Potent inhibitors of the MAP kinase p38

The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.     

Berechnung von Wärmespannungen mit der Methode der finiten Elemente

Einfluß von Wärmedehnungen auf das Spannungs- und Dehnungsverhalten fester Körper und Formulierung der Spannungs- und Dehnungsbeziehungen in Matrizenform für ebene und axialsymmetrische Probleme. Überprüfung der Aussagemöglichkeiten des Verfahrens anhand von Anwendungsbeispielen.     

The development of novel and selective p56lck tyrosine kinase inhibitors

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.     

Die Vorbereitung der Probenoberfläche und ihr Einfluß auf das Ergebnis der Elektronenstrahl-Mikroanalyse

Modellversuche und Untersuchungen an Zweistoffsystemen und technischen Legierungen zur Feststellung der Beeinflussung der Mikrosondenanalysen durch verschiedene Ätzverfahren. Prüfung der Anwendbarkeit von Interferenzaufdampfschichten.     

Validation of the performance of a GMO multiplex screening assay based on microarray detection

A new screening method for the detection and identification of GMO, based on the use of multiplex PCR followed by microarray, has been developed and is presented. The technology is based on the identification of quite ubiquitous GMO genetic target elements first amplified by PCR, followed by direct hybridisation of the amplicons on a predefined microarray (DualChip^® GMO, Eppendorf, Germany). The validation was performed within the framework of a European project (Co-Extra, contract no 007158) and in collaboration with 12 laboratories specialised in GMO detection. The present study reports the strategy and the results of an ISO complying validation of the method carried out through an inter-laboratory study. Sets of blind samples were provided consisting of DNA reference materials covering all the elements detectable by specific probes present on the array. The GMO concentrations varied from 1% down to 0.045%. In addition, a mixture of two GMO events (0.1% RRS diluted in 100% TOPAS19/2) was incorporated in the study to test the robustness of the assay in extreme conditions. Data were processed according to ISO 5725 standard. The method was evaluated with predefined performance criteria with respect to the EC CRL method acceptance criteria. The overall method performance met the acceptance criteria; in particular, the results showed that the method is suitable for the detection of the different target elements at 0.1% concentration of GMO with a 95% accuracy rate. This collaborative trial showed that the method can be considered as fit for the purpose of screening with respect to its intra- and inter-laboratory accuracy. The results demonstrated the validity of combining multiplex PCR with array detection as provided by the DualChip^® GMO (Eppendorf, Germany) for the screening of GMO. The results showed that the technology is robust, practical and suitable as a screening tool.     

Intramammary pressure and udder firmness during a 72-h interruption of milking to simulate dry-off,with and without feed restriction

The goal of the present study was to quantify the increase of intramammary pressure (IMP) in dry-off during an extended milking interval of 72 h. In particular, we tested the hypothesis that feed restriction (no concentrate and roughage with reduced energy) causes earlier cessation of milk secretion and a lower IMP than continued feeding of the lactational diet. In addition to repeated IMP measurements, we tested a noninvasive method that records udder firmness (UF) via external application of pressure on the udder. Two experimental groups consisted of 10 Holstein cows each, with a daily milk yield of 20 to 25 kg. The restricted group (RG) was changed to restricted feeding on the afternoon of the final milking (0 h), whereas late-lactation feeding was continued in the control group (CG). Both IMP and UF were measured before and after the final milking immediately before milking was stopped for 72 h. These measurements represented IMP and UF levels at 10 h and 0 h milking intervals, respectively. Further measurements were performed at 18, 24, 30, 36, 42, 48, and 72 h after final milking. Milk samples (2 mL) were taken through the IMP catheter at each sampling event, for analysis of somatic cell count (SCC) and serum albumin (SA). Both IMP and UF increased with time, and both parameters peaked at 30 h in CG and at 24 h in RG. The mean IMP from 18 to 72 h, compared with the 10-h IMP (normal milking interval) was higher in CG than in RG. The duration of elevated IMP and UF was prolonged in CG compared with RG (>36 h vs. 12 h). The Pearson correlation between IMP and UF was r = 0.67. Thus, the noninvasive measurement of UF is suitable to replace invasive IMP measurements. However, due to individual differences in udder shape, the correlation between UF and IMP was too low to predict exact IMP levels using UF. Both SCC (presented as logSCC) and SA increased after the final milking until the end of the experiment. The mean increase from 18 to 72 h, compared with levels immediately after final milking, was higher in CG than in RG for SCC but did not differ between treatments for SA. In conclusion, feed restriction causes a faster cessation of milk secretion and therefore limits the increase of IMP at dry-off.     

Exposure assessment of carcass disposal options in the event of a notifiable exotic animal disease: application to avian influenza virus

We present a generalized exposure assessment of 28 disposal options for poultry carcasses in the event of a highly pathogenic avian influenza (HPAI) outbreak. The analysis supports a hereto unverified disposal hierarchy for animal carcasses, placing waste processing (e.g., incineration and rendering) above controlled disposal (e.g., landfill), above uncontrolled disposal (e.g., burial on-farm). We illustrate that early stages of the disposal chain (on-farm) pose greater opportunities for exposure to hazardous agents than later stages, where agents are generally contained, wastes are treated, and residues are managed by regulated processes. In selecting carcass disposal options, practitioners are advised to consider the full range of hazards rather than focusing solely on the HPAI agent, and to give preference to technologies that (i) offer high destruction efficiencies for target pathogens; (ii) do not give rise to significant releases of other pathogenic organisms; and (iii) do not release unacceptable concentrations of toxic chemicals. The approach offers an exposure assessment perspective for carcass disposal, thus providing a risk-informed basis for contingency planning and operational intervention. The authors recognize that relevant legislation, public perception, available capacity, and cost also need to be considered when selecting disposal options in the event of HPAI.     

科帕卡格拉纳建筑 奥地利维亚纳

正科帕卡格拉纳位于新多瑙河12.5公里处,毗邻Reichsbrücke大桥。出于同旧有设计保持协调性考虑,力求能让大楼融入当地环境,迎合自身功能性需要,GERNER GERNER PLUS团队充分考虑现有周边环境,对大楼重新规划设计。新的设计突显建筑的特殊性和重要性,面向河流的立面是科帕卡格拉纳大楼最重要的部分,所以设计的重点也放在了这里。现有的城市中轴线是一个参照物,为了视觉上和氛围上形成一体化城市的感     

Characterisation of flavour compounds in Biska – a herbal spirit produced with mistletoe

Mistletoe (Viscum album) is mostly used in its herbal form owing to its content of diverse biologically active substances. In Croatia's Adriatic region, it is used for production of Biska, a strong alcoholic beverage produced by maceration of mistletoe in spirit or brandy, with or without the addition of honey. In this work, Biska was characterised by analysis of aroma compounds and physicochemical parameters and is the first study of the aroma profile of a strong alcoholic beverage produced with mistletoe. The aroma of 14 samples of Biska – five commercial and nine homemade – was analysed using GC/MS with solid‐phase microextraction. A total of 166 aroma compounds were detected. Major components were ethyl esters (medium and long chain fatty acids), fatty alcohols, isopropyl myristate, aldehyde decanal and some terpenes. The distribution of aroma compounds was evaluated by principal component analysis. Some significant differences in physicochemical properties were observed including ethanol concentration (28–44% v/v) and pH (4.4–6.5). Although the colour of Biska was light brown with greenish reflections, there were differences in chromatic parameters. The commercial samples were darker and were less transparent than homemade Biska, perhaps reflecting more extensive maceration/extraction or the addition of caramel. © 2018 The Institute of Brewing & Distilling