VictorJuiz/thesis huggingface dataset:
utx-1 and ash-2 deficiency in old Caenorhabditis elegans extends lifespan and healthspan
Keywords:  Department of Biology
utx-1
aging
chromatin
stanford
genetics
stanford genetics
biology
epigenetics
preteins
RNAi
knockdown
ash-2
healthspan
lifespan
Thesis

Aging is accompanied by functional decline and an increase in many diseases, including neurodegenerative and cardiovascular diseases. As the demographics shift towards older populations world-wide, a better understanding of the aging process is crucial to develop therapeutics that could extend the healthy portion of life. A host of mechanisms contribute to the complex process of aging, including epigenetic modifications, nutrient signaling pathways, and protein homeostasis pathways. Epigenetic modifications that affect chromatin state, including histone modifications, are of particular interest as age-related changes to chromatin state often occur later in life. Thus, targeting the conserved enzymes that add or remove histone modifications has the potential to impact a wide range of processes. One of these enzymes, UTX-1, is a demethylase that acts on trimethylated lysine 27 on Histone H3 (H3K27me3). Consistent with an important link between chromatin and longevity, deficiency in UTX-1 extends the lifespan of the worm Caenorhabditis elegans. Another enzymatic complex involved in longevity is COMPASS, the methyltransferase complex that trimethylates lysine 4 on Histone H3 (H3K4me3). When members of this H3K4me3 complex, such as the methyltransferase ASH-2, are knocked down, the lifespan of C. elegans is increased. However, the mechanism of action, precise tissues of relevance, effects on healthspan, and relevant initiation times are unknown for these lifespan-extending modifications. Here I show that knockdown of utx-1 and ash-2 via RNAi can still extend lifespan in C. elegans when initiated in old adults compared to young adults. Furthermore, knockdown of utx-1 or ash-2, either at young adulthood or late-adulthood, increases thermotolerance (resistance to heat stress) and improves mobility throughout life. I next sought to gain a greater understanding of the molecular mechanism of UTX-1 mediated longevity regulation. I find that contrary to its role in development, the lifespan-extending phenotype of utx-1 deficiency is dependent on UTX-1 demethylase activity. In addition, I have found that UTX-1 acts in several tissues to mediate lifespan extension, but that full lifespan extension can only be obtained when UTX-1 is deficient in more than one tissue. Together, these results indicate the feasibility of impacting healthspan and lifespan in already old individuals through knockdown of evolutionarily conserved chromatin modifiers.
Valence asymmetries in attitude ambivalence [electronic resource]
Keywords: Business.

Existing models of ambivalence suggest that as the number of conflicting attitude components increases, so too does the experience of ambivalence. Interestingly, though, these models overwhelmingly assume that this relationship is independent of valence. Across three studies we observe that this effect is in fact heavily influenced by two established valence asymmetries: negativity bias (greater impact of negative reactions than positive reactions) and positivity offset (baseline positive reactions even in the absence of positive information). Consistent with a negativity bias, we observe that subjective ambivalence is greater when conflicting reactions are negative rather than positive. However, we also document an opposing effect of positivity offset as attitudes become less mixed (i.e., more univalent) that counteracts the valence asymmetry due to negativity bias. This is the first work to describe the opposing roles of these valence asymmetries in attitude ambivalence. Our investigation also uncovers an interesting consequence of these asymmetries: when reactions conflict, people do not experience maximum ambivalence at equal levels of positivity and negativity, as is suggested by canonical ambivalence theory. Rather, subjective ambivalence peaks when positive reactions outnumber negative reactions.
Validation of Novel Host Targets and Drugs Predicted using Bioinformatics Approaches to Combat Dengue Virus Infection
Keywords:  Department of Biology
Dengue virus
Stanford School of Medicine
Infectious Diseases
Molecular Virology
Bioinformatics
Biology
Thesis

Dengue virus (DENV) is a human pathogen that represents a major global health threat, yet there are no approved antivirals or vaccines available. The traditional approach in antiviral development has been to utilize small molecules to inhibit specific viral enzymatic functions. However, the concept of inhibiting the virus by targeting host proteins involved in the viral life cycle has not been fully explored. As such, there is a need to identify and characterize host proteins that may be involved in processes such as viral RNA replication and assembly. To this end, we pursued two parallel bioinformatics approaches developed by the Khatri lab to identify, upregulated genes in DENV infection and candidate drugs targeting host factors with predicted antiviral effects against DENV. GOSR2, a host cell golgi SNAP receptor, was identified using the first approach, however, we were unable to achieve a robust defect in DENV infection upon knockdown of this gene or overexpression of a dominant negative mutant. Using the second approach, we identified two drugs, obatoclax and perphenazine, which exhibited potent antiviral effects against DENV. We specifically demonstrate that obatoclax inhibits DENV entry and RNA replication, while perphenazine inhibits DENV RNA replication and release. More selective inhibitors against the known molecular targets of obatoclax, the pro-survival members of the Bcl2 family, were also effective in inhibiting DENV infection. This suggests that these members of the Bcl2 family are essential to the DENV life cycle and could serve as potential DENV antiviral targets. Furthermore, since multiple viruses may hijack these host proteins, such host targets could form the basis of broad-spectrum antiviral strategies to be employed against a variety of viruses, beyond DENV.
Value distribution of automorphic forms in a family [electronic resource]
Keywords: Mathematics.

Consider the modular surface $X = SL_2(\BZ) \backslash \BH$. One would like to know how the values of holomorphic modular forms/non-holomorphic Maass forms would distribute in the limit. Hejhal and Rackner \cite{HejRac} was the first people to study this problem. They conjectured that (suitably normalized) Maass forms suitably normalized would distribute like the Gaussian with mean 0 and variance $\frac{3}{\pi}$ in the limit. This is known as the random wave conjecture. They also gave a heuristic argument on why the conjecture should hold. This thesis tries to address two questions centered around the random wave conjecture and related problems, such as Quantum Unique Ergodicity. The first part of the thesis (Chapter 3) addresses the discrepancy of predictions by physicists and by mathematicians. For a fixed test function on $X$, Quantum Unique Ergodicity asserts that $$\mu_j (\psi) := \int_X \psi(z) ^kf(z)
VCSEL-based multimode optical links [electronic resource]
Keywords: Electrical Engineering.

High Performance Computing and Data Centers are driving the demand for high bandwidth interconnects. Future exascale supercomputers capable of more than a quintillion operations per second will demand higher performance networks characterized by lower power consumption, lower cost, and higher bit rate. Vertical cavity surface emitting laser (VCSEL) based multimode optical links are one key solution to enable this growth. The work presented here aims to demonstrate solutions that increase bit rate, decrease power consumption, decrease cost, and increase the usable distance of VCSEL-based multimode optical links. Equalization is known to be an effective solution for overcoming the bandwidth limitations in a copper interconnect; however, here it is used to achieve higher bit rate, lower power consumption, and increased margins for a multimode optical link. This dissertation presents a full link employing a 90 nm CMOS driver and 90 nm CMOS receiver amplifier fabricated with IBM's standard bulk 90 nm CMOS process. Using feed-forward equalization at the transmitter, the link achieves a highest serial bit rate of 30 Gb/s, a lowest power consumption of 2.95 pJ/bit at 20 Gb/s, an increased timing margin of 0.17 UI at 23.5 Gb/s, and improved receiver sensitivity by 4 dB at 23.5 Gb/s. Wavelength division multiplexing (WDM) is a technique to combine multiple parallel channels of different wavelengths into a single fiber to reduce system cost. This dissertation presents the design and characterization of a grating-based wavelength division multiplexer formed with injection molded plastic to reduce the number of fibers needed in parallel links. This design uses fewer components than previously demonstrated dielectric filter-based approaches in an effort to minimize the complexity of manufacturing to reduce cost. Care is taken to optimize the design for alignment tolerances associated with assembly, and to ensure the device works across the wide temperature ranges VCSEL-based links must tolerate. Simulations and experimental characterization show 4 channels at 850, 880, 910, and 980 nm multiplexed into a single multimode fiber. The coupling conditions between VCSELs and multimode fiber are studied in this dissertation to improve fiber bandwidth. A novel characterization system based on a spatial light modulator imaging system is used to characterize a VCSEL both spatially and spectrally. The system applies a blazed grating to the spatial light modulator to scan an image of the VCSEL across the core of a single mode fiber and measures the full optical spectrum at each point in the scan. A mode solver is used to develop an analytical model for light propagation down a multimode fiber, which is combined with the experimental VCSEL characterization to design a coupling solution to improve fiber bandwidth. A 6th order spiral phase mask is experimentally shown to modify coupling conditions to increase fiber bandwidth from 6.3 GHz to 17.5 GHz over 300 m of OM3 fiber under typical alignment.
Vibe - 21st century assessment
Keywords: Collaboration
21st century skills
Assessment
Machine Learning
AI
Communication
Thesis

In our new age of 21st-century-skills, collaboration and communication have been highlighted as skills which are essential to thrive in an unknown economic future (Griffin, McGaw, and Care, 2012). Vibe is a tool designed for late primary and secondary school classroom teachers, that measures student habits of collaboration and communication, and provides instructional guides when necessary. Vibe sees these skills as a learning goal -- an end unto itself -- and leverages the affordances of modern technology to collect and interpret formative data in a manner that reduces the time and attention demands on the teacher. The teacher is thus able to assess, give feedback, and plan her next steps in a data driven way - just as is done today in teaching traditional content knowledge.
Vibe takes the form of a set of student wearables paired with a visual interface (app) for the teacher and for student teams. Vibe’s biosensor technology measures student vocal participation and interaction. The teacher interface presents the data visually, in a manner that is easy to interpret and suggestions to help teachers facilitate effective collaborative work both real time and over time. The student group interface will encourage awareness of the collaborative process and support self assessment. Students will receive a select array of insights guided by the teacher.
Virtual analog modeling of audio circuitry using wave digital filters [electronic resource]
Keywords: Music.

The Wave Digital Filter (WDF) approach to discretizing electronic circuits has generated substantial interest in the Virtual Analog research community, which is attracted to the potential for systematic and modular simulation of vintage electronic musical instruments (e.g., synthesizers, drum machines) and audio effects (e.g., guitar amplifiers, distortion pedals). Unfortunately, traditional WDF techniques falter at the complexity of typical audio circuits, which contain complicated (non-series/parallel) topologies and multiple nonlinear devices (e.g., diodes, transistors, triodes). In this dissertation, I review classical WDF techniques and propose novel ways of systematically modeling circuits with complicated topologies and multiple nonlinearities. Throughout, the classic Bass Drum circuit from the Roland TR-808 serves as a motivating example and each of the four chapters contains a case study simulating a different one of its subcircuits. The first two chapters consider linear reference circuits. After deriving the standard WDF building blocks and demonstrating their use in a simulation of the TR-808 Bass Drum's output filter, I explain their substantial limitations in the context of modeling analog audio circuitry. To overcome these limitations, I introduce a novel Modified-Nodal-Analysis-based approach to creating WDFs from circuits with complicated (non-series/parallel) topologies and show it in action on several versions of the Bass Drum's central circuit (the Bridged-T Resonator). The next two chapters consider nonlinear reference circuits. I review the standard WDF technique for handling reference circuits with a single one-port nonlinear device, exemplified by a model of the TR-808 Bass Drum's Pulse Shaper subcircuit. In order to overcome the limitation to a single nonlinearity, I propose a novel approach that accommodates multiple nonlinearities and apply it towards a simulation of the full nonlinear version of the Bass Drum's Bridged-T Resonator. Together, these four case studies form a complete model of the TR-808 Bass Drum that almost exactly matches the behavior of the real circuit, demonstrating the utility of the classical WDF techniques combined with my proposed methods. Beyond this case study, the proposed methods enable the simulation of a huge class of audio circuitry that was previously beyond the scope of WDF modeling.
Virtual feedback on teaching using videos of teaching [electronic resource] : how teaching changes over time with consistent feedback
Keywords: Education.

This research examines how teaching and learning evolved over the course of one school-year in classrooms where the teachers received written feedback on videos of their teaching through an online platform. The study is situated within a university-based teacher professional development program. Participants in the study included two subject-matter coaches and three high school English teachers working on improving one element of pedagogical practice: facilitating classroom discussion. Four videos from each teacher's classroom and all the written feedback comments provided on those videos were examined for the nature of feedback provided and the subsequent changes observed. The analytic scheme was developed from Feedback Intervention Theory and the vast literature on facilitating classroom discussion. Feedback comments to teachers were predominantly descriptive of teacher and student actions observed in the classroom, almost equally positive and critical, and suggested instructional strategies in majority of comments. The pedagogical focus of feedback to teachers, as well as particular instructional strategies to try, varied slightly across the three teachers. The teaching and learning evolved and improved within each of the teachers' classrooms over the course of the year in substantial and nuanced ways as teachers consistently employed the strategies suggested in the feedback comments and attempted to meet the goals of instruction in feedback. These findings offer insights for how the field conceptualizes feedback on teaching and how we study the feedback on teaching. Findings also have implications for how we provide feedback to teachers.
Visualizing energy-relevant phase transitions within individual palladium hydride nanoparticles [electronic resource]
Keywords: Materials Science and Engineering.

Alternative energy technologies such as wind and solar power offer a promising avenue towards reducing our reliance on fossil fuels, but suffer from intermittency. Methods to store energy produced during peak generation periods are among the most crucial advances necessary to enable growth of the renewable energy industry. Many storage systems, including electrical energy storage in lithium ion batteries and chemical energy storage in metal hydrides, rely on ion intercalation into nano-structured materials, inducing a phase change. However, the design rules governing champion nanomaterials for energy storage remain unknown, because it is challenging to directly visualize the phase transformation in-situ. In this dissertation, we examine the thermodynamics and reaction dynamics of nanoscale phase transitions induced by ion intercalation at the single particle level. As a model system, we focus on the palladium/hydrogen system, as it is among the oldest and most well-studied bulk hydrogen-storage systems. Pd nanoparticles undergo a phase change from hydrogen-poor alpha phase to a hydrogen-rich alpha phase. Using in-situ studies in an environmental transmission electron microscope (TEM), we examine the thermodynamics of single-crystalline and multiply-twinned nanoparticles and also follow the reaction in real time to gain insights into the transformation mechanism. First, we use electron energy loss spectroscopy (EELS) to monitor the thermodynamics of the hydrogenation process in single-crystalline particles, including nanocubes and prisms. We find that single nanocrystals absorb hydrogen over a very narrow pressure range and do not show phase coexistence at equilibrium, in striking contrast to studies performed on ensembles of particles. Next, we study multiply-twinned palladium nanoparticles to understand the influence of crystalline irregularities, such as defects and strain. In contrast to single crystals, these particles absorb hydrogen over a relatively wide pressure window and do not hydrogenate completely. EELS mapping, dark field imaging, and electron diffraction allow us to look inside individual nanoparticles, visualizing the local phase with sub-2 nm spatial resolution. We find that highly compressively strained regions exclude hydrogen and that individual crystallites uptake hydrogen at distinct pressures. Finally, we investigate the reaction dynamics of the phase transition, probing the reaction intermediates. Intriguingly, we find that nanoparticles self heal during the absorption process. We show how our work helps to unravel the mechanism of Li-ion insertion in battery electrodes or hydrogen absorption in state-of the-art metal hydride catalysts, and provides a platform to screen for champion nanomaterials in future energy storage systems.
Voices of enthusiasm [electronic resource] : the mobilization of revolutionary emotion in Soviet literature and culture
Keywords: Slavic Languages and Literatures.

"Voices of Enthusiasm: the Mobilization of Revolutionary Emotion in Soviet Literature and Culture" explores how revolutionary emotions were thematized and voiced in early Soviet culture. Since antiquity, the concept of enthusiasm has been applied to phenomena ranging from solitary inspiration to the collective consciousness of congregations, reading publics, warring nations, and revolutionary societies. It was in the early years of the Soviet experiment that enthusiasm was first propagated by the state as a core element of civic virtue and as an emotional disposition necessary for the attainment of political consciousness and the creation of a socialist society. Labor enthusiasm emerged as a key concept during the First Five-Year Plan, when Soviet psychologists were tasked with putting forth a model of the human mind that would both account for its "dialectical" nature and justify the intensification of labor required for the regime's ambitious industrialization campaign. Enthusiasm gave voice to a deep-seated utopian dream shared by many contemporary thinkers: to use the conscious mind to co-opt the energies of the unconscious one. A literary history of this cultural project, Voices of Enthusiasm examines how Soviet artists and intellectuals shaped and were shaped by notions of revolutionary affect. This dissertation focuses on two early Soviet writers: Andrei Platonov, a self-described "proletarian poet" and land-reclamation engineer from the provinces, and Mikhail Zoshchenko, a fellow-travelling satirist from the Petrograd artistic intelligentsia. Platonov and Zoshchenko were masters of skaz, a "tongue-tied" narrative style that, as the author argues, was used by Soviet writers used to portray the mental life of the "ascendant" lower classes. "Speaking in tongues" offered them a literary model for orchestrating the emotionally fraught, individual voices of their contemporaries into a transcendent whole. In the resulting verbal grotesques, Platonov and Zoshchenko countered party slogans with more nuanced pictures of the varyingly intoxicating and traumatizing experience of revolution, imagining alternative paths to the ideological and affective "reforging" that the Soviet regime was imposing by force.
Volumetric optical coherence tomography vibrometry for the study of cochlear mechanics [electronic resource]
Keywords: Electrical Engineering.

Sound is encoded within the auditory portion of the inner ear, the cochlea, after propagating down its length as a traveling wave. For over half a century, vibratory measurements to study cochlear traveling waves have been made using invasive approaches such as laser Doppler vibrometry. Although these studies have provided critical information regarding the nonlinear processes within the living cochlea that increase the amplitude of vibration and sharpen frequency tuning, the data have typically been limited to the surface vibratory measurements of the basilar membrane. This dissertation presents a new vibrometry technique, called volumetric optical coherence tomography vibrometry (VOCTV), which provides depth resolved displacement measurements at high speed inside a 3-D volume of tissue with picometer displacement sensitivity. The mechanics of the mouse cochlea is studied by imaging noninvasively through the surrounding bone to measure sound-induced vibrations of the sensory structures in vivo. Unique vibratory data from inner structures of the cochlea that could not be measured before provided clues to the unsolved questions of how such a complicated microstructure could transduce the complex input sound into neural information efficiently.