VictorJuiz/thesis huggingface dataset:
Meiotic regulation of kinetochore composition and function

The survival and fitness of an organism rely on faithful transmission of the genome. In sexually reproducing organisms, genome transmission requires a specialized cell division named meiosis, in which the parental genome is shuffled and halved. The kinetochore, a conserved protein complex that mediates chromosome segregation, is a key player in meiosis. Here we investigated how the budding yeast kinetochore undergoes dynamic changes in this specialized cell division. The microtubule-binding part of the kinetochore (outer kinetochore) dissociates from the chromosomes in meiotic prophase and reassembles before the meiotic divisions. This dynamic behavior is crucial to establish the meiosis-specific chromosome segregation. We have discovered a multi-level network that regulates the dynamic kinetochore behavior by controlling the abundance of one single kinetochore subunit, Ndc80. Ndc80 is downregulated in meiotic prophase and later re-synthesized during the meiotic divisions. This fluctuation in the Ndc80 level requires regulation on Ndc80 synthesis and turnover. Central to the Ndc80 synthesis regulation is the toggling of two NDC80 mRNAs: (1) a coding mRNA that is translated into Ndc80 protein, and (2) a 5’-extended mRNA termed LUTI. Rather than coding for Ndc80, LUTI expression impedes the expression of the coding mRNA via chromatin modifications, leading to Ndc80 synthesis repression. Two meiotic master transcription factors, Ime1 and Ndt80, regulate the expression of LUTI and the coding mRNA, respectively, and integrate Ndc80 regulation into the larger meiotic program. Besides synthesis, Ndc80 degradation is temporally controlled: Ndc80 is degraded in meiotic prophase and not in metaphase I. Ndc80 degradation requires active proteasomes, a degron sequence at Ndc80’s N-terminus, and Aurora B phosphorylation on Ndc80, which is known to correct erroneous microtubule-kinetochore attachments and is rewired to degrade Ndc80 in meiotic prophase. Crucially, mis-regulation of Ndc80 abundance disrupts chromosome segregation, gamete formation, and progeny fitness, highlighting the importance of Ndc80 modulation. Altogether, this work reveals a beautiful case in evolution in which the gene expression, turnover, and activity of the kinetochore are tuned to accommodate the specialized chromosome segregation program meiosis.

Advisor: Ünal, Elçin
e-mission: an open source, extensible platform for human mobility systems

Transportation is the single largest source of carbon emissions in the US. Decarbonizing it is challenging because it depends on individual behaviors, which in turn, depend on local land use planning. The interdisciplinary field of Computational Mobility, focusing on collecting, analysing and influencing human travel behavior, can frame solutions to this challenge./nInnovation flows in interdisciplinary fields are bi-directional. The flow to the domain is focused on building a strong foundation for methodological improvements. As the improvements are deployed, they result in use-inspired computational research. This temporal dependency results in our initial focus on the modularity, accuracy and reproducibility of e-mission, an extensible platform for instrumenting human mobility. This open source platform has a modular architecture that supports power efficient duty cycling using virtual sensors, a read-only data model and a pipeline with novel algorithm adaptations for smartphone sensing./nWe also perform the first empirical evaluations of smartphone-based platforms in this domain. The architectural evaluation is based on three real world deployments: a classic travel diary, a crowdsourcing initiative, and a behavioral study. The accuracy evaluation is based on an novel procedure that uses artificial trips and multiple parallel phones to mitigate concerns over privacy, context sensitive power consumption and inherent sensing error. Data collected from three artifical timelines was used to evaluate the trajectory, segmentation and classification accuracies vs. power for various configurations./nOn computational side, challenges derived from the deployments can contribute to ongoing CS research in privacy, trustworthiness, incentivization and decision making. On the mobility side, this enables methodological innovations such as Agile Urban Planning for prototyping infrastructure changes.

Advisor: Culler, David E.
Katz, Randy H.
Integral Experiment on Polyethylene Using Radiative Capture and Inelastic Excitation in Indium Foils inside a D-D High Flux Neutron Generator.

Cross-sections nuclear data are invaluable to the nuclear community. As well as providing information on nuclear structure of matter and reaction dynamics, they provide practical support for applications including design and modelling of fission and fusion reactors, shielding geometry for radiation sources such as radiation treatment machines, etc. Evaluated cross section data in form of evaluated nuclear data are the products of experiment and theoretical modelling. Before they can be used, their reliability and accuracy need to be assured. This is done through integral experiments in which prediction from simulation using the evaluated nuclear data is compared to experimental value./nIntegral benchmark experiments are used to test the accuracy and reliability of evaluated nuclear data. They are a rich source of information with which a wide range of validation and comparison exercises can be made [1]. Such benchmark experiments provide global measures of data performance for applications and are a valuable resource for nuclear data testing and evaluation efforts [2]. Integral experiments in reactors play an essential role in nuclear data validation and improvements [3]./nApplications of integral benchmark experiments are found in fission and fusion reactors designs for safety, in fast neutron therapy for shielding calculation. They are a very powerful means of assessing the quality of nuclear data for specific applications, nicely complementing differential measurements [4]./nNeutron generators such as D-D fusion generators can serve the purpose of performing integral benchmark experiment for validation of cross-section data. The Nuclear Engineering department of the University of California Berkeley has D-D neutron generator called the High Flux Neutron Generator (HFNG). It operates in the range of 100-125 keV of accelerating voltage. The generator produces neutron current of the order of 108 per second. These neutrons have energies between 2.2 – 2.8 MeV./nIn this work, neutron elastic and inelastic scattering cross sections on carbon and hydrogen nuclear data in the evaluated nuclear database ENDF/B-VII.1 are compared to experiments via the observation of radiative capture and inelastic excitation of two long-lived isomeric state in 116In and 115In on a foil mounted in the center of the HFNG in order to benchmark scattering on a polyethylene moderator surrounding the generator./nTwo different methods were used: single and double ratios of the products of the two reactions. Results from both methods show generally good agreement with the expected values, although some statistically significant differences are observed. These results highlight the utility of compact DD neutron sources such as the HFNG as integral benchmarks and suggest that further work should be done to improve the evaluation of scattering data on polyethylene due to its important role in shielding applications.

Advisor: Bibber, Karl V
Bernstein, Lee A
Nominalism, Romanticism, Negative Dialectics

This dissertation recovers a neglected dialectical tradition within British empiricism and its Romantic afterlife. Beginning with John Locke, I demonstrate how a dialectical tradition developed as a self-critical response to the political, philosophical, and aesthetic problem of nominalism, which holds that universals do not exist and that everything is particular. As contemporaries like Dugald Stewart and S.T. Coleridge observed, British empiricists had revived the medieval nominalist-realist debates and sided with the nominalists. I show that nominalism – what Karl Marx called the “first form” of materialism – was taken up and critiqued by Romantic poets as an impediment to the task of representing abstract social and historical forces. Romantic poets as distinct as Coleridge, William Blake, and Charlotte Smith suggest that, in questioning the validity of social abstractions, the nominalist bent of empiricism tended to disable critical interrogations of larger social structures that otherwise remain inaccessible to the senses. In diagnosing the abstracting force of historical conditions like the commodification of the literary marketplace, however, the texts I examine also respond by affirming particularity. That is, even as these Romantic texts articulate the need to transcend particulars, they also resist universalizing tendencies by affirming, in Blake’s terms, “minute particularity.” These responses to the problem of nominalism are best understood, I argue, as a series of negative dialectics at odds both with the transcendent, affirmative dialectic of high Romanticism and with the subsequent Romantic particularisms and localisms that accompanied deconstruction and new historicism. Against the deeply engrained view that the Anglo-American tradition is anti-dialectical, the texts I study thus maintain a critical relation to social abstractions while at the same time including them in a more capacious materialism not reducible to matter. In making the case for a negative dialectics that emerges out of a self-critical relation to nominalism and empiricism, this dissertation pushes against the fundamental opposition between dialectics and empiricism asserted by both dialectical and postcritical discourses. In doing so, it presents a tradition in which empiricism and critique are inextricably entwined rather than strictly opposed.

Advisor: Goldsmith, Steven
Special Cycles on GSpin Shimura Varieties

In this thesis we prove that a certain generating function of special cycles on GSpin Shimura varieties is modular. More specifically, we consider the Shimura variety corresponding to the reductive group $\Res_{F/\Q} G$, where $G=\GSpin(V)$ the GSpin group for $V$, a quadratic space over a totally real number field $F$, $[F:\QQ]=d$ with certain conditions at the infinite places. We construct a generating function in the sense of Kudla and Millson and show that its image in cohomology is an automorphic form.

Advisor: Yuan, Xinyi
Chip-Scale Fluorescence Microscope

CMOS image sensors have been widely used for decades, largely displacing CCD technology in cameras, scanners, telescopes, and a variety of medical sensors. Photodiodes are formed in the IC substrate and the technology has been repurposed to make more advanced structures with higher sensitivity, such as pinned or avalanche photodiodes. Less work has gone into generating optical elements using other features of the CMOS process, namely the metal interconnect. The precision deposition and spacing of the metal layers allows a variety of optical structures to be fabricated within the image sensor to perform both spatial and wavelength filtering. This is especially useful for applications where large-scale optical components, such as lenses or fiber optic bundles, cannot be used. For most intraoperative imaging applications and especially for modern minimally-invasive or robotic-assisted cancer surgery, these large optical elements restrict an imager's ability to thoroughly scan an entire tumor cavity./nThis thesis presents an image sensor incorporating angle-selective gratings for resolution enhancement in contact imaging applications. Optical structures designed in the CMOS metal layers above each photodiode form the angle-selective gratings that limit the sensor angle of view to plus or minus 18 degrees, rejecting background light and deblurring the image. The imager is based on a high-gain capacitive transimpedance amplifier pixel using a custom 11fF MOM capacitor, achieving 8.2V/s/pW sensitivity. The pixel also includes a leakage current minimization circuit to remove signal-dependent reset switch leakage and the corresponding dark current is 14aA/um^2. The resulting 4.7mm by 2.25mm sensor (80 by 36 pixels) is designed specifically for intraoperative cancer imaging in order to solve the pervasive challenge of identifying microscopic residual cancer foci in vivo./nA custom amorphous silicon optical wavelength filter is used alongside the image sensor in order to perform fluorescence imaging. The filter rejects excitation light and has over five orders of magnitude rejection at 633nm. Fluorescence emission light above 700nm is allowed to transmit through. Several clinically-tested fluorophores, such as IR700DX, are compatible with this wavelength range. The filter is only 15um thick and is suitable for in vivo contact imaging applications as it maintains the same high rejection for all angles of incident light./nWe demonstrate imaging and detection of foci containing less than 200 cancer cells labeled with fluorescent biomarkers in 50ms and signal-to-noise ratios greater than 15dB using the custom image sensor and optical filter. We also demonstrate the detection of microscopic cancer using human tissue and residual tumor in mice models. The absence of large optical elements enables extreme miniaturization, allowing manipulation within a small, morphologically complex, tumor cavity.

Advisor: Boser, Bernhard E
Synthesis and Defect Science and Engineering of Two-Dimensional Materials

Rapid scaling of silicon-based transistors has enabled remarkable performance enhancements in integrated electronics. However, silicon-based transistors are quickly reaching theoretical scaling limits as a result of short channel effects dictated by silicon’s intrinsic material properties. As such, there is a need for alternative materials that can transcend or better address these limitations. Scaling theory suggests that atomically thin, pristine semiconductors can enable more aggressive shrinking of the gate length. Given these requirements, two-dimensional materials (2DMs) have emerged as promising alternatives because they can be scaled down to single or few atomic layers, have no dangling bonds, and exhibit unique electrical properties./nDespite the burgeoning trove of proof-of-concept demonstrations of 2DM-based devices, large-scale fabrication and commercialization remain elusive. At this time, two of the most pressing shortcomings include (1) the transfer step requirement, wherein the 2DM must be physically transferred from a growth substrate to the target substrate, and (2) the high contact resistance between the 2DM and metal contacts. These device requirements create significant bottlenecks and challenges that limit the current feasibility of 2DM implementation in everyday devices. This work focuses on two particular classes of two-dimensional materials—graphene and transition metal dichalcogenides—and highlights some of the progress made towards addressing both of these device-related issues./nTo start, this work details the development of improved transfer-free graphene synthesis by chemical vapor deposition (CVD) directly on SiO2. We outline an expansion of the parameter space that optimizes process conditions, using nickel and copper as metal catalysts and gaseous methane as the carbon precursor. We introduce a mechanism based on carbon permeability that provides deeper insight into the growth process. Low-energy electron microscopy (LEEM) is used to showcase some of the intrinsic differences between nickel and copper that lead to contrasting results. In the end, we demonstrate reproducible, monolayer graphene with low defect density using nickel as a catalyst, and reproducible, 2-3 layer graphene with uniform coverage using copper as a catalyst./nTo address the high metal–2DM contact resistance, mild hydrogen plasma treatment is applied to WSe2. X-ray photoemission spectroscopy (XPS) indicates that H2 plasma treatment selectively induces selenium vacancies in the WSe2 lattice, resulting in controllable/nn-doping with increasing plasma treatment times. WSe2 n-FETs fabricated with H2 treatment on the contact regions demonstrate two orders of magnitude decrease in contact resistance./nBy addressing some of the challenges related to graphene transfer and TMDC contact resistance, these studies help establish a foundation towards scalable integration of 2DMs in beyond-silicon electronics.

Advisor: Maboudian, Roya
Dynamics of the IFT Machinery at the Ciliary Tip

Intraflagellar transport (IFT) is essential for the elongation and maintenance of eukaryotic cilia and flagella. Due to the traffic jam of multiple trains at the ciliary tip, how IFT trains are remodeled in these turnaround zones cannot be determined by conventional imaging. Using PhotoGate, I visualized the full range of movement of single IFT trains and motors in Chlamydomonas flagella. I observed that anterograde trains split apart and IFT complexes mix with each other at the tip to assemble retrograde trains. Dynein-1b is carried to the tip by kinesin-II as inactive cargo on anterograde trains. Unlike dynein-1b, kinesin-II detaches from IFT trains at the tip and diffuses in flagella. As the flagellum grows longer, diffusion delays return of kinesin-II to the basal body, depleting kinesin-II available for anterograde transport. These results suggest that dissociation of kinesin-II from IFT trains serves as a negative feedback mechanism that facilitates flagellar length control in Chlamydomonas.

Advisor: Yildiz, Ahmet
On the Nearly Spherical Stratified Flame Propagation

Stable and reliable power is critical for not only modern conveniences, but also for basic goods and services needed to ensure protection of both life and property. To ensure a sustainable source of reliability in the global energy sector through current and future environmental and political changes and in concert with alternative and renewable production sources, current and future combustible fuels are needed to be accurately modeled. A key proponent of both natural gas and biogas is methane which has both current natural sources and future supply prospects. However there are still many fundamental questions regarding accurate modeling of the combustion of methane, and in particular within inhomogeneous mixtures. These stratification layers are less well understood in combustion environments than flames propagating through homogeneous mixtures, despite many of the current uses of this gaseous fuel in a variety of engineering systems./nA set of spherical methane-air experiments within a constant volume chamber using Schlieren imaging and pressure traces as well as supporting one dimensional and three dimensional numerical modeling was undertaken to explore stratified flames propagating through methane-air mixtures. With comparisons to past work, an investigation of the effects of the stratification layer’s impact on the observed flame speed, product gas emissions, and to evaluate the possibility of extending the lean limit. To process the Schlieren images, a robust in-house edge tracking code was developed to track the progress of the flame observed in Schlieren images and closely evaluate the transient dynamics of the flame that occur within a flame burning through a stratification layer gradient set up between two mixture concentrations using a soap bubble. A speed up on the order of 20% higher than homogeneous equivalence ratio of 1.1 was observed in the rich to lean stratified cases. The experiments and numerical work agreed reasonably well with past experimental and numerical work. Higher CO was noted while burning in a stratified environment, while lower unburnt hydrocarbons and moderately lower NOx was also noted from stratification layers compared with an equivalent homogeneous mixture. The lean limit appeared to be extended, and a discussion is given in light of the prior work and capabilities within this work./nWhile relative agreement was achieved experimentally with recent work, unexpected in- stabilities were noted in the flame that are difficult to be accounted for with the setup alone. This work adds to the possibility first mentioned and observed by Markstein, Behrens, and Einbinder of an inherent instability within stratified methane-air flames.

Advisor: Chen, Jyh-Yuan
Computationally advancing the predictive power of the nanoporous materials genome

Since tens of thousands of nanoporous materials have been synthesized and millions have been hypothesized, our ability to both predict novel materials and their performance for a given application in a computational setting is becoming increasingly important. Utilizing simulations that can screen for optimal material performance becomes invaluable since exhaustive experimental exploration of this vast chemical space can quickly become experimentally intractable from an expense and time efficiency standpoint. This thesis is therefore dedicated to advancing the computational tools and algorithms that can be used to both predict novel materials and evaluate their performance for clean energy technologies.

Advisor: Smit, Berend
Luminescence-Based Screening Methods for the Identification of Selective Peptoid-Based Ligands

The development of ligands with enhanced selectivity remains a significant challenge for targets across a range of applications, including the industrial extraction of specific components from raw or recovered materials, detection and removal of harmful contaminants, and identification of species in complex environments. In many cases, rational design is not feasible due to a limited understanding of features that confer selectivity. To this end, combinatorial methods have been employed for the identification of new selective ligands through a modular platform. Peptoids, or N-substituted glycine oligomers, were selected as a scaffold due to their facile synthesis and the ability to incorporate high chemical diversity. Libraries of peptoid-based ligands were synthesized and screened for members that displayed apparent selectivity. Two strategies have been developed to identify hits via a luminescent reporter: one uses ligands to sensitize the luminescence of Eu(III) and Tb(III), and the other incorporates a photoinduced electron transfer (PeT) system that exhibits fluorescence turn-on in the event of target binding. In addition to these screening platforms, an electrochemically-active peptoid ligand with selectivity for hexavalent chromium (Cr(VI)) was synthesized for eventual incorporation into a handheld Cr(VI) detector. Finally, indium and lithium extraction selectivity were investigated through the on-resin attachment and evaluation of established selective chelators. The work herein provides new methods for the discovery of selective ligands using luminescence-based platforms and presents initial findings to elucidate mechanisms of selectivity.

Advisor: Francis, Matthew B