This paper examines the relationship between Corporate Social Responsibility (CSR) effortsand sporting success in attracting and retaining sponsors with a focus on the Swedish footballclub Helsingborgs IF (HIF). In 2022, Helsingborgs IF was relegated from Allsvenskan(swedish top-flight football) to Superettan (swedish second tier league) and faces a newexternal situation in relation to competition, attractiveness and commercial development inthe coming season (2023). Thus, it was considered of significant relevance to study theassociation's stakeholder and customer relations - in particular linked to the sponsors'continued willingness to support the organisation in light of HIF´s CSR work.Thus, the main aspiration of our thesis is to determine the extent to which HIF`s CSR workcan supersede on-field performance in sponsorship endeavours. Through qualitative researchmethods, including interviews with a spokesperson from HIF and their sponsors, our findingsindicate that HIF's CSR initiatives positively add to their relationships with their sponsors.Furthermore, the paper concludes that sponsors generally express a favourable attitudetoward CSR activities and do not consider sporting achievements as a central aspect for acontinued sponsorship.However, through our analysis it was shown that a handful of the sponsors chose to withdrawtheir sponsorship following the team's demotion from Allsvenskan in the previous season.This indicates that CSR alone may not suffice as a means of attracting and retaining sponsors,and sporting success still holds significance for some sponsors.Future research on this subject could broaden the sample to include sponsors who terminatedtheir collaboration with HIF after the demotion, providing a more comprehensiveunderstanding of the club's ability to attract and retain sponsors. Overall, this study shedslight on the complex interplay between CSR, sporting success, and sponsorship within HIF.The findings emphasise the importance of striking a balance between CSR efforts and onfieldperformance to effectively engage and retain sponsors in the highly competitive sportsindustry.

The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism, the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia and after incubation with DMOG by Western blot. This could be related to functional effects like an impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects of hydroxylase inhibition on functional changes.

No description available.

Avec plus de 100 milliards de globules rouges produits chaque jour, le lignage érythroïde présente la plus grande capacité de production cellulaire chez le mammifère adulte. Cette production requiert une balance fine entre la prolifération cellulaire, régulée principalement par la voie de signalisation érythropoïétine (Epo)/PI3K/Akt, et la différenciation érythroïde induite par le couple de facteurs de transcription GATA-1/FOG-1. Des interconnexions entre ces deux grands systèmes ont été décrites dans le laboratoire : 1) le facteur de transcription GATA-1 est phosphorylé par Akt en réponse à l’Epo et cette phosphorylation semble avoir un rôle dans la différenciation érythroïde ; 2) GATA-1 est capable d’interagir avec la protéine du rétinoblastome pRb, impliquée dans la régulation du cycle cellulaire, et le complexe formé est nécessaire à l’érythropoïèse terminale.L'objectif de ma thèse était d’étudier les mécanismes moléculaires impliqués dans la balance prolifération/différenciation cellulaire au cours de l’érythropoïèse, et en particulier de déterminer le rôle moléculaire et physiologique de la phosphorylation de GATA-1 par Akt en réponse à l’Epo. Nos travaux ont montré que cette phosphorylation est une des clefs de la dynamique de l’érythropoïèse. Dans sa forme non phosphorylée, GATA-1 ralentit le cycle cellulaire via le complexe GATA-1/pRb/E2F. Cette étape préliminaire est nécessaire à la mise en place de la différenciation érythroïde terminale. La phosphorylation de GATA-1 induit d’une part la dissociation de GATA-1/pRb/E2F favorisant l’expansion cellulaire, et d’autre part la formation du complexe GATA-1/FOG-1 nécessaire à l’activation des gènes érythroïdes. Ce modèle apporte une explication moléculaire au blocage de la différenciation érythroïde terminale induite par le mutant GATA-1V205G qui n’interagit pas avec FOG-1. Ainsi, la phosphorylation constitutive de GATA-1V205G et l’augmentation de la quantité relative de FOG-1 permettent de restaurer la différenciation érythroïde induite par ce mutant in vitro. Enfin, l’étude d’un modèle murin exprimant une protéine GATA-1 non phosphorylable par Akt montre l’apparition d’une anémie létale lorsque la voie IGF-1 est inhibée. Cela démontre l’importance de la dynamique moléculaire induite par la phosphorylation de GATA-1, et met en évidence le rôle majeur de l’IGF-1 dans l’érythropoïèse in vivo.En conclusion, nous proposons un nouveau modèle moléculaire de la régulation de la balance prolifération/différenciation érythroïde dans lequel la phosphorylation de GATA-1 par Akt coordonne la distribution de GATA-1 dans deux complexes protéiques fonctionnels différents : GATA-1/pRb/E2F versus GATA-1/FOG-1. Nous mettons également en évidence l’IGF-1 comme acteur central de la compensation mise en place in vivo pour pallier à l’absence de phosphorylation de GATA-1. / With more than 100 billion red blood cells generated every day, the erythroid lineage has the largest output of cell production in adult mammals. This production requires a tight balance between cell proliferation, mainly controlled by erythropoietin (Epo)/PI3K/Akt signaling pathway, and erythroid differentiation induced by GATA-1 and FOG-1 transcription factors. Various links between these two processes have been previously demonstrated in the laboratory: 1) Epo-activated Akt directly phosphorylates GATA-1 transcription factors, and this phosphorylation seems to be involved in erythroid differentiation; 2) GATA-1 binds to the cell cycle regulator retinoblastoma protein (pRb), and the resulting complex is essential for terminal erythropoiesis.We investigated the molecular mechanisms involved in the cell proliferation/differentiation balance during terminal erythropoiesis; in particular, we studied the molecular and physiological role of Epo-induced GATA-1 phosphorylation. Our findings suggest that this phosphorylation is one of the key processes in erythropoiesis dynamics. In its unphosphorylated form, GATA-1 can break cell cycle progression via GATA-1/pRb/E2F complex. This preliminary step is necessary for terminal erythroid differentiation. GATA-1 phosphorylation promotes GATA-1/pRb/E2F dissociation, allowing cell cycle progression, and GATA-1/FOG-1 binding, necessary to activate erythroid genes. Our model provides a molecular explanation for the arrest of terminal erythroid differentiation observed in the non-FOG-1-binding mutant GATA-1V205G. We show that the constitutive phosphorylation of GATA-1V205G and the increase of FOG-1 protein amount rescue erythroid differentiation in vitro. Finally, knock-in expression of unphosphorylatable GATA-1 in mice leads to lethal anemia when the IGF-1 signaling pathway is inhibited. This shows the importance of the molecular dynamics of GATA-1 phosphorylation, and highlights the major role of IGF-1 in erythropoiesis, in vivo.In conclusion, we propose a new molecular model for the control of the balance between proliferation and erythroid differentiation. GATA-1 phosphorylation by Akt coordinates the involvement of GATA-1 in two different functional protein complexes: GATA-1/pRb/E2F and GATA-1/FOG-1. We also highlight the major role of IGF-1 in compensating for the lack of GATA-1 phosphorylation in vivo.

Interferon regulatory factor 1 (IRF-1), the founding member of IRF family, is a nuclear transcription factor first described as a transcription factor that binds to the upstream region of interferon induced genes following viral infection. In addition, IRF-1 has been reported to be involved in cell growth regulation, induction of apoptosis, immune responses, post-transcriptional modification, and cell transformation by oncogenes. Thus, IRF-1 shows accumulative evidence supporting the theory that IRF-1 functions as a tumour suppressor. However, we still lack the knowledge in the regulation and function behind IRF-1 and many other tumour suppressors due to the lack of synthetic tools that can aid in understanding the mechanism of cancer biology. Here we described the creation of synthetic tools that can be applied to study the role of a transcription factor(s) in cancer biology. Firstly, we described the creation, using recombineering technology, of universal bacterial artificial chromosome (BAC) targeting vector. This targeting vector, carry a cre-conditioned STOP cassette that can be targeted at a desired specific area. The resulted targeting vector can aid the generation of mice models with a conditioned knock-in subtle mutation(s). The resulted cre-conditioned mice models are an essential tool for any outstanding research project in cancer biology. Secondly, we described the development of Flp-In System™ from Invitrogen; the system can ease the generation of isogenic stable mammalian expression cell lines. Using this system, we created two isogenic stable cell lines expressing wild-type IRF-1 and a mutant that abolish IRF-1 DNA binding ability (W11R). Both cell lines were investigated using microarray analysis revealing new IRF-1 target genes. We reported the up-regulation of expected standard interferon regulatory genes such as, interleukin-24 (IL-24) and interferon regulatory factor-2 binding protein-2 (IRF2BP2) and the up-regulation of standard apoptotic genes such as, early growth response-1 (EGR-1) and prostate transmembrane protein, androgen induced-1 (PMEPA1) confirming the role of IRF-1 as a tumour suppressor. However, we also reported the up-regulation of secreted phosphoprotein-1 (SPP1) and SH3 and PX domains-2A (SH3PXD2A) which are matricellular protein produced by cancer cells playing a role in cellular adhesion, invasion, tumour growth progression and metastasis. Thus, we proposed a new biological role of IRF-1 in cellular movement. Thirdly, we described the development of a synthetic stable reporter cell line which can report IRF-1 transcriptional activity; such reporter cell line can be used once large scale screening is needed. The created stable reporter cell line was used to screen a kinase inhibitor library which has revealed C3 as an IRF-1 modifier. The newly identified IRF-1 modifier regulates IRF-1 transcriptional activity by inhibiting platelet-derived growth factor receptor (PDGFR) and/or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase. Finally, we validated the synthetic Flp-In System™ by testing the system using a novel oncoprotein model. We have developed a stable cell line that overexpresses an oncoprotein named Anterior Gradient 2 (AGR-2). We have found that AGR-2 can attenuate IRF-1 protein levels dependent of p53. In addition, AGR-2 has been identified as a cellular survivor factor during unfolding protein response. In conclusion, this study descried the creation and the validation of synthetic tools: synthetic cassette for cre-conditioned mice creation, the Flp-In System™ for isogenic stable cell line creation, and IRF-1 reporter cell line for high throughput screening. All synthetic tools were validated and used to investigate IRF-1, a transcription factor that plays a role in cancer and immune system.

Denna studie handlar om lärares upplevelser kring sitt arbete med en dator per elev, även kallat 1:1. Många kommuner har redan klivit på det digitala tåget och forskning har pågått på området sedan 2007. Resultaten från olika studier har börjat visa sig och regeringen har slagit fast att hela den svenska skolan ska genomgå en radikal förändring där alla elever och lärare ska ha tillgång till en egen dator. Forskningsresultaten visar att den generella inställningen till 1:1 är positiv. Sollentuna kommun arbetar fullt ut med 1:1 och har uppnått bra resultat. Därför valde vi att fördjupa oss i lärarnas upplevelser kring 1:1 och kanske få veta hemligheten bakom deras arbete. Syftet med vår studie är att undersöka hur lärare upplever och implementerar 1:1 i undervisningen, samt i sitt övriga arbete. Studien omfattar sju lärare från sex grundskolor i årskurs 4-9 i Sollentuna kommun. De frågor vi arbetat kring är följande: ·         Vilka problem respektive möjligheter ser lärarna med användandet av 1:1 i undervisningen? ·         Upplever lärarna att deras lärarroll förändrats i och med införandet av 1:1 i undervisningen? ·         Skiljer sig inställningen till 1:1-undervisning bland olika grupper av lärare? ·         Hur påverkar lärarnas inställningar och uppfattningar arbetet med 1:1 i undervisningen? Våra intervjuer genomfördes och därefter bearbetades resultaten och analyserades. Vi kunde skönja två sidor av digitaliseringen, 1:1 hjälper samt 1:1 stjälper, som vi valde som tema för arbetet. Här är det viktigt att påpeka att det inte alltid var två läger av lärare med olika uppfattning, utan en och samma person kunde se stora fördelar men också stora nackdelar med 1:1.     Vad är då slutsatsen av detta arbete? Lärarna verkar, i det stora hela, enade om att datorer i undervisningen är här för att stanna. Trots enigheten slits individerna mellan 1:1:s  starka sidor och dess svaga sidor. För möjligheterna med 1:1 i undervisningen är många, men problemen finns där också och anses av flera som stora. Lärarrollen har förändrats markant och på vilket sätt den förändrats beror på vem du frågar.     Vi fann intressanta skillnader mellan de två grupper som arbetat länge inom lärarkåren och de som arbetat kortare. De som hade längre erfarenhet visade sig vara mer kritiska till 1:1 än de som hade kortare erfarenhet. Gruppen med kortare erfarenhet som lärare hade en mer positiv inställning till 1:1 och integrerade datorerna mer i sin undervisning än gruppen med längre erfarenhet.

Digitaliseringens utveckling i skolan går i takt med den teknologiska utvecklingen av det omgivande samhället. Ny och mer lättillgänglig teknologi skapar nya möjligheter för skolan. Som en följd implementerar allt fler skolor en-till-en på olika grunder. Således är studiens syfte att undersöka fem lärares uppfattningar om och förhållningssätt till en-till-en-konceptet i svenskämnet, årskurs 4–6. Vidare syftar studien att ta reda på hur undervisningen ser ut idag och vad det finns för utvecklingspotential angående en-till-en som arbetssätt. Studien tar sin utgångspunkt i det sociokulturella perspektivet och semistrukturerade intervjuer användes för att samla in studiens material samt besvara följande frågeställningar: Hur använder fem lärare i årskurs 4–6 en-till-en i svenskundervisningen? Hur upplever fem lärare i årskurs 4–6 att en-till-en påverkar sättet att undervisa i svenskämnet? Hur upplever fem lärare i årskurs 4–6 att arbetet med en-till-en i svenskundervisningen kan utvecklas? Resultatet visar att en-till-en i huvudsak används och fungerar som ersättning för den redan befintliga undervisningen, närmare bestämt som ersättning för arbetsbok, penna och papper. Vidare visar resultatet att en-till-en bidrar till en formativ, individanpassad och elevcentrerad undervisning samt att det motiverar eleverna. Slutligen framkommer det av resultatet att skolors system och plattformar eventuellt kan motarbeta digitaliseringen och att en-till-två skulle kunna vara ett alternativt arbetssätt till en-till-en. / The development of digitalization in the school is in step with the technological development of the surrounding society. New and more accessible technology creates new opportunities for the school. As a result, more and more schools are implementing one-to-one on different grounds. Thus, the aim of the study is to examine five teachers' perceptions of and approach to one-to-one in the Swedish subject. Furthermore, the study aims to find out how the teaching looks today and what there is for development potential regarding one-to-one as a way of working. The study takes its point of departure in the socio-cultural perspective and semi-structured interviews were used to collect the study material and answer the following questions: How do five teachers in grades 4-6 use one-to-one in the Swedish subject? How do five teachers in grades 4-6 experience that one-to-one affects the way in which the Swedish subject is taught? How do five teachers in grades 4-6 experience that the work on one-to-one in the Swedish subject can be developed? The result shows that one-to-one is mainly used and serves as a replacement for already existing teaching, more specifically as a replacement for workbook, pen and paper. Furthermore, the result shows that the one-to-one contributes to a formative, individualized and student-centered teaching and that it motivates the pupils. Finally, the result show that schools' systems and platforms can possibly counteract the digitization and that one-to-two could be an alternative to the one-to-one.

Thesis advisor: Diana Pullin / Thesis advisor: Vincent Cho / The existing literature regarding leadership to support technology innovation in schools is limited. This qualitative study employs a multiple case study method to explore the leadership of superintendents in five school districts that have moved toward a 1:1 learning environment. This dissertation examined how superintendents gain acceptance for large-scale technology initiatives by describing the superintendent's own use of technology and their attitude about technology. The study explored the impact a superintendent's attitude and use of technology had on the acceptance of technology initiatives. The study highlights how superintendents use technology both professionally and personally. The study results indicated that while the superintendent's attitude about mobile devices in the hands of students has a profound impact on gaining acceptance for a large-scale technology initiative, it is inconclusive if the superintendent's use of technology has such an impact. The result is an important addition to the literature including recommendations for superintendents seeking to implement a large-scale technology initiative in their district. / Thesis (EdD) — Boston College, 2014. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Leadership and Higher Education.

Le virus de la dengue (DENV) et le virus Zika (ZIKV) sont deux virus transmis par le moustique et responsables de maladies importantes chez l’Homme. En absence de vaccin et de traitements antiviraux efficaces, ces pathogènes représentent des problèmes de santé publique majeurs. Les bases moléculaires des interactions qu’établissent le DENV et ZIKV et la cellule hôte lors de l’entrée virale sont peu connues. Notre laboratoire a récemment identifié, les protéines TIM (TIM-1 et TIM-4) et TAM (Tyro3 et Axl), deux familles de récepteurs à la phosphatidylsérine (PtdSer) impliqués dans la reconnaissance et l’élimination des cellules apoptotiques par phagocytose, comme de nouveaux facteurs d’entrée du DENV. Les récepteurs TIM et TAM permettent l’infection par le DENV en interagissant avec la PtdSer associée aux virions selon un mécanisme similaire à la reconnaissance des cellules apoptotiques (mimétisme apoptotique). L’objectif général de mon travail de thèse a été d’explorer les mécanismes moléculaires et cellulaires par lesquels TIM-1 et Axl médient l’entrée des flavivirus. A l’aide de techniques d’imagerie en temps réel nous avons montré que TIM-1 et DENV sont co-internalisés et que TIM-1 joue un rôle actif dans l’entrée du DENV. Notamment, nous avons montré que deux résidus lysine présentes dans le domaine cytoplasmique de TIM-1 sont importantes pour l’ubiquitination du récepteur et pour l’endocytose du virus. La recherche de partenaires de TIM-1 par des études de spectrométrie de masse a permis d’identifier STAM, un membre du complexe ESCRT-0 impliqué dans le trafic des récepteurs ubiquitinés, comme facteur important pour l’infection. Collectivement, nos résultats suggèrent très fortement que TIM-1 est le premier récepteur bona fide caractérisé pour le DENV.Identifier les facteurs d’entrée du ZIKV représente un enjeu majeur dans la compréhension du tropisme et de la pathogénèse associée à ce virus. Nous avons montré que le récepteur Axl est essentiel pour l’entrée du ZIKV dans les cellules microgliales, les astrocytes du cerveau humain en développement ainsi que dans les fibroblastes de la peau. Nos études ont démontré un double rôle du récepteur Axl dans l’infection par ZIKV. Axl lie et permet l’internalisation des particules virales, mais aussi, contribue à l’établissement d’un environnement favorable à la réplication virale en inhibant la réponse immunitaire innée. En conclusion, ce travail a contribué à améliorer notre compréhension des mécanismes d’entrée des virus DENV et ZIKV. Nos résultats indiquent que ces deux virus exploitent plusieurs récepteurs aux phospholipides pour initier leur cycle infectieux, ce qui pourrait contribuer à l’élargissement de leur tropisme. / Dengue virus (DENV) and ZIKA virus (ZIKV) are two mosquito-borne viruses responsible for important diseases in humans. Since there is currently no vaccine neither antiviral treatment available against these human pathogens, they are two major health concerns. The molecular basis of DENV and ZIKV host cell interactions leading to virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. Our laboratory recently discovered that TIM (TIM-1 and TIM-4) and TAM (Tyro3 and Axl) proteins, two receptor families that contribute to the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, are DENV entry factors. TIM and TAM receptors mediate DENV infection by interacting with virion-associated PtdSer through a mechanism similar to the recognition and engulfment of apoptotic cells by phagocytes (viral apoptotic mimicry). The general objective of my PhD was to establish a detailed understanding of the molecular mechanisms by which TIM-1 and Axl mediated infection. Using live imaging, we demonstrated that TIM-1 and DENV are co-internalised and TIM-1 play an active role during DENV endocytosis. We showed that TIM-1 cytoplasmic domain is essential for DENV internalization, especially, we identified two lysine residues that are essential for TIM-1 ubiquitination and DENV endocytosis. Proteomic analysis of TIM-1 interacting partners identified STAM, a member of the ESCRT-0 complex involved in intracellular sorting of ubiquitinated cargos, as an essential host factor for DENV infection. Collectively our results establish TIM-1 as the first identified DENV bona fide receptor.Identifying ZIKV entry factors represents a major challenge in the understanding of ZIKV tropism and pathogenesis. We showed that Axl is responsible for ZIKV infection of microglial cells and astrocytes in the human developing brain and primary fibroblasts in human skin, suggesting an important role of this receptor during ZIKV life cycle. We also highlighted the dual role of the Axl receptor in ZIKV infection, which simultaneously promotes viral entry and dampens the innate immune response to facilitate a post entry step of the ZIKV life cycle. In conclusion, this work provided new insights in our understanding of the DENV and ZIKV entry program. Both viruses engage phospholipid receptors for their infectious entry, providing a rational to ascertain therapeutic strategies targeting virion-associated phospholipids.

In this thesis, we emphasized on fabrication and anlysis of 1/4 and 1/2 £f mode solidly mounted resonators. First, the reactive RF magnetron sputter used to deposit the highly c-axis-oriented aluminum nitride (AlN) piezoelectric films under different parameters. The various c-axis tilt angle also used it by altering the distance between substrate and target to investigate the characteristics. To accomplish the two modes of different pairs of Bragg reflector, the RF/DC sputter system is adopted alternating layers of quarter-wavelength Mo and SiO2 thin films by different sequence. Finally, depositing the highly c-axis-oriented AlN on reflectors to complete the 1/4 and 1/2 £f mode SMR. The AlN thin film achieve a very low roughness of 1.783nm under AFM measurement, the FWHM of XRD(002) peak is 3.507¢Xand SEM images also exhibit a highly oriented c-axis structure. The optimum frequency responses of 1/2 £f mode SMR is obtained with return loss of -57.23dB at 4 pairs reflectors,which for 1/4 £f mode SMR is -30.68dB at 3 pairs. The maximum electromechanical coupling coefficient (Kt2) of 1/2 £f mode SMR is 7.88%, but the quality factor (Q) of 1/4 £f mode SMR is 4231.29.