Production of influenza virus-like particles by insect cells and removal of baculovirus from virus-like particles and other extracellular vesicles

Enveloped virus-like particles (eVLPs) are a complementary strategy for the manufacturing of vaccines against enveloped viruses. The baculovirus expression vector system (BEVS) in insect cells is an attractive and widely used platform for the expression of eVLPs. Inherent to this system is the co-expression of baculoviruses and other extracellular vesicles, which we could nicely demonstrate by high resolution electron microscopy on one of our expression supernatants (Figure 1). Such heterogenous sample mixtures pose a major bottleneck for effective downstream processing of insect cell-expressed enveloped virus-like particles. eVLPs, baculoviruses and extracellular vesicles are similar in size and share a lot of common surface properties which make chromatographic separation difficult. In addition, immune responses against baculoviruses have been reported in humans, therefore efficient removal is mandatory. Please click Download on the upper right corner to see the full abstract

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058

Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays

Aims To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without acute myocardial infarction (AMI). Methods and results In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays [Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays. Conclusion Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value (ClinicalTrials.gov number, NCT00470587

Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays

Aims We sought to examine the diagnostic and prognostic utility of sensitive cardiac troponin (cTn) assays in patients with pre-existing coronary artery disease (CAD). Methods and results We conducted a multicentre study to examine the diagnostic accuracy of one high-sensitive and two sensitive cTn assays in 1098 consecutive patients presenting with symptoms suggestive of acute myocardial infarction (AMI), of whom 401 (37%) had pre-existing CAD. Measurements of Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, Abbott-Architect cTnI and the standard assay (Roche cTnT) were performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the final diagnosis in 19% of CAD patients. Among patients with diagnoses other than AMI, baseline cTn levels were elevated above the 99th percentile with Roche hs-cTnT in 40%, with Siemens TnI-Ultra in 15%, and Abbott-Architect cTnI in 13% of them. In patients with pre-existing CAD, the diagnostic accuracy at presentation, quantified by the area under the receiver operator characteristic curve (AUC), was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.92; Siemens cTnI-Ultra, 0.94; and Abbott-Architect cTnI, 0.93 vs. AUC for the standard assay, 0.87; P < 0.01 for all comparisons). Elevated levels of cTn measured with the sensitive assays predicted mortality irrespective of pre-existing CAD, age, sex, and cardiovascular risk factors. Conclusion Sensitive cTn assays have high-diagnostic accuracy also in CAD patients. Mild elevations are common in non-AMI patients and test-specific optimal cut-off levels tend to be higher in CAD patients than in patients without history of CAD. Sensitive cTn assays also retain prognostic value. (ClinicalTrials.gov number, NCT00470587

Platelet-derived serotonin links vascular disease and tissue fibrosis

Blocking 5-HT2B receptor provides a therapeutic target for fibrotic diseases caused by activated platelet release of serotonin during vascular damage

Gravitational clustering of relic neutrinos and implications for their detection

We study the gravitational clustering of big bang relic neutrinos onto existing cold dark matter (CDM) and baryonic structures within the flat $\Lambda$CDM model, using both numerical simulations and a semi-analytical linear technique, with the aim of understanding the neutrinos' clustering properties for direct detection purposes. In a comparative analysis, we find that the linear technique systematically underestimates the amount of clustering for a wide range of CDM halo and neutrino masses. This invalidates earlier claims of the technique's applicability. We then compute the exact phase space distribution of relic neutrinos in our neighbourhood at Earth, and estimate the large scale neutrino density contrasts within the local Greisen--Zatsepin--Kuzmin zone. With these findings, we discuss the implications of gravitational neutrino clustering for scattering-based detection methods, ranging from flux detection via Cavendish-type torsion balances, to target detection using accelerator beams and cosmic rays. For emission spectroscopy via resonant annihilation of extremely energetic cosmic neutrinos on the relic neutrino background, we give new estimates for the expected enhancement in the event rates in the direction of the Virgo cluster.Comment: 38 pages, 8 embedded figures, iopart.cls; v2: references added, minor changes in text, to appear in JCA

Two-Year Progress of Pilot Research Activities in Teaching Digital Thinking Project (TDT)

This article presents a progress report from the last two years of the Teaching Digital Thinking (TDT) project. This project aims to implement new concepts, didactic methods, and teaching formats for sustainable digital transformation in Austrian Universities’ curricula by introducing new digital competencies. By equipping students and teachers with 21st-century digital competencies, partner universities can contribute to solving global challenges and organizing pilot projects. In line with the overall project aims, this article presents the ongoing digital transformation activities, courses, and research in the project, which have been carried out by the five partner universities since 2020, and briefly discusses the results. This article presents a summary of the research and educational activities carried out within two parts: complementary research and pilot projects

Postdemokratie und Citizenship. Tagungsbericht

Inwiefern nehmen StaatsbürgerInnen ihr demokratisches Recht auf Gestaltung ihres Lebens wahr und können realpolitisch ihr eigenes Leben und damit auch gesellschaftliche Strukturen mitgestalten? Was heißt, politisch verantwortlich zu handeln, und wo bzw. wie beginnt politisches Handeln überhaupt? Sind wir bereits an die Grenzen der Demokratie gestoßen? Colin Crouch zufolge haben wir die demokratischen Grenzen bereits überschritten und befinden wir uns in einer postdemokratischen Zeit, in der die politischen Verhandlungen hinter verschlossenen Türen stattfinden und Wahlen eher fadenscheinig abgehalten werden - es eben nicht mehr die StaatsbürgerInnen sind, von denen das Recht ausgeht, obzwar im ersten Artikel der Österreichischen Bundesverfassung steht: "Österreich ist eine demokratische Republik. Ihr Recht geht vom Volk aus". In diesem Spannungsfeld zwischen Demokratie, Postdemokratie und ihrem Verhältnis zu StaatsbürgerInnen bewegten sich die in diesem Beitrag vorgestellten Vorträge, Workshops und Diskussionen der Tagung "Postdemokratie und Citizenship" am Bundesinstitut für Erwachsenenbildung in Strobl 2010. (DIPF/Orig.)To what extent do citizens exercise their democratic right to shape their lives and are they able to realistically contribute to the shaping of their own lives and thus also of social structures? What does it mean to act in a politically responsible way and where and how does political action start after all? Have we already reached the limits of democracy? According to Colin Crouch, we have already gone beyond the limits of democracy and find ourselves in a post-democratic time in which political negotiations take place behind closed doors and elections are held in a rather spurious manner. Thus it is no longer the citizens from whom legislative power originates, even though Article 1 of the Austrian Federal Constitution says: “Austria is a democratic republic. Legislative power is in the hands of the people.” This conference report presents the tension between democracy, post-democracy and their relationship to citizens that provides the backdrop for the lectures, workshops and discussions given at the conference “Post-democracy and Citizenship” at the Austrian Federal Institute of Adult Education in Strobl in 2010. (DIPF/Orig.