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The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and MontanideTM ISA61 VG (ISA61, n = 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV, n = 6), (iii) a commercial vaccine (CV, n = 6), or were injected with ISA61 alone (n = 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.

Bovine respiratory disease (BRD) is a major disease of young cattle whose etiology lies in complex interactions between pathogens and environmental and host factors. Despite a high frequency of codetection of respiratory pathogens in BRD, data on the molecular mechanisms and pathogenesis associated with viral and bacterial interactions are still limited. In this study, we investigated the effects of a coinfection with influenza D virus (IDV) and Mycoplasma bovis in cattle. Naive calves were infected by aerosol with a French IDV strain and an M. bovis strain. The combined infection shortened the incubation period, worsened the disease, and led to more severe macroscopic and microscopic lesions compared to these parameters in calves infected with only one pathogen. In addition, IDV promoted colonization of the lower respiratory tract (LRT) by M. bovis and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The gamma interferon (IFN-gamma) gene was shown to be the gene most statistically overexpressed after coinfection at 2 days postinfection (dpi) and at least until 7 dpi, which correlated with the high level of lymphocytes in the LRT. Downregulation of the PACE4 and TMPRSS2 endoprotease genes was also highlighted, being a possible reason for the faster clearance of IDV in the lungs of coinfected animals. Taken together, our coinfection model with two respiratory pathogens that when present alone induce moderate clinical signs of disease was shown to increase the severity of the disease in young cattle and a strong transcriptomic innate immune response in the LRT, especially for IFN-gamma.IMPORTANCE Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. In this study, we showed that coinfection with influenza D virus (IDV) and Mycoplasma bovis increased the severity of the respiratory disease in calves in comparison with IDV or M. bovis infection. IDV promoted M. bovis colonization of the lower respiratory tract and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The IFN-gamma gene in particular was highly overexpressed after coinfection, correlated with the disease severity, immune response, and white cell recruitment in the lungs. In conclusion, we showed that IDV facilitates coinfections within the BRD complex by modulating the local innate immune response, providing new insights into the mechanisms involved in severe respiratory diseases.

Recent studies have identified a new genus of the Orthomyxoviridae family, Influenza D virus (IDV). This virus was shown to infect farm animals including swine and cattle, and to efficiently replicate and transmit in ferrets, the animal model of choice for transmission of influenza A virus to humans. This partnering grant on IDV addressed the need for capacity building at EU level to improve the EU's scientific assessment capacity and international competitiveness. We have promoted cross‐disciplinary cooperation between the partner institutes representing six Member States (BE, FR, IT, LU, NL and SE). We have shown that the available antigen and genome test systems allow reliable influenza D diagnostics in partners laboratories, while for a few of the applied antibody testing methods adjustments are recommended. Tools were developed to study virus‐host range, with a gain of knowledge on host and tissue tropism of IDV in farm animals but also in wild life and very preliminary data was generated on human tissues. Serological results in European cattle suggest that influenza D virus is enzootic. Virus diversity is still unfolding: new virus introductions were identified, as well as new reassortants whose differential clinical impact or cross‐protection levels are still poorly understood. Considering drivers of emergence, IDV was in the top five in comparison with 29 other diseases. The main risk factors of IDV in cattle are related to the animal density, presence of respiratory clinical signs in cattle and contact rates between animals. Simplified quantitative IDV risk assessment exposure model indicated a possible infection of human by IDV through aerosols in cattle farms. Further studies are warranted to fully assess the risk of IDV for both animal and Human health in Europe.

International audience; Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected calves was analysed by tandem mass spectrometry. Proteins were semi-quantified and protein expression was validated by immunoblotting. Correlations between selected proteins and pathology, clinical signs and virus shedding were investigated. Calves with BRSV-induced disease had increased total protein concentrations and a decreased number of proteins identified in BAL. The protein profile was characterised by neutrophil activation and a reduction in identified antioxidant enzymes. The presence of neutrophils in alveolar septa, the expression level of neutrophil-related or antioxidant proteins and LZTFL1 correlated significantly with disease. Citrullinated histone 3, an indicator of extracellular traps (ETs), was only detected in non-vaccinated, BRSV-infected animals. By bringing disequilibrium in the release and detoxification of reactive oxygen species, generating ETs and causing elastine degradation, exaggerated neutrophil responses might exacerbate RSV-induced disease. Neutrophil-mitigating or antioxidant treatments should be further explored.

Syftet med denna studie var att undersöka hur lärare organiserar sin undervisning med matematiska problem. Undersökningen har gjorts med hjälp av fem observationer av undervisningstillfällen samt intervjuer med fem undervisande lärare i matematik. Resultatet från undersökningen visar att kommunikation utgör en stor del av undervisningen med matematiska problem. Lärarna skapar tillfällen till samtal och interaktion i sin undervisning genom hela problemlösningsprocessen trots att deras definition av matematiska problem skiljer sig. Gemensamt för lärarnas undervisning är att den, likt forskning, organiseras i olika faser vilket är ett begrepp som beskrivs ytterligare i bakgrunden av den här studien. Trots denna gemensamma fasindelning visar resultatet att undervisningen organiseras olika inom dessa faser, även i de fall där flera lärare har deltagit i samma typ av fortbildning inom problemlösning. Resultatet visar även att sociomatiska normer är något som påverkar lärarnas organisering av arbetet med matematiska problem samt att undervisning med matematiska problem förekommer i olika stor utsträckning. Matematik

Granskningar av skolans matematikundervisning liksom erfarenheter från min verksamhetsförlagda utbildning visar att undervisningen i matematik i stora drag kännetecknas av enskild räkning i en lärobok. Föregående visar sig trots att matematisk problemlösning har en central roll i skolans läroplan. En viktig faktor för att eleverna ska ha möjlighet att utveckla goda ämneskunskaper är den enskilde lärarens förmåga att undervisa samt lärarens kunskaper i ämnet. Syftet med denna studie är att undersöka om deltagande i fortbildning förändrar hur lärare arbetar med matematisk problemlösning tillsammans med sina elever. Den metod som har använts till studien är en systematisk litteraturstudie vilket innebär att sökningar efter vetenskaplig litteratur har gjorts i olika databaser. Det resultat som framkommit visar att oberoende av hur fortbildningen har organiserats sker en förändring i undervisningen hos de lärare som deltagit i fortbildning. Resultatet visar att majoriteten av de lärare som deltagit i fortbildning förändrar sin undervisning i matematisk problemlösning inom fyra större områden. Dessa områden är lärarnas val av problem, hur problemet introduceras för eleverna, vilket typ av kommunikation och interaktion som finns i klassrummet samt hur presentationen av olika lösningsförslag går till. Beroende på hur fortbildningen har organiserats sker denna förändring i olika stor utsträckning.

Sammanfattning Detta examensarbete, som har utförts på Scania CV (Commercial Vehicles) AB, undersöker hur de kan minimera den planerade nertiden för webbservrarna hos Scania Fleet Management System ett system som har en webbportal där kunderna kan se specik information om sina fordon. I dagsläget tas systemet ner vid systemunderhåll, vilket gör att kunderna inte har åtkomst till systemet under tiden. Intervjuer genomfördes för att få en uppfattning om hur andra företag löst liknande problem. Det undersöktes även om användningen av molntjänster skulle kunna lösa problemet och hur det skulle vara möjligt att göra uppgraderingar utan att användarnas sessioner bryts. Resultatet som framkom var att den arkitektur som rekommenderades oftast är att ha någon form av klustrad lösning med lastbalanserare för webbservrarna. Om rullande uppgraderingar används vid systemunderhåll för sådana arkitekturer kan den planerade nertiden minimeras. Om sessionstillstånden lagras i en databas eller om varje server lagrar alla sessionstillstånd kan problemet med avbrutna sessioner under uppgraderingar lösas. För Scania Fleet Management System rekommenderas driftsättningstekniken blå-grön driftsättning, som kan användas med nuvarande arkitektur även om uppgraderingarna inkluderar datamigrering. Vid användning av de övriga metoderna som tagits upp i rapporten skulle det krävas att det nns ytterligare en databas om uppgraderingen omfattar datamigrering. Abstract This report, which has been written at the company Scania CV (Commercial Vehicles) AB, examines how to minimize planned downtime due to system maintenance for the web servers at Scania Fleet Management System a system that has a web portal where customers can see specic information about their vehicles. During maintenance, the system is shut down, which means that customers cannot access the system during that time. Interviews have been carried out to understand how other companies minimize downtime during maintenance. Cloud computing services were examined as an option to minimize downtime. It was also examined how it is possible to avoid broken sessions during upgrades. Empirical data suggest that a clustered solution with a load balancer could be used with the web servers. Using rolling upgrades for such solutions, the planned downtime could be eliminated. If the session states are stored in a database or if every server store all the session states, broken sessions during upgrades could be avoided. For Scania Fleet Management System the method blue-green deployment is recommended, since the current architecture of the system can be used even if the upgrades include data migration. With the other methods presented in the report, an additional database is required if the upgrades include data migration.

Det är inte lätt för en examinator att hålla ordning på antalet arbetstimmar denne förväntas lägga på handledningstid för examensarbeten. Beroende på vilken typ av examensarbete det gäller och vilket budgetår (kalenderår) som är aktuellt kan olika regler gälla. EXIT är ett system där studierektorer kan lägga till budgetår och examinatorer. Genom att sedan specificera hur mycket arbetstid varje examinator skall lägga på handledning vid examensarbeten gör studierektorn det möjligt för examinatorerna att hålla reda på hur mycket tid de förväntas lägga på handledning och hur mycket tid de har kvar för det aktuella budgetåret. Även studenter har nytta av systemet eftersom de kan se vilka examinatorer som finns tillgängliga när de söker examensarbeten.

Det är inte lätt för en examinator att hålla ordning på antalet arbetstimmar denne förväntas lägga på handledningstid för examensarbeten. Beroende på vilken typ av examensarbete det gäller och vilket budgetår (kalenderår) som är aktuellt kan olika regler gälla. EXIT är ett system där studierektorer kan lägga till budgetår och examinatorer. Genom att sedan specificera hur mycket arbetstid varje examinator skall lägga på handledning vid examensarbeten gör studierektorn det möjligt för examinatorerna att hålla reda på hur mycket tid de förväntas lägga på handledning och hur mycket tid de har kvar för det aktuella budgetåret. Även studenter har nytta av systemet eftersom de kan se vilka examinatorer som finns tillgängliga när de söker examensarbeten.

This thesis deals with the dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (PIV-3) and bovine coronavirus (BCoV) infections in Swedish cattle herds. It also describes the development of a fluorogenic reverse transcription (fRT)-PCR for BRSV diagnosis. Furthermore, BRSV immunostimulating complexes (ISCOMs) and a commercial inactivated BRSV vaccine were evaluated in vivo in calves. By serology, high incidences of PIV-3 and BCoV, and a lower incidence of BRSV, were demonstrated in 118 herds in one area of Sweden and at a Swedish bull testing station for beef breeds. In the dairy herds, absence of these infections and bovine viral diarrhea virus (BVDV) was correlated to absence of respiratory disease, confirming the clinical importance of the viruses. There appeared to be a geographical clustering of BRSV and BCoV infected herds and infections were as common in herds that did or did not introduce new animals, indicating indirect transmission between herds. At the bull testing station, an effective spread of virus within the herd was demonstrated. BRSV was involved in a disease outbreak, emphasizing the need for effective means to prevent this infection. By testing animals prior to admission, the bull testing station was kept free from BVDV during a six-year study period. A single tube BRSV fRT-PCR was shown to be a sensitive, specific and rapid tool to detect BRSV in both naturally and experimentally infected animals. The assay required less laboratory time, had a lower risk of contamination and allowed higher sample throughput than a nested PCR with a comparable sensitivity. Accordingly, the fRT-PCR is suitable for BRSV research as well as for routine diagnostic purposes and was used in the vaccine evaluation. The immunogenicity and protection induced by BRSV-ISCOMs were evaluated and compared to those induced by a commercial vaccine (CV) in calves. An experimental BRSV challenge was used for this purpose. The ISCOMs induced rapid humoral immune responses and strong clinical and virological protection despite maternal antibodies in calves at vaccination. In contrast, calves vaccinated with the CV and control calves all shed virus and developed moderate to severe respiratory disease after challenge. Thus, BRSV-ISCOMs are promising candidates for future industrial production after further evaluation and may also be used to investigate protective immunological parameters against BRSV. The CV needs to be further evaluated in controlled field trials.