VictorJuiz/thesis huggingface dataset:
Development of novel optogenetic and molecular tools and their application to understanding the neurological basis of behavior [electronic resource]
Keywords: Neurosciences.

Successful interaction between an animal and its environment requires the execution of meaningful action in response to external cues and, in most situations, interpretation and integration of sensory inputs in the context of experience. Neurological and psychiatric diseases encompass dysfunction at any point in this pipeline. Neuroscientists seek to understand how the brain is able to complete these tasks in the healthy individual as well as the changes that underlie impairment in disease. The heterogeneous and highly interconnected structure of the brain creates unique hurdles to scientists that ask these questions. In many cases, traditional tools of the trade, namely, electrical and pharmacologic interventions, both fall short when used to derive definitive and generalizable conclusions. To facilitate neuroscience research, our laboratory has discovered, optimized, and diversified an array of single component, optically activated ion channels and pumps for neuronal control. These may be selectively introduced to neurons based on genetic or topological parameters, thereby selecting needles in the haystack of cells within the brain, and are modulated by light on the order of milliseconds, a scale relevant to neuronal activity. The purpose of the studies described here was two-fold: 1) to expand the toolbox through opsin engineering, light delivery methods, and molecular targeting strategies and 2) to apply these to understand the neurological basis of some psychiatric diseases. The use of these tools in understanding anxiety and social behavior circuitry is described briefly, while the application of two novel opsin variants to understanding the role of increased amounts of excitation relative to inhibition within the prefrontal cortex is detailed. The tools described here are designed for and validated within the brain, but may be applied within most biological systems. As experimental approaches expand, so do the range of questions available to science. Answers to these will lead to advances in understanding, managing, and curing injury and disease.
Development of optogenetics for motor systems neuroscience in non-human primates [electronic resource]
Keywords: Bioengineering.

Voluntary movement is such an integral part of common tasks that the loss of this ability is detrimental to quality of life. Effective functional restoration for patients with a limited ability to move requires deep understanding of movement control. However, despite decades of motor system research, the mechanism by which motor cortex controls movement is still unclear. Although technological advances such as electrical microstimulation have been used to investigate this mechanism, its limitations in simultaneous recording and perturbation have prevented us from obtaining more informative measurements. To address this challenge, a multidisciplinary approach was taken to further examine the underlying mechanism of motor control. Specifically, we used optogenetics along with the analytical framework of dynamical systems theory to probe the dynamics of motor preparation. Three major results are presented in this work. Firstly, we characterized and assessed the functionality of optogenetics electrophysiologically and histologically in non-human primates. Although optogenetics has been used extensively in rodents, it is still in a developmental state in primates. Hence, the efficiency of virus transfection, the reliability of neural responses to optical stimulation, the pattern of opsin expression and the safety to animals were investigated to minimize any potential risk and to aid future experimental designs. We also discovered that, in contrast to electrical microstimulation, optical stimulation in cortical motor and premotor areas did not evoke overt skeletal movements. Secondly, we continued the characterization process by injecting a red-shifted opsin, C1V1(TT), in dorsal premotor cortex (PMd) and optically perturbed the neural activity while the animals were actively engaged in an instructed-delay reach task. We found that the optical perturbation in PMd resulted in increased reach reaction times. Moreover, using the dynamical systems perspective, we discovered that, post-perturbation, the neural state did not return to its pre-perturbed state. Instead, it proceeded directly to re-join the normal neural trajectory path to execute the movement. We also observed that optical stimulation did not obliterate task-related activity in light-responsive neurons. In fact, the relationship between task-related and optically-evoked activities appeared to be linearly additive. Lastly, we developed a decoding algorithm to extract kinematics information from optogenetically-perturbed data. We trained a Kalman filter based on a mixture of perturbed and unperturbed data, and found that it provided us with an effective decoder. This decoding performance was achieved despite the fact that the decoder made no attempt to detect whether or not the neural activity was perturbed.
Development of the brain's reading circuitry [electronic resource]
Keywords: Psychology.

Learning to read is at the foundation of academic success. Understanding how the developing brain builds circuits to rapidly translate arbitrary printed symbols into meaningful language representations is a scientific challenge with important implications for education. Successfully learning to read requires the coordination of signals between visual, auditory and language processing regions of the cortex; white matter is essential for the development of this cognitive function. New magnetic resonance imaging (MRI) techniques make it possible to measure the structure and function of the living brain's reading circuitry and understand the coupling between changes in circuit structure, circuit function and human behavior The following sections develop a methodology for measuring the white matter connections of the brain's reading circuitry and quantifying changes in tissue properties over the course of reading instruction. A series of functional MRI and diffusion-weighted MRI experiments elucidate the cortical regions that perform reading related computations and the white matter fascicles that transmit signals between these regions. These measurements show that the dynamics of an individual's white matter development predicts their acquisition of skilled reading. Learning to read is intricately related to active developmental processes in specific white matter tracts. This collection of findings highlights the important role of non-neuronal biological processes in the development of complex cognitive functions.
Differential sensitivity of oligodendrocyte precursor cells to methotrexate in the developing brain
Keywords:  Department of Biology
Oligodendrocyte Precursor Cell
Methotrexate
Chemobrain
Biology
Thesis

Patients exposed to chemotherapy during cancer treatment frequently present with neurocognitive deficits that are debilitating and lasting, commonly known as “chemobrain.” This set of symptoms is anatomically localized to the hippocampus and frontal subcortical white matter, where oligodendrocyte precursor cells (OPCs) are essential to development and maintenance of white matter. Previous studies have shown that these cells are especially vulnerable to chemotherapeutic exposure, suggesting the possibility that OPCs might be a therapeutic target in future treatments for chemotherapy-induced dysfunction. Methotrexate (MTX), an antimetabolite used frequently to treat childhood cancers, has been shown to impair white matter integrity in human patients, but the specific mechanisms of its effects on OPCs have not been elucidated. We show here that there is a significant depletion of the white matter OPC population following chemotherapy administration, while the grey matter OPC population remains intact. This incongruity is not explained by differential survival, as when grey or white matter OPCs are exposed to methotrexate in vitro, neither population exhibits significant cell death at concentrations achieved in the brain following systemic MTX administration. By gaining a better understanding of the cell-intrinsic and microenvironmental mechanisms that govern OPC population dynamics and function, and by creating a faithful mouse model for continued investigation, this research provides compelling evidence for the OPC as a therapeutic target candidate in the treatment of “chemobrain.”
Diffusion distance of MAC1 protein when secreted by Ustilago maydis in Zea mays anthers
Keywords:  Department of Biology
Stanford University
Biology Department
Zea mays
maize
multiple archesporial cells 1
mac1
anther
Ustilago maydis
U. maydis
Thesis

The Maize multiple archesporial cells 1 (mac1) gene plays a crucial role in anther development by regulating cell proliferation and determining cell identity. Archesporial (AR) cells in the anther are hypothesized to secrete MAC1 into the apoplast during development, where it binds to leucine-rich-repeat (LRR) receptor kinases on surrounding L2-d somatic cells. To investigate the function of MAC1 in planta, the basidiomycete fungus Ustilago maydis was used to deliver MAC1 protein directly into the apoplast of anther tissues. A U. maydis construct was generated by homologous recombination to express and secrete a MAC1-mCherry-HA fusion protein into the maize anther apoplast. Confocal microscopy verified successful infections of maize by U. maydis, and the presence of mCherry signal. However, the signal is not confirmed to be MAC1-mCherry-HA fusion protein signal; Western blot data is needed to ensure that the fusion protein is not cleaved in planta by the host plant cell’s proteases.
DIRECTED DIFFERENTIATION of Female Induced Pluripotent Stem Cells Using BMPs and Retinoic Acid
Keywords:  Department of Biology
stem cells
factors
yamanaka
retinoic acid
BMPs
bone morphogenetic proteins
RA
Stanford
Biology
Thesis

Development of the human cell lineages has been the subject of much study since the first derivation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). These cell types can be directed to form early endoderm, mesoderm, ectoderm, trophectoderm, as well as germ cells. Factors such as bone morphogenetic proteins (BMPs) 4 and 8 can differentiate iPSCs to primordial germ cells (PGCs) as well as other lineages such as mesoderm and trophoblast. To address the effect of BMPs and Retinoic Acid (RA) on directed differentiation of female iPSCs, we conducted a 14-day directed differentiation experiment using four treatments and examined the formation of ectoderm, endoderm, pluripotency, germ cell, and trophoblast/mesoderm cell types through analysis of gene expression. Based on previous data from the laboratory, it was hypothesized that the presence of RA during directed differentiation of female iPSCs, in particular, would lead to differentiation of trophoblast or mesoderm tissues, preferentially over other fates including primordial germ cells (PGCs), while BMPs would function to maintain pluripotency and germ cell fates.
Following directed differentiation, pluripotency, mesoderm, germ cell, and ectoderm associated genes experienced a gradual decrease in expression while trophectoderm and endoderm genes exhibited an increase in expression throughout the 14 days across all treatments. The hypothesis that the addition of RA would induce trophoblast was supported by increased expression of associated markers. However, addition of +RA did not upregulate mesoderm as hypothesized, with +BMP resulting in negative regulation. Similarly, the hypothesis that +BMP treatment would upregulate germ cell fates was not supported, with all treatments resulting in significant downregulation of germ cell related genes. Variations from the hypothesis may be due to timing of exposure and an unknown pathway mechanism, which merit further investigation. It was further determined that 1) neuroectoderm may be the default differentiation pathway; 2) +BMP upregulates endoderm cell markers and downregulates PGC and mesoderm markers; 3) +BMP/RA downregulates ectoderm, mesoderm, and pluripotency markers while upregulating endoderm and trophectoderm markers; 4) +RA downregulates ectoderm and mesoderm markers. Overall, +BMP appeared to have a more potent effect in positively or negatively regulating gene expression, often with amplified effects in combination with +RA
Discovering low work function materials for thermionic energy conversion [electronic resource]
Keywords: Electrical Engineering.

The work function is the interfacial parameter of a surface that determines how easily electrons can escape into a vacuum or gas environment, with lower work functions generally facilitating electron emission. This thesis employs density function theory methods to a systematic approach in the discovery of new nanostructured multilayer materials with low work functions. Techniques in density functional theory can enable many promising film coating combinations to be efficiently investigated for the first time. Two main sets of screening studies are described: (1) cesiated transition metal surfaces and (2) alloyed alkali-earth oxide films on tungsten. A model is introduced for the effect of cesium adsorbates on the work function of transition metal surfaces. This model builds on the classic point-dipole equation by adding exponential terms that characterize the degree of orbital overlap between the 6s states of neighboring cesium adsorbates. In addition, the model analyzes the effect of orbital overlap on the strength and orientation of electric dipoles along the adsorbate-substrate interface. This new framework improves upon earlier models in terms of agreement with the work function-coverage curves obtained via first-principles calculations based on density functional theory. All the cesiated metal surfaces have optimal coverages between 0.6 and 0.8 monolayers, in accordance with experimental data. Of all the cesiated metal surfaces considered, tungsten has the lowest minimum work function, also in accordance with experiments. The work function and stability of 570 alloyed alkali-earth oxide films on the (100) surface of tungsten have been calculated within density functional theory. Computational screening of this large phase space is enabled by implementing the virtual crystal approximation, where the degree of freedom in the chemical composition is modeled with virtual atoms of mixed calcium, strontium, and barium character. Low work functions are achieved by doping the films with scandium (1.16 eV) or lithium (~1.2 eV) and alloys containing ~15% to ~20% of calcium. In particular, lithium-doped systems with ~15% calcium also show favorable stability indicated via formation energy calculations. Identification of such film alloys outperforming any of the constituents relies on careful sampling of the chemical composition. Covalent interactions within the film limit the reduction in work function from the dipole normal to the surface. Controlling the electronic screening of these intra-film interactions by oxygen atoms is essential for the design of new low-work function materials.
Distant terrains and decorative fictions [electronic resource] : describing Japan in Second-Empire France
Keywords: Art and Art History.

This dissertation reveals how Japanese imports participated in a new discourse on objects in 1860s Paris. Looking to the specific political and aesthetic context of the Second Empire, this project reconsiders how the descriptive practices of the 1860s determined the early French encounter with Japanese things. Description places new attention on the communicative properties of inanimate objects and dominates the aesthetic and commercial culture of Second-Empire France. This culture of description materializes in naturalist novels, exhibition catalogs, expansive encyclopedias, republican literature, still-life painting, and portraiture during the 1860s and emerges as the primary framework for ordering and understanding the foreign culture of Japan. Imagined through its objects and inscribed into these various descriptive forms, Japan appeals to a French context that finds new political and aesthetic meaning in the accumulation and representation of things. By mapping the early French encounter with Japan across a variety of material forms, this project complicates the standard narrative of Japonsime to suggest that Japan is both politically and culturally encoded through the description of its objects in 1860s France.
Divine institutions [electronic resource] : religious practice, economic development, and social transformation in mid-Republican Rome
Keywords: Classics.

In the course of two and a half centuries, the city-state of Rome rose from central Italian dominance to Mediterranean hegemony. Together with this transformation in the scale and extent of Roman power came a revolution in social, economic and cultural practices. My dissertation argues that the success of this imperial project and the nature of the social revolution it triggered must be understood by reference to Roman religious practices throughout this period. I set out the case for why and how religion in mid-Republican Rome and Roman Italy drove meaningful and highly consequential institutional change over time. A primary mover in this institutional change is trust: religious behaviors, observances, and rituals shaped the creation and perpetuation of the forms of trust that anchored the "quasi-voluntary compliance" regime binding together the citizen body of the expanding Republic and its constellation of allies. With the help of insights gleaned from sociology and political science, I isolate several specific areas through which this dialogue of religiously-mediated trust was promoted and enacted: temples and monumental construction; festivals and festival culture; numismatic iconography; and the announcement and expiation of prodigies. I show how these four domains of cultural practice—shaped and orchestrated according to religious considerations—became sites of institutional innovation, with implications for Rome's imperializing project. This characterization of the middle Roman Republic as a distinctive example of how religion interfaces with community-building, economic development, state formation, and imperial expansion aims to be of interest not only to Romanists and ancient historians but to political theorists, comparative historians, economic historians, and sociologists.
Dixie bound [electronic resource] : a cultural biography of an American legend, 1860-1930
Keywords: English.

Few songs have gained as enduring and contradictory a national legacy as "I Wish I Was in Dixie's Land." The tune was first performed in New York City on the minstrel stage and adapted to new lyrics by Civil War soldiers. President Lincoln requested its performance the day after Appomattox and, though still associated with the Confederate anthem today, it has encouraged generations of Americans to reflect on their national heritage by whistling and wishing that they were in a place called Dixie. But Dixie is not necessarily, or historically, synonymous with the American South. Over the past two centuries, Dixie has played a dominant role in shaping American popular culture, a role derived only in part from Dixie's Southern connotations. By charting Dixie's scandalous and enthralling journey over the turn of the century, Dixie Bound establishes an historical framework for understanding Dixie as a national literary phenomenon that began long before Scarlett and Rhett. Building an archive of previously unexamined tunes, texts, and visual artifacts, this study traces Dixie's circulation from the start of the Civil War through the rise of Tin Pan Alley and Dixieland jazz. These early appearances offer a dramatic counterpoint to present-day notions of Dixie and particularly to our presumptions about Dixie's racial and regional past. Precisely by turning back to the early history of Dixie, Dixie Bound provides necessary insight into the song's unsettling legacy today.
DMRG studies of ferromagnetic phase diagram of infinite-U hubbard ladders [electronic resource]
Keywords: Physics.

The Hubbard model is one of the most important models in theoretical condensed matter physics. The model, which captures the strong interactions among the electrons, has not been solved analytically in more than one dimension. Therefore, over the past tens of year, there has been a tremendous analytic and computational effort to understand the parameter dependent ground state of this model, especially for intermediate strengths of the on-site repulsion U - the regime of parameters relevant to the properties of real material. Possible approaches to understand this model includes perturbative methods which start with the non-interacting kinetic term and treats the potential to low order in an expansion in powers of the interaction strength. A less intuitive approach is to attack the problem from the opposite extreme U> > t, where t is the electron hopping matrix element. In my thesis, I present the results concerning the ground-state phase diagram of Hubbard model in the infinite-U limit with an emphasis on the 2-leg ladder and the extrapolation of these results to the 2D limit. We will show that there is a half metallic ferromagnetic ground state when the density of electrons per site n> =n_c ~ 0.80. When n=0.75, the ground state is a commensurate anti-ferromagnetically ordered plaquette phase with bond density order. We show evidence that in the range of n between n_c and 0.75, the ground state is phase separated between these two states. These properties hold not only for the two-leg ladder, but wider ladders as well, which we assume implies that they continue smoothly to the fully 2D limit. However for 0.75 > n > 0.5 while the ground state is found to be unpolarized for wider ladders, the two leg ladder exhibits a partially polarized ferromagnetic ground state , with a peak in the magnetization density occurring at around n=2/3 where we have demonstrated the existence of another commensurate phase. The ground state of the 2-leg ladder when n=0.5 is an anti-ferromagnetic dimerized phase. A study of the charge carrying elementary excitations in the various commensurate phases suggests that there are further intermediate phases rather than direct first order transitions between them. Moving from infinite to large but finite U, we trace out the boundary of half metallic ferromagnetic phase of the 2-leg ladder as a function of n and U. As the transition seems to be everywhere first order, we propose that outside this phase gives way to a phase-separated ground state between such boundary and the two commensurate phases at n=1 and n=3/4 respectively. The plaquette phase is observed to be stable down to at least values of U~20t, but below a smaller critical value of U/t the ground state enters a stripe ordered phase. We also test the correspondence between Hubbard and t-J at least down to values of U~100t.