Virtual Campus for the University of Jaume I, Castelló, Spain: 3D Modelling of the Campus Buildings using CityEngine

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Evaluation of chemotherapeutic potential of natural extracts using 3D models of colon cancer

Dissertation to obtain master degree in Biotechnology

Development of 3D in vitro models for prediction of hepatic metabolism and toxicity

The development of human cell models that recapitulate hepatic functionality allows the study of metabolic pathways involved in toxicity and disease. The increased biological relevance, cost-effectiveness and high-throughput of cell models can contribute to increase the efficiency of drug development in the pharmaceutical industry. Recapitulation of liver functionality in vitro requires the development of advanced culture strategies to mimic in vivo complexity, such as 3D culture, co-cultures or biomaterials. However, complex 3D models are typically associated with poor robustness, limited scalability and compatibility with screening methods. In this work, several strategies were used to develop highly functional and reproducible spheroid-based in vitro models of human hepatocytes and HepaRG cells using stirred culture systems. In chapter 2, the isolation of human hepatocytes from resected liver tissue was implemented and a liver tissue perfusion method was optimized towards the improvement of hepatocyte isolation and aggregation efficiency, resulting in an isolation protocol compatible with 3D culture. In chapter 3, human hepatocytes were co-cultivated with mesenchymal stem cells (MSC) and the phenotype of both cell types was characterized, showing that MSC acquire a supportive stromal function and hepatocytes retain differentiated hepatic functions, stability of drug metabolism enzymes and higher viability in co-cultures. In chapter 4, a 3D alginate microencapsulation strategy for the differentiation of HepaRG cells was evaluated and compared with the standard 2D DMSO-dependent differentiation, yielding higher differentiation efficiency, comparable levels of drug metabolism activity and significantly improved biosynthetic activity. The work developed in this thesis provides novel strategies for 3D culture of human hepatic cell models, which are reproducible, scalable and compatible with screening platforms. The phenotypic and functional characterization of the in vitro systems performed contributes to the state of the art of human hepatic cell models and can be applied to the improvement of pre-clinical drug development efficiency of the process, model disease and ultimately, development of cell-based therapeutic strategies for liver failure.

A FEM-based model to study the behaviour of corroded RC beams shear repaired by NSM CFRP rods technique

This paper presents the main features of finite element FE numerical model developed using the computer code FEMIX to predict the near-surface mounted NSM carbon-fiber-reinforced polymer CFRP rods shear repair contribution to corroded reinforced concrete RC beams. In the RC beams shear repaired with NSM technique, the Carbon Fibre Reinforced Polymer (CFRP) rods are placed inside pre-cut grooves onto the concrete cover of the RC beam’s lateral faces and are bonded to the concrete with high epoxy adhesive. Experimental and 3D numerical modelling results are presented in this paper in terms of load-deflection curves, and failure modes for 4 short corroded beams: two corroded beams (A1CL3-B and A1CL3-SB) and two control beams (A1T-B and A1T-SB), the beams noted with B were let repaired in bending only with NSM CFRP rods while the ones noted with SB were repaired in both bending and shear with NSM technique. The corrosion of the tensile steel bars and its effect on the shear capacity of the RC beams was discussed. Results showed that the FE model was able to capture the main aspects of the experimental load-deflection curves of the RC beams, moreover it has presented the experimental failure modes and FE numerical modelling crack patterns and both gave similar results for non-shear repaired beams which failed in diagonal tension mode of failure and for shear-repaired beams which failed due to large flexural crack at the middle of the beams along with the concrete crushing, three dimensional crack patterns were produced for shear-repaired beams in order to investigate the splitting cracks occurred at the middle of the beams and near the support.

A FEM-based model to study the behaviour of corroded RC beams shear repaired by NSM CFRP rods technique

This paper presents the main features of finite element FE numerical model developed using the computer code FEMIX to predict the near-surface mounted NSM carbon-fiber-reinforced polymer CFRP rods shear repair contribution to corroded reinforced concrete RC beams. In the RC beams shear repaired with NSM technique, the Carbon Fibre Reinforced Polymer (CFRP) rods are placed inside pre-cut grooves onto the concrete cover of the RC beam’s lateral faces and are bonded to the concrete with high epoxy adhesive. Experimental and 3D numerical modelling results are presented in this paper in terms of load-deflection curves, failure modes and slip information of the tensile steel bars for 4 short corroded beams: two corroded beams (A1CL3-B and A1CL3-SB) and two control beams (A1T-B and A1T-SB), the beams noted with B were let repaired in bending only with NSM CFRP rods while the ones noted with SB were repaired in both bending and shear with NSM technique. The corrosion of the tensile steel bars and its effect on the shear capacity of the RC beams was discussed. Results showed that the FE model was able to capture the main aspects of the experimental load-deflection curves of the RC beams, moreover it has presented the experimental failure modes and FE numerical modelling crack patterns and both gave similar results for non-shear repaired beams which failed in diagonal tension mode of failure and for shear-repaired beams which failed due to large flexural crack at the middle of the beams along with the concrete crushing, three dimensional crack patterns were produced for shear-repaired beams in order to investigate the splitting cracks occurred at the middle of the beams and near the support.

Evaluating ubiquitous computing environments using 3D simulation

Human activity is very dynamic and subtle, and most physical environments are also highly dynamic and support a vast range of social practices that do not map directly into any immediate ubiquitous computing functionally. Identifying what is valuable to people is very hard and obviously leads to great uncertainty regarding the type of support needed and the type of resources needed to create such support. We have addressed the issues of system development through the adoption of a Crowdsourced software development model [13]. We have designed and developed Anywhere places, an open and flexible system support infrastructure for Ubiquitous Computing that is based on a balanced combination between global services and applications and situated devices. Evaluation, however, is still an open problem. The characteristics of ubiquitous computing environments make their evaluation very complex: there are no globally accepted metrics and it is very difficult to evaluate large-scale and long-term environments in real contexts. In this paper, we describe a first proposal of an hybrid 3D simulated prototype of Anywhere places that combines simulated and real components to generate a mixed reality which can be used to assess the envisaged ubiquitous computing environments [17].

A high order model for piezoelectric rods: an asymptotic approach

Preprint submitted to International Journal of Solids and Structures. ISSN 0020-7683

Three-dimensional technology facilitates surgical performance of novice laparoscopy surgeons: a quantitative assessment on a porcine kidney model

Objective To determine whether the use of 3-dimensional (3D) imaging translates into a better surgical performance of naïve urologic laparoscopic surgeons during pyeloplasty (PY) and partial nephrectomy (PN) procedures. Materials and Methods Eighteen surgeons without any previous laparoscopic experience were randomly assigned to perform PY and PN in a porcine model using initially 2-dimensional (2D) and 3D laparoscopy. A surgical performance score was rated by an "expert" tutor through a modified 5-item global rating scale contemplating operative field view, bimanual dexterity, efficiency, tissue handling, and autonomy. Overall surgical time, complications, subjective perception of participating surgeons, and inconveniences related to the 3D vision were recorded. Results No difference in terms if operative time was found between 2D or 3D laparoscopy for both the PY (P =.51) and the PN (P =.28) procedures. A better rate in terms of surgical performance score was noted by the tutors when the study participants were using 3D vs 2D, for both PY (3.6 [0.8] vs 3.0 [0.4]; P =.034) and PN (3.6 [0.51] vs 3.15 [0.63]; P =.001). No complications occurred in any of the procedures. Most (77.2%) of the participating na??ve laparoscopic surgeons had the perception that 3D laparoscopy was overall easier than 2D. Headache (18.1%), nausea (18.1%), and visual disturbance (18.1%) were the most common issues reported by the surgeons during 3D procedures. Conclusion Despite the absence of translation in a shorter operative time, the use of 3D technology seems to facilitate the surgical performance of naive surgeons during laparoscopic kidney procedures on a porcine model.

Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.

The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.

Two different 3D biogeochemical models for the NW mediterranean sea: validation with Meris data and intercomparison

Report for the scientific sojourn carried out at the University of New South Wales from February to June the 2007. Two different biogeochemical models are coupled to a three dimensional configuration of the Princeton Ocean Model (POM) for the Northwestern Mediterranean Sea (Ahumada and Cruzado, 2007). The first biogeochemical model (BLANES) is the three-dimensional version of the model described by Bahamon and Cruzado (2003) and computes the nitrogen fluxes through six compartments using semi-empirical descriptions of biological processes. The second biogeochemical model (BIOMEC) is the biomechanical NPZD model described in Baird et al. (2004), which uses a combination of physiological and physical descriptions to quantify the rates of planktonic interactions. Physical descriptions include, for example, the diffusion of nutrients to phytoplankton cells and the encounter rate of predators and prey. The link between physical and biogeochemical processes in both models is expressed by the advection-diffusion of the non-conservative tracers. The similarities in the mathematical formulation of the biogeochemical processes in the two models are exploited to determine the parameter set for the biomechanical model that best fits the parameter set used in the first model. Three years of integration have been carried out for each model to reach the so called perpetual year run for biogeochemical conditions. Outputs from both models are averaged monthly and then compared to remote sensing images obtained from sensor MERIS for chlorophyll.

Changes in Running Mechanics and Spring-Mass Behaviour during a 5-km Time Trial

Research into the biomechanical manifestation of fatigue during exhaustive runs is increasingly popular but additional understanding of the adaptation of the spring-mass behaviour during the course of strenuous, self-paced exercises continues to be a challenge in order to develop optimized training and injury prevention programs. This study investigated continuous changes in running mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes performed a 5-km running time trial (mean performance: 17 min 30 s) on a 200 m indoor track. Vertical and anterior-posterior ground reaction forces were measured every 200 m by a 5-m long force platform system, and used to determine spring-mass model characteristics. After a fast start, running velocity progressively decreased (- 11.6%; P<0.001) in the middle part of the race before an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+ 8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%; P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring-mass behaviour progressively changes during a 5-km time trial towards deteriorated vertical stiffness, which alters impact and force production characteristics.

Fiscal Sustainability in a New Keynesian Model

Recent work on optimal monetary and fiscal policy in New Keynesian models suggests that it is optimal to allow steady-state debt to follow a random walk. Leith and Wren-Lewis (2012) consider the nature of the timeinconsistency involved in such a policy and its implication for discretionary policy-making. We show that governments are tempted, given inflationary expectations, to utilize their monetary and fiscal instruments in the initial period to change the ultimate debt burden they need to service. We demonstrate that this temptation is only eliminated if following shocks, the new steady-state debt is equal to the original (efficient) debt level even though there is no explicit debt target in the government’s objective function. Analytically and in a series of numerical simulations we show which instrument is used to stabilize the debt depends crucially on the degree of nominal inertia and the size of the debt-stock. We also show that the welfare consequences of introducing debt are negligible for precommitment policies, but can be significant for discretionary policy. Finally, we assess the credibility of commitment policy by considering a quasi-commitment policy which allows for different probabilities of reneging on past promises. This on-line Appendix extends the results of this paper.

Fiscal Sustainability in a New Keynesian Model

Recent work on optimal monetary and fiscal policy in New Keynesian models suggests that it is optimal to allow steady-state debt to follow a random walk. Leith and Wren-Lewis (2012) consider the nature of the timeinconsistency involved in such a policy and its implication for discretionary policy-making. We show that governments are tempted, given inflationary expectations, to utilize their monetary and fiscal instruments in the initial period to change the ultimate debt burden they need to service. We demonstrate that this temptation is only eliminated if following shocks, the new steady-state debt is equal to the original (efficient) debt level even though there is no explicit debt target in the government’s objective function. Analytically and in a series of numerical simulations we show which instrument is used to stabilize the debt depends crucially on the degree of nominal inertia and the size of the debt-stock. We also show that the welfare consequences of introducing debt are negligible for precommitment policies, but can be significant for discretionary policy. Finally, we assess the credibility of commitment policy by considering a quasi-commitment policy which allows for different probabilities of reneging on past promises. This on-line Appendix extends the results of this paper.

The Effects of Experience on Preference Uncertainty: Theory and Empirics for Public and Quasi-Public Environmental Goods

This paper develop and estimates a model of demand estimation for environmental public goods which allows for consumers to learn about their preferences through consumption experiences. We develop a theoretical model of Bayesian updating, perform comparative statics over the model, and show how the theoretical model can be consistently incorporated into a reduced form econometric model. We then estimate the model using data collected for two environmental goods. We find that the predictions of the theoretical exercise that additional experience makes consumers more certain over their preferences in both mean and variance are supported in each case.

Early broncoconstriction in anesthetized sheep: a simplified experimental model of asthma

Résumé Cette étude décrit un modèle expérimental de bronchoconstriction précoce induite par aérosolisation d'un extrait d'Ascaris suum chez des moutons anesthésiés par de l'isoflurane et ventilés mécaniquement. Dix moutons adultes ont été anesthésiés et ventilés mécaniquement puis ont été exposés à un stimulus bronchoconstrictif sous forme d'un aérosol d'extrait d'Ascaris suum durant 25 minutes. Tous les moutons ont été exposés deux fois à huit semaines d'intervalle à ce même stimulus. Les échanges gazeux ainsi que les paramètres respiratoires ont été mesurés régulièrement durant la période d'aérosolisation ainsi que durant les 60 minutes suivantes. A la fin de la période d'aérosolisation, une augmentation significative (p<0.05) des pressions de crête (+114%) et de plateau (+148%), de la résistance expiratoire (+93%) et de la pression partielle artérielle de gaz carbonique PaCO2 (+25%) a été constatée, de même qu'une diminution significative (p<0.05) de la compliance respiratoire (-41 %) et de la pression partielle artérielle d'oxygène PaO2 (-49%). Ces modifications sont restées stables durant toute la période d'observation. Ce modèle expérimental animal de bronchoconstriction offre de nombreux avantages : la stabilité hémodynamique et le confort de l'animal sont améliorés et la réaction de stress est inhibée. Il permet de plus une distribution optimale de l'antigène respiratoire et finalement évite l'utilisation d'un pléthysmographe corporel. Abstract This study describes a simplified experimental model of early bronchoconstriction induced by aerosolization of Ascaris suum extract in isoflurane-anesthetized and mechanically ventilated sheep. Ten adult sheep were anesthetized, mechanically ventilated and then challenged with an aerosol of Ascaris suum extract during 25 minutes. All of them were challenged twice at eight weeks intervals. During the bronchoconstrictive challenges and the following sixty minutes, gas exchange was measured and respiratory mechanics parameters computed from a lung mechanics calculator. At the end of the challenge, a significant increase (p<0.05) was observed in peak (+114%) and plateau (+148%) pressures, expiratory resistance (+93%) and PaCO2 (+25%) along with a significant decrease (p<0.05) in respiratory compliance (-41 %) and PaO2 (-49%). These changes remained stable throughout the 60 minutes study period. This model offers several advantages: hemodynamic stability and animal welfare are improved and the stress response is blunted. It allows an optimal distribution of the antigen and finally avoids the need of a body plethysmograph.