VictorJuiz/thesis huggingface dataset:
Biochemical and Biophysical Regulation of Cell Reprogramming

Cell reprogramming, the reverse process of differentiation, represents a major advancement in cell biology and has wide applications in regenerative medicine, drug screening and disease modeling. Induced pluripotent stem cell (iPSC) reprogramming and direct conversion are two promising approaches to manipulate cell fate. Although extensive studies have been conducted on the role of chemical methods and biomaterials in iPSC reprogramming, their effect on direct reprogramming, the process of converting a somatic cell into a distantly related cell type while avoiding a pluripotent state, have not been fully explored. In this dissertation, we demonstrate, for the first time, that small molecules that disrupt the cytoskeleton, more specifically inhibitors of cell contractility, can significantly improve the direct reprogramming of adult fibroblasts into neurons by modulating gene and protein expression. Furthermore, our findings suggest that focal adhesions and the nuclear lamina play a critical role in this direct reprogramming process. In addition to soluble chemical factors from the microenvironment, the physical microenvironment can also strongly influence cellular processes. Thus, we investigated how biophysical factors regulated induced neuronal conversion. We explored the effects of topography on this process, utilizing poly(dimethylsiloxane) (PDMS) microgrooves and electrospun nanofibrous membranes as our bioengineered substrates in conjunction with lentiviral delivery of specific neurogenic transcription factors. We unraveled that nanoscale cues, in comparison to microscale cues, were more effective at promoting induced neuronal reprogramming. The derivation of induced neuronal cells using direct reprogramming not only serves to provide a platform for neurological disease modeling but moreover, holds great promise for personalized medicine as the generation of patient-specific cells can be valuable for drug discovery and the development of new therapeutics.

Advisor: Li, Song
Triangulated Categories of Motives over fs Log Schemes

This thesis is devoted to constructing the triangulated categories of motives over fs log schemes with rational coefficients and their six operation formalism. Throughout the introduction, let $\Lambda$ be a fixed ring. For simplicity, assume also that every log scheme we deal with in the introduction is a noetherian fs log schemes over the spectrum of a fixed prime field or Dedekind domain.

Advisor: Olsson, Martin
Polynesian Subsistence, Nutrient Flows, and Long-Term Socio-Ecosystem Dynamics: Insights from Stable Isotope Analysis of the Pacific Rat (Rattus exulans) in Island Foodwebs

This dissertation applies stable carbon (δ13C) and nitrogen (δ15N) isotope analysis to archaeological specimens of the human-transported Pacific rat (Rattus exulans) to investigate prehistoric patterns of subsistence, site use, and long-term socio-ecosystem dynamics on Polynesian Islands. The Pacific rat is a small commensal species characterized by low dietary selectivity and a limited home range. Its close association with past Polynesian peoples—and ubiquity in Polynesian archaeological sites—suggests that dietary change in this species can provide insight into changing island landscapes and human subsistence regimes. Pacific rat bone collagen δ13C and δ15N values were compared across three contrastive island socio-ecosystems: Mangareva, the Marquesas, and Tikopia./nSpatiotemporal trends in Pacific rat stable isotope ratios are related to localized changes in human activity and subsistence practices, as well as global ecosystem processes which include avifaunal extinctions, resource depression, and soil nutrient cycling. On Mangareva, temporal variations in δ13C and δ15N values were assessed from three sites: the Onemea site, Taravai Island (TAR-6), Nenega-iti Rockshelter, Agakauitai Island (AGA-3), and Kitchen Cave Rockshelter, Kamaka Island (KAM-1). Declining δ15N values through time at all three Mangarevan sites reflect archipelago-wide socio-ecosystem changes related to site activity and avifaunal population declines. At the Hane dune site, Ua Huka Island (Marquesas), shifts in rat diet provide insight into changing Marquesan settlement and subsistence practices. On the Polynesian Outlier of Tikopia, a 650-year period of stability in rat bone collagen δ13C and δ15N values during the Kiki Phase (800-160 BC) suggests that mechanisms for long-term socio-ecosystem sustainability have been in place on the island for over 2000 years. These results demonstrate the capacity for stable isotope analysis of the Pacific rat to provide a new, low-impact line of evidence towards reconstructing localized patterns of site use, subsistence practices, and island ecology.

Advisor: Kirch, Patrick V
Two dogmas about demonstratives

The literature on demonstratives is largely built around two dogmas: (1) demonstratives are directly-referential and (2) demonstratives are context sensitive. (1) cannot be sustained in the face of data from English and other languages, and there are no compelling reasons for accepting (2). If we give up the dogmas and treat demonstratives as free variables that are interpreted with regard to a pragmatically-determined assignment function, we can explain a host of otherwise problematic data, and do so in a theoretically attractive way.

Advisor: MacFarlane, John
Yalcin, Seth
Polar growth and cell division in Agrobacterium tumefaciens

Agrobacterium tumefaciens is a rod-shaped gram-negative bacterium, which elongates by unipolar addition of new cell envelope material. Approaching cell division, the growth pole transitions to a non-growing old pole, and the division site creates new growth poles in sibling cells. This thesis describes experiments concerning cell division and polar growth in A. tumefaciens. The cell division proteins FtsZ-GFP and FtsA-GFP localize to the growth pole in addition to the Z-ring at the mid-cell. The A. tumefaciens homolog of the Caulobacter crescentus polar organizing protein PopZCc (PopZAt) localizes specifically to growth poles. In contrast, the A. tumefaciens homolog of the C. crescentus polar organelle development protein PodJCc (PodJAt) localizes to the old pole early in the cell cycle and accumulates at the growth pole as the cell cycle proceeds. FtsA and FtsZ also localize to the growth pole for most of the cell cycle prior to Z-ring formation. To further characterize the function of polar localizing proteins, I created a deletion of podJAt . ΔpodJAt cells display ectopic growth poles (branching), growth poles that fail to transition to an old pole, and elongated cells that fail to divide. In ΔpodJAt cells, PopZAt -GFP persists at non-transitioning growth poles post division and also localizes to ectopic growth poles, as expected for a growth pole specific factor. Even though GFP-PodJAt does not localize to the midcell in wild type, deletion of podJAt impacts localization, stability, and function of Z-rings as assayed by localization of FtsA-GFP and FtsZ-GFP. Z-ring defects are further evidenced by minicell production. Together these data indicate that PodJAt is a critical factor for polar growth, and ΔpodJAt displays a cell division phenotype. These results reveal intimate connections between polar growth and cell division in a model system displaying a novel form of cell growth.

Advisor: Zambryski, Patricia C
Characterization of Tau and Anticancer Drug Interactions with Microtubules via Cryo-Electron Microscopy Studies

Microtubules (MTs) are essential components of the eukaryotic cytoskeleton. They form by the polymerization of tubulin into cylindrical polymers composed of protofilaments. MTs are involved in a diverse array of cellular functions due to their dynamic instability, which is modulated by many factors in vivo and in vitro. Agents that modulate MT dynamics include MT associated proteins (MAPs) and naturally occurring compounds known as MT stabilizing agents (MSAs). A number of MSAs have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have used cryo-electron microscopy (cryo-EM) to study the structural basis of action of zampanolide, a taxane-binding site (TBS) MSA, as well as several proteins known to stabilize MTs, with main focus on tau. We have obtained a high-resolution (4.2 Å) cryo-EM reconstruction of microtubules stabilized by zampanolide and have compared it to Taxol, which binds to the same pocket on β-tubulin. We find that each TBS MSA has distinct structural effects on the microtubule (MT) lattice. Binding of Taxol or zampanolide both induce MT heterogeneity, but each affects the longitudinal interface differently./nTau is the prominent neuronal MAP and it has been implicated with Alzheimer disease (AD). Tau is known to bind and stabilize MTs in the axons but its binding mode and stabilizing mechanism are not well understood. Our study shows that tau binds exclusively to the external surface of MTs along protofilaments and that it remains in an extended confirmation. In addition, in the presence of kinesin, full length tau (FL-tau) dissociates from MTs allowing kinesin binding. Surprisingly, sub-stoichiometric amounts of tau result in the formation of GDP-tubulin double rings that disappear upon increasing the amounts of tau added to MTs. FL-tau and minimal 2-R or 4-R tau constructs result in the formation of sleeve-like structures around MTs, suggesting that tau binds to tubulin dimers as well as to fully polymerized MTs. Thus, we hypothesize that tau functions by oligomerizing tubulin dimers leading to a compacted MT lattice that could reinforce the interactions across the longitudinal MT interface. Furthermore, we identified amino acids on the surface of tubulin that could interact with tau. Tau binds to MTs near the C-terminus, and the sequestering of the acidic C-terminus of tubulin could contribute to the stability of MTs in the presence of tau.

Advisor: Downing, Kenneth H
Liu, Fenyong
Nickel- and Palladium-Catalyzed Cross Coupling Reactions: Reaction Development and Mechanistic Studies

The following dissertation discusses the development of a nickel catalyst for the synthesis of Csp2-Csp bonds in addition to the development and mechanistic studies of nickel and palladium catalysts for the synthesis of Csp2-N bonds./nThe first chapter is a review of the cross-coupling reactions discussed in this dissertation. Nickel and palladium will be compared with respect to physical properties and reactivity differences. The challenges associated with nickel-catalyzed cross coupling will be illustrated, while drawing analogies to analogous palladium-catalyzed reactions. The literature background for the synthesis of Csp2-Csp bonds, catalyzed by palladium and palladium/copper catalytic systems, will be reviewed, while highlighting the challenges and limitations of the field. The field of Csp2-N bond-forming reactions will be examined, as the differences in reactivity between nickel and palladium will be emphasized./nChapter 2 discusses our efforts towards the development of a nickel catalyst for the development of a Csp2-Csp bond forming reaction, performed in the absence of a copper co-catalyst./nChapter 3 describes the development of a single-component nickel complex that catalyzes the coupling of aryl chlorides with primary alkylamines. A series of mechanistic experiments, including synthesis of catalytic intermediates and kinetic experiments, were performed to elucidate the mechanism of the reaction./nChapter 4 discusses our report the palladium-catalyzed coupling of aryl halides withammonia and gaseous amines as their ammonium salts. A difference in selectivity between reactions of aryl chlorides and aryl bromides was discovered and investigated./nChapter 5 describes the development of a single-component nickel catalyst for the coupling of aryl chlorides with ammonia and ammonium sulfate to form the corresponding primary arylamines. The application of ammonium salts was extended to the coupling of gaseous amines, such as methylamine and ethylamine, which were subjected to the reaction conditions as their hydrochloride salt.

Advisor: Hartwig, John F.
Middleboxes as a Cloud Service

Today's networks do much more than merely deliver packets. Through the deployment of middleboxes, enterprise networks today provide improved security -- e.g., filtering malicious content -- and performance capabilities -- e.g., caching frequently accessed content. Although middleboxes are deployed widely in enterprises, they bring with them many challenges: they are complicated to manage, expensive, prone to failures, and challenge privacy expectations./nIn this thesis, we aim to bring the benefits of cloud computing to networking./nWe argue that middlebox services can be outsourced to cloud providers in a/nsimilar fashion to how mail, compute, and storage are today outsourced. We begin/nby presenting APLOMB, a system that allows enterprises to outsource middlebox/nprocessing to a third party cloud or ISP. For enterprise networks, APLOMB can/nreduce costs, ease management, and provide resources for scalability and/nfailover. For service providers, APLOMB offers new customers and business/nopportunities, but also presents new challenges. Middleboxes have tighter/nperformance demands than existing cloud services, and hence supporting APLOMB/nrequires redesigning software at the cloud. We re-consider classical cloud/nchallenges including fault-tolerance and privacy, showing how to implement/nmiddlebox software solutions with throughput and latency 2-4 orders of magnitude/nmore efficient than general-purpose cloud approaches. %Some of the technologies discussed in this thesis are presently being adopted by industrial systems used by cloud providers and ISPs.

Advisor: Ratnasamy, Sylvia
Favela ou Comunidade? How demarcating informal settlements from the top-down or the bottom-up can identify, address, and perpetuate health disparities

Place-based effects on health have been well-documented; however, narrow constructions of place, neighborhood and individual- as well as community-level identity hinder our ability to more fully understand the ways in which place affects health outcomes for diverse populations. Informal settlements in Rio de Janeiro (colloquially referred to as favelas) have been demarcated by local and federal government agencies with fixed boundaries for administrative purposes, including identifying areas for infrastructure improvements, renewal or removal. However, local and federal administrative boundaries often do not match each other, and the collective lived experience of residents of these favela communities tend not to be clearly bounded by those official designations./nThis dissertation sets out to address the following questions:/n1) How do administrative boundaries of informal settlements overlap, or not, with the terms and definitions used to describe these places by the people who live there?/n2) How do residents of informal settlements in Rio de Janeiro operate to either reinforce or push back against these officially designated boundaries?/n3) Do narrow constructions of place conceal demographic disparities in access to municipal infrastructure?/nIn my dissertation I first examine how informal settlements in Rio de Janeiro are places constructed by top-down institutional forces, such as administrative processes employed by the State through the national census and local government efforts to push marginalized residents into these areas, as well as removing these parts of the city entirely. Further, I examine how residents contest and reshape the boundaries of their communities, both in pushing back and challenging the official categorizations of the State, as well as embarking on their own boundary-setting practices by mapping and documenting their communities for themselves with the goal of improving community health and well-being. Through these processes of contested place-making, residents help to identify community needs and provide resources for themselves that the State has been unwilling or unable to provide. Running throughout this work is an understanding that place and identity are socially constructed and socially contested, both dynamically responding to pressure exerted by the State from the top-down and community members from the bottom-up

Advisor: Morello-Frosch, Rachel
Scottish Gaelic Clefts: Syntax, Semantics and Pragmatics

This dissertation investigates the syntax, semantics, and pragmatics of clefts in Scottish Gaelic, and represents the first in-depth look at Scottish Gaelic clefts. It also examines the Propositional Cleft. While the Propositional Cleft is acknowledged in Scottish Gaelic grammars, a thorough description and analysis has not been done. The Propositional Cleft is noteworthy for the presence of cleft morphosyntax--the copula, a pro-form, and the relative complementizer--but the absence of a clefted constituent. This lack of a clefted constituent is puzzling if the Propositional Cleft is to be included in the cleft paradigm, since it is the clefted constituent which is typically interpreted as the focus, and the interpretation of focus is typically assumed to be derived from the focus-background bipartite structure created by the cleft construction. This property of lacking a bipartite structure makes the Propositional Cleft, at first glance, an unlikely candidate for membership in the cleft paradigm. Over the course of the dissertation I describe and analyze the pragmatic effect of the Propositional Cleft, and I argue that the Propositional Cleft is in fact a member of the cleft paradigm, but that it instantiates a typologically rare combination of broad sized identificational focus. The syntactic and semantic analysis of clefts proposed here extends straightforwardly to derive the particular meaning and structure of the Propositional Cleft, and shows that broad focus is not incompatible with cleft meaning./nI argue that A-bar dependencies in Scottish Gaelic are movement based, and propose a syntactic account of focus movement in clefts which involves the checking of focus features in C by the movement of the focus phrase to its specifier. This syntactic account of focus allows us to understand the absence of movement in the Propositional Cleft, since the broad size of focus means that the focus constituent is the complement of CP, and so can check the focus features of C in situ.

Advisor: Mikkelsen, Line
Inclusive-Minded Planning for Adept Co-Teaching (IMPACT): The IMPACT Model for Improving Co-Teacher Collaboration for the Inclusive Classroom

Co-teaching is a strategy that some schools use to narrow the disparity of achievement outcomes for students with disabilities. Co-teaching is broadly defined in the research as the pairing of a general education teacher and a special education teacher (or other specialist) who deliver instruction to a general education class, which includes students with disabilities, and the instruction is presented in a manner that flexibly and deliberately meets the learning needs of all students. In this study, grounded in design and action research, I investigated an intervention designed to help co-teacher partners engage in effective co-teaching. After experiencing the intervention, the co-teacher pairs (n = 2), an English and math team at the high school level, showed strong growth in their ability to engage in productive and efficient planning routines and demonstrated moderate growth in their capacity to use a variety of co-teaching methods in the classroom. Analysis of the findings suggests that the intervention worked to increase the ability of the teams to work together within the co-teacher framework to plan and use various co-teaching methods within the classroom. The study findings also indicate that, to enhance the effectiveness of the intervention, future iterations of the intervention need design principles that will foster the ability of the co-teaching teams to connect to the educational needs of all their students and to further learning and achievement for all students.

Advisor: Mintrop, Heinrich
Goerss--Hopkins obstruction theory via model ∞-categories

We develop a theory of model ∞-categories -- that is, of model structures on ∞-categories -- which provides a robust theory of resolutions entirely native to the ∞-categorical context. Using model ∞-categories, we generalize Goerss--Hopkins obstruction theory from spectra to an arbitrary (presentably symmetric monoidal stable) ∞-category. We give a sample application of this generalized obstruction theory in the setting of motivic homotopy theory, where we construct E_∞ structures on the motivic Morava E-theories and compute their automorphism spaces (as E_∞ algebras).

Advisor: Teichner, Peter
Development and Evaluation of Real-Time Volumetric Compton Gamma-Ray Imaging

An approach to gamma-ray imaging has been developed that enables near/nreal-time volumetric (3D) imaging of unknown environments thus improving the/nutility of gamma-ray imaging for source-search and radiation mapping/napplications./nThe approach, herein dubbed scene data fusion (SDF), is based on integrating/nmobile radiation imagers with real-time tracking and scene reconstruction/nalgorithms to enable a mobile mode of operation and 3D localization of/ngamma-ray sources./nThe real-time tracking allows the imager to be moved throughout the environment/nor around a particular object of interest, obtaining the multiple perspectives/nnecessary for standoff 3D imaging./nA 3D model of the scene, provided in real-time by a simultaneous localization/nand mapping (SLAM) algorithm, can be incorporated into the image reconstruction/nreducing the reconstruction time and improving imaging performance./nThe SDF concept is demonstrated in this work with a Microsoft Kinect RGB-D/nsensor, a real-time SLAM solver, and two different mobile gamma-ray imaging/nplatforms./nThe first is a cart-based imaging platform known as the Volumetric Compton/nImager (VCI), comprising two 3D position-sensitive high purity germanium (HPGe)/ndetectors, exhibiting excellent gamma-ray imaging characteristics, but with/nlimited mobility due to the size and weight of the cart./nThe second system is the High Efficiency Multimodal Imager (HEMI) a/nhand-portable gamma-ray imager comprising 96 individual cm$^{3}$ CdZnTe/ncrystals arranged in a two-plane, active-mask configuration./nThe HEMI instrument has poorer energy and angular resolution than the VCI, but/nis truly hand-portable, allowing the SDF concept to be tested in multiple/nenvironments and for more challenging imaging scenarios./nAn iterative algorithm based on Compton kinematics is used to reconstruct/nthe gamma-ray source distribution in all three spatial dimensions./nEach of the two mobile imaging systems are used to demonstrate SDF for a/nvariety of scenarios, including general search and mapping scenarios with/nseveral point gamma-ray sources over the range of energies relevant for/nCompton imaging./nMore specific imaging scenarios are also addressed, including directed/nsearch and object interogation scenarios./nFinally, the volumetric image quality is quantitatively investigated with/nrespect to the number of Compton events acquired during a measurement, the/nlist-mode uncertainty of the Compton cone data, and the uncertainty in the/npose estimate from the real-time tracking algorithm./nSDF advances the real-world applicability of gamma-ray imaging for many/nsearch, mapping, and verification scenarios by improving the tractiblity/nof the gamma-ray image reconstruction and providing context for the 3D/nlocalization of gamma-ray sources within the environment in real-time.

Advisor: Vetter, Kai