Au moins 60% des patients atteints de cancer vont recevoir de la radiothérapie (RT). L’efficacité de la radiothérapie dans le traitement du cancer est limitée par le phénomène de radiorésistance des cellules cancéreuses et par la toxicité des radiations sur les tissus sains. La découverte de nouveaux agents radiosensibilisants et radioprotecteurs permettrait de surmonter ces difficultés. Les modèles cellulaires 3D tels que les sphéroïdes, émergent motivés par le besoin de modèles précliniques plus proches des tumeurs in vivo. L’objectif du projet est d’optimiser un système microfluidique pour tester facilement et à faible coût des agents thérapeutiques avec la RT sur des sphéroïdes dans un contexte de repositionnement. Le système microfluidique développé permet la formation de 336 sphéroïdes homogènes en deux jours avec intervention minimale de l’utilisateur. Les sphéroïdes sont répartis dans 16 chambres de culture séparées par un système de valve magnétique pour éviter des effets bystander entre sphéroïdes irradiés et non-irradiés. Une nouvelle technique d’irradiation a été développée permettant d’exposer un système à 4 doses de radiation différentes. En tout, 4 doses de radiation et 4 concentrations d’agents thérapeutiques peuvent être testées par système. En utilisant cette approche, l’efficacité de trois agents avec la RT a été évaluée avec des tests de survie clonogénique. Nous avons démontré que le Talazoparib, un inhibiteur de PARP, radiosensibilise les cellules de sarcome de tissus mous (STS) cultivés en sphéroïdes à 2 Gy. Le système développé permet d’évaluer le potentiel d’agents thérapeutiques avec la RT et contribue à l’adoption des sphéroïdes comme modèle préclinique. / At least 60% of cancer patients will receive radiotherapy (RT) as part of their treatment. The efficacy of radiotherapy in the treatment of cancer is limited by the phenomenon of radioresistance of cancer cells and by the toxicity of radiation on healthy tissues. The discovery of new radiosensitizers and radioprotectors is essential to overcome these challenges. 3D cellular models such as spheroids emerge motivated by the need for better preclinical models. The objective of the project was to optimize a microfluidic system for easy, fast and low-cost testing of therapeutic agents with RT on spheroids. The developed microfluidic system allows the formation of 336 homogeneous spheroids in two days with minimal user intervention. The spheroids are distributed in 16 culture chambers separated by a magnetic valve system to avoid bystander effects between irradiated and unirradiated spheroids. A new irradiation technique has been developed to expose a system with 4 different radiation doses. In total, 4 radiation doses and 4 concentrations of therapeutic agents can be tested per system. Using this approach, the efficacy of three agents with RT was evaluated with clonogenic assays. Radiosensitizing properties of Talazoparib, a PARP inhibitor, on soft tissue sarcoma (STS) cells cultured as spheroids at 2 Gy were demonstrated. The developed system enables the evaluation of therapeutic agents with RT and contributes to the wide adoption of spheroids as a preclinical model.

This paper highlights street art in the social movement in Sudan and the role of murals andpolitical graffiti in relation to the Sudanese revolution of 2019. Characteristic for thismovement is the appearance of murals depicting the events of the revolutions. In particular,the colourful graffiti during the Sudanese uprisings of 2019 has been a crucial element in thesocial movement in the country.This study explores role of graffiti, its function as an art of resistance and as a communicationmedium during Sudanese movement, how graffiti contributes to Sudanese revolution 2019.Sudanese graffiti creates a profound understanding of the social transformation in Sudan,including most important events after revolution such as the third of June massacre inKhartoum and the political process and solidarity against discrimination. It establishes asocial relational space that ranks high values on collaboration and sharing significance, aswell introduces emancipatory alternative for better future in Sudan.The study uses four-dimensional analytical framework including graffiti as communicationtool, illegality and call for place, visual and verbal language, and graffiti as a public memory.Furthermore, it uses critical discourse analysis method through utilizing three-dimensionalframework including text, discursive practice, and sociocultural context. At the same time, thestudy uses telephone interviews method and photo-elimination method as data collectionmethods and encompassing structure for the research.

I have always known that I would leave my hometown. Always been told that it is too boring for a dreamer, that it is a place where all ambition wanes. None of my childhood friends stayed; we all moved towards something bigger, something better- towards opportunities. We all moved, to some degree, south. Depopulation of rural communities is not unique to Norrland but Tankebanan investigates this topic within the context of the northern inlands of Sweden, exploring its industrial history and local conditions. The project aims to create an infrastructure strengthening the social and cultural capital of the inland by generating educational, entrepreneurial and identity building activities in the region. The site of the project stretches along Malmbanan, the railway transporting iron from the industries of the inland to the ports of Narvik and Luleå. The tracks are a physical trace of the industrial history of the region and therefor a suitable location for the project that proposes three fixed nodes along the railway, each targeting one specific aspect of the knowledge network. The nodes are Creation in Abisko, Education in Kiruna and Entrepreneurship in Gällivare.Tankebanan reprograms old carbarns within the towns into hubs of activity and optimism, aiming to challenge the pessimism often connotated with the region, causing people to leave. It aims to turn struggles into challenges and encourage young people to see the potential within themselves and within Norrland. This phase of the project explores the node of Education in Kiruna, which proposes an alternative university for those who wish to obtain a degree without leaving the north. The program consists of a public library and train station, educational facilities, conference rooms and accommodation for long distance commuters. It is hosted within a modular system, relating to the module of the train car and extending the network of the rails into the building.

Avec le développement des véhicules électriques, la question de la valorisation des batteries lithium-ion (BLI) se pose pour diverses raisons. Pourtant, une filière de valorisation structurée n’existe pas aujourd’hui. Notre travail académique a pour objet l’étude de cette dernière. La filière de valorisation des BLIs est définie comme un système sociotechnique, complexe en émergence. Notre problématique consiste alors à l’étudier d’un point de vue technico-économique, organisationnel et prospectif et ce en tenant compte des différentes complexités. Cette problématique soulève trois questions de recherche : Comment modéliser la filière de valorisation des BLIs comme un système organisationnel complexe en émergence ? Comment faire de la prospective sur la filière de valorisation des BLIs ? Comment analyser la gouvernance de la filière de valorisation des BLIs ?Pour modéliser la filière de valorisation des BLIs, nous mettons en œuvre d’une manière combinée trois méthodes de modélisation systémiques : SCOS’M (Systemics for Complex Organisational Systems’ Modelling), la cartographie cognitive et la dynamique des systèmes. La modélisation a pour objectif la caractérisation de la filière (parties prenantes, sous-systèmes …), la compréhension de ses dynamiques d’évolution et l’identification des variables clés dans ces dynamiques. Cette modélisation est une base pour la suite.Pour faire de la prospective sur la filière de valorisation des BLIs, nous préconisons l’utilisation des scénarios. Ces derniers sont définis à l’aide de la matrice SRI (Stranford Research Institute), en exploitant les variables clés qui interviennent dans les dynamiques d’évolution de la filière. La prospective est permise en simulant le modèle dynamique des systèmes avec différents scénarios, afin d’analyser les aspects technico-économiques. Pour l’étude de la gouvernance de la filière de valorisation des BLIs, le périmètre a été restreint à l’activité de reconditionnement. Dans ce cas, l’étude de la gouvernance revient à analyser des combinaisons de répartition (application 2nde vie, partie prenante). Une méthodologie d’aide à la décision a été développée pour cette fin. D’une manière générale, cette thèse a identifié les enjeux et questions qui se posent lors de l’étude de la valorisation des batteries lithium-ion des véhicules électriques. A travers notre modélisation, nous avons établi une base d’analyse utile à l’aide à la décision. Nous avons répondu à certaines questions (aspects technico-économiques et organisationnels) et ouvert la voie pour d’autres (aspects logistiques et environnementaux). / With the development of electric vehicles, the recovery of lithium-ion batteries (LIB) arises for various reasons. However, a structured recovery network does not exist today. Our academic work aims to study this latter. The LIBs recovery network is defined as a socio-technical complex emerging system. Our problematic is then to study it from a technical-economic, organizational and prospective perspective, taking into account the different complexities. This problematic raises three research questions: How to model the LIBs recovery network as a complex organizational emerging system? How to foresight on the LIBs recovery network? How to analyze the LIBs recovery network governance?To model the LIBs recovery network, we apply with combination three systemic modeling methods: SCOS'M (Systemics for Complex Organisational Systems' Modelling), cognitive mapping and system dynamics. The modeling aims to characterize the recovery network (stakeholders, subsystems ...), understand its dynamics and identify the key variables in these dynamics. This model is the basis for the following research questions.To Foresight on the LIBs recovery network, we recommend the use of scenarios. These are defined using the SRI matrix (Stranford Research Institute), exploiting the key variables. Foresight is permitted by simulating the system dynamics model with different scenarios to analyze the technical-economic aspects. For the study of the LIBs recovery network governance, the scope was restricted to the repurposing activity. In this case, the study of the governance comes down to analyzing the combinations (2nd life application, stakeholder). A decision aid methodology has been developed for this purpose. In general, this thesis identified the questions that arise when considering the recovery of LIBs. Through our modeling, we have established a useful basis for decision aid. We answered some questions (technical-economic and organizational aspects) and paved the way for others (logistical and environmental aspects).

Indiana University-Purdue University Indianapolis (IUPUI) / The rapid innovations in biotechnology have led to an exponential growth of data and electronically accessible scientific literature. In this enormous scientific data, knowledge can be exploited, and novel discoveries can be made. In my dissertation, I have focused on the novel molecular mechanism and therapeutic discoveries from big data for complex diseases. It is very evident today that complex diseases have many factors including genetics and environmental effects. The discovery of these factors is challenging and critical in personalized medicine. The increasing cost and time to develop new drugs poses a new challenge in effectively treating complex diseases. In this dissertation, we want to demonstrate that the use of existing data and literature as a potential resource for discovering novel therapies and in repositioning existing drugs. The key to identifying novel knowledge is in integrating information from decades of research across the different scientific disciplines to uncover interactions that are not explicitly stated. This puts critical information at the fingertips of researchers and clinicians who can take advantage of this newly acquired knowledge to make informed decisions. This dissertation utilizes computational biology methods to identify and integrate existing scientific data and literature resources in the discovery of novel molecular targets and drugs that can be repurposed. In chapters 1 of my dissertation, I extensively sifted through scientific literature and identified a novel interaction between Vitamin A and CYP19A1 that could lead to a potential increase in the production of estrogens. Further in chapter 2 by exploring a microarray dataset from an estradiol gene sensitivity study I was able to identify a potential novel anti-estrogenic indication for the commonly used urinary analgesic, phenazopyridine. Both discoveries were experimentally validated in the laboratory. In chapter 3 of my dissertation, through the use of a manually curated corpus and machine learning algorithms, I identified and extracted genes that are essential for cell survival. These results brighten the reality that novel knowledge with potential clinical applications can be discovered from existing data and literature by integrating information across various scientific disciplines.

The construction and demolition (C&D) waste produced by the Canadian construction industry accounts for 27% of the total municipal solid waste disposed in landfills. However, more than 75% of C&D waste has residual value and, consequently, could be salvaged, recycled, and/or reused. The need for comprehensive and integrated waste management mechanisms, technologies, rating systems, and policies is widely recognized. A waste management hierarchy tool exists for reducing and managing waste that follows this order: preventing, minimizing, reusing, recycling, energy recovering, and finally, disposing of the waste. It appears that the highest level attained by the concrete industry in Canada is recycling (e.g., crushing concrete and using it as base aggregate). This study aims to explore the opportunities and barriers to advance to the next level in the waste management hierarchy by reclaiming concrete from decommissioned structures for reuse with minimal reprocessing. A survey was distributed to members of the Canadian concrete industry to answer two main sets of questions: 1) to what degree, if any, is the Canadian construction industry currently reclaiming waste concrete by recycling and/or reusing it? and 2) what is the perception of industry professionals on concrete reuse? What are the perceived benefits and challenges of such a practice? A total of 125 participants responded to the survey. Although the environmental advantages of concrete reuse were clear to all, views on the financial benefits were mixed. Many participants highlighted that a successful approach to concrete reuse should involve all parties and stakeholders. Overall, there is positive interest in the concept of concrete reuse; however, there is apparent uncertainty on how to approach it and, thus, there is a need for practical guidance to address various technical, logistical, and liability concerns in a comprehensive and holistic manner. Two cases studies – one for a bridge and one for a building – were developed to address some of the technical challenges associated with reusing concrete in structural applications. The case studies were based on local existing structures that were hypothetically disassembled then repurposed in conceptual redesigns. The design of connections to effectively recouple the deconstructed structural components was a focal, and challenging, aspect of the case studies; in support of shifting towards a circular economy, the connection designs were engineered to be reversible to facilitate future adaptation and/or further dismantlement. It is important to highlight that a desirable reuse project starts in the initial design phase, where the ultimate disassembly and repurposing of the structure is considered from the start (i.e., cradle to cradle design). However, since this is presently not mainstream practice, these case studies focus on the more complex task of deconstructing existing structures that were not designed with the intention of reuse. Although several challenges were encountered, this approach is an essential first step in the present framework to move the discussion forward in the context of reuse of structural concrete members.

To counter hybrid threats – for example, international terrorism, transnational organised crime and (cyber-)attacks – security and intelligence communities increasingly gather, process and exchange vast amounts of data on presumably suspect individuals. This trend has been enabled by recent developments in surveillance capacities related to Information and Communications Technologies (ICTs). As a result, cross-border data transfers have become not only an element of international trade but also an important component of law enforcement strategies. Nevertheless, the exchange of data for policing purposes is not always smooth. Rather, there are frictions that emerge therein as well as technical and legal issues relating to the combination of data from different information systems and under different formats. This study advances the concept of data lifecycle in relation to the practices, such as the collection, entry, processing, storing, and analysis that direct data in specific ways to create multiple “cycles” of uses. Through the analytical lens of the lifecycle I aim to examine specifically how data are repurposed, not only by digital technologies, but also by provisions regulating access, storage and use of information for criminal matters. The core task consists in identifying the socio-political, legal and technical conditions of possibility that allow for the exchange of data at the pan-European level. By bringing together multiple conceptual and methodological subfields, I shed light on the politicality of EU data infrastructures that appear physically very remote or less visible, yet in a way that people do not realise how mundane they have become. Investigating the data lifecycle as a network of practices generates findings that are useful for understanding how security is enacted through the collection and use of different forms of data and hence for interpreting the evolving landscape of data-driven security governance in the EU.

No description available.

Colorectal cancer (CRC) is the third most widespread and fourth most fatal malignancy disease. The CRC from a primary site can spread to other tissues, forming secondary tumours. CRC can metastasise to the liver through the effect of K-Ras and Pten mutation (Mt.) (Abbas et al. 2020). This study aimed to assess the hypothesis that the Ran inhibitor mebendazole MBZ reduces cell invasion and metastasis of CRC. I have investigated MBZ effect on the CRC isogenic human cell lines with specific mutations (HCT-116 K-Ras, DLD-1 K-Ras and Pten deletion and wild type HCT-116 and DKO-3. I used qRT-PCR and western blotting to identify expression levels of various genes and signalling molecules after treatment with 0.5 mM MBZ. In addition, several assays were performed to investigate MBZ effect on biological properties of the cells such as proliferation, migration, invasion, and colony formation. MBZ downregulated Ran and induced apoptosis through inhibition of Bcl-2 expression as well as inducing caspase -3, -7, -9 and PARP cleavage. Moreover, MBZ showed an effect on immune response by down regulating C5a, IL-1ß and IL-1α analysed at mRNA level. When treated with MBZ, the migration, invasion and colony formation abilities of HCT-116 K-Ras Mt., DLD-1 K-Ras Mt. and HCT-116 Pten-/- were significantly reduced compared to a control treated cell line. This was also the case with wild type cell lines such as HCT-116 and DKO-3. Furthermore, signalling molecules such as p- Erk 1/2 and p- Akt were upregulated after MBZ treatment and exert inhibition on Akt 1/2/3 and VEGFR1/2 mRNA levels. In conclusion; MBZ which is a Ran inhibitor, has significantly reduced proliferation, colony formation, and migration in colorectal cell lines with K-Ras and Pten gene deletion compared to wild type cells in a dose-dependent manner. This work paves the way to clinical validation of MBZ as a combination therapy for reducing the invasion of CRC cells.

Date:    2nd June 2024 Level:    Master Thesis in Product- and Process Development, Advanced     level, 30 credits                                                                                  Institution:   School of Innovation, Design and Engineering, Mälardalens University Authors:   Farin Hasan & Soumik Karim Title:    Role of digitalization and digital capabilities to implement second-life business models for electric vehicle batteries Keywords:   Second-life EV batteries, Digitalization in circular economy, Industry 4.0 technologies, EV battery life cycle, Circular economy models, Battery recycling/repurposing Purpose:   The aim of this thesis study is to develop and evaluate a digitalization framework with the goal of improving the second life management of EV batteries.  Research questions:  “What type of Industry 4.0 technologies and digital capabilities are key for the implementation of second-life business models for EV batteries and how do they support ecosystem actors?”  , “How should ecosystem actors prepare and integrate these     technologies and capabilities to implement second-life business models for EV batteries? Methodology:   The study was conducted using an abductive research approach,   employing qualitative methods. The theoretical framework was developed through a systematic literature review of existing literature within the research scope. Data collection involved an  extensive literature review and archival study. Thematic analysis was applied to the data to identify patterns and themes, which were further analyzed to construct a framework.                                                     Conclusion:   The study concludes that integrating industry 4.0 technologies enhances the management and repurposing of EV batteries for second-life applications. These technologies enable effective monitoring, predictive maintenance, and secure data management, which supports ecosystem actors in developing sustainable and economically viable second-life business models.