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  • Evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures

     Cáceres, Neus; Vilaplana, Cristina; Prats Soler, Clara; Marzo, Elena; Llopis Fuste, Isaac; Valls Ribas, Joaquim; Lopez Codina, Daniel; Cardona, Pere-Joan
    Tuberculosis
    Vol. 93, num. 6, p. 690-698
    DOI: 10.1016/j.tube.2013.08.003
    Date of publication: 2013-11
    Journal article

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    The aim of this study was to evaluate the evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures according to growth time and conditions. Thus, in standard culture using aerated 7H9 Middlebrook broth supplemented with 0.05% Tween 80, a dramatic CFU decrease was observed at the end of the exponential phase. This phase was followed by a stable stationary phase that led to dissociation between the optical density (O.D.) and CFU values, together with the formation of opaque colonies in solid culture. Further analysis revealed that this was due to cording. Scanning electron microscopy showed that cording led to the formation of very stable coiled structures and corded cell aggregations which proved impossible to disrupt by any of the physical means tested. Modulation of cording with a high but non-toxic concentration of Tween 80 led to a slower growth rate, avoidance of a sudden drop-off to the stationary phase, the formation of weaker cording structures and the absence of opaque colonies, together with a lower survival at later time-points. An innovative automated image analysis technique has been devised to characterize the cording process. This analysis has led to important practical consequences for the elaboration of M. tuberculosis inocula and suggests the importance of biofilm formation in survival of the bacilli in the extracellular milieu.

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    A two years simulation using a real data cellular automaton: A predictive case study with the schistosomiasis expansion process along the coastline of Brazil  Open access

     Albuquerque, Jones O.; Bocanegra, Silvana; Ferrer-Savall, Jordi; Lopez Codina, Daniel; de Souza, Marco Antônio; Souza Santos, Reinaldo; Barbosa, Constança
    systema: connecting matter, life, culture and technology
    Vol. 1, num. 3, p. 83-89
    Date of publication: 2013
    Journal article

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    This work presents a Cellular Automata model to characterize the social and environmental factors which contribute for the analysis of the expansion process of Schistosoma mansoni infection in Pernambuco - Brazil. The model has been experimented with a set of two years real data from a study area at North Coast of Pernambuco ¿ Brazil. The main constraint equations, the modelling process and the results obtained until now with the simulating scenarios generated are presented here. The results identify, as in field works, endemic areas and human risk infection areas. Furthermore, predictive scenarios for a look ahead with a perspective into fifteen years are also presented.

    This work presents a Cellular Automata model to characterize the social and environmental factors which contribute for the analysis of the expansion process of Schistosoma mansoni infection in Pernambuco - Brazil. The model has been experimented with a set of two years real data from a study area at North Coast of Pernambuco – Brazil. The main constraint equations, the modelling process and the results obtained until now with the simulating scenarios generated are presented here. The results identify, as in field works, endemic areas and human risk infection areas. Furthermore, predictive scenarios for a look ahead with a perspective into fifteen years are also presented.

  • Spatial growth of Mycobacterium tuberculosis in lungs: the bubble model

     Prats Soler, Clara; Valls Ribas, Joaquim; Vilaplana, Cristina; Marzo, Elena; Cardona, Pere-Joan; Lopez Codina, Daniel
    International Conference on Environmental, Industrial and Applied Microbiology
    p. 513-
    Presentation's date: 2013-10-03
    Presentation of work at congresses

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  • A proposal for automatic diagnosis of malaria

     Oliveira, Allisson D.; Cabral, Giordano; Lopez Codina, Daniel; Firmo, Caetano; Zarzuela Serrat, F; Albuquerque, Jones O.
    International World Wide Web Conference
    p. 681-682
    Presentation's date: 2013-05
    Presentation of work at congresses

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    This paper presents a methodology for automatic diagnosis of malaria using computer vision techniques combined with artificial intelligence. We had obtained an accuracy rate of 74% in the detection system.

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    Low dose aerosol fitness at the innate phase of murine infection better predicts virulence amongst clinical strains of mycobacterium tuberculosis  Open access

     Cáceres, Neus; Llopis Fuste, Isaac; Marzo, Elena; Prats Soler, Clara; Vilaplana, Cristina; García de Viedma, Darío; Samper, Sofia; Lopez Codina, Daniel; Cardona, Pere-Joan
    PLoS one
    Vol. 7, num. 1, p. e29010-
    DOI: 10.1371/journal.pone.0029010
    Date of publication: 2012-01-03
    Journal article

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    Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 102 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance: The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection.

  • A biphasic model for fitting optical density measurements to bacterial cell counts and its application on the instantaneous growth rate evaluation

     Ye, Wei Hong; Prats Soler, Clara; Bover-Cid, Sara; Garriga, Margarita; Lopez Codina, Daniel
    International ICFMH Symposium (Food Micro)
    p. 612
    Presentation's date: 2012-09-04
    Presentation of work at congresses

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  • A two-compartment system allows lymphatic tissues to control M. tuberculosis infection in the peripheral organs

     Vilaplana Massaguer, Cristina; Prats Soler, Clara; Marzo, Elena; Barril, Carles; Llopis Fuste, Isaac; Díaz, Julio; Valls Ribas, Joaquim; Lopez Codina, Daniel; Cardona, Pere-Joan
    European Congress of Immunology
    Presentation's date: 2012-09-07
    Presentation of work at congresses

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  • Agent-based Models in malaria elimination strategy design

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Valls Ribas, Joaquim
    European Meeting on Cybernetics and Systems Research
    Presentation's date: 2012-04
    Presentation of work at congresses

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    Thermodynamic concepts in the study of microbial populations: age structure in plasmodium falciparum infected red blood cells  Open access

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vidal-Mas, Jaume; Gargallo-Viola, Domingo; Guglietta, Antonio; Giro Roca, Antoni
    PLoS one
    Vol. 6, num. 10, p. e26690 1-e26690 11
    DOI: 10.1371/journal.pone.0026690
    Date of publication: 2011-10-31
    Journal article

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    Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities.

  • Mart XXI o de com anar de la secundària a la universitat passant per Mart

     Almansa Lagunas, Clara; Blay Carreras, Estel; Casas Carbonell, Montserrat; Delgado Muñoz, Luis; Gutierrez Cabello, Jorge Luis; Jove Casulleras, Roger; Lopez Codina, Daniel; López Rubio, Juan; Loren Aguilar, Pablo; Marando, Graciela; Monfort Peligero, Lluís; Nebra, Norbert; Pera, Francesc; Portell Canal, Xavier; Ramírez Alcantara, Jorge; Sagardoy, Juli; Sánchez, Álex
    Date: 2011-11-22
    Report

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  • Premi a la millor tesi doctoral en Ciencies 2010

     Ferrer Savall, Jordi; Lopez Codina, Daniel; Valls Ribas, Joaquim
    Award or recognition

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  • Modelización basada en el individuo (IBM) perspectiva multidisclipinar en microbiologia aplicada: alimentos, medioambiente y salud

     Prats Soler, Clara; Valls Ribas, Joaquim; Carbo Moliner, Rosa; Ginovart Gisbert, Marta; Giro Roca, Antoni; Gras Moreu, Anna Maria; Portell Canal, Xavier; Ferrer Savall, Jordi; Silbert, Moises; Lopez Codina, Daniel
    Competitive project

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  • New insights on the virulence determination of M. tuberculosis clinical strains by applying different "in vitro" and "in vivo" strategies

     Cáceres, Neus; Llopis Fuste, Isaac; Marzo, Elena; Vilaplana, Cristina; Díaz, Jorge; Alonso, María; García de Viedma, Darío; Alonso, Henar; Samper, Sofia; Prats Soler, Clara; Lopez Codina, Daniel; Cardona, Joan Pere
    International Conference on the Pathogenesis of Mycobacterial Infections
    p. 97
    Presentation's date: 2011-07-01
    Presentation of work at congresses

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  • Método de valoración de virulencia de cepas de Mycobacterium tuberculosis complex y uso de los agregados bacilares de cepas de Mycobacterium tuberculosis complex en cultivo líquido para dicha valoración

     Prats Soler, Clara; Llopis Fuste, Isaac; Lopez Codina, Daniel; Caceres Casademunt, Neus; Cardona Iglesias, Pere Joan; Vilaplana Massaguer, Cristina
    Date of request: 2011-06-22
    Invention patent

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    Método de valoración de virulencia de cepas de Mycobacterium tuberculosis complex y uso de los agregados bacilares de cepas de Mycobacterium tuberculosis complex en cultivo líquido para dicha valoración.

    Tras constatar que la mayor capacidad virulenta de cepas de Mycobacterium tuberculosis se relacionaba con el tamaño de las agrupaciones bacilares contenidas en el cultivo bacilar, el método propone valorar dicha virulencia a partir de la determinación de la distribución de tamaños de los agregados bacilares de cada cepa analizada a partir de muestras obtenidas tras su crecimiento en un medio líquido hasta la fase tardía del crecimiento logarítmico.

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    On the evolution of cell size distribution during bacterial growth cycle: experimental observations and individual-based model simulations  Open access

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel; Giro Roca, Antoni; Vives-Rego, Josep
    African journal of microbiology research
    Vol. 4, num. 5, p. 400-407
    Date of publication: 2010-03
    Journal article

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  • Individual-based modeling of Plasmodium falciparum erythrocyte infection in in vitro cultures  Open access

     Ferrer Savall, Jordi
    Department of Physics and Nuclear Engineering, Universitat Politècnica de Catalunya
    Theses

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    La malària és encara avui en dia una malaltia que causa aproximadament un milió de morts a l'any a tot el món. La seva eradicació suposa un gran repte per a la humanitat i per a la comunitat científica, en particular. El cultiu in vitro del paràsit és essencial per al desenvolupament de nous medicaments. Els mètodes de cultiu actuals es basen en l'heurística i requereixen millores.En aquesta tesi es presenta una aproximació teòrica al procés d'infecció a eritròcits en cultius in vitro amb Plasmodium falciparum, un dels protozous paràsits causants de la malària. El treball està centrat en la construcció i avaluació de models d'una complexitat adequada per tractar els problemes específics detectats pels experts en l'àmbit, i inclou també la formulació d'algorismes de simulació i el disseny de protocols experimentals.Aquest tipus de treball requereix de la col·laboració multidisciplinària. La visió dels experts en malària es complementa amb la modelització i simulació, que permet la comprovació dels supòsits preestablerts, la comprensió de fenòmens observats i la millora dels mètodes de cultiu actuals. Així doncs, cal establir i desenvolupar eines que permetin crear, analitzar i compartir models amb grups que estudien la malària des d'altres perspectives. En aquesta tesi, s'ha optat per la modelització basada en l'individu (IbM) i orientada a la reproducció de múltiples patrons (PoM). El model s'ha formulat seguint l'ODD, un protocol estàndard en el camp de l'ecologia teòrica, que s'ha adaptat a la representació de comunitats microbianes.Els models basats en l'individu (IbMs) defineixen un conjunt de normes que regeixen el comportament de cada cèl·lula i les seves interaccions amb les altres cèl·lules i amb el seu entorn immediat. A partir d'aquestes regles, i tenint en compte una certa diversitat dins de la població i un cert grau d'aleatorietat en els processos individuals, els IbMs mostren explícitament el comportament emergent del sistema en conjunt. Complementàriament, s'han aplicat conceptes propis de la termodinàmica per tal d'entendrel'aparició de patrons macroscòpics a partir de l'estructura de la població (per exemple de la distribució de les fases d'infecció entre els glòbuls vermells infectats).Aquesta recerca ha comportat la la creació i aplicació del model i simulador INDISIM-RBC, que ha demostrat ser una bona eina per millorar la comprensió dels cultius estudiats. Es tracta d'un model mecanicista, basat en l'individu, que reprodueix quantitativament els patrons observats en cultius reals a diferents nivells de descripció, i que en prediu el comportament sota determinades condicions.Hem demostrat que INDISIM-RBC pot ser emprat per a estudiar en detall alguns aspectes del cultiu del paràsit causant de la malària que calia aclarir. Permet realitzar experiments virtuals i així impulsar noves línies de recerca i explorar noves tècniques de cultiu. En particular, INDISIM-RBC s'ha utilitzat per millorar els protocols experimentals actuals del cultius estàtics, definint la geometria òptima de l'hematòcrit i els protocols de subcultiu més adequats per als cultius continus.El treball realitzat en malària s'ha comparat amb la investigació duta a terme pel grup de recerca em relació amb d'altres comunitats microbianes. D'aquesta manera, podem estudiar les propietats emergents dels sistemes microbians en general en relació als efectes de la individualitat de la cèl·lula, la diversitat de les poblacions, l'heterogeneïtat en el medi, o el caràcter local de les interaccions, entre d'altres. Aquesta visió general proporciona eines conceptuals que poden ser emprades per refinar l'anàlisi dels processos d'infecció sota estudi.

    Malaria is still a major burden that causes approximately one million deaths annually worldwide. Its eradication supposes a great challenge to the humanity and to the scientific community, in particular. In vitro cultivation of the parasite is essential for the development of new drugs. Current culture methods are based on heuristics and demand for specific improvements.The present thesis is a theoretical approach to in vitro cultivation of the protozoan parasite Plasmodium falciparum infecting human red blood cells. It mainly focuses on the process of building a model of appropriate complexity to deal with the specific demands above mentioned, but it also includes the formulation and implementation of algorithms, and the design and execution of experimental trials.This kind of work requires multidisciplinary collaboration: the insight of the experts in malaria research is complemented with modeling and simulation, which allows for checking settled assumptions, increasing the understanding on the system and improving the current culturing methods.The use of tools for building, analyzing and sharing models is an imperative to this end. In this thesis, Pattern-oriented Modeling (PoM) has been adopted as the most appropriate way for raising of models and the ODD protocol (Objectives, Design Concepts and Details) has been proposed as the standard tool for communicating them.Individual-based Modeling (IbM) has been used to tackle malaria culture systems. IbMs define a set of rules governing each cell, its interactions with others and with its immediate surroundings. From this set of rules, and taking into account diversity within the population and a certain degree of randomness in the individual processes, IbMs explicitly show the emerging behavior of the system as a whole. Methods from statistical thermodynamics have been applied to understand the emergence of macroscopic patterns from the population structure (e.g. distribution of infection stages among infected red blood cells).The research resulted in the development of the model and simulator INDISIM-RBC, which has proved to be a good tool to improve understanding of the cultures under study. It is a mechanistically rich individual-based model and it quantitatively reproduces and predicts several patterns observed in real cultures at different levels of description.We demonstrated that INDISIM-RBC can be used to study in detail several aspects of malaria cultivation that remained unclear, as well as to perform virtual experiments. Consequently, it can be used to open novel lines of research and to examine potential experimental techniques. INDISIM-RBC has also been used to improve the current experimental culturing protocols in static cultivation by obtaining the optimal geometry of the hematocrit layer and subcultivation periods in the continuous cultures.This study on malaria has been compared to the research carried out by the group regarding other microbial communities. Thereby studying general emerging properties of microbial systems in general, with regard to the effect of cell individuality, heterogeneity and diversity, the local nature of interactions; and biological and spatial complexity. In doing so, the acquired holistic view has been used to develop tools that allow for a better characterization and study of the infection process, in particular.

  • Contribution of individual-based models in malaria elimination strategy design

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Valls Ribas, Joaquim; Gargallo Viola, Domingo
    Parasite to prevention, advandes in understanding malaria
    p. 27
    DOI: 10.1186/1475-2875-9-S2-P9
    Presentation's date: 2010-10-20
    Presentation of work at congresses

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    Analysis of the population structure of Plasmodium falciparum-infected erythrocytes  Open access

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Gargallo Viola, Domingo; Valls Ribas, Joaquim
    Current opinion in celular host-pathogen interactions
    p. 3
    Presentation's date: 2010-09-05
    Presentation of work at congresses

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    Population-based and individual-based modelling of high hydrostatic pressure effect in Listeria monocytogenes on sliced dry-cured ham  Open access

     Prats Soler, Clara; Bover Cid, Sara; Garriga, Margarita; Aymerich Calvet, Teresa; Ferrer Savall, Jordi; Lopez Codina, Daniel
    International ICFMH Symposium (Food Micro)
    p. 174
    Presentation's date: 2010-09-01
    Presentation of work at congresses

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  • Microbiología predictiva: una herramienta imprescindible en seguridad alimentaria  Open access

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel
    Reunión Científica Hispano-Marroquí sobre Seguridad Alimentaria
    p. 34-35
    Presentation's date: 2009-10-20
    Presentation of work at congresses

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  • Mathematical modelling methodologies in predictive food microbiology: a SWOT analysis

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vives-Rego, Josep
    International journal of food microbiology
    Vol. 134, num. 1-2, p. 2-8
    Date of publication: 2009-08
    Journal article

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  • Optimization methods for individual-based model parameter estimation in predictive microbiology

     Prats Soler, Clara; Bernaerts, K.; Standaert, A.; Ferrer Savall, Jordi; Lopez Codina, Daniel; Van Impe, J.
    Vienna Conference on Mathematical Modelling
    p. 2635-2638
    Presentation's date: 2009
    Presentation of work at congresses

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    In the framework of microbiology, Individual-based Models are discrete models in which the main entities are microbes. Their use in simulations as ‘virtual experiments’ to predict the evolution of populations under specific conditions requires accurate setting of the parameters involved. We adapted and tested two optimization methods for Individual-based Model parameter estimation: the Nelder-Mead Threshold Accepting (NMTA) and the NEWUOA. These methods presented no convergence problems, and the best results in terms of time expenditure were derived with the latter.

  • Individual-based modelling and flow cytometry: two suitable tools for predictive microbiology

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel; Vives-Rego, J
    International Conference on Simulation and Modelling in the Food and Bio-Industry
    p. 91-95
    Presentation's date: 2008
    Presentation of work at congresses

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  • Individual-based modelling of bacterial cultures in the study of the lag phase  Open access

     Prats Soler, Clara
    Department of Applied Physics, Universitat Politècnica de Catalunya
    Theses

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    La microbiologia predictiva és una de les parts més importants de la microbiologia dels aliments. En el creixement d'un cultiu bacterià es poden observar quatre fases: latència, exponencial, estacionària i mort. La fase de latència té un interès específic en microbiologia predictiva; al llarg de dècades ha estat abordada des de dues perspectives diferents: a nivell cel·lular i intracel·lular (escala microscòpica), i a nivell de població (escala macroscòpica). La primera estudia els processos que tenen lloc a l'interior dels bacteris durant la seva adaptació a les noves condicions del medi, com els canvis en l'expressió gènica i en el metabolisme. La segona descriu l'evolució de la població bacteriana per mitjà de models matemàtics continus i d'experiments que avaluen variables relacionades amb la densitat cel·lular. L'objectiu d'aquest treball és millorar la comprensió de la fase de latència dels cultius bacterians i dels fenòmens intrínsecs a la mateixa. Aquest objectiu s'ha abordat amb la metodologia Individual-based Modelling (IbM) amb el simulador INDISIM (INDividual DIScrete SIMulation), que ha calgut optimitzar. La IbM introdueix una perspectiva mecanicista a través de la modelització de les cèl·lules com a unitats bàsiques. Les simulacions IbM permeten estudiar el creixement d'entre 1 i 106 bacteris, així com els fenòmens que emergeixen de la interacció entre ells. Aquests fenòmens pertanyen al que anomenem escala mesoscòpica. Aquesta perspectiva és imprescindible per entendre l'efecte en la població dels processos d'adaptació individuals. Per tant, la metodologia IbM és un pont entre els individus i la població o, el que és el mateix, entre els models a escala microscòpica i a escala macroscòpica.En primer lloc hem estudiat dos dels diversos mecanismes que poden causar la fase de latència: inòculs amb massa mitjana petita, i canvis de medi.S'ha verificat també la relació de la durada de la latència amb variables com la temperatura o la grandària de l'inòcul. En aquest treball s'ha identificat la distribució de biomassa del cultiu com una variable cabdal per analitzar l'evolució del cultiu durant el cicle de creixement. S'han definit les funcions matemàtiques que anomenem distàncies per avaluar quantitativament l'evolució d'aquesta distribució.Hem abordat, també, la fase de latència des d'un punt de vista teòric. L'evolució de la velocitat de creixement al llarg del cicle ha permès distingir dues etapes en la fase de latència que anomenem inicial i de transició. L'etapa de transició s'ha descrit per mitjà d'un model matemàtic continu validat amb simulacions INDISIM. S'ha constatat que la fase de latència ha de ser vista com un procés dinàmic, i no com un simple període de temps descrit per un paràmetre. Les funcions distància també s'han utilitzat per avaluar les propietats del creixement balancejat.Alguns dels resultats de les simulacions amb INDISIM s'han corroborat experimentalment per mitjà de citometria de flux. S'ha comprovat, al llarg de les diverses fases del creixement, el comportament de la distribució de biomassa previst per simulació, així com l'evolució de les funcions distància. La coincidència entre els resultats experimentals i els de simulació no és trivial, ja que el sistema estudiat és molt complex. Per tant, aquests resultats permeten comprovar la bondat de la metodologia INDISIM.Finalment, hem avançat en l'optimització d'eines per parametritzar IbMs, un pas essencial per poder utilitzar les simulacions INDISIM de manera quantitativa. S'han adaptat i assajat els mètodes grid search, NMTA i NEWUOA. Aquest darrer mètode ha donat els millors resultats en termes de temps, mantenint una bona precisió en els valors òptims dels paràmetres. Per concloure, podem afirmar que INDISIM ha estat validat com una bona eina per abordar l'estudi dels estats transitoris com la fase de latència.

    Predictive food microbiology has become an important specific field in microbiology. Bacterial growth of a batch culture may show up to four phases: lag, exponential, stationary and death. The bacterial lag phase, which is of specific interest in the framework of predictive food microbiology, has generally been tackled with two generic approaches: at a cellular and intracellular level, which we call the microscopic scale, and at a population level, which we call the macroscopic scale. Studies at the microscopic level tackle the processes that take place inside the bacterium during its adaptation to the new conditions such as the changes in genetic expression and in metabolism. Studies at the macroscopic scale deal with the description of a population growth cycle by means of mathematical continuous modelling and experimental measurements of the variables related to cell density evolution.In this work we aimed to improve the understanding of the lag phase in bacterial cultures and the intrinsic phenomena behind it. This has been carried out from the perspective of Individual-based Modelling (IbM) with the simulator INDISIM (INDividual DIScrete SIMulation), which has been specifically improved for this purpose. IbM introduces a mechanistic approach by modelling the cell as an individual unit. IbM simulations deal with 1 to 106 cells, and allow specific study of the phenomena that emerge from the interaction among cells. These phenomena belong to the mesoscopic level.Mesoscopic approaches are essential if we are to understand the effects of cellular adaptations at an individual level in the evolution of a population.Thus, they are a bridge between individuals and population, or, to put it another way, between models at a microscopic scale and models at a macroscopic scale.First, we studied separately two of the several mechanisms that may cause a lag phase: the lag caused by the initial low mean mass of the inoculum, and the lag caused by a change in the nutrient source. The relationship among lag duration and several variables such as temperature and inoculum size were also checked. This analysis allowed identification of the biomass distribution as a very important variable to follow the evolution of the culture during the growth cycle. A mathematical tool was defined in order to assess its evolution during the different phases of growth: the distance functions.A theoretical approach to the culture lag phase through the dynamics of the growth rate allowed us to split this phase into two stages: initial and transition. A continuous mathematical model was built in order to shape the transition stage, and it was checked with INDISIM simulations. It was seen that the lag phase must be defined as a dynamic process rather than as a simple period of time. The distance functions were also used to discuss the balanced growth conditions.Some of the reported INDISIM simulation results were subjected to experimental corroboration by means of flow cytometry, which allow the assessment of size distributions of a culture through time. The dynamics of biomass distribution given by INDISIM simulations were checked, as well as the distance function evolution during the different phases of growth. The coincidence between simulations and experiments is not trivial: the system under study is complex; therefore, the coincidence in the dynamics of the different modelled parameters is a validation of both the model and the simulation methodology.Finally, we have made progress in IbM parameter estimation methods, which is essential to improve quantitative processing of INDISIM simulations.Classic grid search, NMTA and NEWUOA methods were adapted and tested, the latter providing better results with regard to time spent, which maintains satisfactory precision in the parameter estimation results.Above all, the validity of INDISIM as a useful tool to tackle transient processes such as the bacterial lag phase has been amply demonstrated.

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    Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures  Open access

     Ferrer Savall, Jordi; Rosal, M; Vidal, J; Prats Soler, Clara; Valls Ribas, Joaquim; Herreros, E; Lopez Codina, Daniel; Gargallo, D
    Malaria journal
    Vol. 7, num. 203
    DOI: doi:10.1186/1475-2875-7-203
    Date of publication: 2008-10
    Journal article

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    Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model.

  • Analysis and IbM simulation of the stages in bacterial lag phase: basis for an updated definition

     Prats Soler, Clara; Giro Roca, Antoni; Ferrer Savall, Jordi; Lopez Codina, Daniel; Vives-Rego, J
    Journal of theoretical biology
    Vol. 252, num. 1, p. 56-68
    DOI: doi:10.1016/j.jtbi.2008.01.019
    Date of publication: 2008-05
    Journal article

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    The lag phase is the initial phase of a culture that precedes exponential growth and occurs when the conditions of the culture medium differ from the pre-inoculation conditions. It is usually defined by means of cell density because the number of individuals remains approximately constant or slowly increases, and it is quantified with the lag parameter l. The lag phase has been studied through mathematical modelling and by means of specific experiments. In recent years, Individual-based Modelling (IbM) has provided helpful insights into lag phase studies. In this paper, the definition of lag phase is thoroughly examined. Evolution of the total biomass and the total number of bacteria during lag phase is tackled separately. The lag phase lasts until the culture reaches a maximum growth rate both in biomass and cell density. Once in the exponential phase, both rates are constant over time and equal to each other. Both evolutions are split into an initial phase and a transition phase, according to their growth rates. A population-level mathematical model is presented to describe the transitional phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check the outcomes of this analysis. Simulations allow the separate study of the evolution of cell density and total biomass in a batch culture, they provide a depiction of different observed cases in lag evolution at the individual-cell level, and are used to test the population-level model. The results show that the geometrical lag parameter l is not appropriate as a universal definition for the lag phase. Moreover, the lag phase cannot be characterized by a single parameter. For the studied cases, the lag phases of both the total biomass and the population are required to fully characterize the evolution of bacterial cultures. The results presented prove once more that the lag phase is a complex process that requires a more complete definition. This will be possible only after the phenomena governing the population dynamics at an individual level of description, and occurring during the lag and exponential growth phases, are well understood.

  • Individual-based modelling: an essential tool for microbiology

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    Journal of biological physics
    Vol. 34, num. 1-2, p. 19-37
    Date of publication: 2008-04
    Journal article

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    Micro-organisms play a central role in every ecosystem and in the global biomass cycle. They are strongly involved in many fields of human interest, from medicine to the food industry and waste control. Nevertheless, most micro-organisms remain almost unknown, and nearly 99% of them have not yet been successfully cultured in vitro. Therefore, new approaches and new tools must be eveloped in order to understand the collective behaviour of microbial communities in any natural or artificial setting. In particular, theoretical and practical methodologies to deal with such systems at a mesoscopic level of description (covering the range from 100 to 108 cells) are required. Individualbased modelling (IBM) has become a widely used tool for describing complex systems made up of autonomous entities, such as ecosystems and social networks. Individual-based models (IBMs) provide some advantages over the traditional whole-population models: (a) they are bottom-up approaches, so they describe the behaviour of a system as a whole by establishing procedural rules for the individuals and for their interactions, and thus allow more realistic assumptions for the model of the individuals than population models do; (b) they permit the introduction of randomness and individual variability, so they can reproduce the diversity found in real systems; and (c) they can account for individual adaptive behaviour to their environmental conditions, so the evolution of the whole system arises from the dynamics that govern individuals in their pursuit of optimal fitness. However, they also present some drawbacks: they lack the clarity of continuous models and may easily become rambling, which makes them difficult to analyse and communicate. All in all, IBMs supply a holistic description of microbial systems and their emerging properties. They are specifically appropriate to deal with microbial communities in non-steady states, and spatially explicit IBMs are particularly appropriate to study laboratory and natural microbiological systems with spatial heterogeneity. In this paper, we review IBM methodology applied to microbiology. We also present some results obtained from the application of Individual Discrete Simulations, an IBM of ours, to the study of bacterial communities, yeast cultures and Plasmodium falciparum-infected erythrocytes in vitro cultures of Plasmodium falciparum-infected erythrocytes

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    Ciencia y tecnología para el desarrollo: una inversión necesaria  Open access

     Lopez Codina, Daniel; Ortega Roig, Xavier; Pérez Foguet, Agustí; Vendrell, Eva
    Congreso Nacional Universidad y Cooperación al Desarrollo
    p. 1-7
    Presentation's date: 2008-11-12
    Presentation of work at congresses

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    BAETULO XXI, o de com arribar a Mart des de la secundària  Open access

     Ayza, Assumpta; Berenguer Sau, Jordi; Carnerero Lopez, Sheila; Crespo Artiaga, Daniel; Lopez Codina, Daniel; López Rubio, Juan; Loren Aguilar, Pablo; Melo Vera, Maria Jesús; Monfort Peligero, Lluís; Pijuan, Caterina; Portell Canal, Xavier; Ramírez Alcantara, Jorge; Serrano Porta, Lydia
    Congrés d'Enginyeria i Cultura Catalana
    Presentation's date: 2008-12-05
    Presentation of work at congresses

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  • Mathematical modelling methodologies in predictive food microbiology: a SWOT analysis

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vives-Rego, J
    International ICFMH Symposium
    p. 78
    Presentation's date: 2008
    Presentation of work at congresses

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  • INDISIM, an Individual-based Model to simulate microbial cultures

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    Annual conference of agent-based modelers, platform developers and users
    p. 1
    Presentation of work at congresses

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  • Individual based Modelling (IbM) de sistemas microbiológicos para el desarrollo sostenible: medio ambiente, seguridad alimentaria y salud

     Giro Roca, Antoni; Prats Soler, Clara; Lopez Codina, Daniel; Silbert, Moises; Valls Ribas, Joaquim; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta; Portell Canal, Xavier; Ferrer Savall, Jordi
    Competitive project

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  • IbM: An essential tool for microbiology

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    International Conference of Biological Physics
    p. 91
    Presentation of work at congresses

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  • Âfrica, Universitat Politècnica de Catalunya i cooperació al desenvolupament: 15 anys d'aprenentatge  Open access

     Lopez Codina, Daniel; Ortega Roig, Xavier; Pérez Foguet, Agustí; Vendrell, Eva
    Congrés UPC Sostenible 2015
    p. 225-229
    Presentation's date: 2007-07-12
    Presentation of work at congresses

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    En aquest document es pretén revisar una part del treball realitzat pel CCD. En concret, s’analitzen les accions desenvolupades a l’Àfrica que, si bé comencen a integrar un bagatge considerable, encara tenen un pes menor en el conjunt d’iniciatives de cooperació impulsades des del CCD.

  • Evolution of biomass distribution during bacterial lag phase through flow cytometry, particle analysis and Individual-based Modelling

     Prats Soler, Clara; Ferrer Savall, Jordi; Flix, B; Giro Roca, Antoni; Lopez Codina, Daniel; Vives-Rego, J
    International Conference Predictive Modelling in Foods
    p. 301-304
    Presentation of work at congresses

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  • Individual-based model and simulation of Plasmodium falciparum infected erythrocyte in vitro cultures

     Ferrer Savall, Jordi; Vidal, J; Prats Soler, Clara; Valls Ribas, Joaquim; Herreros, E; Lopez Codina, Daniel; Giro Roca, Antoni; Gargallo, D
    Journal of theoretical biology
    Vol. 248, num. 3, p. 448-459
    Date of publication: 2007-10
    Journal article

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    Malaria is still one of the most fatal diseases in the world. Development of an effective treatment or vaccine requires the cultivation of the parasite that causes it: Plasmodium falciparum. Several methods for in vitro cultivation of P. falciparum infected erythrocytes have been successfully developed and described in the last 30 years. Some problems arising from the current harvests are the low parasitaemia and daily human supervision requirements. The lack of a suitable model for global culture behavior makes the assay of new methodologies a costly and tenuous task. In this paper we present a model and simulation tool for these systems. We use the INDividual DIScrete SIMulation protocol (INDISIM) to qualitatively reproduce the temporal evolution of the erythrocyte and merozoite populations. Whole system dynamics are inferred by setting the rules of behavior for each individual red blood cell, such as the nutrient uptake, metabolism and infection processes, as well as the properties and rules for the culture medium: composition, diffusion and external manipulation. We set the individual description parameters according to the values in published data, and allow population heterogeneity. Cells are arranged in a three-dimensional grid and the study is focused on the geometric constraints and physical design of experimental sets. Several published experimental cultures have been reproduced with computer simulations of this model, showing that the observed experimental behavior can be explained by means of individual interactions and statistical laws.

  • Flocculation in brewing yeast: a computer simulation study

     Ginovart Gisbert, Marta; Lopez Codina, Daniel; Giro Roca, Antoni; Silbert, Moises
    Biosystems
    num. 83, p. 51-55
    Date of publication: 2006-01
    Journal article

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  • Spatial properties in Individual- based modelling of microbial systems. Study of the composting process.

     Prats Soler, Clara; Ferrer Savall, Jordi; Giro Roca, Antoni; Lopez Codina, Daniel; Valls Ribas, Joaquim
    Date of publication: 2006-10
    Book chapter

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  • A mathematical analysis of the stages in bacterial lag phase

     Prats Soler, Clara; Giro Roca, Antoni; Lopez Codina, Daniel; Ferrer Savall, Jordi; Valls Ribas, Joaquim; Vives-Rego, Josep
    International ICFMH Symposium
    Presentation's date: 2006-08-30
    Presentation of work at congresses

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  • A physical interpretation of the microbial growth rate temperature dependence

     Prats Soler, Clara; Ferrer Savall, Jordi; Giro Roca, Antoni; Lopez Codina, Daniel; Valls Ribas, Joaquim
    Sitges Conference on Statistical Mechanics
    p. 161-163
    Presentation of work at congresses

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  • Individual-based modelling of bacterial cultures to study the microscopic causes of the lag phase

     Prats Soler, Clara; Lopez Codina, Daniel; Giro Roca, Antoni; Ferrer Savall, Jordi; Valls Ribas, Joaquim
    Journal of theoretical biology
    Vol. 241, num. 4, p. 939-953
    Date of publication: 2006-08
    Journal article

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    The lag phase has been widely studied for years in an effort to contribute to the improvement of food safety. Many analytical models have been built and tested by several authors. The use of Individual-based Modelling (IbM) allows us to probe deeper into the behaviour of individual cells; it is a bridge between theories and experiments when needed. INDividual DIScrete SIMulation (INDISIM) has been developed and coded by our group as an IbM simulator and used to study bacterial growth, including the microscopic causes of the lag phase. First of all, the evolution of cellular masses, specifically the mean mass and biomass distribution, is shown to be a determining factor in the beginning of the exponential phase. Secondly, whenever there is a need for an enzyme synthesis, its rate has a direct effect on the lag duration. The variability of the lag phase with different factors is also studied. The known decrease of the lag phase with an increase in the temperature is also observed in the simulations. An initial study of the relationship between individual and collective lag phases is presented, as a complement to the studies already published. One important result is the variability of the individual lag times and generation times. It has also been found that the mean of the individual lags is greater than the population lag. This is the first in a series of studies of the lag phase that we are carrying out. Therefore, the present work addresses a generic system by making a simple set of assumptions.

  • A mathematical analysis of the stages in bacterial lag phase

     Prats Soler, Clara; Giro Roca, Antoni; Lopez Codina, Daniel; Ferrer Savall, Jordi; Valls Ribas, Joaquim; Vives-Rego, Josep
    International ICFMH Symposium
    p. 550
    Presentation's date: 2006
    Presentation of work at congresses

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  • Individual-based Modelling of microbial activity to study mineralization of C and N and nitrification process in soil

     Ginovart Gisbert, Marta; Lopez Codina, Daniel; Gras Moreu, Anna Maria
    Nonlinear analysis: real world applications
    Vol. 6, p. 773-795
    Date of publication: 2005
    Journal article

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    This work models the dynamics and evolution of carbon (C) and nitrogen (N) related to organic matter in soils by using individual-based simulations. The simulator INDISIM-SOM controls a group of microbial cells at each time step, using a set of time-dependent variables for each microorganism. The space is divided into square cells. In each spatial cell, the amounts of different types of organic compounds are controlled. These are identified as polymerized organic C and N, labile organic C and N, mineral compounds likeNNH4,NNO3,CO2 andO2. The model takes into account the activity of two prototypes of microbial cells: ammonifier microorganisms and nitrifier bacteria. Different metabolic pathways and sources of C and N they can use are identified. Some state variables and parameters related to soil organic matter and microbial activity: growth and decay of microbial biomass, and temporal evolutions of mineralized intermediate N, mineral N in ammonium and nitrate, CO2 and O2 are studied. The calibration of the simulation model has made use of data from laboratory incubation experiments performed on two different types of Mediterranean soils. Both, conceptual validation during the development of the model and agreement of the simulation results with experimental.

  • Individual based modelling of plasmodium falciparum in vitro cultures

     Ferrer Savall, Jordi; Lopez Codina, Daniel; Prats Soler, Clara; Valls Ribas, Joaquim
    International Congress For Tropical Medecine And Malaria
    p. 237
    Presentation of work at congresses

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  • Spatial properties in individual based modelling of microbiological systems. Study of the composting process

     Prats Soler, Clara; Lopez Codina, Daniel; Giro Roca, Antoni; Ferrer Savall, Jordi
    International Conference on Environmental, Industrial and Applied Microbiology
    Presentation's date: 2005-03-15
    Presentation of work at congresses

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