Aim was to analyze the DDoS attacks focused on exploitation of DNS. Attack sources, targets, and characteristics observed in DDoS attack traffic will be analyzed and an assessment of vulnerabilities and single points of failure that threaten the resilience of the DNS under DDoS attack will be conducted. By combining these two perspectives, actionable intelligence will be used to improve the resilience of the DNS against attacks, while facilitating prevention of DNS attacks.

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Alzheimer’s Disease (AD) is a severe age-related condition characterized by extracellular amyloid beta protein aggregation, intraneuronal tau protein accumulation, reactive microgliosis and severe neurodegeneration. Although genetic and environmental components that predispose to AD have been identified, the disease pathogenesis is still poorly understood, but point towards a key role for microglia, the macrophages of the brain. To further understand its pathogenesis, I propose to characterize the transcriptional and epigenetic profiles of microglia from early- and late onset AD post- mortem brain tissue using state–of-the-art genomics approaches such as single cell (sc) and population RNA-seq, ATAC-seq, ChIP-seq, in conjunction with whole-genome genotyping. I will use these datasets to address 4 main aims: Aim 1 is to identify disease-associated microglia populations associated with early and late AD stages. Aim 2 is to characterize the epigenetic landscape of these subpopulations, and identify transcriptional regulators that drive them. Aim 3 is to test whether disease-associated microglia are enriched for subsets of AD associated single nucleotide polymorphisms, that affect enhancer formation and gene expression. Aim 4 is to test the functional consequences of the identified transcriptional regulators by targeted knock-out and overexpression studies in zebrafish microglia. My overall aim is to integrate these findings in order to build a model that describes the temporal order of events of AD pathogenesis encompassing disease-associated microglia populations, in relation to the key genetic and epigenetic regulatory factors in a patient specific manner. Identification of transcriptional regulators associated with disease-associated cellular populations would be a major step forward for the field, and can identify putative targets for drug development. Taken together, these studies will result in a high-resolution map of AD, that can be used to identify putative drug target candidates, and will hence set the stage for individualized medicine development.