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A Systematic Analysis of the Concordance Between Chromatin Accessibility and Gene Expression Changes
No full textA major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genome, which are thought to correspond to transcription factor binding events. In concert with RNA-sequencing, these data in principle enable such mappings; however, few studies have looked at their concordance over short duration treatments with specific perturbations. Here, we used tandem, bulk ATAC-seq and RNA-seq measurements from MCF-7 breast carcinoma cells to systematically evaluate the concordance between changes in accessibility and changes in expression in response to retinoic acid and TGF-β. We found two classes of genes whose expression showed a significant change: those that showed some change in accessibility of nearby chromatin, and those that showed virtually no change despite strong changes in expression. The peaks associated with genes in the former group had a lower baseline accessibility prior to exposure to signal. Analysis of paired chromatin accessibility and gene expression data from distinct paths along the hematopoietic differentiation trajectory showed a much stronger correspondence, suggesting that the multifactorial biological processes associated with differentiation may lead to changes in chromatin accessibility that reflect rather than drive altered transcriptional status. Together, these results show many gene expression changes can happen independent of changes in accessibility of local chromatin in the context of a single-factor perturbation and suggest that some changes to accessibility changes may occur after changes to expression, rather than before. Furthermore, we establish the role of cell-intrinsic differences in clonal melanoma cell lines leading to a rare subpopulation of cells that demonstrate invasive behavior both in vitro and in vivo. This population is molecularly characterized by the high expression of SEMA3C, and knockout studies demonstrate that the formation of the invasives subpopulation is negatively regulated by the transcription factor NKX2.2. Overall, these results establish a role for non-genetic differences in important cancer attributes such as cellular invasion
Developing Pedagogical Content Knowledge for STEM Integration Through Data Literacy: A Case Study of High School Science Teachers
No full textIn our data-rich world, there are strong calls for greater focus on data literacy as increasingly, 21st century jobs require some level of data literacy. Data literacy is inherently STEM integration, especially when working with real-world scenarios, as it requires bringing math and technology into the science classroom to interpret and engage with authentic data. Since teachers are often trained in one specific subject, they need additional support to accomplish STEM integration. In addition to subject matter knowledge of data literacy, this support must focus on the pedagogical content knowledge (PCK) required to implement and support student learning. This study sought to add an extra treatment to an existing STEM integration PD which focused specifically on teachers’ PCK for data literacy. There is a major dearth of research on PCK for data literacy. Therefore, this study built on the limited research done on PCK for STEM integration and for statistics education to begin to develop an understanding of PCK for data literacy, an under-explored concept. This was an exploratory research multiple case study of four secondary school science teachers in an urban school district, who participated in the existing bioinformatics summer PD, then engaged in approximately 20 hours of workshop sessions focused on PCK development throughout the school year as they taught the bioinformatics unit. The initial findings show that there are unique components of PCK for data literacy that are different from those for science education. The participating teachers were able to surface their knowledge of student understanding of data and strategies for teaching with and about data to define a number of components of PCK that begin to build a framework for what PCK for data literacy might look like in a generalized form that could be used to support additional teachers seeking to growth their ability to teach with complex data. Additionally, strategies used in the extension PD, such as CoRes and video reflections were shown to offer support for teachers in their implementation of authentic data literacy in their classrooms
Algebraic And Geometric Properties Of Big Mapping Class Groups
Get PDFThis thesis investigates mapping class groups of infinite-type surfaces, also called big mapping class groups, by studying their actions on certain graphs whose vertices are arcs and curves on the underlying surface. In particular, we show that the extended mapping class group of any surface with a finite, positive number of punctures is isomorphic to the relative arc graph of that surface; that the mapping class group of any translatable surface is quasi-isometric to that surface\u27s translatable curve graph; and that the mapping class group of a sphere minus a Cantor set is quasi-isometric to that surface\u27s loop graph
Three Essays On Mental Health And Pain In The United States
Get PDFThis dissertation contains three chapters on adult mental health and pain in the contemporary United States, paying special attention to social inequalities therein. In the first chapter I use data from the 2002-2014 National Health Interview Survey Linked Mortality Files (NHIS-LMF) to explore sociodemographic differences in the intersection of physical and psychological pain (referred to as the “pain–distress nexus”) and its relationship to mortality among adults ages 25 to 64. I find the combination of both high distress and high pain is most prevalent and most strongly predictive of mortality among socioeconomically disadvantaged, non-Hispanic Whites. In the second chapter I use data from the 2015, 2017, and 2019 Behavior Risk Factor Surveillance Survey (BRFSS) to examine associations between informal caregiving and self-rated pain intensity among middle-aged and older adults with provider-diagnosed arthritis. I find that informal caregiving status is associated with higher pain intensity. Among informal caregivers, caring for a spouse/partner, providing care for 5+ years, providing care for 20+ hours/week, and helping with personal care or household tasks were all linked to higher pain intensity. Associations were stronger for male caregivers than for female caregivers. In the third chapter, I use data from the 2002-2018 National Health Interview Survey (NHIS) to examine and decompose trends in mental distress among non-Hispanic White and Black adults aged 25-44 and 45-64. I find that mental distress significantly increased over time among all groups. Steep increases in mental distress among Whites, particularly among those aged 25-44, suggest narrowing Black-White disparities over time. My decomposition analyses reveal that changes in population composition, specifically the increase in heavy alcohol use and physical pain, largely explained the increase in mental distress among Blacks, while the increase in mental distress remained largely unexplained among Whites. Together, these three chapters illustrate the intricate nature of inequalities in psychological and physical pain
Mechanical Properties Of Fibrous Network Materials
Get PDFWe discuss mechanical behavior of specific fibrous network materials, including the evolution of tension in fibrin clots, compression of pulmonary emboli, and fracture of Whatman filter paper.The first material, fibrin clots, consist of random networks of fibrin fibers. When clots form by polymerization they develop tensile pre-stresses. We construct a mathematical model for the evolution of tension in isotropic fibrin gels. As the fiber diameter grows over time, properties which depend on it, such as the stored energy per unit length of a single fiber, the force-stretch relation of a fiber, and therefore the tension in the network as a whole, also evolve over time. The second fibrous network is pulmonary emboli, which consist of random networks of fibrin fibers with fluid-filled pores and red blood cells (RBCs). Stress-strain responses of human pulmonary emboli under cyclic compression were measured, revealing that emboli exhibit hysteretic stress-strain curves characteristic of foams. We describe the hysteretic response of emboli using a model of phase transitions, in which the compressed embolus is segregated into coexisting rarefied and densified phases whose fractions change as compression progresses. Our model takes into account RBC rupture in compressed emboli and stresses due to fluid flow through their small pores. The mechanical response of emboli is shown to vary depending on their RBC content. The third fibrous network is Whatman filter paper. The effect of humidity on properties such as out-of-plane fracture toughness of Whatman filter paper is studied for a broad range of relative humidities. Crack growth is modeled using traction-separation laws, whose parameters are fitted to experiments. Additionally, a novel model is developed to capture the high peak and sudden drop in the experimental force measurement caused by the existence of an initiation region, an imperfect zone ahead of a nascent crack. The relative effect of each independent parameter is explored to better understand the humidity dependence of the traction-separation parameters. The materials studied have biological, clinical, and industrial applications, and the methods described here are also applicable to other fibrous network materials
Investigations Of Pincer Iridium Complexes For Glycerol Deoxygenation And For Alkane Dehydrogenation
Get PDFGreen chemistry is being paid increased attention with the growing awareness of the environmental impact of the chemical industry. Catalysis is important in the development of green processes as it reduces the waste that is generated and lowers the energy required. Abundant feedstocks such as natural gas or biomass can be catalytically converted to value-added chemicals. Catalysts are employed in a wide range of applications, and innovations in green catalysis are crucial to achieve sustainability. To reduce the dependency on the unsustainable petroleum feedstock, biodiesel has been recognized as an effective, sustainable alternative. During biodiesel production, by-product glycerol is generated in a large amount. Catalyst development for the deoxygenation of low-cost glycerol to value-added 1,3-propanediol is discussed in Chapter 2.Alkane dehydrogenation to olefin is energy-intensive due to the endothermic nature of the reaction. A selective, energy-efficient catalyst is essential for sustainability. Immobilization of a homogeneous catalysts on heterogeneous supports can provide active, selective catalysts with robustness and recyclability. The immobilization enables the implementation of gas-phase continuous-flow reaction design. In the flow system, the by-product H2 can be effectively removed to achieve higher TON. Chapter 3 demonstrates catalytic dehydrogenation and hydrogenation reactions by an immobilized (POCOP)Ir complex on silica. Since homogeneous (Phebox)Ir and (CCC)Ir complexes have been demonstrated to activate C-H bonds, immobilization of those complexes on silica were attempted. The synthesis of Phebox and CCC ligands with functional groups to allow immobilization to silica are outlined in Chapter 4
Fragments Of The Concrete: Ecology And Technical Media In German Romanticism
Get PDFThis dissertation investigates how German romantic speculation concerning the possibility of constructing a perpetuum mobile sheds light on the central role played by technical media in the relationship between politics, poetics, and the life sciences around 1800. Focusing on the figures of Novalis, Schelling, Goethe, and Hölderlin, the project traces the contours of a discursive shift in the romantic reception of what Immanuel Kant calls the “technic of nature,” a concept Kant employs as a heuristic device for explaining the appearance of self-motivated activity in nature. While for Kant, this term refers to the ways internal forms of human cognition lead the observer to perceive a distinction between the autotelic activity of organic life and events determined by mechanical causality, for Kant’s romantic readers, the ‘technic of nature’ comes to signify a reciprocal mode of material relationality between humans and nature that combines organic and mechanical processes. This relational, exteriorizing comportment towards the making of technical objects and natural knowledge, what the philosopher of technology Gilbert Simondon calls mechanology in his overlooked engagement with romanticism, becomes the basis for a series of thought experiments concerning perpetual motion which seek to develop a negentropic ecology of spatial relations for romantic poetics and nature philosophy
Case Studies on Social Impact Centers and Their Influence on Undergraduate Business Students to Develop an Interest in Social Change
No full textIt is a tradition at many institutions of higher education to develop civic-mindedness in their students, and they use a number of strategies to do it. As the world has become more globalized, the sense of community that is inherent in civic engagement also has expanded. Global citizenship has roots in civic engagement and describes people who have developed cross-cultural empathy and a broadened sense of their place in the world through lived experiences. Awareness, responsibility, and participation are three primary components of global citizenship. Business schools are motivated to prioritize developing global citizenship in students due to the increasing global business environment and criticism that there needs to be more done to prepare moral and ethical business leaders prepared to work in more complex global businesses and environments. Expectations from shareholders are increasing for businesses to have robust environmental, social, and governance programs, and students are becoming more interested in working for companies that are environmentally and socially responsible. Due to pressure from students and employers, social impact centers, social innovation programs, and socially responsible investment experiences in business schools are emerging as a way to engage students in experiential learning opportunities designed to build a desire to be more ethically, socially, and environmentally minded. In order for business schools to prepare undergraduate students successfully to be global citizens and ethical business leaders capable of solving the increasingly complex social and environmental problems the world is now facing, they will need to better understand how the programs they offer meet the needs of their students and increase participation. Case studies of business schools with established social impact centers that successfully have integrated social impact curricula and programs into their institution can provide a model for business schools with similar aspirations to instill a sense of global citizenship and an interest in influencing social change in their students
Regulation of the Tubulin Code in Cardiac Hypertrophy and Failure
No full textA proliferated and post-translationally modified microtubule network underlies cellular growth in cardiac hypertrophy and contributes to contractile dysfunction in heart failure. Yet how the heart achieves this modified network is poorly understood. Determining how the tubulin code – the permutations of tubulin isoforms and post-translational modifications – is rewritten upon cardiac stress may provide new targets to modulate cardiac remodeling. Further, while tubulin can autoregulate its own expression, it is unknown if autoregulation is operant in the heart or tuned in response to stress. Here I use heart failure patient samples and murine models of cardiac remodeling to interrogate transcriptional, autoregulatory, and post-translational mechanisms that contribute to microtubule network remodeling at different stages of heart disease. I find that autoregulation is operant across tubulin isoforms in the heart and leads to an apparent disconnect in tubulin mRNA and protein levels in heart failure. I also find that within 4 hours of a hypertrophic stimulus and prior to cardiac growth, microtubule detyrosination is rapidly induced to help stabilize the network. This occurs concomitant with rapid transcriptional and autoregulatory activation of specific tubulin isoforms and microtubule motors. Upon continued hypertrophic stimulation, there is an increase in post-translationally modified microtubule tracks and anterograde motors to support cardiac growth, while total tubulin content increases through progressive transcriptional and autoregulatory induction of tubulin isoforms. My work provides a new model for how the tubulin code is rapidly rewritten to establish a proliferated, stable microtubule network that drives cardiac remodeling, and provides the first evidence of tunable tubulin autoregulation during pathological progression
How a Small Scribal Error Left a Medieval Document Unprinted for 500 Years: Report from a Cataloguing Project at Copenhagen City Archives
Get PDFThis annotation describes how a small scribal error in a late medieval Danish document led to that document being left out of the later printed source edition, because the scribe’s correction of his own mistake was not recognized by the man who registered the document later on in the city archives in Copenhagen. It talks about how this sealed the fate that the document remained unknown and unpublished until a registration project at Copenhagen City Archives rediscovered and redated it in 2017 finally resulting in the making of the first-ever printed source edition in 2019. It also discusses the implications this has had for the intellectual knowledge of the history of Copenhagen and even for the understanding of modern cultural heritage in the streets of Copenhagen