Identification of numerical chromosome aberrations in archival tumours by in situ hybridization to routine paraffin sections: Evaluation of 23 phaeochromocytomas

We have applied non-isotopic in situ hybridization (ISH) to interphase cell nuclei of 23 phaeochromocytomas (18 primary and 5 metastatic tumours) within routine paraffin-embedded tissue sections. Each tumour was screened for numerical aberrations with a defined alphoid repetitive DNA probe set containing DNA probes specific for chromosomes 1, 7, 15, and Y. Normal adrenal medullas and other normal human cell types served as cytogenetic controls. Preservation of tissue morphology enabled targeted analysis of tumour cells. The presence of numerical chromosome changes in the tumour cells could easily be evaluated by comparing the ISH results of the DNA probes. Numerical abnormalities not previously reported in this neoplasm included overrepresentation of chromosomes 1 and 7, loss of chromosome 15, and both gain and loss of chromosome Y (P values <0.01). The percentage of aneuploid cell nuclei in a tumour correlated well with the percentage of cells in the 4C peak of flow cytometric DNA histograms from these neoplasms. We conclude that interphase ISH can be used for the identification of new and reported cytogenetic changes in tumour cell nuclei within archival tissue sections. This novel procedure also allows for retrospective analysis of previously not karyotyped material

Enhanced antiviral activity of human surfactant protein d by site-specific engineering of the carbohydrate recognition domain

Innate immunity is critical in the early containment of influenza A virus (IAV) infection and surfactant protein D (SP-D) plays a crucial role in innate defense against IAV in the lungs. Multivalent lectin-mediated interactions of SP-D with IAVs result in viral aggregation, reduced epithelial infection, and enhanced IAV clearance by phagocytic cells. Previous studies showed that porcine SP-D (pSP-D) exhibits distinct antiviral activity against IAV as compared to human SP-D (hSP-D), mainly due to key residues in the lectin domain of pSP-D that contribute to its profound neutralizing activity. These observations provided the basis for the design of a full-length recombinant mutant form of hSP-D, designated as “improved SP-D” (iSP-D). Inspired by pSP-D, the lectin domain of iSP-D has 5 amino acids replaced (Asp324Asn, Asp330Asn, Val251Glu, Lys287Gln, Glu289Lys) and 3 amino acids inserted (326Gly-Ser-Ser). Characterization of iSP-D revealed no major differences in protein assembly and saccharide binding selectivity as compared to hSP-D. However, hemagglutination inhibition measurements showed that iSP-D expressed strongly enhanced activity compared to hSP-D against 31 different IAV strains tested, including (pandemic) IAVs that were resistant for neutralization by hSP-D. Furthermore, iSP-D showed increased viral aggregation and enhanced protection of MDCK cells against infection by IAV. Importantly, prophylactic or therapeutic application of iSP-D decreased weight loss and reduced viral lung titers in a murine model of IAV infection using a clinical isolate of H1N1pdm09 virus. These studies demonstrate the potential of iSP-D as a novel human-based antiviral inhalation drug that may provide immediate protection against or recovery from respiratory (pandemic) IAV infections in humans

Detection of SARS-CoV-2 in Air and on Surfaces in Rooms of Infected Nursing Home Residents

There is an ongoing debate on airborne transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a risk factor for infection. In this study, the level of SARS-CoV-2 in air and on surfaces of SARS-CoV-2 infected nursing home residents was assessed to gain insight in potential transmission routes. During outbreaks, air samples were collected using three different active and one passive air sampling technique in rooms of infected patients. Oropharyngeal swabs (OPS) of the residents and dry surface swabs were collected. Additionally, longitudinal passive air samples were collected during a period of 4 months in common areas of the wards. Presence of SARS-CoV-2 RNA was determined using RT-qPCR, targeting the RdRp- and E-genes. OPS, samples of two active air samplers and surface swabs with Ct-value ≤35 were tested for the presence of infectious virus by cell culture. In total, 360 air and 319 surface samples from patient rooms and common areas were collected. In rooms of 10 residents with detected SARS-CoV-2 RNA in OPS, SARS-CoV-2 RNA was detected in 93 of 184 collected environmental samples (50.5%) (lowest Ct 29.5), substantially more than in the rooms of residents with negative OPS on the day of environmental sampling (n = 2) (3.6%). SARS-CoV-2 RNA was most frequently present in the larger particle size fractions [>4 μm 60% (6/10); 1-4 μm 50% (5/10); <1 μm 20% (2/10)] (Fischer exact test P = 0.076). The highest proportion of RNA-positive air samples on room level was found with a filtration-based sampler 80% (8/10) and the cyclone-based sampler 70% (7/10), and impingement-based sampler 50% (5/10). SARS-CoV-2 RNA was detected in 10 out of 12 (83%) passive air samples in patient rooms. Both high-touch and low-touch surfaces contained SARS-CoV-2 genome in rooms of residents with positive OPS [high 38% (21/55); low 50% (22/44)]. In one active air sample, infectious virus in vitro was detected. In conclusion, SARS-CoV-2 is frequently detected in air and on surfaces in the immediate surroundings of room-isolated COVID-19 patients, providing evidence of environmental contamination. The environmental contamination of SARS-CoV-2 and infectious aerosols confirm the potential for transmission via air up to several meters

Verbetering door isolatie: Na-isolatie aan de binnenzijde van bestaande woningen

Het doel van dit afstudeeronderzoek is het verkrijgen van inzicht in het ontwerpen van isolatie aan de binnenzijde van verschillende bestaande woningen, rekening houdend met de eisen aan het isolatiepakket en de veranderingen in temperatuurverloop en vochthuishouding die het aanbrengen van het isolatiepakket met zich meebrengen. Woningbouwcorporatie Stadgenoot heeft op dit moment veel woningen die een energielabel E zouden krijgen. Het doel van de corporatie is om de woningvoorraad binnen een beperkt aantal jaren ingrijpend te verbeteren. Dit heeft zowel een gunstig effect op de energieprestatie van de woning als de verhuurbaarheid en levensduur. Het na-isoleren van de woningen is in dit opzicht een goede mogelijkheid, echter brengt dit problemen met zich mee. De twee belangrijkste problemen zijn dat de ruimte die nodig is voor de isolatie van het woningoppervlak af zal gaan en dat door de veranderingen in warmte- en vochtverloop vochtproblemen, waaronder schimmelvorming, kunnen plaats vinden. Om de gevolgen van de binnengevelisolatie te onderzoeken is een computermodel in COMSOL ontwikkeld waarbij delen van verschillende gebouwen onderzocht kunnen worden. Verschillende isolatiematerialen zijn daarbij toegepast om zodoende een goede vergelijking te kunnen maken en om de keuze voor een bepaald isolatiemateriaal te onderbouwen. Door het analyseren van de resultaten van dit drie dimensionale model kunnen oplossingen met een klein en groot risico op vochtproblemen worden uitgelicht. Van de resultaten uit het model is een aantal tabellen gemaakt waarin verschillende oplossingen worden vergeleken. Omdat het materiaal en de isolatiewaarde niet de enige punten zijn die tot een beslissing voor een bepaalde oplossing leiden zijn ook de kosten, de werkelijke energiebesparing, de kosten en moeilijkheden bij aanbrengen en de kosten voor het milieu in de tabellen verwerkt.Design and ConsrtuctionCivil Engineering and Geoscience

Rijksbeleid brengt risico's met zich mee voor natuur en landschap

Het huidige kabinet voert een aantal belangrijke wijzigingen door in het rijksnatuur- en landschapsbeleid. Om welke wijzigen gaat het en wat mag van deze verschuivingen verwacht worden voor natuur en landschap? Deze bijdrage vanuit het Natuurplanbureau is gebaseerd op de Natuurbalans 200

The case of Rotterdam

This book is one of the outcomes of the DIVERCITIES project. It focuses on the question of how to create social cohesion, social mobility and economic performance in today’s hyperdiversified cities. The project’s central hypothesis is that urban diversity is an asset; it can inspire creativity, innovation and make cities more liveable and harmonious. To ensure a more intelligent use of diversity’s potential, a re-thinking of public policies and governance models is needed. Headed by Utrecht University in the Netherlands, DIVERCITIES is a collaborative research project comprising 14 European teams. DIVERCITIES is financed by the European Commission under the 7th Framework Programme (Project No. 319970). There are 14 books in this series, one for each case study city. The cities are: Antwerp, Athens, Budapest, Copenhagen, Istanbul, Leipzig, London, Milan, Paris, Rotterdam, Tallinn, Toronto, Warsaw and Zurich. This book is concerned with Rotterdam. The texts in this book are based on a number of previously published DIVERCITIES reports