On the plasma permeability of highly porous ceramic framework materials using polymers as marker materials

Highly porous framework materials are of large interest due to their broad potential for application, for example, as sensors or catalysts. A new approach is presented to investigate, how deep plasma species can penetrate such materials. For this purpose, a polymer (ethylene propylene diene monomere rubber) is used as marker material and covered with the porous material during plasma exposure. Water contact-angle and X-ray photoelectron spectroscopy measurements are used to identify changes in the polymer surface, originating from the interaction of plasma species with the polymer. The method is demonstrated by studying the plasma permeability of tetrapodal zinc oxide framework materials with a porosity of about 90% in an oxygen low-pressure capacitively coupled plasma. Significant differences in the penetration depth ranging from roughly 1.6–4 mm are found for different densities of the material and different treatment conditions

Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.publishedVersio

DNA translocation activity of the multifunctional replication protein ORF904 from the archaeal plasmid pRN1

The replication protein ORF904 from the plasmid pRN1 is a multifunctional enzyme with ATPase-, primase- and DNA polymerase activity. Sequence analysis suggests the presence of at least two conserved domains: an N-terminal prim/pol domain with primase and DNA polymerase activities and a C-terminal superfamily 3 helicase domain with a strong double-stranded DNA dependant ATPase activity. The exact molecular function of the helicase domain in the process of plasmid replication remains unclear. Potentially this motor protein is involved in duplex remodelling and/or origin opening at the plasmid replication origin. In support of this we found that the monomeric replication protein ORF904 forms a hexameric ring in the presence of DNA. It is able to translocate along single-stranded DNA in 3′–5′ direction as well as on double-stranded DNA. Critical residues important for ATPase activity and DNA translocation activity were identified and are in agreement with a homology model of the helicase domain. In addition we propose that a winged helix DNA-binding domain at the C-terminus of the helicase domain could assist the binding of the replication protein specifically to the replication origin

Notch Lineages and Activity in Intestinal Stem Cells Determined by a New Set of Knock-In Mice

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFPSAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues

Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma : the first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)

Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were >= 18 years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4 weeks ago. BI 2536 200-250 mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3-4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14-15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. (C) 2010 Elsevier Ltd. All rights reserved

Infrared imaging systems for wall protection in the W7-X stellarator (invited)

Wendelstein 7-X aims at quasi-steady state operation with up to 10 MW of heating power for 30 min. Power exhaust will be handled predominantly via 10 actively water cooled CFC (carbon-fiber-reinforced carbon) based divertor units designed to withstand power loads of 10 MW/m2 locally in steady state. If local loads exceed this value, a risk of local delamination of the CFC and failure of entire divertor modules arises. Infrared endoscopes to monitor all main plasma facing components are being prepared, and near real time software tools are under development to identify areas of excessive temperature rise, to distinguish them from non-critical events, and to trigger alarms. Tests with different cameras were made in the recent campaign. Long pulse operation enforces additional diagnostic design constraints: for example, the optics need to be thermally decoupled from the endoscope housing. In the upcoming experimental campaign, a graphite scraper element, in front of the island divertor throat, will be tested as a possible means to protect the divertor pumping gap edges during the transient discharge evolution