SACM - Netherlands
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14154/68623
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Item Restricted Dissecting Symbiosis Permissiveness in Parasponia andersonii(Wageningen University and Research, 2024-12-17) Alhusayni, Sultan Awwadh Sultan; Geurts, ReneNutrient limitations often constrain plant growth, leading to the use of chemical fertilizers, which can harm the environment. Biological nitrogen fixation, involving nitrogen-fixing bacteria in plant roots, provides a sustainable alternative. My research aligns with this goal, focusing on non-legume plants, particularly the non-nodulating Trema orientalis RG33 and the nodulating Parasponia andersonii species. One key gene I investigated was SYMRK, essential for root nodules and AM symbioses in legumes. In T. orientalis RG33, I identified a point mutation in this gene, and when introduced into the P. andersonii SYMRK gene, it did not disrupt the gene's function, successfully restoring both root nodule formation and AM symbiosis in a P. andersonii symrk mutant. I also explored the ectopic expression of NSP2, which enhanced AM mycorrhization but inhibited nodulation in Parasponia. Lastly, I discovered that the autoregulation of nodulation (AON) pathway, which regulates nodule numbers, is conserved in both legumes and non-legumes, providing a promising strategy for engineering nitrogen fixation in non-nodulating plants.7 0Item Embargo From Oil to Identity: Place branding for urban transformation in a top-down society (A case study of Saudi Arabia)(Erasmus University Rotterdam, 2024-12-11) Alsayel, Abdulrhman; Edelenbos, Jurian; De Jong, Martin; Fransen, JanThis dissertation investigates the transformation of Saudi Arabian cities under the ambitious Vision 2030 framework, focusing on the role of place branding within a centralized governance system. The research seeks to understand how cultural, institutional, and governance factors influence the effectiveness of place branding strategies in Saudi Arabia, offering a departure from Western-centric models that emphasize participatory and bottom-up approaches. By using Riyadh as a principal case study, the thesis sheds light on the implications of top-down city branding on urban development, cultural preservation, and social inclusivity. The research is structured into four interconnected papers. The first paper explores the tension between economic growth and social inclusivity through a comparative analysis involving Dubai, Amsterdam, and Toronto. The findings reveal that while creative city branding can drive innovation and attract investment, it often neglects inclusivity, leading to social exclusion. The second paper examines how various multi-level governance models impact the success of place branding in Saudi Arabia, demonstrating that cities directly aligned with central government resources tend to achieve more effective branding, though this can exacerbate regional disparities. The third paper delves into the cultural and institutional factors affecting place branding, emphasizing that while central government involvement can streamline efforts, it may limit local stakeholder engagement. The final paper focuses on the rebranding of Riyadh, drawing comparisons with global cities like Barcelona and Tokyo to reveal both the opportunities and social challenges associated with rapid urban transformation, such as gentrification and cultural homogenization. This thesis concludes that while centralized governance can expedite urban development and enhance city branding, maintaining cultural integrity and fostering social equity are essential to sustainable growth. The research advocates for future studies to employ mixed-method approaches for broader applicability and to explore comparative case studies in other centralized systems, such as China and the UAE, to enrich the understanding of place branding in non-Western contexts.22 0Item Restricted Improving Sleep Quality in Nurses Who Work Irregular Shifts: Necessity and first steps towards intervention(Maastricht University, 2024) Albakri, Uthman; Meertens, Ree; Kant, IJmert; Gabrio, AndreaThe primary aim of this dissertation was to develop and design a sleep health promotion intervention to improve sleep quality among nurses working irregular shifts, including night shifts. The initial step involved conducting an umbrella review to provide an overview of existing sleep health promotion interventions aimed at improving sleep quality and/or duration among healthy populations and to identify under-researched areas, one of which is nurses working irregular shifts. While the effects of shift work on health and sleep quality among shift workers are well-documented, the impact of irregular shifts specifically on nurses’ sleep quality has not been adequately evaluated. Moreover, the association between sleep quality and the need for recovery—often detrimental to health—remains largely unexplored. This significant research gap has not received sufficient attention. Given the limited evidence on how nurses cope with irregular shifts, understanding their coping mechanisms is crucial for developing effective sleep health promotion strategies to enhance their sleep quality and overall health. Although sleep hygiene strategies have been proposed for the general population, these do not all apply to nurses working irregular shifts, and the effectiveness of such strategies may vary from individual to individual. Additionally, the literature lacks clear guidelines on sleep hygiene strategies specifically tailored for nurses coping with this shift type. Therefore, it is essential to first develop personalized sleep hygiene strategies and assess their feasibility and effectiveness in improving sleep quality among these nurses.17 0Item Restricted THE ROLE OF ARTIFICIAL INTELLIGENCE IN ENHANCING KPIS AND OPTIMIZATION OF HUMAN RESOURCE MANAGEMENT(The Hague University, 2024-09-28) Alsamhan, Khulud; Le Fever, HansMANAGEMENT SUMMARY This thesis explores how artificial intelligence (AI) can enhance human resource management (HRM), particularly in recruitment and onboarding. The study focuses on LinkedIn's AI tools, aiming to understand their effectiveness in improving key performance indicators (KPIs) and optimizing HR processes. The research draws on a broad literature review, examining the evolution of AI in HR. AI has shown potential in automating tasks like candidate screening and onboarding, but there are challenges, including biases in AI systems and the need for continuous improvement. Using Saunders' research onion framework, a mixed-methods approach was adopted, combining surveys and interviews with HR professionals who use LinkedIn's AI tools. This approach provided a comprehensive view of AI's impact on HRM. The results indicate that AI tools significantly enhance effectiveness by automating repetitive tasks and improving candidate matching, thus reducing the time-to-hire and increasing accuracy. However, some challenges remain, such as occasional inaccuracies and the need for better user training. It's clear that refining AI algorithms and incorporating human oversight can help address these issues. In onboarding, AI tools have been successful in automating administrative tasks and personalizing the onboarding experience. Feedback suggests that AI-driven processes help new hires feel more supported and prepared. The study concludes with recommendations for further research and practical steps for implementation. It highlights the need for ongoing refinement of AI tools, better integration practices, and comprehensive training for HR professionals. Future research should focus on long-term impacts and best practices for AI in HRM. In summary, AI has the potential to transform HRM by enhancing KPIs and optimizing processes. However, a balanced approach that combines technology with human judgment is essential for maximizing these benefits. This thesis provides a foundation for future advancements in using AI in HRM.24 0Item Restricted A NEW PERSPECTIVE ON RECOVERY ACTIVITIES(Maastricht University, 2024-10-15) Alameer, Khalid; Uitdewilligen, Sjir; Hüsheger, UteRecovery activities—such as physical, social, and low effort activities—play a vital role in mitigating the impact of work demands on health and in enhancing workplace functioning (Sonnentag, 2001; Sonnentag et al., 2022). Yet, understanding of the complex relationship between recovery activities and their outcomes, along with the mechanisms underlying this interplay, remains underdeveloped. This dissertation aims to structure and increase the existing knowledge on recovery activities by focusing on three primary objectives. The first objective is to develop an effective conceptual framework and measurement approach for recovery activities. This involves identifying and defining the dimensions that capture the spectrum of activities individuals engage in to recover from work-related stress and examining how these dimensions were differentially related to recovery experiences and recovery outcomes. The second objective is to identify the evening profiles —a mixture of different characteristics of recovery activities that a person participates in during their off-job time—and to explore how these profiles relate to recovery experiences and recovery outcomes such as work engagement and emotional exhaustion. The final objective is to investigate the reciprocal relations between recovery activities and employee well-being by examining how these variables influence each other on a weekly and bi-weekly basis. Chapter 1 provides a general introduction, highlighting the importance of regular recovery from work-related stress to alleviate its detrimental effects on health and well-being. This chapter discusses the rich history of recovery activities in the work and organization literature, the psychological mechanisms underlying their benefits, and the significant gaps in understanding the diversity of recovery activities and their specific impacts. It emphasizes the need for a differentiated approach to conceptualizing recovery activities and outlines the aims and research questions of the dissertation. Chapter 2 introduces the Recovery Activity Characteristics (RAC) framework, identifying seven dimensions of recovery activities—physical, social, creative, mental, spiritual, virtual, and outdoor. This chapter describes the development and validation of the RAC questionnaire and demonstrated how different dimensions of recovery activities uniquely influence recovery experiences and recovery outcomes within individuals. For instance, physical, mental, and creative dimensions were positively related to mastery experiences and morning vigor, while social and outdoor activities were related to enhancing psychological detachment and reducing emotional exhaustion. Chapter 3 explores profiles of evening recovery activity engagement using a multilevel latent profile analysis across different cultural samples and timeframes. Using data from a 10-day diary study and an 8-week weekly survey, distinct profiles (e.g., virtual-mental, outdoor-physical) were identified, which associated with specific recovery experiences and outcomes. For example, on evenings that employees fell into the "virtual-mental" profile, they experienced low psychological detachment and relaxation. Additionally, when they fell into the "outdoor-physical" profile, they showed high psychological detachment and low emotional exhaustion. The findings revealed that the impact of recovery activities on well-being depended on the unique combination of activity characteristics, highlighting the importance of considering the holistic context of recovery activities. Chapter 4 examines the reciprocal and temporal relationships between recovery activities and well-being indicators using the Random Intercept Cross-Lagged Panel Model (RI-CLPM). The shortitudinal study, which spanned eight weeks, showed that creative engagement in one week predicts an increase in work engagement the following week. However, not all hypothesized relations were significant, suggesting complex dynamics that need further investigation. Chapter 5 synthesizes the main findings, discussing their theoretical, methodological, and practical implications. This chapter highlights the importance of a multidimensional approach in studying recovery activities for promoting employee well-being and shows how different activity dimensions and profiles (i.e., a combination of dimensions) affect recovery experiences and outcomes. The chapter concludes with recommendations for future research to further explore the causal pathways and practical applications of recovery activities in diverse organizational settings. In conclusion, this dissertation advances the understanding of recovery activities by introducing a novel dimensional framework and exploring the complex interactions of recovery activities and employee well-being. It offered valuable theoretical insights and practical implications for enhancing employee health and productivity. Future research should continue to investigate the causal pathways and practical applications of recovery activities to foster healthier and more productive organizational environments.14 0Item Restricted Diplomatic Families and Immunity in the Vienna Convention on Diplomatic Relations: Between Theory and Practice(Leiden University, 2024) Almohaidib, Rassel; Lam, OceanThe Vienna Convention on Diplomatic Relations (VCDR) remains a cornerstone in formalizing international diplomatic practices, offering a structured framework for state interaction since its adoption in 1961. This research has explored both the theoretical foundations and practical applications of diplomatic immunities under the VCDR, revealing the convention’s adept balance between granting essential protections to diplomats and ensuring respect for the laws of host states. Our study underscores the intricate balance the VCDR strikes between the necessity of diplomatic immunity and the duty of diplomats to respect local laws, as exemplified by Article 41. The convention classifies diplomatic personnel with varying levels of immunity, demonstrating a nuanced understanding of their roles within diplomatic missions. However, the practical implementation of diplomatic immunities is a complex interplay of international norms, security concerns, and bilateral agreements, posing ongoing challenges in enforcement and accountability. State practices show a significant level of stability in defining ‘family’ within diplomatic contexts, mainly adhering to domestic legislation and mutual understanding despite cultural differences. Our findings suggest that changes in discriminatory practices are more likely to stem from cultural shifts rather than legal modifications. While Article 37(1) does not necessitate immediate changes, introducing mechanisms for addressing family-related claims could enhance the framework’s effectiveness. This research examined the alignment between diplomatic immunity for family members and the VCDR’s theoretical framework, the definition of ‘family’ on the application of diplomatic immunity, and the criteria within international law for defining a family member. Additionally, it aimed to understand the importance of a specific family definition that respects cultural differences and the implications of discrepancies between the VCDR’s theoretical framework and actual practices. Our findings indicate that while there is alignment with the theoretical framework, the inherent ambiguities make it challenging to pinpoint discrepancies. States generally agree on including spouses and minor children as family members but differ on other relatives, reflecting a need for a more specific yet culturally sensitive definition. Looking ahead, the ever-evolving dynamics of global diplomacy underscore the imperative for continuous evaluation and adaptation of diplomatic norms. Future research should be geared towards enhancing clarity in interpreting the VCDR, addressing gaps in diplomatic law, and fostering international cooperation in the face of shifting geopolitical landscapes. In conclusion, while the VCDR provides a robust foundational framework for diplomatic interactions, its practical implementation demands ongoing dialogue, collaboration among states, and adherence to evolving global standards. By navigating these complexities thoughtfully, we can uphold diplomatic integrity and foster productive international relations in the 21st century.7 0Item Restricted Assessing Discourses on Sustainability in Public-Private Collaboration for Promoting Coffee Programs in Saudi Arabia(Wageningen University and Research, 2024-03-22) Alshehri, Jamela; Mangnus, Ellen; Biesbroek, RobbertThe research examines sustainable programs aimed at improving coffee production in Saudi Arabia, specifically focusing on policies related to environmental and socio-economic concerns. The overarching objective is to provide recommendations that can enhance coffee production regulations and ultimately contribute to their improvement. Accordingly, two methodologies were utilized to address the research inquiries: stakeholder analysis and discourse analysis employing Dryzek's approach. Relevant data was gathered from official sources, including documents related to coffee production programs as well as speeches delivered by members of relevant organizations. The findings obtained from the initial method stress the importance of a coordinated approach, particularly through collaboration between government and private partners under the leadership of the Saudi Coffee Company, and to identify an entity that can unify efforts among diverse stakeholders. Moreover, the discourse analysis revealed three primary sustainability discourses identified throughout the document analysis, which are: 1. The integration discourse encompasses the three common dimensions of sustainability and ensures the translation of sustainability into actionable measures by leveraging technology; 2. the economic capitalism discourse with the aim of fostering economic growth for the area, including farmers and related sectors, while also targeting local demand and increasing global contribution; and 3. the discourse surrounding water scarcity emerges as a crucial aspect, necessitating investment in water-efficient technologies amidst rising competition for resources. The argumentative structure within the coffee program discourse highlighted the tension between economic development and environmental concerns by shedding light on the necessity of striking a balance to sustain coffee production while also considering environmental conservation and social responsibility. Exploring the challenges surrounding coffee production from multiple discourses' perspectives allows for a deeper understanding of the multifaceted nature of these challenges. Sustainable production programs, aimed at contributing to the economic growth of the country, could be threatened by these challenges. Therefore, the research ends by formulating recommendations to help identify some of the root causes of these challenges and explore possible solutions.15 0Item Restricted Securing Power Side Channels by Design(Delft University of Technology, 2024-02-27) Aljuffri, Abdullah; Hamdioui, Said; Taouil, MottaqiallahThe security of electronic devices holds the greatest importance in the modern digital era, with one of the emerging challenges being the widespread occurrence of hardware attacks. The aforementioned attacks present a substantial risk to hardware devices, and it is of utmost importance to comprehend the potential detrimental effects they may cause. Side-channel attacks are a class of hardware attacks that exploit information unintentionally leaked by a device during its operation. These leaks manifest in various forms, including power consumption, time variations, and thermal dissipation. The fundamental danger posed by side-channel attacks is their ability to infer sensitive information from these unintended emissions. To address the heightened risks associated with side-channel attacks, this thesis focuses on three main research topics. Side Channel Analysis: Side-channel attacks can manifest in various forms, depending on the specific leakage channels employed. The present study primarily focused on the investigation of three distinct categories of leakage, as it is hypothesized that these specific forms of leakage present the greatest potential risks. The aim of the analysis is to identify the optimal channels for creating an assessment framework. The selected leakages for analysis cover power consumption, temporal variations, and thermal attacks. Power consumption measurements provide valuable insights into the behavior and execution patterns of algorithmic operations, facilitating the identification of specific operations that are particularly vulnerable to attacks. There are other types of leakages that are similar, such as electromagnetic emissions. However, it is important to note that power consumption demonstrates considerably lower levels of noise. The use of time variations in evaluating operations is subject to certain limitations due to the need to wait for a response. Nevertheless, one notable advantage of these systems is their ability to offer convenient remote access, facilitated by their software-based calculation capabilities. Despite its inherent noise, thermal monitoring is employed in nearly all devices as a means to prevent overheating. The ability to remotely access this monitoring system is facilitated through software. Consequently, a meticulous examination is necessary to identify potential modes of assault. Countermeasures: Cryptographic algorithms and other security primitives are the basic components of any cryptosystem. In their most optimized versions, these algorithms are frequently thought to be prone to side-channel attacks (SCAs), which necessitates the development of countermeasures. In this thesis, four countermeasures that have been developed are thoroughly analyzed. The countermeasures that were devised covered a wide range of algorithms, such as GIFT, RSA, and AES, and they were suitable for a variety of applications, including lightweight ones. The first countermeasure that has been developed makes use of an Advanced Encryption Standard (AES) implementation that is based on neural networks. This countermeasure's principal goal is to confuse the attacker by causing random fluctuations in power consumption. The second countermeasure is developed for asymmetric algorithms. This countermeasure's goal is to balance the leakage by making power consumption similar among all its executions. The goal of developing the third algorithm was to provide a countermeasure that is lightweight and tailored to symmetric algorithms. This countermeasure is based on the integration of balancing and randomization techniques. To ensure that the results of these two operations show balanced power behaviors in a random way, two instances of the SBOX operation are generated to complement each other. The fourth countermeasure involves the optimization of a widely known countermeasure named Domain-Oriented Masking (DOM) to adapt to lightweight applications. The countermeasure used in this research combines optimization techniques like resource sharing, module optimizations, and key-expansion bypassing. Pre-silicon Leakage Assessment: After recognizing the importance of mitigating side-channel leakages and developing various countermeasures, the subsequent phase entails establishing a framework for evaluating these vulnerabilities. In contrast to software vulnerabilities, which can be addressed through patching at any given time, the mitigation of hardware vulnerabilities necessitates expensive modifications to the physical hardware. Hence, it is essential to develop a leakage assessment framework that can effectively evaluate the system during the design phase. In this thesis, we present an innovative and pioneering methodology that relies on the application of Generative Neural Networks (GANs). The methodology described herein signifies a substantial advancement in the pursuit of enhanced security in the field of chip design. This framework demonstrates outstanding ability to rapidly produce traces that closely correspond to those obtained from computer-aided design (CAD) processes. As a result, it enables the efficient validation of numerous countermeasures within a realistic timeframe.16 0Item Restricted Towards Energy-Efficient Residential Buildings in Jeddah, Saudi Arabia: Exploring Energy Retrofitting Options and Assessing Their Feasibility.(Delft University of Technology, 2024) Felimban, Ahmed; Ulrich, KnaackThe thesis investigates the energy retrofitting of existing residential buildings in the Kingdom of Saudi Arabia (KSA), the building sector responsible for a significant proportion of the nation's energy consumption. The research introduces a comprehensive methodology tailored for the unique architectural and social contexts of KSA, aimed at significantly improving energy efficiency and thereby aiding the country in achieving its net-zero emissions target for 2060. Utilizing a case study, the methodology incorporates a detailed analysis of energy performance, identifies suitable retrofitting measures, and evaluates their cost-effectiveness. The study extends beyond the technical aspects of energy retrofitting to address its social relevance. It posits that implementing such measures can lead to substantial energy savings, improved indoor comfort, and superior housing quality. These interventions can also foster greater societal awareness of energy efficiency, counteracting the primary factors contributing to increased electricity costs. Despite the manifold benefits, the research identifies potential resistance from residents, which could arise from heightened expectations of energy upgrade providers. Interestingly, this reluctance may serve as a catalyst for providers to improve the quality of their products and services, ultimately enhancing market standards for energy-efficient solutions. Furthermore, the thesis argues that energy retrofitting could stimulate job creation and elevate the status of architectural specialties, thereby supporting broader economic development and social well-being. The thesis concludes by recommending that state decision-makers actively incentivize energy retrofitting to harvest its multitude of benefits, from enhancing energy efficiency to contributing to economic growth and sustainable development. The proposed methodology offers a robust framework for stakeholders, paving the way for a more energy-efficient, economically viable, and socially responsible residential building sector in KSA.28 0Item Restricted Inside Cancer Pathology: Human Polyomavirus and Bovine Meat and Milk Factors(Saudi Digital Library, 2023-11-21) Mobaraki, Ghalib Ibrahim; Hausen, Axel zur; Speel, Ernst-Jan; Winnepenninckx, VéroniqueEven though cancer incidence is increasing rapidly around the world, the cause and cure of many malignant neoplasms remain largely unknown. Studies suggest that 20% of cancers worldwide may be due to high-risk infectious agents. There has been a long-standing link between the development of cancer and viral infections. Up to 15% of all human malignancies have been linked to viruses. In the last two decades, new molecular technologies such as Next Generation Sequencing have enabled us to come across new members of human polyomaviruses (HPyVs), however few have been found to be connected to cancerous diseases in humans; mainly Merkel cell carcinoma (MCC) which is caused by MCPyV in 80% of cases. Researching further into HPyVs and their involvement in tumorigenesis needs more exploration. Other infectious agent such as BMMFs have been recently found in colon, pancreases, lung and in our study of RCC cohort. The primary objective of this thesis was to screen and test for novel HPyVs and BMMFs in various cancer tissues to gain a better understanding of the role and possible involvement of these infectious agents in human tumorigenesis. Our goal was to detect HPyVs at single-cell levels within the histomorphological context using FFPE tissues and a variety of sensitive and specific molecular techniques for BMMFs DNA detection. Chapter 1 provides a general introduction of how DNA and RNA tumor viruses and BMMFs contribute to carcinogenesis, either directly or indirectly. Moreover, this chapter focused more on describing the polyomaviruses in general, then giving a brief background of each known HPyV as well as BMMFs. Furthermore, the outline and the purpose of this thesis are discussed. Chapter 2 reviews the current evidence to evaluate a possible role of HPyV6 and 7 in the etiopathogenesis of neoplastic human diseases. The frequent prevalence of HPyV6 and 7 DNA in non-neoplastic and neoplastic tissues along with their high seropositivity in the normal population indicate that both viruses have long-term latency in humans. Interestingly, HPyV6 prevalence was higher in skin malignancies than that of HPyV7. In contrast, HPyV7 was more frequently detected in non-cutaneous malignancies such as cholangiocarcinoma and renal cell carcinoma . Notably, previous studies revealed that the seropositivity of HPyV6 was found to be higher than HpyV7 and increased with age. In conclusion, HpyV6 and 7 remain important putative candidates that may contribute to the etiopathogenesis of human diseases, especially skin cancer. Chapter 3, we assess the relation of BKPyV-positive urine cytology specimens (UCS) to the detection of UCC in a large UCS database and the following evaluation of BKPyV in the UCC of the urinary bladder. In addition, we aimed to evaluate the relation of BKPyV to intravesicular BCG or mitomycin treatment of UCC patients. Our results shown that PCR detected BKPyV- DNA in urine samples of patients with either in situ or invasive UCC of the urinary bladder, while BKPyV-IHC and PCR were negative at the FFPE level of primary UCCs and metastases. However, the BKPyV detected in urine was not linked to previously resected urothelial cell carcinomas, excluding this virus as a possible cause of conventional type UCC in our cohort. BKPyV-reactivation has been observed not only in immunocompromised individuals, but also among those with urothelial cell carcinoma and no prior history of transplantation, malignancy or chronic diseases. The intravesical treatment could be associated with the reactivation of the latent BKPyV. Moreover, Cystitis may be behind the reactivation of the latent BKPyV in immunocompetent patients. Therefore, evaluating for BKPyV presence in post-UCC patients might be pertinent for assessing the risk of BKPyV-nephropathy and further studies are necessary to understand this complex relationship. Recently, we studied the association between the BKPyV infection and urothelial cell carcinoma in patients with urine cytology positive for Decoy cells. However, in our patient cohort, both primary and recurrent UCC tissues tested negative for BKPyV by PCR and immunohistochemistry (IHC) as outlines in chapter 3. Chapter 4 evaluates the presence of JCPyV, HPyV6, HPyV7, and MCPyV in the UCC samples and in the voided urine in the patients, diagnosed with UCC and with Decoy cells in urine cytology. JCPyV-DNA was detected in the urine and urothelial cell and MCPyV was detected in urothelial cell carcinoma. However, both HPyV6 and 7 were not detected in all UCCs and urine specimens. Since there is inadequate evidence of a role for JCPyV in carcinogenicity in UCC, these findings support the hypothesis that JCPyV infection could play a role in urothelial carcinoma tumorigenesis. Going forward, it is important to define whether or not both JCPyV and MCPyV are involved in UCC tumorigenesis. The Chinese research group recently detected HPyV6 DNA in 27% of the bile fluid from cholangiocarcinoma (CCA) patients, prompting us to look further into this possible link. In Chapter 5, we aimed to investigate the prevalence of HPyVs in CCA tissues to elucidate possible clinicopathological correlations between HPyVs and CCA. Interestingly, HPyV7 (69%) was highly prevalent in the CCA cohort, the next most frequent was MCPyV (24%) followed by HPyV6 (14%). An important finding of this study was that HPyV7, HPyV6, and MCPyV are hepatotropic viruses and able to infect non-neoplastic human hepatocytes, bile duct epithelium, and CCA tumor cells. However, it's still not known if they contribute to or cause CCA. The frequent finding of HPyVs in adjacent peritumoral hepatocytes could suggest a robust indirect role for these viruses in inducing CCA transformation through chronic inflammation as outlines in chapter 1. Chapter 6, to investigate possible clinicopathological correlations between HPyVs and RCC, we screened for the prevalence of HPyVs in in various formalin-fixed and paraffin-embedded (FFPE) RCC tissues by human polyomavirus consensus and virus specific PCR in RCC tissues including adjacent non-neoplastic kidney tissues. PCR positive cases were further tested by FISH, RISH and IHC. Of note, 80% (44/55) of RCC and its non-tumoral tissues tested positive for one or more of the HPyVs (i.e., MCPyV, HPyV6, HPyV7, BKV, JCV and WUyV) in the same specimen. 27 (61%) specimens were positive for only one of HPyV, 13 (29.5%) specimens were positive for 2 HPyVs, 3 (6.8%) specimens were positive for 3 HPyVs, and only one (2.27%) RCC specimen was positive for 4 HPyVs on the same specimen. However, 11 (20%) RCC specimens were negative for all PCR approaches. Interestingly, MCPyV was seen in 22/55 (40%) of RCC tissues, HPyV7 was observed in 13/55 (23.6%) of RCC, and HPyV6 in 7 (12.7%) of RCC tissues. However, 9/55 RCC specimens share positivity for both MCPyV and HPyV7, while 2/55 RCC specimens have positivity for both HPyV6 and HPyV7. 0/55 was seen among MCPy and HPyV6 or for these 3 viruses on the same time. Our findings strongly suggest that MCPyV, HPyV7, HPyV6, BKV, JCV and WUPyV could potentially infect both RCC and surrounding tumor tissues. While all six HPyVs have shown a tendency to target the kidneys, we observed that MCPyV and HPyV7 were more commonly present in neoplastic and non-neoplastic cells within our subset of RCC samples compared to HPyV6, BKV, JCV and WUPyV. This study is the first to not only map these HPyVs in various distances of RCC tissues but also report the presence of MCPyV and HpyV6 on a single cell level. We utilized various molecular techniques to examine the presence and bioactivity of these viruses from DNA to protein levels. The frequent identification of HPyVs, particularly MCPyV and HPyV7 in kidney tissues may also indicate a possible involvement in other kidney diseases. Our results may suggest an indirect link between these HPyVs and carcinogenesis through inflammation, further investigation is needed to fully understand their role in the development of RCC. There have been contradictory results from epidemiological studies on diet and kidney cancer, including renal cell carcinoma (RCC). Interestingly, the geographic distribution of RCC incidence also reveals a significant degree of epidemiological agreement with the geographic distribution of colon and breast cancer incidences, suggesting a link with diet. In the recent discovery of bovine meat and milk factors (BMMFs), a novel class of infectious agents is distinguished between bacterial plasmids and single-stranded circular DNA viruses in terms of their ancestral origins. Recently, it has been shown that exogenous BMMF DNA derived from milk or meat is able to replicate in human embryonic kidney (HEK) cells and found in other cancer such as colon, pancrease and lung. Chapter 7, we aimed to test the most common subtypes of RCC, i.e., CCRCC, and PRCC for the possible presence of BMMFs in formalin- fixed and paraffin-embedded (FFPE) RCC tissues. Indeed, we were able to reliably detect BMMFs-DNA in the RCC FFPE tissues. It is highly interesting that BMMF-DNA is more frequently found in non-tumoral tissues compared to RCC in both collection groups. These findings are potentially in line with the proposed model for BMMF-induced indirect colon carcinogenesis, which includes the presence of BMMFs in adjacent non-tumoral tissues. Due to the frequent finding of BMMF2-DNA in the non-tumoral FFPE kidney tissues of the retrospective RCC collection, we also tried to amplify other parts of this specific BMMF2 genotype. By using seven different BMMF2-specific primer pairs covering the rest of the BMMF2 genome, we were able to amplify all parts of the respected BMMF genome in the tested cases. This approach confirmed the results of the BMMF2 broad-range PCR and indirectly possibly suggests that the whole BMMF2 genome is present in these tissues.12 0