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Bottom-up Tissue Engineering: The Effect of 3D Tissue Fabrication Strategies on Cellular Behavior.
No full textOrgan failure is one the biggest problems, doctors face every day. Many patients are not able to get a transplant, but even those who recieved it, may undergo painful process of organ rejection and be on the transplant waiting list again. Organ transplants shortage is severe problem in current medicine that has many ethical and medical issues. To solve this problem, the new direction in regenerative medicine was formed, organ prinitng. The main goal of organ printing is fabrication of organ replacements that would mimic the original ones in terms of complexity and functionality. By direct fabrication and maturation of organs in vitro, the problem of organ shortage can be solved, moreover, based on the advances in cell therapy, these organs can be printed with patients own cells, which will eliminte the problem of transplant rejection.
Organ printing is multistep and complex process, composed of three main steps: tissue design, or theoretical modelling of replacement composition; tissue fabrication, or direct cell encapsulation and controlled assembly of building units; at last, tissue maturation to reach desirable functionality of the replacement. In the past decade, there was developed a variety of methods for the second step of organ printing, cell encapsulation, which is practicaly the main procedure for tissue fabrication. However, all these methods of cell encapsulation are complex and they might affect cells viability and functionality, which will result in changed tissue function. Thus, starting from the detailed analysis of the tissue fabrication process (encapsulation and assembly methods) the list of possible cell behavior affectors was composed. Based on this list, we designed a multistep protocol for coherent evaluation of cells behavior parameters, in terms of viability, functionality and activity during the tissue fabrication and its maturation steps. Three main materials were used for this study, two naturally (alginate and modified gelatin) and one synthetically (polyethilene glycol) derived polymers. The encapsulation step was performed with two different methods based on chemical or photo crosslinking of the material. Cell parameteres were evaluated on the molecular level for variety of parameters, including viability, activity, proliferation, stress markers expression, at last ability to adapt artificial environment to the cell functional niche with extracellular matrix markers expression, and proteoglycans. The innovation of the presented study consists in the developing a unique protocol for detailed cell functionality evaluation during the organ printing procedures. In fact, based on the conducted study, it was proved the safety of the encapsulation methods. Moreover, based on the cell parameters post-encapsulation, there was suggested the optimal time for tissue maturation for application of the fabricated structures in organ printing, but also in other fileds, like developmental and pathological biology, or drug screening. Eventully, a novel way of simple blocks assembly into 3D complex structures was developed and proved to be safe for cell parameters.
At last, for the future research in organ printing, a detailed study over a cell behavior and functionality has to be performed for every fabrication method, what will improve the organ production process drastically
Migration flows and local systems of production: new comparative evidence on Italy and Spain
No full textThe thesis explores the question of whether immigrants can spur the internationalization and innovation activities of the local production systems of their countries of destination. It is composed of two parts. In the first part, migrants' pro-trade effects is analysed through a theory-consistent gravity model augmented with migration variables. The analysis takes subnational units, i.e. NUTS3 regions, and compares Italy and Spain. The empirical model allows for subnationally heterogeneous multilateral resistance term. An econometric strategy based on Head and Mayer (2014) is implemented to address the main econometric issues and to select the suitable estimator. This leads to selecting the Gamma PML estimator in the case of Spain and the OLS estimator in the Italian case. The results suggest that applying the same model to different contexts can lead to different results: immigration is found to have a positive trade facilitating effect in the Spanish case and a negative trade-diverting role in the Italian case. This difference is attributed to specificities in the composition and integration patterns of the immigrant population in the two countries; tentative explanations are proposed for the negative effect. The second part of the thesis analyses the determinants of immigrants’ employment focussing, in a comparative perspective, on two case studies of local systems specialized in the mechanic sector, i.e. Reggio Emilia in Italy and Elgoibar in Spain. The two are similar in many respects - income and employment levels, sectoral specialisation, high levels of local social capital - but are marked by quite different capacity of integrating immigrant labour in the core industry. Drawing on the availability of two sets of similar firm-level microdata at the corresponding NUTS2 levels, cluster and discriminant analysis are performed to outline the characteristics of firms hiring immigrants in each context. The comparison of the two regions shows that, in the more inclusive context, immigrants are also much more frequently employed in knowledge-oriented firms. The subjective determinants for hiring immigrants are deepened in a series of semi-structured interviews with the employers. In the local system marked by bridging social capital, immigrants’ employment is found to be determined by a wider set of considerations that span well beyond labour replacement in manual tasks. Diverse work teams are reported to contribute to product development and innovation allowing a combination of cost-saving standardization and cultural-specific customizability to serve foreign tastes
Enhancing the relationship between the landscape of energy transition and the ecosystem services
No full textGovernments adopt strategies to follow the objective Europe 2020 and focus on the development of Renewable Energy Technologies, RET, to improve the transition of the production of energy from fossil fuels sources to renewable energy sources, RES. More than decades before, the energy transition towards renewable energies emerges as a relevant objective of the European governments. The fluctuating prices of oil and the uncertainty on the future supply of fossil fuels open new challenges for communities to actuate an energy transition towards RES. The RET can afflict deeply the landscape structure and by this point of view the energy transition is one of the most relevant drivers in the landscape change of the last three decades. In several cases energy transition may face opposition from regions and communities because of the change that RET produce in local landscapes and related economic, cultural and ecological functions. This change has been defined as a conflict between the local narrative of the right to the landscape by local communities and the global narrative that aims at a low carbon future. Exploring the relationship between Ecosystem Services (ES) and Renewable Energy (RE), the conflict among a global perspective and a local perspective has been resumed by several authors as a trade-off among provisioning and regulating ES from one side and cultural ES from the other. The overcoming of this conflict can be based on bottom-up processes that enhance the energy transition starting by local organizations of communities that want to reach a self-sufficieny in renewable energy supply. Transition management is possible if we produce innovation at local scale. An ES approach supports the transition management and the envisioning future energy landscapes by offering transparent trade-offs, exposing risks and benefits. If societies produce clean energy it may happen that RET afflict other ES. The main paradigm for the sustainability of a energy landscape is that the introduction of RET should not cause crucial trade-offs among the other ES, this is why this research wants to study this relationship, as several authors have already stressed. By the literature review it is possible to state a general gap of knowledge in integrated approaches in the evaluation of RET, considering diverse RES and ES provided by the landscape and evaluating a trade-off through a participatory process. To fulfill such gap and produce an enhancement of knowledge, this research follows the main objective of introducing a trade-off analysis into a design approach to formulate long-term visions for sustainable energy landscapes. The results we got indicate that it is possible to plan and design with the ES sustainable energy landscape.This process facilitates a sustainable energy transition of communities through a participatory landscape design that reduce the trade-off between the Renewable Energy and the ES supplies
Semantic Aware Representing and Intelligent Processing of Information in an Experimental domain:the Seismic Engineering Research Case
No full textSeismic Engineering research projects’ experiments generate an enormous amount of data that would benefit researchers and experimentalists of the community if could be shared with their semantics. Semantics is the meaning of a data element and a term alike. For example, the semantics of the term experiment is a scientific research performed to conduct a controlled test or investigation. Ontology is a key technique by which one can annotate semantics and provide a common, comprehensible foundation for the resources on the Semantic Web. The development of the domain ontology requires expertise both in the domain to model as well as in the ontology development. This means that people from very different backgrounds, such as Seismic Engineering and Computer Science should be involved in the process of creating ontology. With the invention of the Semantic Web, computing paradigm is experiencing a shift from databases to Knowledge Bases (KBs), in which ontologies play a major role in enabling reasoning power that can make implicit facts explicit to produce better results for users. To enable an ontology and a dataset automatically exploring the relevant ontology and datasets from the external sources, these can be linked to the Linked Open Data (LOD) cloud, which is an online repository of a large amount of interconnected datasets published in RDF. Throughout the past few decades, database technologies have been advancing continuously and showing their potential in dealing with large collection of data, but they were not originally designed to deal with the semantics of data. Managing data with the Semantic Web tools offers a number of advantages over database tools, including classifying, matching, mapping and querying data. Hence we translate our database based system that was managing the data of Seismic Engineering research projects and experiments into KB-based system. In addition, we also link our ontology and datasets to the LOD cloud.
In this thesis, we have been working to address the following issues. To the best of knowledge the Semantic Web still lacks the ontology that can be used for representing information related to Seismic Engineering research projects and experiments. Publishing vocabulary in this domain has largely been overlooked and no suitable vocabulary is yet developed in this very domain to model data in RDF. The vocabulary is an essential component that can provide logistics to a data engineer when modeling data in RDF to include them in the LOD cloud. Ontology integration is another challenge that we had to tackle. To manage the data of a specific field of interest, domain specific ontologies provide essential support. However, they alone can hardly be sufficient to assign meaning also to the generic terms that often appear in a data source. That necessitates the use of the integrated knowledge of the generic ontology and the domain specific one.
To address the aforementioned issues, this thesis presents the development of a Seismic Engineering Research Projects and Experiments Ontology (SEPREMO) with a focus on the management of research projects and experiments. We have used DERA methodology for ontology development. The developed ontology was evaluated by a number of domain experts. Data originating from scientific experiments such as cyclic and pseudodynamic tests were also published in RDF. We exploited the power of Semantic Web technologies, namely Jena, Virtuoso and VirtGraph tools in order to publish, storage and manage RDF data, respectively. Finally, a system was developed with the full integration of ontology, experimental data and tools, to evaluate the effectiveness of the KB-based approach; it yielded favorable outcomes. For ontology integration with WordNet, we implemented a semi-automatic facet based algorithm. We also present an approach for publishing both the ontology and the experimental data into the LOD Cloud. In order to model the concepts complementing the vocabulary that we need for the experimental data representation, we suitably extended the SEPREMO ontology. Moreover, the work focuses on RDF data sets interlinking technique by aligning concepts and entities scattered over the cloud
Spatial planning to integrate climate change adaptation at local level
No full textClimate change is directly or indirectly affecting cities, regions or even nations in multiple ways. Impacts are exponential and repetitive with increased instability of climate pattern, socio-ecological systems, increased inequalities and distribution of resources. It is therefore necessary that social and economic hubs and potential resource rich region should become the catalyst that encourages the focus on climate change policies. Despite having various international and national climate change frameworks and forums it is unclear how international, national and even local governments develop response actions to climate concerns and integrate them into different spatial scales. Developing and mainstreaming effective response actions to climate change into numerous sectors, cross-sectoral policies is a complex issue which has plagued policy makers at different spatial scales and on different policy arenas. In order to efficiently integrate and sensitizing society towards climate change issues, decision makers and different stakeholders have to develop insightful information bases, share awareness of climate change risks, vulnerability patterns and finally develop response actions at all level of policy preparation through policy integration, implementation or structural reforms.
This study contributes towards understanding climate change risks and perception within spatial planning policies at local level. This has been undertaken by investigating, testing or developing real spatial planning policies, vulnerability assessment frameworks and decision support systems that aim to improve current spatial planning tools intended at building climate resilient living spaces. This study was divided into three main stages 1) To develop and test an assessment framework to track integration of climate change issues into spatial planning, 2) To identify hot spots of climate change at urban/regional levels by applying spatial vulnerability assessment tools and 3) To apply eco-system based adaption responses to climate change in an urban region and identifying barriers. Drawing the case study from India, in the first stage, an attempt was made to understand how spatial plans in India are incorporating climate change issues and identifying potential gaps. Spatial plans across various cities in India were examined with the help of a review framework that was developed upon Moser and Loer’s (2008) work on ''Managing climate risks''. The second stage presents a climate change vulnerability assessment framework and its working methodology at local spatial scale, considering three main components: exposure, sensitivity and adaptive capacity. The vulnerability assessment framework was applied to an urban area in India, namely, Bangalore and a hill district of Eastern Himalaya namely Darjeeling. In the final stage of this study, ecosystem services based adaptation responses within spatial planning was studies to understand how it can increase adaptive capacity and address climate changes issues.
The results of this study identified key concerns to climate change issues and its integration in India. The policy analysis shows that the role of spatial plans to integrate climate change issues at local levels like urban areas and regions in India are still limited. Local policies and spatial plans shows low level of awareness, moderate level of analytical capability and limited action responses to integrate climate change issues at local level. Spatial policies in India are still limited to physical and economic issues and undermine the issues of climate change. The application of vulnerability assessment framework demonstrated that it successfully provided a spatial assessment of climate change vulnerability patterns. The spatial pattern of vulnerability identifies areas requiring urgent attention to adaptation action, enabling policy intervention and prioritizing action. At the same time an analysis of the perception of people also confirmed the results of vulnerability assessment at local level. Finally the results showed how ecosystem services based response actions when applied within spatial planning can play an important role to mitigate the effects of climate change and adapt to local climate concerns with least negative repercussions. The findings of this study creates a platform for discussion on decision making process and the potential aspects where climate change issues can become a part of spatial planning policy. Climate change mitigation and adaptation for short terms may fulfill objectives for current climate scenarios but may impose externalities in future. So, policy makers and local development organization need to carefully narrate future climate resilient scenarios. This study is the reflection of the interrelationship between the existing information bases, knowledge gaps, policy preparation practices, analytical capability, participation and technological innovation in climate change integration at local spatial scale
Voting in Context: a theory of environmental effects on electoral behavior
Get PDFThe work aims at addressing in a unified framework a variety environmental/contextual factors (geographical, campaign- and network-related). In doing so, theoretical and empirical relation between these various levels are investigated, as well as responses by which individuals can react to environmental stimuli. From the methodological side, hypotheses of the work are tested by means of multilevel regression models and agent-based simulations
Translational control mechanisms in the p53 response network
No full textThe sequence-specific transcription factor p53 is considered a master gene of cellular responses to homeostasis changes. It is also a prominent tumor suppressor gene with the title of “guardian of the genome”. The increasing number of transcriptome analyses in cell lines treated with different agents activating p53, continues to add complexity to the vast transcriptional networks p53 regulates. To investigate mRNA translational control as an additional dimension of p53-directed gene expression responses, we performed translatome analyses upon its activation either by different agents or cellular contexts. Considered as a proxy for the proteome, the translatome allows us to characterize the translational status of each mRNA, independently from transcriptional modulations, and to evaluate the implications or correlations of changes in relative mRNA translation efficiencies with the phenotypic outcome.
We first performed treatment-specific translatome profiling in MCF7 cells upon Doxorubicin and Nutlin-3a treatments. Among translated genes, we detected the presence of translationally enhanced mRNAs with a virtually absent transcriptional modulation; those genes were enriched for apoptotic functions, suggesting that the apoptotic phenotype might be controlled not only at the transcriptional, but also at the translational level. Seeking mechanisms underlying the mRNAs translational rate upon p53 activation, we identified the modulation of six RNA-binding proteins, where hnRNPD (AUF1) and CPEB4 are direct p53 targets, whereas SRSF1, DDX17, YBX1 and TARDBP are indirect targets, modulated at the translational level in a p53-dependent manner. In detail, we demonstrated the contribution of at least two p53-dependent translational mechanisms related to YBX1 translational repression, suggesting the presence of a controlled regulon at the crossroad of YBX1 mRNA translation. Given our finding that apoptotic genes appear to be controlled by p53 also at the translational level, we decided to explore whether mRNAs translational control mechanisms are indeed an additional checkpoint to the phenotype. To this aim, we performed a cell-type specific translatome study upon Nutlin-3a treatment, a drug with evident therapeutic prospective. SJSA1, HCT116 and MCF7 cells were chosen as they exhibit different cellular responses to Nutlin-3A (cell cycle arrest, apoptosis, or both, respectively). Our preliminary data suggests that translational modulation can affect the complex process of cell fate choice upon p53 activation. Indeed, a lack of overlap among genes differentially modulated at the translational level was evident. Motif search analysis at the 5’- and 3’-UTR of those genes highlighted the presence of different motifs in the three cell lines and the specific correlation of a C-rich motif with the apoptotic phenotype. Preliminary data on this motif will be presented and discussed. Two independent projects will be presented as appendixes, both of them related to the general idea that more than one factor may determine the p53 response. Starting from the analysis of possible p53 interactions with other transcriptional co-factors, we investigated the cooperative interaction between p53 and NFκB. For the second project, combining data previously obtained by means of yeast-based p53 transactivation assays, we developed an algorithm, p53retriever, to scan DNA sequences and thus identify p53 response elements and classify them based on their transactivation potential
Enhancement of verb retrieval: Neuromodulation, repetition priming, and aphasia rehabilitation
No full textThere is a need to increase the efficacy and efficiency of aphasia rehabilitation protocols. In order to do this, we may rely on knowledge about how the language system may be changed by experience, including it’s plasticity to behavioral training and to neuromodulation. In this thesis, I study mechanisms of language facilitation in healthy individuals and mechanisms of language recovery in
individuals with aphasia. I use both behavioral modification techniques (repeated naming in healthy individuals, and linguistically motivated aphasia therapy in individuals with aphasia), and neuromodulation (transcranial direct current stimulation, tDCS). The data in this thesis indicate that, in healthy individuals, language facilitation by repetition priming reflects changes in implicit processing of stimuli (at the level of lexical retrieval), and explicit episodic retrieval of the prior occurrence of the stimuli. In patients with aphasia, the data indicates that the observation of item-specific improvement after treatment depend on pre-treatment levels accessibility to the lexeme level via semantics, and also on short term memory skills and/or post-lexical processing skills. Generalization may occur when damage to abstract features is present(semantic and/or grammatical), and when knowledge of abstract features is engaged during treatment. tDCS has been successfully used in prior research to enhance language training and rehabilitation effects. However, our data from healthy individuals did not reveal effects of neuromodulation, and the data with patients was ambigous: it is not possible to discern whether tDCS indeed incrteased the effects of therapy or wether the data are better explained as reflecting a ceiling effect
Evolutionary Test Case Generation via Many Objective Optimization and Stochastic Grammars
No full textIn search based test case generation, most of the research works focus on the single-objective formulation of the test case generation problem. However, there are a wide variety of multi- and many-objective optimization strategies that could offer advantages currently not investigated when addressing the problem of test case generation. Furthermore, existing techniques and available tools mainly handle test generation for programs with primitive inputs, such as numeric or string input. The techniques and tools applicable to such types of programs often do not effectively scale up to large sizes and complex inputs. In this thesis work, at the unit level, branch coverage is reformulated as a many-objective optimization problem, as opposed to the state of the art single-objective formulation, and a novel algorithm is proposed for the generation of branch adequate test cases. At the system level, this thesis proposes a test generation approach that combines stochastic grammars with genetic programming for the generation of branch adequate test cases. Furthermore, the combination of stochastic grammars and genetic programming is also investigated in the context of field failure reproduction for programs with highly structured input
Cosmologies of destinations: rootes and routes of Eritrean forced migration towards Europe
No full textCosmologies of destinations investigates some commonly neglected dimensions of forced migration. It examines the key symbolic structures and social mechanisms which encourage and sustain the mobility trajectories of Eritreans from their home country to Ethiopia, Sudan, Italy and beyond. The central argument is that, in refugee-producing countries which suffer from protracted crisis and livelihood disruption, refugee movements become much more than a form of reactive mobility. Within these communities, becoming a refugee is not only a way to escape oppressive conditions but also the outcome of socially and symbolically embedded strategies aimed at personal realization and family well-being. Building on a multi-sited ethnography of the everyday life of Eritrean refugees in a number of settings (including homes, refugee camps, urban squats, and other settings of sociability) in their home country as well as in Ethiopia, Sudan and Italy, the thesis explores the range of social and economic resources needed to circumvent legal and geographic borders, and the moral and cultural norms that underpin these practices. It contributes to the theorization of refugee mobility, which is currently somewhat underdeveloped, by providing a framework to analyse high-risk forced migration, based on an emic understanding and systematic description of the living conditions, life aspirations and risk perceptions of Eritreans in their home country and in transit to Europe. The study feeds into the broader debate on the blurring boundaries between labour and forced migration by emphasising the social and cultural, along with the structural, determinants of mobility and immobility. The thesis is divided into five chapters. The first analyses the conditions that make exit a widespread and legitimate, albeit controversial, option for young people in Eritrea. The second chapter provides accounts of refugees' everyday lives in the first safe countries (Ethiopia and Sudan), chronicling the dynamics that trigger secondary movements towards Europe. The third analyses the lives of Eritrean refugees in Italy, documenting the conditions that activate further mobility within Europe. The fourth chapter describes the migratory infrastructures that allow for these refugee movements, including the role played by transnational marriages, smugglers and family networks. The final chapter provides a micro-analysis of decision-making, aimed at explaining the willingness of refugees to take great risks at different stages of the migration process. A methodological note narrates how the research was carried out in the various sites and analyses the implications of multi-sited ethnographic fieldwork with refugees