817 resultados para Music therapeutic caregiving
Resumo:
Populärkulturen har i dagens läge kommit att utgöra en allt mer viktig och central inspirationskälla för allt fler människors konstruktion av den egna religiösa identiteten även inom traditionella och institutionella kristna sammanhang. Denna avhandling belyser denna utveckling i ljuset av den finländska kristna metallmusik-kulturen - en sällsynt stark sammanblanding av protestantisk kristendom och en utpräglad och kontroversiell populärmusikform och dess kultur. Fokus riktas framför allt på hur den kristna metallmusik-kulturen blir meningsfull för sina medlemmar genom de sätt på vilka den konstrueras diskursivt, dvs. genom de sätt på vilka den representeras och talas om bland sina egna anhängare. Den diskursiva konstruktionen av den kristna metallmusik-kulturen utforskas på ett såväl bredare transnationellt som ett finländskt nationellt plan. Studien redogör även för den kristna metalmusikens och -kulturens huvudsakliga verbala, visuella och estetiska kännetecken. Uppbyggnaden och spridningen av dagens transnationella kristna metallmusik-kultur undersöks även i ljuset av det teoretiska konceptet scene. Avhandlingens centrala argument är att den kristna metallmusikscenen erbjuder sina medlemmar en mängd resurser för skapandet av ett alternativt och komplementärt religiöst uttrycksätt, religiös praxis och en alternativ kristen identitet.
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Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.
Resumo:
For the past two decades the music digitalization has been considered the most significant phenomenon in the music industry as the physical sales have been decreasing rapidly. The advancement of the digital technology and the internet have facilitated the digitalization in the music industry and affected all stages of the music value chain, namely music creation, distribution and consumption. The newly created consumer culture has led to the establishment of novel business models such as music subscriptions and à-la-carte downloads websites and live streaming. The dynamic digital environment has presented the music industry stakeholders with the challenge to adapt to the requirements of the constantly changing modern consumers’ needs and demands. The purpose of this study was to identify how music digitalization can influence change in the Finnish music industry value chain; i.e. how digitalization affects the music industry stakeholders, their functions and inter-relatedness and how the stakeholders are able to react to the changes in the industry. The study was conducted as a qualitative research based entirely on primary data in the form of semi-structured interviews with experts from different units of the Finnish music industry value chain. Since the study offers assessment of diverse viewpoints on the value chain, it further provides an integrated picture of the Finnish music industry current situation and its competitive environment. The results suggest that the music industry is currently in a turbulent stage of experimentation with new business models and digital innovations. However, at this point it is impossible to determine which business model will be approved by the consumers in the longer run. Nevertheless, the study confirmed the claim that consumption of music in its digital form is to become dominant over the traditional physical copies sales in the nearest future. As a result the music industry is becoming more user-oriented; that is the focus is shifting from music production towards artist branding and management and visibility to the audience. Furthermore, the music industry is undergoing the process of integration with other industries such as media, social networks, internet services providers and mobile phone manufacturers in order to better fulfill the consumers’ needs. The previously underrated live music and merchandising are also increasing their significance for the revenues in the stagnant music markets. Therefore, the music industry is developing at present towards becoming an integrated entertainment industry deeply penetrating every point of modern people’s leisure activities.
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Kirjallisuusarvostelu
Resumo:
Recurrent castration resistant prostate cancer remains a challenge for cancer therapies and novel treatment options in addition to current anti-androgen and mitosis inhibitors are needed. Aberrations in epigenetic enzymes and chromatin binding proteins have been linked to prostate cancer and they may form a novel class of drug targets in the future. In this thesis we systematically evaluated the epigenenome as a prostate cancer drug target. We functionally silenced 615 known and putative epigenetically active protein coding genes in prostate cancer cell lines using high throughput RNAi screening and evaluated the effects on cell proliferation, androgen receptor (AR) expression and histone patterns. Histone deacetylases (HDACs) were found to regulate AR expression. Furthermore, HDAC inhibitors reduced AR signaling and inhibited synergistically with androgen deprivation prostate cancer cell proliferation. In particular, TMPRSS2- EGR fusion gene positive prostate cancer cell lines were sensitive to combined HDAC and AR inhibition, which may partly be related to the dependency of a fusion gene induced epigenetic pathway. Histone demethylases (HDMs) were identified to regulate prostate cancer cell line proliferation. We discovered a novel histone JmjC-domain histone demethylase PHF8 to be highly expressed in high grade prostate cancers and mediate cell proliferation, migration and invasion in in vitro models. Additionally, we explored novel HDM inhibitor chemical structures using virtual screening methods. The structures best fitting to the active pocket of KDM4A were tested for enzyme inhibition and prostate cancer cell proliferation activity in vitro. In conclusion, our results show that prostate cancer may efficiently be targeted with combined AR and HDAC inhibition which is also currently being tested in clinical trials. HDMs were identified as another feasible novel drug target class. Future studies in representative animal models and development of specific inhibitors may reveal HDMs full potential in prostate cancer therapy