Botnetsimulatie in een gedistribueerd virtueel computer security lab

Sinds de geboorte in 1983 van het Internet kunnen computersystemen over de gehele wereld vrijelijk met elkaar communiceren. Door het open karakter van het Internet is beveiliging van deze computersystemen een steeds grotere rol gaan spelen, mede omdat deze systemen ook kunnen worden misbruikt door kwaadwillende software zoals botnets. De werking en het gedrag van deze botnets kunnen worden geanalyseerd door deze te simuleren in een afgesloten computerlab. In dit afstudeeronderzoek zijn de mogelijkheden verkend om het 'Distributed Virtual Computer Security Lab' (DVCSL) in te zetten voor deze botnetsimulaties. Door de ontwerpprincipes en -condities van zowel botnets als het DVCSL te analyseren en te vergelijken, is vastgesteld dat botnetsimulaties zijn uit te voeren in het DVCSL. Er is een botnetsimulatie uitgevoerd met een open-source botnet om de mogelijkheden en beperkingen van het DVCSL vast te stellen. Door het uitvoeren van een botnetsimulatie waarin een aanval is gesimuleerd die zich ook op het 'echte' Internet voordoet, is aangetoond dat botnetsimulaties mogelijk zijn in het DVCSL

Large-Scale Electron Microscopy Maps of Patient Skin and Mucosa Provide Insight into Pathogenesis of Blistering Diseases

Large-scale electron microscopy (“nanotomy”) allows straight forward ultrastructural examination of tissue, cells, organelles, and macromolecules in a single data set. Such data set equals thousands of conventional electron microscopy images and is freely accessible (www.nanotomy.org). The software allows zooming in and out of the image from total overview to nanometer scale resolution in a ‘Google Earth’ approach. We studied the life-threatening human autoimmune blistering disease pemphigus, using nanotomy. The pathomechanism of cell–cell separation (acantholysis) that underlies the blistering is poorly understood. Ultrastructural examination of pemphigus tissue revealed previously unreported findings: (i) the presence of double-membrane structures between cells in all pemphigus types; (ii) the absence of desmosomes around spontaneous blisters in pemphigus foliaceus (PF); (iii) lower level blistering in PF when force induced; and (iv) intercellular widening at non-acantholytic cell layers. Thus, nanotomy delivers open-source electron microscopic maps of patient tissue, which can be analyzed for additional anomalies from any computer by experts from different fields

Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

Contains fulltext : 214010.pdf (publisher's version ) (Open Access

Amyloid-β, p-tau, and reactive microglia load are correlates of MRI cortical atrophy in Alzheimer's disease

INTRODUCTION: The aim of this study was to identify the histopathological correlates of MRI cortical atrophy in (a)typical Alzheimer’s disease (AD) donors. METHODS: 19 AD and 10 control donors underwent post-mortem in-situ 3T-3DT1-MRI, from which cortical thickness was calculated. Upon subsequent autopsy, 21 cortical brain regions were selected and immunostained for amyloid-beta, phosphorylated-tau, and reactive microglia. MRI-pathology associations were assessed using linear mixed models. Post-mortem MRI was compared to ante-mortem MRI when available. RESULTS: Higher amyloid-beta load weakly correlated with a higher cortical thickness globally. Phosphorylated-tau strongly correlated with cortical atrophy in temporo-frontal regions. Reactive microglia load strongly correlated with cortical atrophy in the parietal region. Post-mortem scans showed high concordance with ante-mortem scans acquired <1 year before death. DISCUSSION: Distinct histopathological markers differently correlate with cortical atrophy, highlighting their different roles in the neurodegenerative process. This study contributes in understanding the pathological underpinnings of MRI atrophy patterns

Antisense Oligonucleotide-mediated Exon Skipping as a Systemic Therapeutic Approach for Recessive Dystrophic Epidermolysis Bullosa:Exon Skipping as Systemic Therapy for RDEB

The “generalized severe” form of recessive dystrophic epidermolysis bullosa (RDEB-gen sev) is caused by bi-allelic null mutations in COL7A1, encoding type VII collagen. The absence of type VII collagen leads to blistering of the skin and mucous membranes upon the slightest trauma. Because most patients carry exonic point mutations or small insertions/deletions, most exons of COL7A1 are in-frame, and low levels of type VII collagen already drastically improve the disease phenotype, this gene seems a perfect candidate for antisense oligonucleotide (AON)-mediated exon skipping. In this study, we examined the feasibility of AON-mediated exon skipping in vitro in primary cultured keratinocytes and fibroblasts, and systemically in vivo using a human skin-graft mouse model. We show that treatment with AONs designed against exon 105 leads to in-frame exon 105 skipping at the RNA level and restores type VII collagen protein production in vitro. Moreover, we demonstrate that systemic delivery in vivo induces de novo expression of type VII collagen in skin grafts generated from patient cells. Our data demonstrate strong proof-of-concept for AON-mediated exon skipping as a systemic therapeutic strategy for RDEB

Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa

Human skin graft mouse models are widely used to investigate and develop therapeutic strategies for the severe generalized form of recessive dystrophic epidermolysis bullosa (RDEB), which is caused by bi-allelic null mutations in COL7A1 and the complete absence of type VII collagen (C7). Most therapeutic approaches are focused on reintroducing C7. Therefore, C7 and anchoring fibrils are widely used as readouts in therapeutic research with skin graft models. In this study, we investigated the expression pattern of human and murine C7 in a grafting model, in which human skin is reconstituted out of in vitro cultured keratinocytes and fibroblasts. The model revealed that murine C7 was deposited in both human healthy control and RDEB skin grafts. Moreover, we found that murine C7 is able to form anchoring fibrils in human grafts. Therefore, we advocate the use of human-specific antibodies when assessing the reintroduction of C7 using RDEB skin graft mouse models. This article is protected by copyright. All rights reserved