48670 research outputs found
Sort by
Rapid, Scalable, Amplified Rna Detection In Situ With Clampfish 2.0
No full textRNA labeling in situ has enormous potential to visualize transcripts and quantify their levels in single cells, but it remains challenging to produce high levels of signal while also enabling multiplexed detection of multiple RNA species simultaneously. Here, we describe clampFISH 2.0, a method that uses an inverted padlock design to efficiently detect and exponentially amplify signals from many RNA species at once, while also reducing time and cost compared to the prior clampFISH method. We leverage the increased throughput afforded by multiplexed signal amplification and sequential detection by demonstrating the ability to detect 10 different RNA species in over 1 million cells. We also show that clampFISH 2.0 works in tissue sections. We expect the advantages offered by clampFISH 2.0 will enable many applications in spatial transcriptomics
Our Indio-Genius Within : A Cross-Cultural Literacy Project between the Philippines and the U.S.
No full textThis dissertation research study describes and analyzes a cross-cultural literacy project that connected high school students in the Philippines and college students in the United States. The interconnected histories of the United States and the Philippines can be traced as early as the late 19th century when the Americans defeated the Spanish in 1898. This important event definitively marked the end of 300 years of Spanish colonial rule in the Philippines and ushered a new colonial rule from the Americans for the next 50 years (Francia, 2010). The relationship between the United States and Philippines brought an extreme mix of progress and devaluation and today, Filipino and Filipino Americans continue to grapple with their national and cultural identity centuries after formal colonial rule ended (Bonus & Maramba, 2013; Francia, 2010; Ocampo, 2016). Inspired by Strobel’s (2010) call to finding our “indio-genius/indigenous within,” this cross-cultural literacy project invited students and educators in the Philippines and the United States, online and in person, to critically explore the cultural, social, and educational issues that affect them. The Philippine Herald (1920), a publication written by Filipino students studying in the U.S. in the early 20th century, also inspired our in-person activities and public online project when we shared our project’s activities with a wider audience. Guided by participatory methods, indigenous data analysis methodologies (Chilisa, 2012; Louis, 2007; Yunkaporta & Moodie, 2019), and grounded in a conceptual framework of identity, counter-storytelling, community partnerships, and critical literacy and critical consciousness, our co-constructed project focused on the students’ and educators’ interactions and discussions. We used digital tools, surveys, student-generated materials, interviews, researcher memos and fieldnotes, photos, audio and video recordings throughout our cross-cultural project to facilitate our project’s goals as well as develop and maintain our relationships with each other. The key findings from this dissertation research include building rituals, indio-genius storytelling, and utilizing a relational axiology for cross-cultural partnerships. This dissertation study illustrates the ways that students and educators expanded their learning and understanding of themselves, their overseas peers, and their individual and collective legacies
Biomass Valorization Using Doped Oxides and Inverse Catalysts
No full textWith the increasing demands for sustainable energy and growing concerns of global warming, the use of biomass as a replacement for conventional petroleum has received considerable attention. Phenolic and furanic compounds derived from biomass could potentially serve as platform molecules with valuable chemical structures. However, the technologies to upgrade and utilize such molecules are still under development. This thesis aims to study the capabilities of oxides doped with metal-atom catalysts and metal-oxide, inverse catalysts to transform biomass platform molecules into useful chemicals, such as fuel, surfactant, and lubricants. Firstly, NbOx on Pt was found to be extremely active, selective, and stable for the direct deoxygenation of m-cresol, a model compound for phenolics. The metal-oxide overlayer was found to be the active site for the reaction while Pt itself hydrogenated the aromatic ring. This well-defined inverse catalyst structure was prepared by strong metal-support interactions (SMSI). To provide the H2 economically for the deoxygenation process, different oxides doped with isolated Co atoms were investigated for the dehydrogenation of ethane to ethylene. Atomic layer deposition (ALD) was shown to be able to synthesize the single atom structure readily, which is the active site for dehydrogenation. Lastly, aldol condensation of furfural, a furanic model compound, was investigated over the solid-base catalyst, CaO, to increase the carbon chain length. It was found that the aldol condensation rates are high when small ketones were used as the reactants. When larger ketones were used, the Cannizaro reactions could override the aldol condensation and lower the selectivity of furfural to high carbon products. The contributions from these studies should help develop catalytic processes for biomass valorization
Cosmology via the Sunyaev-Zeldovich Effect
No full textThe study of clusters of galaxies is one of the most exciting and fruitful sub-fields of astronomy today; their number and distribution serve as powerful probes of the underlying cosmology, while their inner workings and structure are laboratories for astrophysics. In the Sunyaev-Zeldovich (SZ) effect photons from the Cosmic Microwave Background (CMB) inverse Compton scatter off of hot electrons in the intracluster media (ICM). The SZ effect directly probes the pressure of the ICM and is nearly redshift independent, and hence is a powerful tool for both detecting clusters and investigating their structure. Currently, CMB survey instruments are creating large, mass limited catalogs of galaxy clusters out to redshifts of ~1.75, and in the near future next generation CMB experiments will push these catalogs out to nearly a redshift of 3. Simultaneously, high resolution sub-millimeter experiments are mapping the structure of clusters, giving us insight into the astrophysics that govern these clusters and their interface to cosmology. In this thesis I detail work done in the design, integration, and testing of the Large Aperture Telescope Receiver (LATR) for the next generation CMB experiment, Simons Observatory (SO). The LATR will create field leading cluster catalogs, allowing us to test cosmology out to a redshift of 3. In particular this work will focus on simulations performed in the service of the LATR design process, as well as thermal validation tests that were done to validate the performance of the LATR. In addition, I report on the calibration of the mass-richness scaling relation for the Massive and Distant Clusters of Wise (MaDCoWS) cluster catalog using the current generation Atacama Cosmology Telescope (ACT). Finally, I report on the measurement by the MUSTANG-2 instrument of the thermodynamic state of a pair of X-ray cavities in the cluster MS 0735.6+7421 which were formed by the action of an active galactic nucleus. The mechanism of support for these cavities is not well understood, and the measurements we make of their thermodynamic state help to shed light on this topic
Single Molecule Approaches to Studying Tau Function and Dysfunction
No full textTau is an intrinsically disordered protein found mainly in neurons, composed of four main domains, the N-terminal domain, the proline rich region, the microtubule binding region, and the C-terminal domain. Tau regulates the dynamic instability of microtubules by facilitating the polymerization of tubulin. Tau is also a key component of the aggregates found in several neurodegenerative diseases collectively known as tauopathies, the most prevalent of which is Alzheimer’s disease. In this disease pathology, normally soluble tau aggregates to form insoluble neurofibrillary tangles. The presence of aggregated tau spreads from one region of the brain to another suggesting that tau propagates from cell to cell. Understanding the mechanisms by which tau interacts with microtubules and the aggregation pathway leading to the spread of disease pathology is vital for diagnosis and treatment of tauopathies. In this work, we primarily use single molecule fluorescence techniques to study three mechanisms of tau. We studied the initiation of aggregation of tau in the presence of polyphosphates, a biologically relevant polyanionic molecule. We find that the proline rich region contains multiple binding sites and contributes to the three mechanisms by which polyphosphates can initiation aggregation; a change in conformation towards a more aggregation-prone conformation, charge-screening to increase local concentrations of tau, and intermolecular crosslinking. We also studied the propagation of monomer tau between neuronal cells. We find that the proline rich region of tau has a unique ability to diffuse passively through a lipid membrane, and that tau has higher affinity to lipid membranes with more ordered structure, higher cholesterol content mimicking lipid rafts. Lastly, we investigated the effects of the R5L mutation on tau’s binding to tubulin. We find that the mutation found on the N-terminal domain of the protein doesn’t affect binding affinity to microtubules or tubulin in high molarity buffers but has a higher affinity for tau in the 3R isoform of tau in a low salt buffer. Together, this provides us with an insight into the importance of the domain dependence of tau in its functions and dysfunctions, as well as an insight into tau’s preference for binding partners
Single-Component Optogenetic Tools Fo Cytoskeletal Rearrangements
No full textThe Rho family of small GTPases coordinate actin cytoskeletal rearrangements underlying crucial cell processes including migration and mechanotransduction. Dysregulation in these signaling pathways has been associated with neurodegenerative disease and cancer. Rho GTPase signaling is tightly controlled in space and time: GTPases are activated by guanine nucleotide exchange factors (GEFs) and inactivated by GTPase accelerating proteins (GAPs) at the plasma membrane. To study Rho GTPase signaling, several optogenetic tools have been developed, most of which use light to induce a protein-protein interaction, recruiting a GTPase-activating GEF to the plasma membrane. Other optogenetic strategies involve the use of single-chain photoswitches sterically occluding a constitutively active GTPase, which can result in undesirable high dark-state activity of the tool. We sought to create single-component optogenetic tools to perturb Rho GTPase signaling at the GTPase, GEF, and GAP level, resulting in lower dark state activity and easier implementation in mammalian systems. In this work, we used BcLOV4, a fungal photoreceptor which directly binds membrane lipids in response to blue light inputs, to recruit Rho signaling proteins to the membrane, resulting in spatiotemporally precise signaling perturbation. We created BcLOV4 activation tools using the GTPase and GEF from the three best studied Rho GTPase pathways: RhoA, which induces cell contraction through stress fiber formation; Rac1, which induces sheet-like lamellipodial protrusions; and Cdc42, which induces spiky filopodial protrusions. Notably, we demonstrated that the BcLOV4 system is compatible with wildtype GTPases, resulting in lower unintended pathway activation in the dark state. We also report progress toward the creation of RhoA termination tools using GAP domains and dominant-negative GTPases, allowing for the induction of signaling activation and termination on the same optogenetic platform. Using structural knowledge we gained from Rho GTPase tool development, we created a plasmid set and cloning workflow to simplify BcLOV4 tool engineering for other signaling targets. Together, the BcLOV4 optogenetic toolbox will further the study of Rho GTPase signaling and enable others to use this technology for single-component optogenetic membrane recruitment
Defining and Aligning Expectations: A Hermeneutic Phenomenological Study of the Expectations of Professional Academic Advisors and Undergraduate Students
No full textThis dissertation investigated the expectations both professional academic advisors and undergraduate students, respectively, possessed of academic advising and of the advisor role. As students come to their postsecondary endeavors with increased needs, expectations, and consumer-mentalities, it is important to understand their expectations – and meet those expectations – to improve student satisfaction with advising (Propp & Rhodes, 2006). Given the increased use of professional academic advisors across higher education institutions, the literature does not speak to their expectations of academic advising. It is also difficult to ascertain how to best perform academic advising to meet student expectations in various contexts because there is a lack of standardization within the academic advising profession (Johnson et al., 2019). Although mass standardization is not the goal (Menke, Duslak, & McGill, 2020), academic advising should be purposefully structured based on institutional and student characteristics (Ender, Winston & Miller, 1982), the strengths of different advisor types (Allen & Smith, 2008a; Reinarz, 2000), and student needs (NACADA, 2005) and expectations (Anderson et al., 2014). Therefore, this hermeneutic phenomenological study explored students’ and professional academic advisors’ expectations of academic advising and of the advisor’s role. Through document review, semi-structured interviews, reflective journaling, and member reflections, I analyzed the lived experiences of students and advisors in order to understand how their expectations converge and diverge. Two of the main findings of the study were a.) previous experiences, in various ways, informed both advisor and student expectations, and b.) student and advisor expectations were aligned in terms of important skills for advisors to demonstrate and important outcomes of academic advising. The results of the study have future implications to inform advisor training and development, and the way in which advising is formally structured across and within various institutions to meet students’ needs and expectations of academic advising
Optical And Spin Dynamics Of Quantum Emitters In Hexagonal Boron Nitride At Room Temperature
Get PDFHexagonal boron nitride (h-BN) is a van der Waals material that hosts defect-based quantum emitters (QEs) at room temperature, providing an unparalleled platform for realizing devices for quantum technologies and studying light-matter interactions. Recent observations suggest the existence of multiple distinct defect structures responsible for QEs. Theoretical proposals suggest vacancies, substitutional atoms, and their complexes as likely defect candidates. However, experimental identification of the QEs’ electronic structure is lacking, and key details of the QEs’ charge and spin properties remain unknown. This thesis focuses on understanding the optical and spin dynamics of QEs in h-BN at room temperature. Starting with the motivation for studying quantum systems and QEs in Chapter 1, this thesis introduces QEs in h-BN in Chapter 2 and discusses its current understanding in Chapter 3. Chapter 4 discusses the materials and methods developed and utilized during the course of this thesis. Chapter 5 discusses the optical dynamics acquired using photoluminescence spectroscopy and photon emission correlation spectroscopy (PECS) and shows several QEs exhibit pure single-photon emission. It discusses the complex optical dynamics associated with excitation and relaxation through multiple electronic excited states - revealed by PECS and polarization-resolved excitation and emission. Following, it presents the optical dynamics simulations of electronic structure models that are consistent with the observations, and discusses the results in the context of ab initio theoretical calculations. Chapter 6 discusses magnetic-field-dependent PECS that can be used as a framework to probe the presence of single spins that are otherwise elusive. Following, it presents detection and confirmation of single spin using optically detected magnetic resonance. Finally, it discusses the spin dynamics and time-domain measurements acquired using optical and microwave pulse protocols crucial to developing methods to coherently control the QE’s spin. To conclude, Chapter 7 discusses the future directions that can help identify the chemical nature of QEs in h-BN and establish it as a scalable material platform for quantum technologies
Collation Model for Ms. Codex 6: Persii opera
Get PDFTwo humanist manuscripts of similar format and date bound together. Collection of the Satires of Persius (A. Persius Flaccus) on parchment, together with an unidentified commentary written in the margins around the text as well as interlinear glosses (f. 1r-14v). Also includes the Ibis of Ovid (P. Ovidius Naso) on paper, with several interlinear and marginal glosses (f. 15r-27r). Folio 32v and the inside lower cover have a number of Latin aphorisms written in a second, slightly later hand. Folios 27v-32r are blank. Written in Italy[?] in the second half of the 15th century.https://repository.upenn.edu/sims_models/1101/thumbnail.jp
A Sentiment Analysis of Influencer and Brand Instagram Comments Before and After Scandal
Get PDFBrands are turning to social media for the marketing of their products. With the rise of social media marketing came the emergence of influencers, key opinion leaders with social media followings. As influencer marketing continues to be employed by brands, their concern of being implicated in an influencer scandal grows. This study investigates the impact of scandal on social media sentiment related to the influencer and a brand they endorse. A sentiment analysis was conducted using comments made on Instagram posts of the influencer and brand shortly before and after the scandal. Results show an increase in the strength and positivity of sentiment towards the influencer post-scandal. Results also indicate that comment sentiment towards the brand post-scandal is not significantly different from pre-scandal