Neutronics analysis and thermodynamics studies of several DEMO breeding blankets for the development of the AINA safety code

By 2050 the energy consumption is expected to increase considerably.The production might be mostly based on renewable energy mix driven by the nuclear fusion which could potentially deliver continuous, large-scale power for the long-term without harming the environment. Regrettably, the nuclear fusion still requires numerous developments, which are undergoing around the word, to prove the design feasibility and to evaluate the safety relatad aspects which are to sorne extent embraced this thesis. In light of this, during the last ten years the Nuclear Engineering Research Group (NERG-UPC) has being developing a safety code callad AJNA (acron of Analyses of IN-vessel Accidents) to evaluate the magnetic fusion reactor plasma-wall transients in case of ex-vessel LOCA and overfuelling , determining thermal wall profiles as well as checking the integrity of in-vessel components (melting). Considering the e'v'Olution of technologies and related methodologies, a substantial renewal/improvement plan for AJNA were established. Two specific development tasks are part of this PhD thesis. (i) The definition, standardization and validation of an enhanced methodology to develop new AJNA versions in order to obtain robust models, estimating as accurately as possible the behaviour of the studied systems. (ii) The re-design, generalization and optimization of thermal-hydraulics routines for the determination of the AJNA thermal-wall distributions both in normal and accident scenarios in substitution of the former unverified/unqualified ones. In addition, the thermal­ hydraulic routines have been validated against commercial software as ANSYS Fluent. Consequently, the code has been almost rewritten, improved and consolidated giving special attention on document, comment and V&Vaccording to the current software standard requirements . lndeed, severa! novel features have been introduced to extend the modelling capacity of the AJNA application solver and to estimate the errors . Afterward, two specific AJNA blanket thermal-wall models have been developed: the Water Cooled Pebble Sed JAPANESE­ DEMO and the Helium Cooled Pebble Bed EUROPEAN-DEMO. According to the established methodology, the complete process of design, improvement and validation has included the complete set of compulsory radiation transport analyses , thermal-hydraulic studies and AJNA thermal-wall model tuning. Furthermore, preliminary assessments of the transient accident scenarios and sensibility studies haw been also performed. So, starting from fully detailed neutronics and thermal­ hydraulic results, a simplified and conservatiw wall model has been implemented in AJNA obtaining reliable results in a short calculation time validating the approach proposed. lndeed, simplified models haw been iteratiwly built and adjusted, achieving a good agreement with the fully detailed simulation and yielding a maximum absolute temperature differences around 10%. The determination and coherence of the temperature distribution obtained using independenttool s and approaches, ANSYS® Fluent® vs AJNA thermal-hydraulic routines, supports the proposed methodology, hence validating the whole results obtained. Newrtheless, the 1D non-conservatiw temperature field, where present, could be compensated by the application of scaling functions , obtaining a perfect match with the most conservative 30 distribution. In this innovative approach, the scaling functions correspond to the ratios between the most conservatiw radial distribution in the fully detailed and the 10 simulations . Moreowr, thanks to the simplified and endorsed model, sensitivities and screening assessment can be easily perforrned showing how the system reacts as consequences of loads, boundary conditions and perturbations. In light of this, the detailed number of study can be extensively reduced. To conclude, this multidisciplinary activity has requested the establishment of a specific framework , including skills and tools.En el año 2050 la producción de energía podría estar distribuida principalmente entre fuentes renovables lideradas por la fusión nuclear que potencialmente puede proveer grande cantidades de energías para largos tiempos, sin afectar considerablemente el ambiente. Desafortunadamente, la fusión nuclear requiere aun numerosos desarrollos para demostrar entre otros la validez del diseño y la seguridad nuclear, argumentos que son tratados en esta tesis doctoral. Durante los últimos diez años, el Nuclear Engineering Research Group (NERG-UPC) ha estado desarrollando un código de seguridad nuclear denominado AINA (Analyses of IN-vessel Accidents) para evaluar los transitorios de plasma-pared en los TOKAMAK, reactores de fusión nuclear a confinamiento magnético, en caso LOCA ex-vessel y accidentes de combustible. El programa determina las consecuencias en componentes in-vessel como la temperatura de los mismos y su integridad. Teniendo en cuenta la ewlución de las tecnologías, un plan de renovación para AINA ha sido puesto en marcha incluyendo dos tareas específicas en esta tesis.(i) La definición, estandarización y validación de una metodología para el desarrollo de nuevas versiones de AINA para obtener modelos simplificados y fiables que puedan estimar de manera precisa el comportamiento de los componentes estudiados. (ii) El rediseño, generalización y optimización de las rutinas termo-hidráulicas para la determinación de los perfiles de temperatura evaluados por AINA, en caso estacionario o transitorios con el fin de remplazar las anteriores. Así mismo, dichas funciones han sido evaluadas y verificadas a través de comparaciones directas a software comerciales como ANSYS Fluent. De esta manera, AINA ha sido casi completamente replanteado, mejorado y consolidado con especial atención a la documentación, comentarios y verificación en línea con los estándares de software actuales. Novedosas técnicas han sido introducidas para añadir la capacidad de modelación y su capacidad

Evaluation of microarray technology and cell line models in modern toxicology

Modern toxicology puts together existing knowledge of classical biology with new technologies to study effects of perturbations and to predict adverse outcomes resulting from those perturbations. Modern toxicology employs high throughput technology as microarray and cell lines as in vitro models to investigate the effect of potential toxic compounds. In my thesis I evaluate the usefulness and reproducibility of microarray technology and cell line models. I have been mainly interested in the study of the effects on the regulation of gene transcription in cell lines. I used HepG2 cell line as a model for liver to study cadmium-induced cytotoxicity, Caco-2 as model for intestinal epithelial to study nanoparticles and HeLa cells from cervical cancer to evaluate genomic instability. Cadmium is currently classified as carcinogen for human. In my first study, gene expression is used to explain the possible toxic mechanism of cadmium carcinogenity, using HepG2 cell line. A suggested mechanism of cadmium-induced carcinogenicity involves defects in the cell response to DNA damage and in the resistance to apoptosis. In this regard, I focused on the tumour suppressor protein P53, since its inactivation is a common feature found in human cancers and it is a crucial component of the cellular response to DNA damage. The results presented in this thesis demonstrate that in HepG2 cells exposed to cadmium, P53 was correctly moved and accumulated into the nucleus to accomplish its function as a transcription factor. However, in spite of this correct nuclear localization, the signals for the cell cycle arrest were not activated. In this context, the important mediator of cell cycle arrest P21, a P53 downstream protein, was upregulated at the gene level but not at the protein level. These results could be explained by the involvement of a post-transcriptional activity mediated by miRNA, as demonstrated by the upregulation of mir-372 in cadmium-treated HepG2 cells, which was able to affect p21 expression and to promote cell proliferation. Recent advances in materials science have resulted in the creation of particles in the nano-scale range and their use is spreading. This creates the need to evaluate their possible toxic effect on human health. In the second study, gene expression is applied to evaluate nanoparticle effect on Caco-2 cells as in vitro model of intestinal epithelial cells. The main focus was to compare the effect of gold nanoparticles (AuNP) of two sizes (30 nm and 5 nm), using microarray technology. Smaller AuNPs (5 nm) inhibit Caco-2 cell growth. Gene expression analysis shows a broad range of responses induced by small size AuNPs. A bioinformatics reconstruction of the possible pathways regulated by smaller AuNPs indicates that Caco-2 cells activate defence responses even if it was not enough to prevent the observed toxic effect. The response at the transcriptome level upon exposure to larger AuNPs (30 nm) is very weak. This effect can be due to the low uptake of these larger AuNPs. The third study focuses on the issue concerning cell line variability using different batches of HeLa cells obtained from different laboratories. The microarray expression analysis was performed on different batches of HeLa cells exposed to hypoxic conditions. In response to a hypoxic stimulus, each cell line batch activated different pathways, although the regulation of genes related to hypoxia is conserved. A genetic analysis show the high level of extensive chromosome instability in HeLa clones obtained from different laboratories. Each clone accumulates genomic variability in a time-dependent manner. The large differences in gene expression profiles suggest that the use of uncharacterized clones may lead to faulty conclusions and to irreproducible results in studies of gene function and pathway analysis. In the three papers presented in this thesis I have not only shown the reproducibility of microarray by comparison to real time PCR, the gold standard technique for mRNA quantification, but also the potential to create possible model for the mechanistic effects on biological pathways. In my thesis I have used different cell lines as in vitro models. They have shown that they have many advantages and that can give strong support for modern toxicology and be used to study biological mechanism. However, a possible drawback, which should be taken into account, is highlighted in the third study showing a high variability in the responses of different batches of the same cell line

Evaluation of microarray technology and cell line models in modern toxicology

Modern toxicology puts together existing knowledge of classical biology with new technologies to study effects of perturbations and to predict adverse outcomes resulting from those perturbations. Modern toxicology employs high throughput technology as microarray and cell lines as in vitro models to investigate the effect of potential toxic compounds. In my thesis I evaluate the usefulness and reproducibility of microarray technology and cell line models. I have been mainly interested in the study of the effects on the regulation of gene transcription in cell lines. I used HepG2 cell line as a model for liver to study cadmium-induced cytotoxicity, Caco-2 as model for intestinal epithelial to study nanoparticles and HeLa cells from cervical cancer to evaluate genomic instability. Cadmium is currently classified as carcinogen for human. In my first study, gene expression is used to explain the possible toxic mechanism of cadmium carcinogenity, using HepG2 cell line. A suggested mechanism of cadmium-induced carcinogenicity involves defects in the cell response to DNA damage and in the resistance to apoptosis. In this regard, I focused on the tumour suppressor protein P53, since its inactivation is a common feature found in human cancers and it is a crucial component of the cellular response to DNA damage. The results presented in this thesis demonstrate that in HepG2 cells exposed to cadmium, P53 was correctly moved and accumulated into the nucleus to accomplish its function as a transcription factor. However, in spite of this correct nuclear localization, the signals for the cell cycle arrest were not activated. In this context, the important mediator of cell cycle arrest P21, a P53 downstream protein, was upregulated at the gene level but not at the protein level. These results could be explained by the involvement of a post-transcriptional activity mediated by miRNA, as demonstrated by the upregulation of mir-372 in cadmium-treated HepG2 cells, which was able to affect p21 expression and to promote cell proliferation. Recent advances in materials science have resulted in the creation of particles in the nano-scale range and their use is spreading. This creates the need to evaluate their possible toxic effect on human health. In the second study, gene expression is applied to evaluate nanoparticle effect on Caco-2 cells as in vitro model of intestinal epithelial cells. The main focus was to compare the effect of gold nanoparticles (AuNP) of two sizes (30 nm and 5 nm), using microarray technology. Smaller AuNPs (5 nm) inhibit Caco-2 cell growth. Gene expression analysis shows a broad range of responses induced by small size AuNPs. A bioinformatics reconstruction of the possible pathways regulated by smaller AuNPs indicates that Caco-2 cells activate defence responses even if it was not enough to prevent the observed toxic effect. The response at the transcriptome level upon exposure to larger AuNPs (30 nm) is very weak. This effect can be due to the low uptake of these larger AuNPs. The third study focuses on the issue concerning cell line variability using different batches of HeLa cells obtained from different laboratories. The microarray expression analysis was performed on different batches of HeLa cells exposed to hypoxic conditions. In response to a hypoxic stimulus, each cell line batch activated different pathways, although the regulation of genes related to hypoxia is conserved. A genetic analysis show the high level of extensive chromosome instability in HeLa clones obtained from different laboratories. Each clone accumulates genomic variability in a time-dependent manner. The large differences in gene expression profiles suggest that the use of uncharacterized clones may lead to faulty conclusions and to irreproducible results in studies of gene function and pathway analysis. In the three papers presented in this thesis I have not only shown the reproducibility of microarray by comparison to real time PCR, the gold standard technique for mRNA quantification, but also the potential to create possible model for the mechanistic effects on biological pathways. In my thesis I have used different cell lines as in vitro models. They have shown that they have many advantages and that can give strong support for modern toxicology and be used to study biological mechanism. However, a possible drawback, which should be taken into account, is highlighted in the third study showing a high variability in the responses of different batches of the same cell line

Geostatistics as a tool to improve the natural background level definition: An application in groundwater

The Natural Background Level (NBL), suggested by UE BRIDGE project, is suited for spatially distributed datasets providing a regional value that could be higher than the Threshold Value (TV) set by every country. In hydrogeochemically dis-homogeneous areas, the use of a unique regional NBL, higher than TV, could arise problems to distinguish between natural occurrences and anthropogenic contaminant sources. Hence, the goal of this study is to improve the NBL definition employing a geostatistical approach, which reconstructs the contaminant spatial structure accounting geochemical and hydrogeological relationships. This integrated mapping is fundamental to evaluate the contaminant's distribution impact on the NBL, giving indications to improve it. We decided to test this method on the Drainage Basin of Venice Lagoon (DBVL, NE Italy), where the existing NBL is seven times higher than the TV. This area is notoriously affected by naturally occurring arsenic contamination. An available geochemical dataset collected by 50 piezometers was used to reconstruct the spatial distribution of arsenic in the densely populated area of the DBVL. A cokriging approachwas applied exploiting the geochemical relationships among As, Fe andNH4+. The obtained spatial predictions of arsenic concentrationswere divided into three different zones: i) areas with an As concentration lower than the TV, ii) areas with an As concentration between the TV and the median of the values higher than the TV, and iii) areas with an As concentration higher than the median. Following the BRIDGE suggestions, where enough samples were available, the 90th percentile for each zone was calculated to obtain a local NBL (LNBL). Differently from the original NBL, this local value gives more detailed water quality information accounting the hydrogeological and geochemical setting, and contaminant spatial variation. Hence, the LNBL could give more indications about the distinction between natural occurrence and anthropogenic contamination

Insomnia, Time Perspective, and Personality Traits: A Cross-Sectional Study in a Non-Clinical Population

Insomnia disorder is considered a public health problem and additional studies should investigate predisposing and perpetuating factors. This study examined the relationship between Big Five personality traits, time perspective, and insomnia. In a cross-sectional study, 400 participants (227 women; age range 18–74 years) were administered the Big Five Inventory—10 items, the Zimbardo Time Perspective Inventory, and the Insomnia Severity Index (ISI). A measure of chronotype was also included for control purposes. The results show that insomniacs reported lower scores for conscientiousness and extraversion, and for past-positive (PP) and future (F) perspectives, whereas they obtained higher scores for past-negative (PN) perspectives and deviation from a balanced time perspective. The correlations confirmed these findings, but negative correlations between presenthedonistic (PH) perspective and ISI score, and between emotional stability and ISI score, were also found. The mediation analyses showed that F played an indirect role in the relationship between consciousness and ISI score, PN had an indirect effect on the relationship between emotional stability and ISI or between extraversion and insomnia, and PH had an indirect effect on the relationship between extraversion and ISI score. The current outcomes shed light on the mechanisms which serve to mediate the relationship between insomnia and personality traits

‘Do You Want a Receipt?’ Combating VAT and RST Evasion with Lottery Tickets

Governments both in developed and developing countries are facing the problem of value added tax (VAT) and retail sales tax (RST) evasion. This explains a growing interest in policies alternative to the traditional methods of deterrence. This paper describes the achievements resulting from a zero cost policy against VAT and RST evasion based on rewards. Customers are encouraged to request an invoice by changing the invoice into a lottery ticket, thereby making VAT and RST fraud and evasion more difficult for suppliers. Such a policy has, for example, been introduced in some Asian countries. After having characterized VAT and RST evasion as a special kind of public good situation, a theoretical explanation based on behavioral Economics models of the success empirically registered by this policy will be discussed. Given this theoretical framework, we then introduce an empirical test in order to verify the ex-ante applicability of the policy described in different socio-economic contexts. Finally we discuss the possible countervailing effects as well as the positive long-term side-effects of the introduction of the policy

Possession is Nine-Tenths of the Law: possession, property, and coordination in a Hawk–Dove Experiment

In all legal systems, possession and property are inextricably linked. Game theory captures this relationship in the Hawk–Dove game: players competing for an asset are better off when the possessor plays Hawk and the intruder plays Dove (the bourgeois strategy) so that property can emerge as a spontaneous convention. This theory has been supported by large experimental evidence with animals. This paper presents a lab experiment where possession is manipulated to study the emergence of the property convention with human subjects. We show that the highest coordination emerges when possession is achieved meritoriously and that possession induces only bourgeois coordination (never antibourgeois)