona la accesibilidad del espacio público y políticas públicas de personas con discapacidad en el distrito de San Martin de Porres, 2021. La investigación fue de tipo básica, y mediante un enfoque cuantitativo, de diseño no experimental, transversal, de tipo descriptivo y correlacional, y a través de una muestra de 49 personas con discapacidad se obtuvieron los siguientes resultados: (r=0,877) y (p=0,000). Se concluyó que existe una relación fuerte y perfecta entre las variables. Se recomienda la revisión de las políticas establecidas, a efectos de su real cumplimiento en beneficio de la población afectada

Apparent digestibility and metabolizable energy content of lipid sources in poultry

A trial was conducted to determine the apparent digestibility (ATTD) and AME content of different lipid sources in 21d-old broilers. There were a control diet based on corn and soybean meal without any supplemental fat and 6 additional diets forming a 3x2 factorial with 3 sources of fat (soy oil, SBO; reconstituted monoglyceride oil, RMG; and reconstituted triglyceride oil, RTG) included in the diet (3 or 6%) at expenses (wt:wt) of the basal diet

Optimal Control of Collective Electrotaxis in Epithelial Monolayers

Epithelial monolayers are some of the best-studied models for collective cell migration due to their abundance in multicellular systems and their tractability. Experimentally, the collective migration of epithelial monolayers can be robustly steered e.g. using electric fields, via a process termed electrotaxis. Theoretically, however, the question of how to design an electric field to achieve a desired spatiotemporal movement pattern is underexplored. In this work, we construct and calibrate an ordinary differential equation model to predict the average velocity of the centre of mass of a cellular monolayer in response to stimulation with an electric field. We use this model, in conjunction with optimal control theory, to derive physically realistic optimal electric field designs to achieve a variety of aims, including maximising the total distance travelled by the monolayer, maximising the monolayer velocity, and keeping the monolayer velocity constant during stimulation. Together, this work is the first to present a unified framework for optimal control of collective monolayer electrotaxis and provides a blueprint to optimally steer collective migration using other external cues

Influencia de la micronización y el origen de la harina de soja en los redimientos productivos en lechones destetados

La harina de soja (HS) es la fuente de proteína de elección en dietas para cerdos. La HS contiene diversos factores anti nutricionales (FAN), tales como los inhibidores de tripsina (IT; Huisman y Jansman, 1991) y los oligosacáridos (Clarke y Wiseman, 2005) que afectan al crecimiento y limitan los niveles de inclusión en dietas para lechones. El procesado térmico del haba y su composición (De Coca Sinova et al., 2008) afectan al contenido de nutrientes así como la respuesta de los animales a su inclusión en piensos. Morgan et al. (1984) y Dilger et al. (2004) han demostrado que un aumento en el contenido de fibra bruta de la dieta o de la HS utilizada disminuye la digestibilidad de los nutrientes en monogástricos y De Coca et al. (2008) observaron una relación lineal entre el contenido de proteína bruta (PB) y la digestibilidad de los aminoácidos en HS. Por lo tanto, la inclusión de HS de alto contenido en PB (AP-HS) en sustitución de HS de menor contenido proteico (BP-HS) podría mejorar el crecimiento de los lechones. Los concentrados de soja (CPS) tienen un alto contenido en PB y bajo contenido de fibra bruta y en FAN (Shon et al., 1994). Por lo tanto, la sustitución de HS por CPS, podría mejorar el rendimiento de los cerdos al destete. Los efectos del tamaño medio de partícula (GMD) del pienso sobre el crecimiento es un tema de debate (Goodband et al., 1995). La mayoría de estudios llevados a cabo con cereales han encontrado una relación directa positiva entre la GMD y el índice de conversión (IC) en cerdos (Goodband y Hines, 1988; Healy et al., 1994). Sin embargo, los resultados disponibles sobre los efectos de la molturación fina de la HS sobre la productividad en lechones son escasos y no concordantes (Fastinger y Mahan, 2003; Lawrence et al., 2003; Valencia et al., 2008). El objetivo de este experimento fue evaluar los efectos de la inclusión de diferentes tipos de soja en los que variaba el contenido de PB y el tamaño de partícula sobre el crecimiento de los lechones