9,994 research outputs found

    Investigating neural differentiation capacity in Alzheimer’s disease iPSC-derived neural stem cells

    Get PDF
    Neurodegeneration in Alzheimer’s disease (AD) may be exacerbated by dysregulated hippocampal neurogenesis. Neural stem cells (NSC) maintain adult neurogenesis and depletion of the NSC niche has been associated with age-related cognitive decline and dementia. We hypothesise that familial AD (FAD) mutations bias NSC toward premature neural specification, reducing the stem cell niche over time and accelerating disease progression. Somatic cells derived from patients with FAD (PSEN1 A246E and PSEN1 M146L heterozygous mutations) and healthy controls were reprogrammed to generate induced pluripotent stem cells (iPSC). Pluripotency for patient and control iPSC lines was confirmed, then cells were amplified and cryopreserved as stores. iPSC were subjected to neural specification to rosette-forming SOX2+/nestin+ NSCs for comparative evaluations between FAD and age-matched controls. FAD patient and control NSC were passaged under defined steady state culture conditions to assess stem cell maintenance using quantitative molecular markers (SOX2, nestin, NeuN, MAP2 and βIII-tubulin). We observed trends towards downregulated expression of the nestin coding gene NES (p=0.051) and upregulated expression of MAP2 (p=0.16) in PSEN1 NSC compared with control NSC, indicative of a premature differentiation phenotype induced by presence of the PSEN1 mutation. Cell cycle analysis of PSEN1 NSC showed that compared with controls, a greater number of PSEN1 NSC were retained in G0/G1 phase of the cell cycle (p=0.39), fewer progressed to S-phase (p=0.11) and fewer still reached G2 phase (p=0.23), suggesting cell cycle progression may be impaired in PSEN1 NSC. Nuclear DNA fragmentation was increased (p=0.10) in FAD NSC compared with controls, indicative of elevated cell death/apoptosis. Flow cytometry-based analysis of live, nestin+ NSC and NPC indicated increased apoptosis (p=0.14) in FAD NSC compared with controls, as well as increasing levels of apoptosis (p=0.33) in FAD NSC as they specified to neural progenitor cells. Global RNA sequencing was used to identify transcriptomic changes occurring during both disease and control neural specification. GO analysis of DEGs between PSEN1 and control NSC at P3 revealed significant upregulation (FDR<0.0000259) of 5 biological processes related to transcription and gene expression as well as significant upregulation (FDR<0.000000725) of 12 molecular functions related to DNA binding and transcription factor activity. These data suggest significant changes in gene expression were occurring in PSEN1 NSC at P3 compared with control NSC at the same stage in neural specification. The number of DEGs (p<0.05) between PSEN1 and control NSC at P3 was 9.92-fold higher than the number of DEGs between PSEN1 and control NSC at P2, suggesting transcriptomic differences between PSEN1 and control NSC become more pronounced as cells specify further down the neural lineage. Gene ontology (GO) analysis of differentially expressed genes (DEGs) specific to AD neural differentiation revealed significant dysregulation (FDR p<0.05) of genes related to neurogenesis, apoptosis, cell cycle, transcriptional control, and cell growth/maintenance as PSEN1 NSC matured from P2 to P3. The number of DEGs (p<0.05) in PSEN1 neural differentiation was 4.7-fold higher than the number of DEGs seen in control neural differentiation, indicating more transcriptional changes occurred in PSEN1 NSC than in controls at the same time point in neural specification. Dysregulation of Notch signalling was specific to PSEN1 neural differentiation and Notch related DEGs significantly upregulated (p<0.05) in PSEN1 NSC at P3 compared with P2 included NCOR2, JAG2, CHAC1 and RFNG. qPCR based validation displayed significant upregulation of RFNG (p=0.04) in PSEN1 NSC at P3 compared with PSEN1 NSC at P2, and indicated a trend towards upregulation of JAG2 expression, correlating with RNA sequencing data. Data generated in this study indicate that presence of the PSEN1 mutation significantly increases the number of transcriptional changes occurring during neural differentiation. It is plausible that transcriptional changes to Notch signalling cause dysregulated neural specification and increased apoptosis in PSEN1 NSC, ultimately resulting in depletion of the NSC niche

    The American brass band movement in the twenty-first century: a study of past influences via an investigation into the future direction of performance and composition

    Get PDF
    In 1889, it was estimated that there were ten thousand brass bands across America and by the beginning of the twentieth century, that number had increased to over eighteen thousand (Hazen & Hazen, 1987). These brass bands were an integral part of American culture and one of the most commonplace musical ensembles at the time. However, by the mid-twentieth century, the number of brass bands had declined radically, presumably as a result of the concert band finding greater popularity and establishing itself as the dominant amateur ensemble. Despite this, through the continued opportunities provided by groups such as the Salvation Army and the formation of a national organisation, the North American Brass Band Association in 1983, brass bands have seen a notable resurgence in America in the last twenty-five years. This study looks to explore ways to support the growth of British-style brass bands in America through a cross-cultural study of compositional and performance techniques. The research aims to draw from historical context and idiomatic characteristics within the traditional style to assist the translation of fundamental principles to a new generation of American musicians, conductors and composers. Thus, providing an alternative approach to emulate the traditional brass band sound practices that currently exist. The core body of research presents four projects aimed at engaging and educating about the British-style brass band directly from the podium in my role as a conductor-educator. It is hoped that the outcomes from the study will address common musical and logistical considerations, as well as create resources that aid the development of new American musicians participating within the medium

    Utilitarianism and the Social Nature of Persons

    Get PDF
    This thesis defends utilitarianism: the view that as far as morality goes, one ought to choose the option which will result in the most overall well-being. Utilitarianism is widely rejected by philosophers today, largely because of a number of influential objections. In this thesis I deal with three of them. Each is found in Bernard Williams’s ‘A Critique of Utilitarianism’ (1973). The first is the Integrity Objection, an intervention that has been influential whilst being subject to a wide variety of interpretations. In Chapter Two I give my interpretation of Williams’s Integrity objection; in Chapter Three I discuss one common response to it, and in Chapters Four and Five I give my own defence of utilitarianism against it. In Chapter Six I discuss a second objection: the problem of pre-emption. This problem is also found in Williams, but has received greater attention through the work of other authors in recent years. It suggests that utilitarianism is unable to deal with some of the modern world’s most pressing moral problems, and raises an internal tension between the twin utilitarian aims of making a difference and achieving the best outcomes. In Chapter Seven I discuss a third objection: that utilitarianism is insufficiently egalitarian. I find this claim to be unwarranted, in light of recent social science and philosophy. My responses to Williams’s objections draw upon resources from the socialist tradition – in particular, that tradition’s emphasis on the importance of social connections between individuals. Socialists have often been hostile to utilitarianism, in part for socialist-inflected versions of Williams’s objections. Thus, in responding to these objections I aim to demonstrate that socialist thought contains the means to defuse not only mainstream philosophy’s rejection of utilitarianism but also its own, and thus to re-open the possibilities for a productive engagement between the two traditions

    Southern Adventist University Undergraduate Catalog 2022-2023

    Get PDF
    Southern Adventist University\u27s undergraduate catalog for the academic year 2022-2023.https://knowledge.e.southern.edu/undergrad_catalog/1121/thumbnail.jp

    Improving public policy using behavioural understanding:The behavioural insights group Rotterdam

    Get PDF

    Ferramenta, retalho ou papel de parede: a música de catálogo na criação audiovisual online

    Get PDF
    Esta tese aborda a música de catálogo (conhecida internacionalmente como stock ou library music): faixas musicais compostas especificamente para uma futura utilização em produções audiovisuais, e apresentadas em catálogos sob categorias relativas a géneros musicais, emoções, instrumentação, entre outras. Embora a clientela desta indústria musical se limitasse inicialmente a profissionais do audiovisual, com o desenvolvimento de tecnologias digitais e das plataformas de partilha de vídeo da Web 2.0 afirma-se um novo mercado composto por videógrafos amadores e semiprofissionais. A música de catálogo representa então hoje uma atividade remunerada à qual um número significativo de compositores se dedica, bem como um recurso musical presente numa quantidade importante de audiovisuais. Adotando uma perspetiva interdisciplinar que conta com a sociologia da música nos seus alicerces teórico-metodológicos, proponho identificar as especificidades definidoras da música de catálogo, procurando compreender os padrões e convenções que fazem dela um mundo artístico próprio. Para explorar esta questão, parto de uma amostra de catálogos europeus e norte-americanos ativos nos últimos vinte anos. Com base em entrevistas a compositores e utilizadores de música de catálogo, bem como na análise de materiais publicitários e didáticos online a eles dirigidos, coloco em diálogo os pontos de vista de diversos agentes que interagem com esta música ao longo da sua produção, categorização ou utilização. O cruzamento de testemunhos de compositores situados em diferentes pontos do espectro desta indústria musical revela uma experiência heterogénea e multifacetada, complexificando assim retratos simplistas que predominam sobre a música de catálogo. Destaco também a relevância de examinar a música de catálogo como resultado da ação conjunta de indivíduos que intervêm de forma decisiva nos potenciais significados de uma faixa, seja através da sua etiquetagem, da sua alteração ou da sua inserção em novos contextos audiovisuais. Atender às perspetivas destes agentes permite demonstrar a importância do propósito de funcionalidade na música de catálogo: o facto de ser desde a sua génese concebida como música funcional destinada a audiovisuais é uma particularidade que governa não só as suas características sonoras como todo o seu percurso, desde a sua composição, categorização e promoção à sua modificação e articulação com imagens. Esse estatuto assumidamente utilitário constitui uma das propriedades específicas mais centrais à música de catálogo a partir da sua emergência na primeira metade do século XX. Desde então, esta age como um repositório das tendências e estereótipos musicais que marcam a produção cinematográfica e televisiva em determinado momento. Nesse sentido, os catálogos refletem e simultaneamente reforçam associações tipificadas entre música, imagens e narrativas que integram um vocabulário cultural amplamente partilhado. Para além de discernir velhos hábitos que se mantêm na produção e uso desta música, realço também novas dinâmicas e critérios que surgiram neste mundo artístico com a expansão de formatos digitais e da Web 2.0. Salienta-se nomeadamente a procura por faixas que possam ser desmontadas e rearranjadas o mais possível. Identifico assim um entendimento crescente da música de catálogo como uma matéria-prima que se encontraria incompleta até ao momento da sua transformação por outros agentes que não os seus compositores.This thesis focuses on library music (also known as stock or production music): tracks that are specifically composed for future use in audiovisual media, and categorized in catalogues according to musical genre, mood, instrumentation, among other possibilities. Although the client base of this music industry was initially limited to professional audiovisual creators, the growth of digital technologies and of Web 2.0’s video sharing platforms fostered a new market of amateur and semiprofessional videographers. Today, library music represents a source of income for a significant number of composers, as well as a musical resource extensively used in audiovisual productions. Departing from an interdisciplinary angle that counts the sociology of music as one of its theoretical and methodological foundations, I identify the essential specificities of library music, seeking a deeper understanding of the patterns and conventions that define it as a distinct art world. To examine this question, I focus on a sample of European and North-American libraries active in the last twenty years. Drawing from interviews to library music composers and users, as well as from an analysis of online promotional and instructional materials that address them, I inquire into the perspectives of various agents who interact with library music during its production, categorisation or usage. Observing the activity of composers who engage in a wide range of practices in this industry reveals their heterogeneous and multifaceted experience, emphasizing the need to move beyond the overly simplistic image of library music that is still prevalent today. I also stress the relevance of understanding this music as resulting from the joint action of individuals who intervene decisively in the possible meanings of a track, be it with its tagging, editing or inclusion in new audiovisual contexts. Comparing the discourses and viewpoints of these agents allows us to demonstrate the vital importance of the functional purpose that underlies library music: the fact that it is from the start conceived as functional music for media governs its sonic characteristics and composition, as well as its categorisation, promotion, modification and synchronisation with images. Library music’s explicitly utilitarian status has been central to its definition since its beginnings in the first half of the twentieth century. Since then, library music has acted as a repository of musical formulas that were commonplace in film and television productions in given moments. In that respect, libraries both reflect and simultaneously reinforce stereotyped associations between music, visuals and narratives that are part of a widely shared cultural vocabulary. In addition to ascertaining old habits that endure to the present day in the production and use of library music, I also shed light on new dynamics and criteria that have emerged in this art world with the expansion of digital formats and Web 2.0. Among these, I highlight the demand for tracks that can be deconstructed and rearranged as much as possible. I thus identify a growing understanding of library music as a raw material that is considered incomplete until its transformation and use by agents other than its composers

    Sounds of Unseen Boundaries: A Digital Portfolio Dissertation of Seven Original Compositions for Data-driven Instruments

    Get PDF
    Digital Portfolio Dissertation files include: descriptive text document; README; zipped computer files; and 7 performance videos linked for streaming at this URL on University of Oregon Panopto service: https://uoregon.hosted.panopto.com/Panopto/Pages/Sessions/List.aspx#folderID=a45a8cd1-312d-45d7-9079-afbe01839275 . Archival copies of videos have been preserved by the UO Libraries.Sounds of Unseen Boundaries: A Digital Portfolio Dissertation of Seven Original Compositions for Data-driven Instruments is presented as a Digital Portfolio Dissertation of seven compositions for data-driven instruments. The entirety of the Digital Portfolio Dissertation consists of video documentation of each piece, software and score material used in performance, and a text document serving as an accompanying analytical guide to each composition and its respective data-driven instrument. This document contains definitions related to the conceptual frameworks of data-driven instruments, an analysis of the design and implementation of each instrument, data mapping strategies used, compositional structures, and issues and practices in their performance. The compositions included in this Digital Portfolio Dissertation are: unFamiliar, Within the Tallest Tree, Things Look Different Here, A Need to Be Free, A Musical Interpretation on the Findings of Voyager 2, family, friends, and Virtualability

    The Ephemeral City : Songs for the Ghost Quarters

    Get PDF
    The towers of the Stockholm skyline twine with radio transmissions, flying out over the city, drifting down through the streets and sinking into the underground telephone system below. Stockholm has buildings that have been there for centuries, but is also full of modern and contemporary architectures, all jostling for their place in parallel collective memory. In taking the city up as a subject, this artistic PhD project in music expands allegories to these architectural instruments into the world of the mechanical and the electrical. By taking up and transforming the materials of the cityscape, this project spins ephemeral cities more subtle than the colossal forces transforming the cityscape. The aim is to empower urban dwellers with another kind of ownership of their city.The materials in the project are drawn around themes of urban memory and transformation, psychogeography and the ghosts of the imagined city. There are three questions the artistic works of this project reflect on and address. The first is about the ability of city-dwellers to regain or create some sense of place, history or belonging through the power of their imaginations. The second reflects on the possibility for imagined alternatives to re-empower a sense of place for the people who encounter them. The third seeks out the points where stories, memories, or alternative futures are collective, at what point are they wholly individual, and how the interplay between them plays out in listening.There is an improvisatory practice in how we relate to urban environments: an ever-transforming inter-play between the animate and inanimate. Each individual draws phantoms of memory and imagination onto the cityscape, and this yields subtle ways people can be empowered in their surroundings. The artistic works of this project are made to illuminate those subtleties, centering around a group of compositions, improvisations, artistic collaborations and sound installations in music and sound, utilizing modular synthesizers, field recordings, pipe organs, multi-channel settings; PureData and SuperCollider programs, string ensembles with hurdy-gurdy and nyckelharpa or violin, and sound installations. This choice of instruments is as an allegory to the architecture of Stockholm. The final result is a collection of music and sound works, made to illuminate the imagined city. Taken as a whole, the works of the project create an imaginary city–The Ephemeral City–in order to argue that this evocation of ephemeral space is a way to empower urban dwellers through force of imagination, immune to the vast forces tearing through the fabric of Stockholm life by virtue of the ghostly, transitory and mercurial, as compelling to the inner eye as brick and mortar to the outer life

    Modelling, Monitoring, Control and Optimization for Complex Industrial Processes

    Get PDF
    This reprint includes 22 research papers and an editorial, collected from the Special Issue "Modelling, Monitoring, Control and Optimization for Complex Industrial Processes", highlighting recent research advances and emerging research directions in complex industrial processes. This reprint aims to promote the research field and benefit the readers from both academic communities and industrial sectors
    • …
    corecore