A scalable adenovirus production process, from cell culture to purified bulk

Adenovirus (AdV) vectors are commonly used in cancer gene therapy trials, evaluated in gene therapy and used as vaccines for various diseases. AdV vectors are well studied and are suitable as vaccine vectors due to their ability to infect different cell types, remain episomal and produce stable high titer material. Manufacturing of safe and efficacious clinical-grade virus relies on a scalable and cost-effective production process. In this study, we have combined experimental work and process economy calculations, from AdV production in cell culture to purified bulk product up to 10L scale. An efficient and scalable process for AdV production was developed by evaluation of each process step. The most studied vector is serotype 5, making this a suitable system for process development of AdV vectors. Human AdV5 expressing the green fluorescent protein (GFP) was used for process development. First, suspension HEK 293 cells adapted to serum-free cell culture medium were optimized for AdV production and evaluated in different single use bioreactor systems. Tween 20 was used for cell lysis as a replacement for the traditionally used Triton X-100 (now on the Authorization list (Annex XIV) of REACH, the regulation on Registration, Evaluation, Authorization and restriction of Chemicals). A residual Tween 20 assay with low detection limit was set-up. Filters and conditions for clarification, concentration and buffer exchange by tangential flow filtration were optimized. Anion exchange based capture step alternatives were compared, including different chromatography resins and membrane formats. Finally, core bead technology was evaluated as an alternative to size exclusion chromatography for the polishing step before the final formulation. Analytical methods for virus titer are challenging and depend on purity and quality of the sample. For total virus titer, qPCR and HPLC methods were used. Furthermore, a method based on surface plasmon resonance (Biacore) was developed for analysis of adenovirus titer. For infectious virus titer, we have used a cell based assay with automatic image analysis. Based on analytical data different downstream process alternatives were compared regarding load capacity, recovery and purity and we propose a robust and scalable process with a favorable process economy. Please click Additional Files below to see the full abstract

Preselection and expert advice

"The final authenticated version is available online at https://doi.org/10.1007/s00182-016-0551-9We study the effects of preselection on an expert’s advice about the execution of a project if its execution yields more precise estimates about the expert’s expertise. The in troduction of a preselection stage, in which the decision maker evaluates the project before asking for advice, alters the expert’s perception of the problem. We identify conditions under which preselection occurs in equilibrium. We show that if the expert adjusts his behavior, the option to preselect may reduce the expected utility of the decision maker.Collaborative Research Center 88

Technology in Preschools : A Study of How Preschool Teachers Work with Technology

Denna studies syfte är att belysa hur förskollärare definierar ämnet teknik och hur de arbetar med ämnet i verksamheten. Dessutom kommer de hinder förskollärarna upplever i arbetet med teknik belysas. Ursprunget till studien är våra tidigare erfarenheter, där vi upplevt att ämnet teknik inte arbetas med i större utsträckning i förskolan. Teknik är ett intressant och aktuellt ämne som är relativt nytt i förskolans läroplan och som kommer att lyftas ännu mer i den kommande läroplanen 2018. Empiri har samlats in genom sex semistrukturerade intervjuer med utbildade förskollärare. Deltagare kommer från fem olika förskolor belägna i tre olika kommuner. Resultaten som framkommit tyder på att förskollärare har skilda uppfattningar om vad0 teknik är och att ämnet upplevs som svårt av många. Detta påverkar vad som undervisas och hur undervisningen genomförs, vilket medför att barn i olika förskolor inte får samma möjligheter till en likvärdig utbildning. En likvärdig utbildning är något som ska eftersträvas enligt förskolans styrdokument. Vidare framkommer i resultatet att ett medforskande arbetssätt förespråkas av förskollärarna i studien. Detta arbetssätt framkommer dock inte i resultatet hos de flesta förskollärarna i studien när det gäller ämnet teknik. Den förförståelse och de erfarenheter vi hade med oss in i denna studie har delvis besannats, men däremot förvånades vi över att tidpunkten för när förskolläraren gick sin utbildning inte verkar ha någon betydelse

The Swedish Platform for Sustainable Work inHorizon2020: in retrospect

The nationwide Swedish advocacy platform “Sustainable work as a resource for health, innovation and growth” started in 2013 with the aims of i) identifying possible openings for the research area within Horizon 2020, ii) implementing a strategy to impact Horizon2020, and iii) to connect Swedish and European researchers.   The basis for this agenda was that although work and working conditions have a major influence on the health, wellbeing and prosperity, these aspects were lacking or extremely fragmented in Horizon2020. Since this is a strong research area in Sweden and seen as strategically important by the Social partners, it should be a Swedish priority for Horizon2020.  The initiative was funded by Vinnova, co-funded by the participating universities, and supported by the Social partners and other stakeholders.   The platform has extended the dialogue on the European research agenda within the Swedish research community, and gradually built a strategy to impact H2020. Over the years, our advocacy has also developed in interaction with the EU Agencies Eurofound and EU-OSHA, and with PEROSH. The focus has been on the pillars of Leadership and Societal Challenges (Horizon2020). The impact on the early Calls in Horizon2020 was minor, while work and working life is much more visible in the later calls, and on the agenda in the drafts for Horizon Europe (FP9). The focus will now be on making the opportunities known to Swedish researchers, and on facilitating participation in applications. &nbsp

Satuja ja kertomuksia

Onnettaren lahja / kirjoittanut Elisabeth Lundberg ; kuvittanut Lydia Skottsberg. Kuinka velhot veivät makeuden talonpojan joulujuomasta ja joululeivästä / kirjoittanut Anna Tengström ; kuvittanut Lydia Skottsberg. Maunu Ahnuri / kirjoittanut Sophie Linge ; kuvittanut E. Hedberg. Setä Yrjänä / kirjoittanut Elin Afzelius ; kuvittanut Elin Westman. Vanha rahakaappi / kirjoittanut Anna Wahlenberg ; kuvittanut Elin Westman. Hyrrä / kirjoittanut N.P. Ödman ; kuvittanut Anna Ch. Sjöberg. Kun kukko piti vieraspidot / kirjoittanut Hugo Gyllander ; kuvittanut Louis Moe. Joulukuusi / kirjoittanut Paul Nilsson ; kuvittanut Karl Aspelin. Mufti mestariluotsi ja jäälautalla purjehtija / kirjoittanut Alfred Smedberg ; kuvittanut Nils Larson. Prinsessa, joka ei tahtonut mennä naimisiin / kirjoittanut Sigrid Sköldberg-Pettersson ; kuvittanut Lisa Lindberg. Suuri joululahja / kirjoittanut Hedvig Lagerlöf ; kuvittanut Brita Ellström