Expression Regulation of Major Histocompatibility Complex Class I and Class II Encoding Genes

Major histocompatibility complex (MHC)-I and MHC-II molecules play an essential role in the immune response to pathogens by virtue of their ability to present peptides to CD8+ and CD4+ T cells, respectively. Given this critical role, MHC-I and MHC-II genes are regulated in a tight fashion at the transcriptional level by a variety of transcription factors that interact with conserved cis-acting regulatory promoter elements. In addition to the activities of these regulatory factors, modification of chromatin also plays an essential role in the efficient transcription of these genes to meet with local requirement for an effective immune response. The focus of this review is on the transcription factors that interact with conserved cis-acting promoter elements and the epigenetic mechanisms that modulate induced and constitutive expression of these MHC genes

Therapeutic drug monitoring in Tuberculosis treatment:the use of alternative matrices and sampling strategies

Tuberculosis (TB) is the deadliest infectious disease worldwide. In 2018, approximately 1.45 million people died due to TB and an estimated 10 million individuals fell ill with TB. TB is transmitted by inhalation of small airborne droplets, containing the tubercle bacillus, produced by coughing or sneezing by individuals with contagious pulmonary TB. The treatment of TB starts with a combination of rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months followed by 4 months of rifampicin and isoniazid. Nowadays, a major problem is the increase in antibiotic resistance. When the tubercle bacillus is resistant to both rifampicin and isoniazid, this is defined as multidrug-resistant TB (MDR-TB). Treatment of MDR-TB is less successful and these drugs cause more side effects than drug-susceptible TB treatment. Antibiotic resistance can be developed by insufficient drug exposure; this means the blood concentration of a drug is too low to be effective. Even using standardized dosing, drug exposure shows large inter-individual variation. Therapeutic drug monitoring (TDM) is a method to determine the optimal dose for an individual by measuring the drug concentrations in collected blood samples with dose adjustment if needed. In this thesis we investigated methods to reduce the burden of TDM for patients and medical personnel by using saliva samples instead of blood samples, by reducing the number of required blood samples, and by centralising TDM in specialised laboratories. Using these methods, we want to increase feasibility of TDM in TB endemic areas to improve treatment success rates and decrease emergence of drug resistance

Exploring the determinants of digital transformation in its different stages in Dutch SMEs: A digital dynamic capabilities perspective

Digital transformation (DT) has become a crucial strategic imperative for organizations seeking to thrive in the rapidly evolving business environment. While digital transformation has been extensively studied in large organizations, there remains a need for more available evidence in the context of (Dutch) SMEs and how organizations go through different DT phases. This dissertation aims to address this gap by adopting a digital dynamic capabilities perspective to explore the determinants of digital transformation in Dutch SMEs and investigate how these determinants change over the different digital transformation phases. This thesis has met these aims by integrating an extensive review of the relevant literature and implementing a qualitative study. The latter includes nine interviews with experts from different Dutch SMEs and an expert panel to validate these findings. The primary conclusions produced by this study include five internal determinants, five external determinants, three sub-capabilities, each of the sensing, seizing, transforming, and safeguarding digital dynamic capability clusters, and five desired digital transformation outcomes. ‘Digital safeguarding’ has emerged as a novel capability cluster focusing on skills required from the implementation onwards. In conclusion, this study has contributed to a deeper understanding of the differences in the digital transformation determinants and capabilities between large organizations and SMEs. Moreover, this thesis has identified that boundaries between the different digital transformation phases could be fading due to the continuity of digital transformation. Simultaneously, this research has practical relevance as these findings could support Dutch SMEs in navigating their digital transformations. Alternatively, the study could help Joanknecht, a Dutch financial advisory firm, improve its consultancy services. Looking ahead, future researchers should seek to validate and expand upon the presented findings.

Weather and Photoperiod Indices of Autumn and Winter Dabbling Duck Abundance in the Mississippi and Atlantic Flyways of North America

Climate change may influence autumn and winter distributions of dabbling ducks throughout the Atlantic and Mississippi Flyways of North America. To determine how weather and photoperiod influenced autumn-winter abundances of dabbling ducks at staging areas in eastern North America, I modeled weather and photoperiod variables with rate of change in relative abundance of various dabbling duck species over space and time. Latitude was incorporated into models to determine if changes in duck abundance in relation to weather severity were influenced by locale. Changes in abundance were best described by weather models incorporating temperature and snowfall variables for all species except blue-winged teal (Anas discors), which was best explained by photoperiod. Latitude was present in all top models for all study species. My findings aid wildlife management efforts in predicting potential changes in the non-breeding distribution of ducks resulting from climate change

Exploring Language Loss and Identity: Aboriginal perspectives

The arrival of a new dominant European colonial power had great consequences for the Aboriginal peoples of what was to become Canada. New languages such as English and French were introduced and active policies aiming to assimilate Aboriginal peoples into larger Euro-Canadian society resulted in the loss and decline of many Aboriginal languages. Languages once spoken by large communities are now extinct or in need of revitalization and maintenance strategies to ensure language use by future generations. The loss and decline of these languages had a great impact on Aboriginal culture and identity. This study explores that history of loss, revitalization and identity from both an academic and an Aboriginal perspective. The stories and experiences shared in ten interviews give voice to several Cree and Kwakwaka'wakw perspectives on these topics. As it turns out, many see a future for their Aboriginal language, despite it's endangered status and the continued pressure on the language, precisely because it is such an important marker of their identity

Belangstelling uit het buitenland

De perspectieven om in zorgvastgoed te investeren zijn positief en de investeringen zullen dan ook toenemen. Dat betoogt Jan Veuger, lector Maatschappelijk Vastgoed aan de Hanzehogeschool Groningen in zijn Barometer Zorgvastgoed 2015