An Agent-Based Simulation of Blood Coagulation Processes

This article describes the creation of an agent-based model of blood coagulation within the Lindsay Composer (LC) computational framework, which can be used to simulate and visualize physiological processes inside the human body. Swarm Graph Grammars (SGG), a generic modelling language, are used to design the interaction behaviours of the involved bio- agents which represent the cellular and chemical structures found in human blood. Physical interactions among the agents, such as collisions and binding, are computed by an embedded physics engine. In order to effectively retrace and to accurately model coagulation, comparisons with the results of established mathematical models are drawn. The blood coagulation simu- lation accounts for the formation, expression, and propagation of blood clots within the injured area of a blood vessel. We demonstrate how 3-dimensional, interactive agent-based models and programming frameworks provide complementary tools for research, for learning and for exploring the complicated nature of physiological processes

MicroBioRobots for Single Cell Manipulation

One of the great challenges in nano and micro scale science and engineering is the independent manipulation of biological cells and small man-made objects with active sensing. For such biomedical applications as single cell manipulation, telemetry, and localized targeted delivery of chemicals, it is important to fabricate microstructures that can be powered and controlled without a tether in fluidic environments. These microstructures can be used to develop microrobots that have the potential to make existing therapeutic and diagnostic procedures less invasive. Actuation can be realized using various different organic and inorganic methods. Previous studies explored different forms of actuation and control with microorganisms. Bacteria, in particular, offer several advantages as controllable micro actuators: they draw chemical energy directly from their environment, they are genetically modifiable, and they are scalable and configurable in the sense that any number of bacteria can be selectively patterned. Additionally, the study of bacteria inspires inorganic schemes of actuation and control. For these reasons, we chose to employ bacteria while controlling their motility using optical and electrical stimuli. In the first part of the thesis, we demonstrate a bio-integrated approach by introducing MicroBioRobots (MBRs). MBRs are negative photosensitive epoxy (SU8) microfabricated structures with typical feature sizes ranging from 1-100 μm coated with a monolayer of the swarming Serratia marcescens. The adherent bacterial cells naturally coordinate to propel the microstructures in fluidic environments, which we call Self-Actuation. First, we demonstrate the control of MBRs using self-actuation, DC electric fields and ultra-violet radiation and develop an experimentally-validated mathematical model for the MBRs. This model allows us to to steer the MBR to any position and orientation in a planar micro channel using visual feedback and an inverted microscope. Examples of sub-micron scale transport and assembly as well as computer-based closed-loop control of MBRs are presented. We demonstrate experimentally that vision-based feedback control allows a four-electrode experimental device to steer MBRs along arbitrary paths with micrometer precision. At each time instant, the system identifies the current location of the robot, a control algorithm determines the power supply voltages that will move the charged robot from its current location toward its next desired position, and the necessary electric field is then created. Second, we develop biosensors for the MBRs. Microscopic devices with sensing capabilities could significantly improve single cell analysis, especially in high-resolution detection of patterns of chemicals released from cells in vitro. Two different types of sensing mechanisms are employed. The first method is based on harnessing bacterial power, and in the second method we use genetically engineered bacteria. The small size of the devices gives them access to individual cells, and their large numbers permit simultaneous monitoring of many cells. In the second part, we describe the construction and operation of truly micron-sized, biocompatible ferromagnetic micro transporters driven by external magnetic fields capable of exerting forces at the pico Newton scale. We develop micro transporters using a simple, single step micro fabrication technique that allows us to produce large numbers in the same step. We also fabricate microgels to deliver drugs. We demonstrate that the micro transporters can be navigated to separate single cells with micron-size precision and localize microgels without disturbing the local environment

A Survey of Agent-Based Modeling Practices (January 1998 to July 2008)

In the 1990s, Agent-Based Modeling (ABM) began gaining popularity and represents a departure from the more classical simulation approaches. This departure, its recent development and its increasing application by non-traditional simulation disciplines indicates the need to continuously assess the current state of ABM and identify opportunities for improvement. To begin to satisfy this need, we surveyed and collected data from 279 articles from 92 unique publication outlets in which the authors had constructed and analyzed an agent-based model. From this large data set we establish the current practice of ABM in terms of year of publication, field of study, simulation software used, purpose of the simulation, acceptable validation criteria, validation techniques and complete description of the simulation. Based on the current practice we discuss six improvements needed to advance ABM as an analysis tool. These improvements include the development of ABM specific tools that are independent of software, the development of ABM as an independent discipline with a common language that extends across domains, the establishment of expectations for ABM that match their intended purposes, the requirement of complete descriptions of the simulation so others can independently replicate the results, the requirement that all models be completely validated and the development and application of statistical and non-statistical validation techniques specifically for ABM.Agent-Based Modeling, Survey, Current Practices, Simulation Validation, Simulation Purpose

Controlling Microbial Multicellular Behaviors With Saccharide Derivatives

Microbial multicellular behaviors like biofilm formation and swarming motility are known to increase their tolerance against antimicrobials. From microbial standpoint, nonmicrobicidal agents that do not impede growth are tolerable and therefore, there is a lower propensity to develop resistance against such agents as compared to microbicidal ones (antibiotics). This study describes a new antibiofilm approach of using nonmicrobicidal saccharide derivatives for controlling the multicellular behaviors of gram-negative bacteria, Pseudomonas aeruginosa and fungus, Candida albicans. Pseudomonas aeruginosa is known to secrete rhamnolipids, a class of biosurfactants that plays an important role in maintaining the architecture of its biofilm and promoting its swarming motility. Here we show the ability of certain synthetic nonmicrobicidal disaccharide derivatives (DSDs) to mimic the biofunctions of rhamnolipids. The rhlA mutant of P. aeruginosa is incapable of synthesizing rhamnolipids and also unable to swarm on semi-solid agar gel. When the natural ligands, rhamnolipids were externally added into the semi-solid agar gel in a concentration dependent manner, the swarming of the rhlA mutant reactivated at lower concentrations (10 μM) and then at relatively higher concentrations (15 μM), the swarming reactivation was reversed. When some active synthetic DSDs were tested on the rhlA mutant, the bacterial swarming first reactivated and then the activation reversed at higher DSD concentrations, similar to the effect of externally added rhamnolipids. Previously, a known bacterial signalling molecule has been shown to exhibit a similar concentration dependent activation and then activation reversal for light simulation by Vibrio fischeri. Some DSDs having disaccharide stereochemistries (cellobiose or maltose) and a bulky aliphatic tail (3, 7, 11-trimethyl-dodecanyl) caused swarming reactivation of the rhlA mutant at concentrations lower than that caused by the externally added rhamnolipids. The synthetic nonmicrobicidal DSDs were also very effective at inhibiting the adhesion of P. aeruginosa to polystyrene surface, and at inhibiting the bacterial biofilm formation. These DSDs were also potent dispersers of pre-formed biofilm of P. aeruginosa. The potent antibiofilm (inhibition and dispersion) activities were observed for those DSDs that possessed a disaccharide (cellobiose or maltose) stereochemistry and a bulky aliphatic chain such as 3, 7, 11-trimethyl-dodecanyl. These potent DSDs had half-maximal inhibitory concentrations for biofilm inhibition (IC50) and dispersion (DC50) comparable to those of known potent antibiofilm agents against P. aeruginosa. Gene-reporting assays indicate that the mechanism of action of such DSDs is not via the known las or rhl quorum sensing systems of P. aeruginosa but that the adhesin potein, pilin maybe a likely target of such molecules. Biofilms formed under natural settings are usually formed by both bacteria and fungus that co-reside in the same microenvironment. Therefore, agents that can prevent mixed biofilms are desirable from a therapeutic standpoint. Despite being nonmicrobicidal to both fungal blastospores and hyphae, the synthetic DSDs were able to inhibit the biofilm formation of fungus Candida albicans. Microscopic evaluation showed that most DSDs did not prevent the blastospores-to-hyphae morphogenesis. The DSDs were effective at inhibiting biofilm formation of Candida albicans when applied within five minutes of seeding the test surface with fungal cells. Using a surface based assay it was shown that one DSD dramatically reduced the surface adhesion of Candida albicans hyphae. The antibiofilm activity of such DSDs against Candida albicans is probably due to their ability to prevent hyphae surface adhesion

The Enemy Within: An Investigation of the Intracellular Bacteria in Urinary Tract Infections

Urinary tract infections (UTIs) are common diseases that are associated with significant morbidities. Multiple studies have indicated that multiple species of uropathogenesis bacteria invade and persist within bladder epithelial cells as a necessary step of uropathogenesis. Interestingly, many of these species are not canonically associated with intracellular infections. Although the first study describing bacteria within the urothelium was published two decades ago, this critical step of uropathogenesis remains relatively understudied. I established a murine model of community-acquired A. baumannii UTI, a previously unstudied manifestation of the disease. While immunocompetent mice resolved their infections quickly, immunocompromised mice displayed high bacterial burdens throughout their urinary tracts for several weeks. I found that mice infected using this model retained A. baumannii intracellular reservoirs (ABIRs) in their urothelium long after the resolution of the initial colonization event. Inserting a catheter into the bladders of these resolved mice triggered a same-strain UTI in over 50% of the mice. Stringent experimental controls suggest that these resurgences came from bacterial reservoirs within the resolved host. Further testing implicates the ABIRs as the most likely source. I have also characterized the intracellular phenotypes of multiple uropathogenic E. coli (UPEC) clinical isolates. While each isolate had unique strain-specific characteristics, all three of the phylogroup A strains proved to be incapable of properly undergoing the intracellular steps of uropathogenesis. I have also studied an important process used by intracellular UPEC, lactose metabolism. UPEC isolates with mutations in their lac operons formed significantly smaller intracellular bacterial communities, and were unable to complete IBC development. However, I found that UPEC strains with deficient lactose permeases were still capable of importing lactose-like sugars. Overall, my dissertation contributes to field of intracellular uropathogenesis in multiple ways. With E. coli, I have identified a potential link between bacterial genetics, specifically when a bacterium is a member of phylogroup A, and intracellular phenotype in the bladder. I have also established that lacY-deficient UPEC isolates are capable of internalizing lactose-like sugars, which suggests the presence of a secondary mechanism. I have also developed a murine model of community-acquired UTI for A. baumannii and have investigated both the pathogenesis and the prevalence of this manifestation. I have also developed the first murine model of resurgent infections for A. baumannii and have identified a potential reservoir bringing novel strains into the hospital in the form of host reservoirs. Previous Acinetobacter UTI research has focused primarily on complicated UTIs. Together, my findings expand our knowledge of Acinetobacter uropathogenesis in the previously unstudied, community-acquired model of infection

Abstractions, Analysis Techniques, and Synthesis of Scalable Control Strategies for Robot Swarms

Tasks that require parallelism, redundancy, and adaptation to dynamic, possibly hazardous environments can potentially be performed very efficiently and robustly by a swarm robotic system. Such a system would consist of hundreds or thousands of anonymous, resource-constrained robots that operate autonomously, with little to no direct human supervision. The massive parallelism of a swarm would allow it to perform effectively in the event of robot failures, and the simplicity of individual robots facilitates a low unit cost. Key challenges in the development of swarm robotic systems include the accurate prediction of swarm behavior and the design of robot controllers that can be proven to produce a desired macroscopic outcome. The controllers should be scalable, meaning that they ensure system operation regardless of the swarm size. This thesis presents a comprehensive approach to modeling a swarm robotic system, analyzing its performance, and synthesizing scalable control policies that cause the populations of different swarm elements to evolve in a specified way that obeys time and efficiency constraints. The control policies are decentralized, computed a priori, implementable on robots with limited sensing and communication capabilities, and have theoretical guarantees on performance. To facilitate this framework of abstraction and top-down controller synthesis, the swarm is designed to emulate a system of chemically reacting molecules. The majority of this work considers well-mixed systems when there are interaction-dependent task transitions, with some modeling and analysis extensions to spatially inhomogeneous systems. The methodology is applied to the design of a swarm task allocation approach that does not rely on inter-robot communication, a reconfigurable manufacturing system, and a cooperative transport strategy for groups of robots. The third application incorporates observations from a novel experimental study of the mechanics of cooperative retrieval in Aphaenogaster cockerelli ants. The correctness of the abstractions and the correspondence of the evolution of the controlled system to the target behavior are validated with computer simulations. The investigated applications form the building blocks for a versatile swarm system with integrated capabilities that have performance guarantees

Analysis of catabolic gene in marine bacteria for polycyclic aromatic hydrocarbon degradation

The aim of the present study was to analyze the biodegradation of Polycyclic Aromatic Hydrocarbons (PAHs) compound by the bacterial isolates and localization of the PAH-ring hydroxylating dioxygenase genes. (PAHs) are widely distributed in nature and are known to be toxic and carcinogenic. Some micro-organisms are capable of transforming and degrading PAHs. These potential abilities may be useful in removal of PAHs from the environment. Bacterial isolates capable of degrading Napthalene and Phenanthrene were isolated from Rushikuliya estuary (Odisha) water sample by selective enrichment. The isolates were screened for the ability to degrade Napthalene and Phenanthrene when provided as the sole source of carbon. Five isolates, designated as KR-2, KR-5, KR-7, KR-10 and KR-15 were selected after initial screening. Isolates were characterized by gram staining, citrate utilization, sugar fermentation, swimming and swarmming motility and antibiotic sensitivity test. In 7 days KR-2, KR-5, KR-7, KR-10 and KR-15, found to degrade 50.88%, 50.96%, 50.81%, 50.4% and 50.77% of phenanthrene and 70.01%, 66.01%, 78.18%, 74.1% and 71% of napthelene respectively. Genomic DNA was extracted and ring hydroxylating dioxygenase gene was amplified by primer- Forward primer - (GAG ATG CAT ACC ACG TKG GTT GGA) and Reverse primer - (AGC TGT TGT TCG GGA AGA YWG TGC MGT T). Of the five selected PAH degrading bacteria, KR-2 showed amplification of dioxygenase gene

Development of enzyme-functionalized hybrid mesoporous nanodevices for advanced chemical communication

Tesis por compendio[ES] La presente tesis doctoral se centra en el diseño, síntesis y caracterización de varios nanodispositivos híbridos orgánico-inorgánicos, utilizando como soporte nanopartículas de sílice mesoporosa equipadas con enzimas y puertas moleculares, los cuales muestran capacidades comunicativas además de la evaluación de diferentes estrategias de comunicación. El primer capítulo incluye un resumen de diferentes conceptos sobre los que se fundamentan los estudios realizados tales como nanotecnología, materiales de sílice mesoporosa, materiales con puertas moleculares que reaccionan a estímulos específicos, partículas Janus y biocomputación. Finalmente, se incluyen conceptos básicos acerca de la comunicación química, materiales y estrategias empleados hasta ahora y ejemplos representativos. A continuación, en el segundo capítulo, se presentan los objetivos generales de esta tesis doctoral que son abordados en los siguientes capítulos experimentales. El tercer capítulo muestra un sistema de biocomputación para liberación basado en nanopartículas Janus de oro-sílice mesoporosa capaces de comunicarse con el entorno procesando la información e imitando la función lógica booleana propia de un demultiplexer y que resulta en la liberación controlada de la carga. Se muestra que dicho nanodispositivo puede llevar a cabo sus funciones en medios complejos como en células cancerígenas. En el cuarto capítulo, se presenta un modelo circular de comunicación dentro de una red de tres nanopartículas diferentes basado en el intercambio jerárquicamente programado de mensajes químicos. La parte mesoporosa del nanodispositivo 1 (S1βgal) es cargada con la especie fluorescente [Ru(bpy)3]Cl2 y tapada con cadenas de oligo(etilenglicol) que contienen puentes disulfuro y que funcionan como puertas moleculares, mientras que la enzima β-galactosidasa es unida a la parte del oro. En la nanopartícula 2 (S2galox), la enzima galactosa oxidasa es inmovilizada en la cara del oro mientras que la sílice mesoporosa es cargada con 4-(bromometil)benzoato de metilo y los poros tapados con un derivado de arilboronato autoinmolante sensible a H2O2 que forma un complejo huéspedanfitrión con β-ciclodextrina. Finalmente, el nanodispositivo 3 (S3est) es funcionalizado con la enzima esterasa en la parte del oro, cargada con la especie reductora hidroclururo de tris(2-carboxietil)fosfina (TCEP) en la parte mesoporosa y tapada con una nanoválvula supramolecular que responde a pH (βciclodextrina:benzimidazol). En el quinto capítulo, se muestra un modelo interactivo de comunicación química entre una nanopartícula Janus abiótica y un organismo vivo (Saccharomyces cerevisiae). En particular, el nanodispositivo está basado en nanopartículas funcionalizadas con glucosa oxidasa en la parte del oro, cargadas con el genotóxico fleomicina y tapadas con la puerta molecular sensible a pH (βciclodextrina:benzimidazol). El microorganismo usado en el estudio es una levadura modificada que expresa GFP bajo el control del promotor del gen RNR3; la transcripción de dicho gen es inducida con la exposición a agentes que dañan el ADN. La ruta de comunicación interactiva empieza con la adición de sacarosa (estímulo de entrada) la cual es hidrolizada en glucosa por la invertasa localizada en el espacio periplásmico de las levaduras y que difunde al nanodispositivo donde es trasformada en el correspondiente ácido por la glucosa oxidasa de la parte del oro. La bajada local de pH da lugar a la apertura de la nanoválvula sensible a pH del nanovehículo y con ello a la liberación de fleomicina (mensaje de vuelta) que induce la expresión de GFP (señal de salida) en las levaduras. En el sexto capítulo, proponemos una estrategia para establecer una comunicación lineal entre dos microorganismos diferentes que no interactúan entre ellos mediada por un nanodispositivo que actúa como traductor químico. Finalmente, las conclusiones generales de la presente tesis doctoral son expuestas en el capítulo siete. El estudio de las capacidades comunicativas de los nanodispositivos mesoporosos funcionalizados con enzimas permite la construcción de estrategias de cooperación entre diferentes entidades que permiten funcionalidades que van más allá que aquellas llevadas a cabo por agentes individuales.[CA] La present tesi doctoral es centra en el disseny, síntesi i caracterització de diversos nanodispositius híbrids orgànic-inorgànics, utilitzant com a suport nanopartícules de sílice mesoporosa equipades amb enzims i portes moleculars, i que mostren capacitats comunicatives a més de l’avaluació de diferents estratègies de comunicació. El primer capítol inclou un resum de diferents conceptes sobre els quals es fonamenten els estudis realitzats com ara nanotecnologia, materials de sílice mesoporosa, materials amb portes moleculars que reaccionen a estímuls específics, partícules Janus i biocomputació. Finalment, s’inclouen conceptes bàsics sobre la comunicació química, materials i estratègies utilitzades fins ara i exemples representatius. A continuació, en el segon capítol, es presenten els objectius generals d’aquesta tesi doctoral que són abordats en els següents capítols experimentals. El tercer capítol mostra un sistema de biocomputació per alliberament basat en nanopartícules Janus d’or-sílice mesoporosa capaços de comunicar-se amb l’entorn processant la informació i imitant la funció lògica booleana pròpia d’un demultiplexer i que resulta en l’alliberament controlat de la càrrega. Es mostra que aquest nanodispositiu pot dur a terme les seves funcions en mitjans complexos com en cèl·lules canceroses. En el quart capítol, es presenta un model circular de comunicació dins d’una xarxa de tres nanopartícules diferents basat en l’intercanvi jeràrquicament programat de missatges químics. La part mesoporosa del nanodispositiu 1 (S1βgal) es carrega amb l’espècie fluorescent [Ru(bpy)3]Cl2 i es tapa amb cadenes d’oligo(etilenglicol) que contenen ponts disulfur i que funcionen com portes moleculars, mentre que l’enzim β-galactosidasa s’immobilitza a la part de l’or. A la nanopartícula 2 (S2galox), l’enzim galactosa oxidasa s’immobilitza a la cara de l’or mentre que la sílice mesoporosa es carrega amb 4-(bromometil)benzoat de metil i els porus són tapats amb un derivat d’arilboronat autoimmolant sensible a H2O2 que forma un complex hoste-amfitrió amb β-ciclodextrina. Finalment, el nanodispositu 3 (S3est) es funcionalitza amb l’enzim esterasa en la part de l’or, es carrega amb l’espècie reductora hidroclurur de tris (2-carboxietil) fosfina (TCEP) a la part mesoporosa i es tapa amb una nanoválvula supramolecular que respon a pH (β-ciclodextrina:benzimidazol). En el cinqué capítol, es mostra un model interactiu de comunicació química entre una nanopartícula Janus abiòtica i un organisme viu (Saccharomyces cerevisiae). En particular, el nanodispositiu està basat en nanopartícules funcionalitzades amb glucosa oxidasa en la part de l’or, carregades amb el genotòxic fleomicina i tapades amb la porta molecular sensible a pH (βciclodextrina:benzimidazol). El microorganisme utilitzat en l’estudi és un rent modificat que expressa GFP sota el control del promotor del gen RNR3; la transcripció d’aquest gen és induïda amb l’exposició a agents que danyen l’ADN. La ruta de comunicació interactiva comença amb l’addició de sacarosa (estímul d’entrada) la qual és hidrolitzada en glucosa per la invertasa localitzada en l’espai periplasmàtic dels rents i que difon al nanodispositiu on és transformada en el corresponent àcid per la glucosa oxidasa de la part de l’or. La baixada local de pH dona lloc a l’obertura de la nanoválvula sensible a pH del nanovehicle i amb això l’alliberament de fleomicina (missatge de tornada) que indueix l’expressió de GFP (senyal de sortida) en el rent. En el sisé capítol, proposem una estratègia per establir una comunicació lineal entre dos microorganismes diferents que no interactuen entre ells facilitada per un nanodispositiu que actua com a traductor químic. Finalment, les conclusions generals de la present tesi doctoral són exposades en el capítol set. L’estudi de les capacitats comunicatives dels nanodispositius mesoporosos funcionalitzats amb enzims permet la construcció d’estratègies de cooperació entre diferents entitats que permeten funcionalitats que van més enllà que aquelles dutes a terme per agents individuals. Esperem que els resultats obtinguts inspiren aplicacions futures en diferents àrees com ara biomedicina, nanorobots, materials que imiten la naturalesa i tecnologies de la informació.[EN] This PhD Thesis is focused on the design, synthesis and characterization of several hybrid organic-inorganic nanodevices using mesoporous silica nanoparticles equipped with enzymes and molecular gates which display communication capabilities as well as the design and evaluation of different communication strategies. The first chapter includes an overview of the different concepts which lay the foundations of the presented studies such as nanotechnology, mesoporous silica materials, stimuli-responsive gated materials, Janus particles and biocomputing. Basic concepts of chemical communication, materials and enabling technologies employed so far and representative examples in this field are also included. Next, in the second chapter, the general objectives of this PhD Thesis that are addressed in the following experimental chapters are presented. The third chapter shows a biocomputing delivery system based on Janus gold-mesoporous silica nanoparticles capable of chemically communicating with the environment and processing the information mimicking a demultiplexer Boolean logic function which results in a programmed cargo release. Finally, it is shown that such nanodevice is operative in complex media such as cancer cells. In the fourth chapter, it is presented a circular model of communication within a network of three different nanoparticles based on the hierarchically programmed exchange of chemical messages. The mesoporous face of nanodevice 1 (S1βgal) is loaded with the fluorescent dye [Ru(bpy)3]Cl2 and capped with disulfidecontaining oligo(ethylene glycol) chains acting as gatekeepers, whereas the enzyme β-galactosidase is attached to the gold face. In nanoparticle 2 (S2galox), the enzyme galactose oxidase is immobilized on the Au face, while the mesoporous silica is loaded with methyl 4-(bromomethyl)benzoate and the mesopores capped with a H2O2-sensitive self-immolative arylboronate derivative which forms a host-guest complex with β-cyclodextrin. Finally, the nanodevice 3 (S3est) is functionalized with the enzyme esterase on the Au face, loaded with the reductive species tris(2- carboxyethyl)phosphine hydrochloride (TCEP) in the mesoporous face and capped with a pH-responsive supramolecular nanovalve (β-cyclodextrin:benzimidazole). In the fifth chapter, it is showed an interactive model of chemical communication between an abiotic Janus nanoparticle and a living organism (Saccharomyces cerevisiae). In particular, the nanodevice is based on Janus goldmesoporous silica nanoparticles functionalized with glucose oxidase on the Au face, loaded with the genotoxin phleomycin and capped with a pH-responsive (βcyclodextrin:benzimidazole) gatekeeper. The microorganism used in the studies is an engineered budding yeast that expresses GFP under the control of the RNR3 promoter; RNR3 gene transcription is induced upon exposure to DNA-damaging agents. The interactive communication pathway starts with the addition of sucrose (input) which is hydrolyzed into glucose by invertase located in periplasmic space of yeasts and diffuses to the nanodevice where it is transformed into the corresponding acid by glucose oxidase on the Au face. The local drop in pH leads to uncapping of the pH-sensitive nanovalve in the nanocarrier and the release of phleomycin (feedback messenger) that induces GFP expression (output) in yeasts. In the sixth chapter, we propose a strategy to establish linear communication between two different non-interacting microorganisms mediated by a nanodevice which acts as a chemical “nanotranslator”. Finally, the general conclusions from this PhD Thesis are presented in chapter seven. The study of communication capabilities of enzyme-functionalized mesoporous nanodevices enables the construction of strategies of cooperation between different entities allowing sophisticated functionalities that go beyond those carried out by individual agents. We hope that the obtained results inspire future applications in different areas such as biomedicine, nanorobots, life-like materials and information technologies.The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, UE), CTQ2017-87954-P), the Generalitat Valenciana (PROMETEO 2018/024), the Comunidad de Madrid (IND2017/BMD7642) and CIBER-BBN (NANOCOMMUNITY project) for support.De Luis Fernández, B. (2021). Development of enzyme-functionalized hybrid mesoporous nanodevices for advanced chemical communication [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171506TESISCompendi

Multi-Agent based modeling and simulation of metabolic networks

Master'sMASTER OF ENGINEERIN

Actinobacteria and Myxobacteria

Bacterial infections cause millions of deaths globally, particularly in children and the elderly, and four of the 10 leading causes of death are infectious diseases in low- and middle-income countries. The continuous use of antibiotics has resulted in multi-resistant bacterial strains all over the world, such as Community-associated Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamases (ESBLs), and, as expected, hospitals have become breeding grounds for human-associated microorganisms, especially in critical care units