VictorJuiz/thesis huggingface dataset:
Investigating the role of neurexin 2 in mouse cerebral cortical synapse development

Neurexins (Nrxns) are a family of three presynaptic transmembrane cell-adhesion proteins that are known to be involved in central nervous system synapse development. In recent years, mutations in NRXN genes have been linked to neuropsychiatric disorders such as schizophrenia and autism spectrum disorders, the pathogenesis of which appears to partly involve abnormalities in synapse development. However, because the fundamental role of Nrxns in the brain is poorly understood, it remains unclear why they are linked with these disorders. As synapse development in the mouse cerebral cortex occurs over the first several postnatal weeks, studying Nrxns during this time period may prove especially informative. The present study investigated the role of Nrxns in synapse development by creating a temporal expression map of the three NRXN genes in the mouse cerebral cortex by measuring mRNA levels. In addition, because NRXN2 is the least studied of the three NRXN genes, the present study focused on the synaptic role of NRXN2 by characterizing excitatory and inhibitory synapse development in a novel NRXN2 conditional knockout mouse model. Here, we show that NRXN2 exhibits a distinct expression pattern relative to NRXN1 and NRXN3, as measured by mRNA levels. Furthermore, blind analysis of puncta density, size, and intensity confocal microscopy images of cultured mouse cortical neurons was carried out, and revealed that knocking out NRXN2 expression in vitro results in an approximately 25% reduction in both an excitatory synapse marker and an inhibitory synapse marker, suggesting that NRXN2 is involved in regulating excitatory and inhibitory synapse density. The results from this study represent a step forward in understanding the synaptic role of NRXN2, which may eventually prove to be a useful foundation in the development of future therapies for neuropsychiatric disorders that NRXN mutations have been linked to.

Keywords:  Department of Biology
Biology
developmental neurobiology
synapse development
cell adhesion molecules
neurexin
conditional knockout mouse model
quantitative reverse transcriptase polymerase chain reaction
confocal microscopy
Thesis
Advisor: Südhof Thomas
McConnell Susan
Investigating the Significance of Anther-Enriched Phased Small RNAs Between Differing Inbred Lines of Zea mays

Maize fertility is a major topic in academic and agricultural fields. Phased small RNAs are enriched in anther tissues and are spatiotemporally dynamic. Most research conducted on phasiRNAs had been conducted in the W23 background. Through a 4X44K microarray comparison between B73 and W23 lines, high conservation of differential expression patterns and qualitative transcriptome profiles was observed. Probes corresponding to both 21-nt and 24-nt PHAS cleaved precursors hybridized to both inbreds despite being designed from B73 sequences. High similarity in expression between lines indicates shared mechanisms in underlying regulatory processes. Additionally, B73 plants were subjected to JA, PCZ and control injections; these resulted in no significant differences between anther and tassel growth. However, JA and BR-related transcripts were less conserved than all-protein coding genes in the array, possibly indicating greater sensitivity of JA response in W23 plants as compared to B73 lines.

Keywords:  Department of Biology
Biology
Plant Biology
Maize Genetics
Anthers
phasiRNA
Thesis
Advisor: Walbot Virginia
Long Sharon
Investigating the Spatial and Temporal Dynamics of Fungal Endophyte Community Structure in Quercus lobata and its Mistletoe Parasite, Phoradendron villosum

Fungal endophytes have been found in the asymptomatic tissue of every plant species analyzed to date. These cryptic and highly diverse symbionts often have profound impacts on host fitness and ecology, yet much is still unknown about the dynamics of endophyte communities. To investigate the temporal and spatial variation in foliar endophyte community structure, I collected leaf samples from a deciduous tree, Quercus lobata, and its evergreen, canopy parasite, Phoradendron villosum, over a three-month period. Using molecular sequencing data, I show that the endophyte communities of both deciduous and evergreen hosts undergo strong temporal changes in composition. Furthermore, I found that the endophyte communities of Q. lobata and P. villosum converged within a month, suggesting widespread host generalism among endophytic fungi. My results suggest that horizontal transmission between hosts is the main vector of foliar endophytic infection, supporting much of the prior research into non- clavicipitaceous endophytes. This study also aimed to investigate the hypothesis that P. villosum may serve as an endophyte reservoir for Q. lobata during leaf abscission. Preliminary data suggests that the presence of P. villosum may systemically impact the foliar endophyte communities of its canopy host, suggesting vascular transmission of fungal endophytes. This study has demonstrated the complex and dynamic nature of endophyte communities and highlights the need for future work addressing these topics.

Keywords:  Department of Biology
Biology
Fungal Ecology
Endophyte
Thesis
Advisor: Dirzo Rodolfo
Peay Kabir
Investigation of doping effects in hafnium oxide-based non-volatile resistance-change random access memory [electronic resource]

Computer memory is divided into a complex architecture: caches built on SRAM, main memory built on DRAM, and nonvolatile memory provided by flash or magnetic hard disks. Each memory technology has significant tradeoffs: SRAM and DRAM are fast and volatile, while flash is slower but nonvolatile. Although flash exhibits significantly faster random access times than its predecessor, magnetic hard drives, it is still much slower than DRAM, sometimes resulting in memory bottlenecks when loading large programs or databases into memory. The rise of data-centric computing has created a need for a new layer between DRAM and flash in the memory hierarchy, called storage class memory (SCM). Several new memory technologies, all based upon fundamentally different physical mechanisms, are competing to be used in the new SCM layer. One of the most promising technologies is resistance-change random access memory (RRAM). RRAM is capable of achieving the same bit densities as flash, but at lower power and higher speed. However, while RRAM has been a topic of intense research, device variability and retention remain major hurdles to widespread adoption. Many strategies have been used to try to improve these characteristics, and one of the most promising has been doping, but relatively few dopant materials have been investigated. In this work, the properties of hafnium dioxide (HfO2) RRAM devices are explored from a fundamental perspective using density functional theory (DFT). DFT is uniquely suited for achieving clarity on the quantum mechanical and materials aspects of RRAM operation. First, DFT is applied to hafnium dioxide (HfO2) to quantify the thermodynamic properties of HfO2 and their impact on RRAM device operation. Of particular interest is the connection of electronic and ionic processes, i.e. how charge trapping affects the formation and rupture of conductive filaments. These results can be used to add defect charge state to the phenomena that drive device switching, along with electric field and joule heating. In the second part of this work, the addition of hydrogen impurities to HfO2 is explored. Hydrogen has been experimentally found to improve HfO2 RRAM device properties, but a physical explanation for this improvement is lacking. It is found that the presence of hydrogen shifts the energetics and kinetics of HfO2 in a direction that is favorable for resistive switching. In the last part of this work, the hydrogen study is expanded into a study of all possible dopant species. Here, high-throughput DFT calculations are used to systematically quantify the properties of 50 different dopants. These calculations uncover the underlying trends that govern dopant behavior and predict which dopants will provide optimum device properties.

Keywords: Electrical Engineering.
Advisor: Nishi Yoshio
Magyari-Köpe Blanka
Wong S.
Investigation of Neuronal Nitric Oxide Synthase (nNOS) in Stroke Recovery

Our lab has recently demonstrated that optogenetic neuronal stimulation of either the ipsilesional motor cortex (iM1) or contralesional cerebellar dentate nucleus (cDN) can enhance post-stroke recovery. Interestingly, in both models neuronal stimulation downregulates mRNA expression of neuronal nitric oxide synthase (nNOS), an enzyme responsible for the production of nitric oxide (NO). Previously, activation of nNOS has been shown to worsen ischemic damage in acute stroke however, its role in stroke recovery is unclear. Here, using a mouse stroke model, we investigated the effects of pharmacological inhibition of nNOS on functional recovery after stroke. The experimental group received a pharmacological nNOS inhibitor (ARL 17477 dihydrochloride; 10 mg/kg and 1 mg/kg) daily from post-stroke day 5-14; the control group received saline. Their motor-sensory recovery was evaluated using a horizontal rotating beam test. The mice were sacrificed and brains removed for histology and western blots. Stroke mice treated with 10 mg/kg of nNOS inhibitor were found to recover significantly worse than vehicle treated mice; stroke mice treated with 1 mg/kg showed similar recovery results to vehicle treated mice. These results demonstrate a dosage-dependent negative correlation between nNOS inhibition and stroke recovery.

Keywords:  Department of Biology
Biology
Stroke
Neurosurgery
Optogenetics
Thesis
Advisor: Steinberg Gary
Gozani Or
Investigations of homogeneous ruthenium and cobalt complexes for electrocatalytic transformations [electronic resource]

Transition metal hydrides are key intermediates implicated in a wide range of chemical and electrochemical transformations. Herein, select examples of molecular transition metal hydride complexes and their applications in critical hydrogen transfer reactions, specifically transfer hydrogenation, electrocatalytic alcohol oxidation, and electrocatalytic hydrogen evolution, are presented. An octahedral Ru-hydride complex reacts rapidly and irreversibly with CO2 under ambient conditions to yield the Ru-formate. The analogous insertion of various ketones yields an equilibrium mixture of the hydride and alkoxide complexes, for which the equilibrium constants are measured by 1H NMR. Density functional theory is used to compare the mechanism of acetone and CO2 insertion. Investigations on the kinetic profile of transfer hydrogenation with the Ru-hydride complex reveal some key aspects of the mechanism. The Ru-hydride undergoes an irreversible oxidation at low potential by cyclic voltammetry. In the presence of alcohol and alkoxide base, large current enhancement is observed at this potential, consistent with electrocatalytic alcohol oxidation. The synthesis and characterization of a family of dicationic Co(III) complexes with bidentate nitrogen ligands are presented. Upon addition of protonated N, N-dimethylformamide buffer, electrocatalytic hydrogen evolution is observed at onset potentials near -1.1 V. Further studies demonstrate that these complexes decompose under acidic reducing conditions to form an active species at the electrode surface. A Co(III)-azopyridine complex exhibits a reversible 2e- reduction at very mild potentials. Chemical reduction with cobaltocene yields a neutral complex as an air stable, diamagnetic solid. Spectroscopic and crystallographic studies illuminate key structural and electronic changes that occur upon reduction, indicating that the neutral complex is best described as a highly delocalized system. Protonation of the neutral species yields a monocationic hydrazino complex. All three cleavage modes (i.e. proton, hydride, and hydrogen atom) for this ligand N-H bond are demonstrated. Studies on the stoichiometric reactivity of this complex with the triphenylcarbenium cation and TEMPO radical are explored.

Keywords: Chemistry.
Advisor: Waymouth Robert M. primary advisor. Thesis advisor
Chidsey Christopher E. D. (Christopher Elisha Dunn)
Xia Yan
Ion-pairing strategies for electrostatic control of selectivity in homogeneous catalysis [electronic resource]

Controlling the selectivity of catalytic reactions remains an enduring challenge in synthetic chemistry, limiting the utility of many known chemical transformations. Reaction selectivity is often achieved through steric and/or electronic modification of catalysts. An alternative mode of selectivity uses electrostatic interactions to differentiate between competing transition states based on their charge distributions via (de)stabilizing interactions with proximal charge. Ion pairing can be used to position a charge very close to an ionic product-determining transition state, enforcing strong electrostatic (charge--dipole) interactions. This is a mode of ion pairing-- mediated selectivity that has not previously been addressed in homogeneous catalysis. In this work, efforts to understand and exploit electrostatic interactions to achieve regioselectivity in Au(I)-catalyzed reactions are described. The Au(I)-catalyzed rearrangement of 3-substituted aryl alkynyl sulfoxides to form dihydrobenzothiepinones is examined as a model reaction. The placement of an anion near a cationic Au(I)-bound transition state is achieved through ion pairing, which is modulated by solvent dielectric. Pulsed-field gradient diffusion NMR experiments show that cationic Au(I) catalysts form strong ion pairs with their weakly coordinating counterions in low-dielectric solvents. The regioselectivity of the rearrangement increases monotonically as solvent dielectric decreases, and independent of molecular properties of the solvent. DFT calculations of putative product-determining transition states show that the magnitude of the ion pairing effect on selectivity correlates with the magnitude of the differences in dipole moments between these transition states. The strongest electrostatic effect is observed in low-dielectric solvents, and stabilizes the more polar of two competing transition states. The understanding of ion pairing and electrostatic effects garnered from studies of the model sulfoxide rearrangement reaction is used to enable the regioselective synthesis of 2H-chromenes via Au(I)-catalyzed hydroarylation of phenyl propargyl ethers. The strength of electrostatic stabilization is tuned by the choice of catalyst, counterion, substrate, and reaction solvent. Where competing product-determining transition states differ significantly in charge distribution, up to 7-fold changes in regioselectivity are achieved by electrostatic stabilization. Ion pairing acts in concert with steric effects to achieve up to 14:1 regioselectivity for 7- substituted 2H-chromenes. In sum, the results show that selectivity in homogeneous catalysis can be enabled by the control of ion pairing-induced electrostatic interactions.

Keywords: Chemistry.
Advisor: Kanan Matthew William
Burns Noah
Du Bois Justin advisor. Thesis advisor
Island bonds [electronic resource] : the civil war in Crete and the rise of mass protest in the Ottoman Empire, 1895-1912

This dissertation examines the civil war on the island of Crete during the mid-1890s that led to a major refugee crisis when tens of thousands of Cretan Muslims emigrated to Asia Minor, Syria, and North Africa. The limited scholarship on Crete has generally regarded the violence in the 1890s as a revolt instigated by Christian islanders against the Ottoman administration. By investigating this episode as a case of civil war, this dissertation differs from earlier works in that it offers a novel way of conceptualizing violence between social groups with shared cultural characteristics. In addition to presenting an account of local history, this dissertation explores the Cretan refugee crisis in its international context by discussing the policies of the European powers regarding the displaced Muslims. The story told in this dissertation ends with the discussion of the impact of the Cretan crisis in the Ottoman world. Drawing on source material from Ottoman, Greek, French, and British archives—a collection of documents which has never been combined in a study of this period—this dissertation explores social and political transformation set in motion by a sovereignty crisis over Crete between Greece and the Ottoman Empire (1908-1912). It argues that the Ottoman collapse requires a novel interpretation, one that highlights the social upheavals triggered by Crete. This dissertation offers such an appraisal through an investigation of popular rallies and the first long-lived movement of economic boycott across the Ottoman Middle East and the Balkans.

Keywords: History.
Advisor: Rodrigue Aron primary advisor. Thesis advisor
Beinin Joel
Naimark Norman M. advisor. Thesis advisor
Isotopic constraints on the marine environment and biogeochemical cycles during major periods of animal evolution and extinction [electronic resource]

The evolution of life is intricately linked to the evolution of Earth's geochemical cycles. In particular, the connections between ancient life and the biogeochemical cycles of carbon and oxygen have been intensively scrutinized because these elements are fundamental components of organic matter, determine the pathways through which organisms can obtain energy, and are critical for defining habitability. Despite this attention, significant questions remain about how the evolution of life is intertwined with environmental conditions. To this end, I analyze uranium (U) and calcium (Ca) isotopes in carbonate rocks and reconstruct two major processes that control carbon and oxygen in the ocean-atmosphere system: the degree of ocean oxygenation and variations in carbonate chemistry. These isotopic records can also constrain the carbon isotope record, the predominant tool for understanding the past carbon cycle. Here, I focus on fluctuations in marine environmental conditions during two critical time intervals in the history of animals in order to understand the primary factors governing marine biogeochemical cycles: the Cryogenian non-glacial interval (660 to 640 Ma) and the recovery from the end-Permian mass extinction (252 to 235 Ma). Combined, these studies employ non-traditional isotopic approaches to investigate how global patterns of environmental change, evolution, and extinction are related. Indeed, the results described herein emphasize that critical events in the history of animals are accompanied by dramatic variations in biogeochemical cycles and environmental conditions.

Keywords: Geological Sciences.
Advisor: Maher Katharine primary advisor. Thesis advisor
Payne Jonathan L. primary advisor. Thesis advisor
Sperling Erik advisor. Thesis advisor
Jazz in the Harlem moment [electronic resource] : performing race and place at the cotton club

As a whites-only venue in the heart of Harlem that capitalized on exotic and stereotyped conceptions of black culture, predicated on the "slumming" economy of Harlem nightlife, the Cotton Club (active 1923-1936) has met its share of censure and reprobation. As home to some of the most influential jazz musicians, performers and songwriters of the 1920s and 30s, however—Duke Ellington, Cab Calloway, Harold Arlen, Ethel Waters, Bill "Bojangles" Robinson, Adelaide Hall, to name a few—the significance of this singular institution cannot be denied. I argue that training a spatial lens on interwar Harlem jazz provides access to this complex musical world, bypassing valuations of the Cotton Club's "good and bad" cultural aspects or perceived musical authenticity and focusing instead on the everyday lives of the musicians and audiences who labored in and consumed the Harlem nightlife industry. Triangulating the performance of music, race and space over a decade of Harlem life, through a single institution, reveals not a monolithic Harlem scene but a multivalent "Harlem moment." The oral histories of Cotton Club performers, rare press materials, and the reporting of historic black newspapers together reveal another side of Harlem, beyond the spectacle of the Jazz Age. Close studies of the Cotton Club tenures of Ellington, Calloway and Arlen in the three core chapters of this dissertation examine the early careers of these seminal figures by treating their output not as "pure" musical expression but as a negotiation between competing pressures of art and commerce; modernism and primitivism; high and low culture; racial fact and fiction. In doing so, paradigmatic compositions such as "The Mooche" (1928), "Minnie the Moocher" (1931) and "Stormy Weather" (1933) take on new meaning and resonance, while a host of forgotten music assumes relevance.

Keywords: Music.
Advisor: Kronengold Charles (Charles Stewart) primary advisor. Thesis advisor
Grey Thomas S.
Schultz Anna
Kant on what corresponds to sensation [electronic resource]

Through a detailed account of Kant's category of Reality and its historical roots, I show how Kant argues that concepts of moving forces must be the fundamental representations of empirical content, and are the only way we have to articulate a rudimentary, and important, notion of objectivity. The category of Reality expresses the notion of an independent "matter" of sensation that is "informed" by spatio-temporal properties. I claim that in order to make clear what he means by this notion, Kant describes the procedure that brings the form of sensation to bear on its matter, thereby developing a new, tractable conception of intensional magnitudes. Kant's concepts of causation and force then emerge as steps in this procedure of quantifying qualities. My account begins with 17th century debates that culminate in the vis viva controversy, tying together several themes from Leibniz -- including substantial forms, the law of continuity, and the genus-species relation -- that form the background for Kant's category of Reality. I then proceed to reconstruct a line of argument running through Kant's essay on Negative Magnitudes, the Critique of Pure Reason, and the Metaphysical Foundations of Natural Science, tracing the route from the abstract concept of Reality to the concrete concept of a moving force. Finally, I explain how Kant was able to construe Newton's derivation of gravity in the Principia in terms of genus-species relations holding among empirical contents or "realities.".

Keywords: Philosophy.
Advisor: Friedman Michael
Anderson R. Lanier advisor. Thesis advisor
Hills David James
Warren Daniel
Wood Allen W.