15,202 research outputs found

    Ideograph: A Language for Expressing and Manipulating Structured Data

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    We introduce Ideograph, a language for expressing and manipulating structured data. Its types describe kinds of structures, such as natural numbers, lists, multisets, binary trees, syntax trees with variable binding, directed multigraphs, and relational databases. Fully normalized terms of a type correspond exactly to members of the structure, analogous to a Church-encoding. Moreover, definable operations over these structures are guaranteed to respect the structures' equivalences. In this paper, we give the syntax and semantics of the non-polymorphic subset of Ideograph, and we demonstrate how it can represent and manipulate several interesting structures.Comment: In Proceedings TERMGRAPH 2022, arXiv:2303.1421

    Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021

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    É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio

    Exploring Potential Domains of Agroecological Transformation in the United States

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    There is now substantial evidence that agroecology constitutes a necessary pathway towards socially just and ecologically resilient agrifood systems. In the United States, however, agroecology remains relegated to the margins of research and policy spaces. This dissertation explores three potential domains of agroecological transformation in the US. Domains of transformation are sites of contestation in which agroecology interfaces with the industrial agrifood system; these material and conceptual spaces may point to important pathways for scaling agroecology. To explore this concept, I examine formal agroecology education (Chapter 1), extension services and statewide discourses around soil health (Chapter 2), and models of farmland access not based on private property (Chapter 3). While these constitute three distinct topics, I seek to demonstrate that they are linked by similar forces that enable and constrain the extent to which these domains can be sites of agroecological transformation. First, I use case study methodology to explore the evolution of an advanced undergraduate agroecology course at the University of Vermont. I examine how course content and pedagogy align with a transformative framing of agroecology as inherently transdisciplinary, participatory, action-oriented, and political. I find that student-centered pedagogies and experiential education on farms successfully promote transformative learning whereby students shift their understanding of agrifood systems and their role(s) within them. In my second chapter, I zoom out to consider soil health discourses amongst farmers and extension professionals in Vermont. Using co-created mental models and participatory analysis, I find that a singular notion of soil health based on biological, chemical, and physical properties fails to capture the diverse ways in which farmers and extension professionals understand soil health. I advocate for a principles-based approach to soil health that includes social factors and may provide a valuable heuristic for mobilizing knowledge towards agroecology transition pathways. My third chapter, conducted in collaboration with the national non-profit organization Agrarian Trust, considers equitable farmland access. Through semi-structured interviews with 13 farmers and growers across the US, I explore both farmer motivations for engaging with alternative land access models (ALAMs) and the potential role(s) these models may play within broader transformation processes. I argue that ALAMs constitute material and conceptual ‘third spaces’ within which the private property regime is challenged and new identities and language around land ownership can emerge; as such, ALAMs may facilitate a (re)imagining of land-based social-ecological relationships. I conclude the dissertation by identifying conceptual and practical linkages across the domains explored in Chapters 1-3. I pay particular attention to processes that challenge neoliberal logics, enact plural ways of knowing, and prefigure just futures. In considering these concepts, I apply an expansive notion of pedagogy to explore how processes of teaching and (un)learning can contribute to cultivating foundational capacities for transition processes

    OLIG2 neural progenitor cell development and fate in Down syndrome

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    Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21) and is the most common genetic form of intellectual disability. It is unknown precisely how triplication of HSA21 results in the intellectual disability, but it is thought that the global transcriptional dysregulation caused by trisomy 21 perturbs multiple aspects of neurodevelopment that cumulatively contribute to its etiology. While the characteristics associated with DS can arise from any of the genes triplicated on HSA21, in this work we focus on oligodendrocyte transcription factor 2 (OLIG2). The progeny of neural progenitor cells (NPCs) expressing OLIG2 are likely to be involved in many of the cellular changes underlying the intellectual disability in DS. To explore the fate of OLIG2+ neural progenitors, we took advantage of two distinct models of DS, the Ts65Dn mouse model and induced pluripotent stem cells (iPSCs) derived from individuals with DS. Our results from these two systems identified multiple perturbations in development in the cellular progeny of OLIG2+ NPCs. In Ts65Dn, we identified alterations in neurons and glia derived from the OLIG2 expressing progenitor domain in the ventral spinal cord. There were significant differences in the number of motor neurons and interneurons present in the trisomic lumbar spinal cord depending on age of the animal pointing both to a neurodevelopment and a neurodegeneration phenotype in the Ts65Dn mice. Of particular note, we identified changes in oligodendrocyte (OL) maturation in the trisomic mice that are dependent on spatial location and developmental origin. In the dorsal corticospinal tract, there were significantly fewer mature OLs in the trisomic mice, and in the lateral funiculus we observed the opposite phenotype with more mature OLs being present in the trisomic animals. We then transitioned our studies into iPSCs where we were able to pattern OLIG2+ NPCs to either a spinal cord-like or a brain-like identity and study the OL lineage that differentiated from each progenitor pool. Similar to the region-specific dysregulation found in the Ts65Dn spinal cord, we identified perturbations in trisomic OLs that were dependent on whether the NPCs had been patterned to a brain-like or spinal cord-like fate. In the spinal cord-like NPCs, there was no difference in the proportion of cells expressing either OLIG2 or NKX2.2, the two transcription factors whose co-expression is essential for OL differentiation. Conversely, in the brain-like NPCs, there was a significant increase in OLIG2+ cells in the trisomic culture and a decrease in NKX2.2 mRNA expression. We identified a sonic hedgehog (SHH) signaling based mechanism underlying these changes in OLIG2 and NKX2.2 expression in the brain-like NPCs and normalized the proportion of trisomic cells expressing the transcription factors to euploid levels by modulating the activity of the SHH pathway. Finally, we continued the differentiation of the brain-like and spinal cord-like NPCs to committed OL precursor cells (OPCs) and allowed them to mature. We identified an increase in OPC production in the spinal cord-like trisomic culture which was not present in the brain-like OPCs. Conversely, we identified a maturation deficit in the brain-like trisomic OLs that was not present in the spinal cord-like OPCs. These results underscore the importance of regional patterning in characterizing changes in cell differentiation and fate in DS. Together, the findings presented in this work contribute to the understanding of the cellular and molecular etiology of the intellectual disability in DS and in particular the contribution of cells differentiated from OLIG2+ progenitors

    Lift EVERY Voice and Sing: An Intersectional Qualitative Study Examining the Experiences of Lesbian, Gay, Bisexual, and Queer Faculty and Administrators at Historically Black Colleges and Universities

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    While there is minimal literature that address the experiences of lesbian, gay, bisexual, and trans* identified students at Historically Black Colleges and Universities (HBCUs), the experiences of Black, queer faculty and administrators at HBCUs has not been studied. This intersectional qualitative research study focused on the experiences of lesbian, gay, bisexual, and queer identified faculty and administrators who work at HBCUs. By investigating the intersections of religion, race, gender, and sexuality within a predominantly Black institution, this study aims to enhance diversity, equity, and inclusion efforts at HBCUs by sharing the experiences of the LGBQ faculty and administrators that previously or currently work at an HBCU as a full-time employee. The research questions that guided this study were 1) How have LGBQ faculty and staff negotiated/navigated their careers at HBCUs? and 2) How do LGBQ faculty and staff at HBCUs influence cultural (relating to LGBQ inclusion) change at the organizational level? The main theoretical framework used was intersectionality and it shaped the chosen methodology and methods. The Politics of Respectability was the second theoretical framework used to describe the intra-racial tensions within the Black/African American community. The study included 60-120 minute interviews with 12 participants. Using intersectionality as a guide, the data were coded and utilized for thematic analysis. Then, an ethnodramatic performance engages readers. The goals of this study were to encourage policy changes, promote inclusivity for LGBQ employees at HBCUs, and provide an expansion to the body of literature in the field pertaining to the experiences of LGBQ faculty and administrators in higher education

    Toward Optimization of Medical Therapies with a Little Help from Knowledge Management

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    This chapter emphasizes the importance of identifying and managing knowledge from Informally Structured Domains, especially in the medical field, where very short and repeated serial measurements are often present. This information is made up of attributes of both patients and their treatments that influence their state of health and usually includes measurements of various parameters taken at different times during the duration of treatment and usually after the application of the therapeutic resource. The chapter communicates the use of the KDSM methodology through a case study and the importance of paying attention to the characteristics of the domain to perform appropriate knowledge management in the domain

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    Healthcare Innovation Absenteeism: The Rise of Physician Entrepreneurs & Medical Startups

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    For years, warning signs have illuminated imminent days of reckoning for stalled healthcare innovation across the dynamic American healthcare landscape. An evolving epic battle for healthcare innovation delivery has silently raged and set arena stages throughout the healthcare industry. Urgent innovative healthcare delivery is needed to ameliorate longstanding points of failures in providing healthcare delivery to society. Historically, the science of medicine has fostered cultural practices of innovation absenteeism and resistance to change. Mired by archaic processes, legacy systems, and fractionally useful equipment, our current healthcare ecosystems are unsustainable. Recently, some unhindered frontline physicians opted to take on a portion of critical healthcare challenges and followed their ideas to leverage clinical expertise and drive the agenda for changing healthcare innovation delivery. Our qualitative multi-case study design centered around empirical evidence that answered the research question: How do physician entrepreneurs navigate decision-making strategies for medical startups from ideation, innovation, to commercialization of new medical products and services? We examined 21 cases of physician founded medical startups to understand particularizations around physician entrepreneurship. Findings suggest three contributions towards knowledge accumulation about physician entrepreneurs and medical startups: exclusive decision-making processes, industry-specific insights, and illuminations of physician voices that might not otherwise be heard
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