VictorJuiz/thesis huggingface dataset:
Lensless Computational Imaging using Random Optics

Efficiently capturing high-dimensional optical signals, such as temporal dynamics, depth, perspective, or spectral content is a difficult imaging challenge. Because image sensors are inherently two-dimensional, direct sampling of the many dimensions that completely describe a scene presents a significant engineering challenge. Computational imaging is a design approach in which imaging hardware and digital signal processing algorithms are designed jointly to achieve performance not possible with partitioned design schemes. Within this paradigm, the sensing hardware is viewed as an encoder, coding the information of interest into measurements that can be captured with conventional sensors. Algorithms are then used to decode the information. In this dissertation, I explore the connection between optical imaging system design and compressed sensing, demonstrating that extra dimensions of optical signals (time, depth, and perspective) can be encoded into a single 2D measurement, then extracted using sparse recovery methods. The key to these capabilities is exploiting the inherent multiplexing properties of diffusers, pseudorandom free-form phase optics that scramble incident light. Contrary to their intended use, I show that certain classes of diffuser encode high-dimensional information about the incident light field into high-contrast, pseudorandom intensity patterns (caustics). Sparse recovery methods can then decode these patterns, recovering 3D images from snapshot 2D measurements. This transforms a diffuser into a computational imaging element for high-dimensional capture at video rates. Efficient physical models are introduced that reduce the computational burden for image recovery as compared to explicit matrix approaches (the computational cost remains high, however). Lastly, analysis and theory is developed that enables optimization of customized diffusers for miniaturized 3D fluorescence microscopy.

Advisor: Waller, Laura
Ng, Yi-Ren
The Role of FG Nucleoporins Amino Acid Sequence Composition in Nucleocytoplasmic Transport

Bidirectional transport of molecules through the nuclear envelope (nucleocytoplasmic transport) is a vital, yet very complex process inside eukaryotic cells. This process is facilitated by thousands of nanoscale pores embedded in the nuclear envelope, named nuclear pore complexes (NPCs). The remarkable feature of NPC is that it facilitates transport in a fast, yet selective manner. Despite numerous studies, the underlying mechanism of NPC’s function is unknown. The intricate function of NPC cannot be fully captured via experimental techniques due to small scale and rapid movement of the FG Nucleoporins, which are intrinsically disordered proteins rich in phenylalanine-glycine repeats, responsible for facilitating the transport process./nIn this dissertation, using a range of computational approaches, the role of FG Nups in the nuclear transport process is explored. FG Nups do not have a well-defined secondary structure and it is believed that their sequence composition and conformational ensemble are critical for their function in the NPC. In this dissertation, for the first time, specific sequence patterns in the charge distribution of FG Nups were identified that were not observed in other intrinsically disordered proteins. These patterns are extended sub-sequences that only contain positively charged residues, have low charge density, and are located toward the N-terminus of FG Nups. We named these evolutionarily conserved patterns like charge regions (LCRs)./nAdditionally, the role that LCRs play in the conformational ensemble and function of FG Nups was examined, using coarse-grained molecular dynamics simulations. Our simulations in multiple levels (single Nups, ring cross sections of NPC, and whole NPC) show that number of charged residues in the LCR impact the conformational ensemble of FG Nups and movement of the cargo complex. Our simulations also suggest that the number of charged residues in LCR can regulate the interaction of cargo complex with FG Nups. Since conformational ensemble of FG Nups and their interaction with cargo complex are two governing factors of the transport process, we suggest that LCRs, the unique and evolutionarily conserved features of FG Nups, are major regulators of the nucleocytoplasmic transport.

Advisor: Mofrad, Mohammad R.K.
Molecular Basis of Natural Phytochemical Effects on Mammalian Signal Transduction and Membrane Ion Transport

Natural products have been used for their medicinal properties throughout history, from ancient Mesopotamia to modern day herbal medicine. It is also estimated that 60% of currently available drugs are derived, either directly or indirectly, from natural products. Natural phytochemicals have been shown to exert strong anti-cancer, anti-obesity, and anti-bacterial effects as well as play a protective role against inflammation in the body and the brain. Due to their pleiotropic effects, these natural compounds have tremendous potential for treatment in diseases, such as melanoma and traumatic brain injury, where the heterogeneity within the tumor and among patients, respectively, has been shown to impede the development of new pharmacological agents for treatment. Melanoma, accounting for 3% of all skin cancers, but responsible for 65% of all skin-cancer related deaths, represents a great burden continuously on the rise. Current treatment options for metastatic melanoma offer short-term reprieve as resistance, due to intratumor heterogeneity, occurs within several months. Therefore, identification of a compound that can inhibit cell proliferation, regardless of the phenotype, is of dire need. Here, we show the anti-proliferative effects of 3’3-diindolylmethane (DIM), a bioactive compound found in cruciferous vegetables, on a diverse selection of melanoma cell lines. DIM inhibits cell growth in all treated melanoma cells through the down-regulation of the “master-regulator” of melanoma biology, the transcription factor, MITF-M. Due to its low toxicity, combining DIM with already established direct target therapies, could help patients overcome tumor heterogeneity driven- resistance without the deleterious effects of “cocktail-mixing”. We also describe for the first time a novel activator of the inwardly-rectifying potassium channel, Kir7.1. Progesterone, known for its positive effects following traumatic brain injury, was shown to potentiate Kir7.1 current in multiple cell types, including choroid plexus epithelial cells, in a G-protein independent manner. We found this progesterone-induced activation of Kir7.1 was inhibited in the presence of 20μM ursolic acid. Here, we describe for the first time an endogenous activator and natural phytochemical inhibitor of the Kir7.1, a vital ion channel in mammalian physiology.

Advisor: Firestone, Gary
Lishko, Polina
Authorship in Crisis: German Cinema and the Changing Roles of the Writer

In my dissertation I examine the ways in which the concept of authorship, and its related discourses of authority, control, and artistic value, were destabilized by the introduction of the new film medium. Film not only represented collaborative work on an unprecedented scale, it was a mechanical technology that functioned without the spoken word. These characteristics resisted association with literary and artistic value, understood in the German context primarily through the figure of the Dichter (poet). This not only made it an object of intense criticism as supposedly valueless entertainment, the very way in which films were made, marketed, and received struggled to find language and frameworks to conceptualize film and filmmakers. I trace these changes through analyses of the reception of the films Der Student von Prag (1913), Phantom (1922), and Die Dreigroschenoper (1931). In particular I look at the way the writers, producers, directors, or actors of these films are represented as the originators, primary creative “voices,” or authorities of the production.

Advisor: Kaes, Anton
Transcriptional Correlates of Homeostatic Plasticity and Neuronal Diversity at the Neuromuscular Junction

Synapses are specialized intercellular junctions between a neuron and its target that allows for rapid communication between cells. Neurons and their synapses have multiple adaptive mechanisms to stabilize communication in response to a barrage of different environmental challenges. While there is an enormous body of literature on the mechanisms of these phenomena from a functional standpoint, less is known about (1) how these processes are orchestrated at the genetic level and (2) how differences in neuron type inform the capacity to enact such mechanisms./nTo address these questions I turn to the Drosophila larval neuromuscular junction (NMJ). The Drosophila NMJ is a model glutamatergic synapse in which a motor neuron communicates with the body wall muscles to control motor output. Each muscle fiber receives input from two different types of glutamatergic neurons, each of which has unique physiological properties. Previous work has shown that blocking the receipt of glutamate by the downstream muscle by genetic mutation results in a retrograde homeostatic mechanism that potentiates synaptic transmission in a manner specific to neuronal subtype. The molecular and genetic determinants of this process are a mystery in the field, opening up even more questions about how gene expression can control a neuron's capacity to adapt to imbalances in network activity and synaptic strength./nIn this dissertation, I use the tools of functional genomics to investigate different homeostatic mechanisms at this model synapse and to characterize transcriptional diversity within Drosophila larval motor neurons. First, I demonstrate that specific loss of key proteins in synaptic transmission in motor neurons induces homeostatic compensation, which features an increase in activity and altered expression of proteins that contribute to neuronal firing. Second, I show that mutation of a gene involved in the organization of the muscular cytomatrix mimics a classic model of presynaptic homeostatic potentiation. This new model also has alterations in cell-adhesion molecules which may be causal for this mode of homeostasis. Finally, I characterize the transcriptional diversity of glutamatergic motor neurons in this system, revealing that the expression of ion channels and activity regulated genes is correlated with temporal identity.

Advisor: Isacoff, Ehud Y
Cosserat Curves: Descriptions of Peristalsis and a Discrete Model

In this work, problems and developments in the mechanics of slender, or rod-like bodies,/nare presented. We begin by offering a modern perspective on Green and Naghdi’s developments of the latter half of the 20th century for a directed rod. This review serves as background material to the more novel parts of this dissertation, which include applications and a discretization of the continuous theory. Governing equations for rods are developed by derivation from three-dimensional continuum mechanics and by direct approach. A treatment of constraints is also presented./nAfter the background material is reviewed, we thoroughly describe a model for peristaltic locomotion using Green and Naghdi’s directed rod theory. The resulting model is applied to simulating motions of a compressible soft robot which uses Poisson’s effect for peristalsis. In addition, a calibration of parameters results in a validation of the model for use in biomimetic modeling of earthworm locomotion. Incompressibility of the worm is enforced as an internal constraint of the directed rod. In addition, a pair of muscle actuation models for a single continuum is included in our discussion./nFinally, a discrete model for elastic rods undergoing planar motions is presented based on the theory of the directed rod. Discrete edge vectors and directors are used to capture cross section deformations including stretch, stretch gradients, shear, shear gradients, and the Poisson effect. In addition, deformations such as longitudinal stretch and bending are also incorporated. The model is validated with the help of known analytical solutions to benchmark problems from Green and Naghdi’s continuous rod theory.

Advisor: O'Reilly, Oliver
Superconducting Qubit Enabled Single Microwave Photon Detection

Superconducting quantum bits (qubits) are a leading candidate towards realizing a processor that is able to outperform existing classical computers at select tasks. One particular qubit architecture, the transmon, boasts long coherence times compared to required gate lengths and flexibility with respect to circuit couplings as these 'artificial atoms' are photolithographically defined. These attributes allow qubits to be leveraged for other tasks as well — such as efficiently detecting itinerant microwave photons. Such a device may prove useful for remote entanglement protocols, quantum optics experiments in the microwave regime, and as a detector for low-mass dark matter./nThrough a blend of circuit quantum electrodynamics (cQED) and waveguide quantum electrodynamics (wQED) theories, high detector performance was achieved even when the photon arrival time was not known. Utilizing an ensemble (N = 4) of identical transmon absorbers, photon mediated interactions along a common waveguide enable absorbed itinerant photons to be trapped for longer than the inverse of the bandwidth of an individual qubit. This extended trapping time allows for sufficient integration of the dispersively shifted readout resonator to resolve deviations from vacuum with high fidelity.

Advisor: Siddiqi, Irfan
Biosynthesis of Antimycin-Type Depsipeptides and Cyclohexylcarbonyl-CoA

From the original medicinal plants to the modern formulation laboratories, natural products have played a central role in pharmaceutical science. As technologies have improved from crude extraction to product isolation, and then to heterologous expression and chemical and semi-synthesis, the field of natural product chemistry has expanded greatly. It has produced potent antibiotics, immunosuppressants and anti-cancer drugs. But central to drug discovery is derivitization and the development of new drugs. This can be accomplished by discovering and characterizing new natural product biosynthetic pathways or by developing individual biocatalysts for the alteration of chemical scaffolds. Included in this work are examples of both strategies and each lends new insight and new tools to metabolic engineering and biocatalysis./nThe complete characterization of the 15-membered ring depsipeptide neoantimycin biosynthetic gene cluster establishes a biosynthetic route to producing a potent anti-cancer natural product scaffold. Moving this to a heterologous host allowed further engineering of that assembly line with the potential for producing novel neoantimycin derivatives. To demonstrate this, two separate engineering strategies were carried out, and eventually combined, to generate novel analogs. This engineerable hosts suggests that the bioproduction of a small library of neoantimycin analogs for drug discovery may be possible. Additionally, the characterization of a ring expanded antimycin assembly line, provides the necessary knowledge of future study and engineering of the entire family of antimycin depsipeptides./nTo address the use of individual biocatalysts in natural product production, two enzymes from the cyclohexylcarbonyl-CoA biosynthetic pathway were fully characterized. The first, a shikimate-CoA synthetase, was shown to be highly promiscuous toward a wide range of small, cyclic carboxylic acids. This has the potential to contribute to drug discovery through the generation of novel thioesters for incorporation into natural product scaffolds. Similarly, an acyl-CoA dehydrogenase was shown to in fact be an acyl-CoA dehydratase that could lead to a new precursor supply of novel thioesters. Together, this work contributes significant new knowledge to the field of biosynthesis and biocatalysis. It provides two new enzymes to the metabolic engineering toolbox, and establishes a system for producing a bioactive scaffold for anti-cancer drug discovery.

Advisor: Zhang, Wenjun
Nomura, Daniel
Camp as a Weapon: Chicano Identity and Asco's Aesthetics of Resistance

This dissertation examines the aesthetic phenomenon of camp in the work of the East Los/nAngeles-based art group, Asco. Founded by Harry Gamboa, Jr., Gronk, Willie Herrón,/nIII, and Patssi Valdez in the early 1970s, Asco produced a distinct blend of conceptual/nand performance-based art, which they exhibited in alternative art spaces and distributed/nas correspondence art. The group’s name, which means “nausea” in Spanish, speaks to/nthe sensation their often provocative and politically motivated art ostensibly produces./nThe basis of this reaction lies in the stark contrast of Asco’s work to established Chicano/nart that emerged during the Chicano Movement./nI organize my study through a consideration of each of Asco’s camp targets, or the/nobjects of their critiques. These include the exploitation and oppression of the Chicano/ncommunity, the limitations and liberation in Chicano muralism, and the glamour and/nbiases of Hollywood. Each of these denote cultures and movements with which the young/nartists were enamored as well as alienated from in a complex insider/outsider relationship/nthat enables camp critique./nThrough analysis of Gronk’s proto-Asco performance Caca-Roaches Have No Friends/n(1969), I establish a clear foundation for camp that corresponds to Moe Meyer’s assertion/nthat camp is a specifically queer tactic of disidentification. I refer to the infamously/nprovocative scene in Gronk's play starring Cyclona (Robert Legorreta) as horror drag to/nemphasize the intended camp target: homophobia within the Chicano community./nThrough a investigation of Asco’s early street performances and No Movies I further/ndemonstrate that Asco uses Chicano rasquache and domesticana tactics, as described by/nTomas Ybarra Frausto and Amalia Mesa-Bains respectively, in order to critique Chicano/nand Anglo-American cultures. Asco deploys these three aesthetic tactics to challenge/nproblematizing identifiers of ethnicity, gender, sexuality, and class.

Advisor: Bryan-Wilson, Julia
Coisotropic Branes on Tori and Homological Mirror Symmetry

Homological mirror symmetry (HMS) asserts that the Fukaya category of a symplectic manifold/nis derived equivalent to the category of coherent sheaves on the mirror complex manifold./nWithout suitable enlargement (split closure) of the Fukaya category, certain objects of it are/nmissing to prevent HMS from being true. One possible solution is to include coisotropic/nbranes into the Fukaya category. This thesis gives a construction for linear symplectic tori of/na version of Fukaya category including coisotropic branes by using a doubling procedure, and/ndiscussing the relation between the Fukaya category of the doubling torus and the Fukaya/ncategory of the original torus.

Advisor: Auroux, Denis
Statistical Mechanics and Hydrodynamics of Active Fluids

In this thesis, I present work pertaining to the continuum modeling of active fluids. The main results are as follows. I derive Green-Kubo equations for the components of the viscosity in two-dimensional fluids with and without internal angular momentum. These equations illustrate the connection between the breaking of time-reversal symmetry at the microscopic level and the emergence of odd viscosity, a non-dissipative transport coefficient. They also show the potential for a new, previously unconsidered rotational viscosity in fluids in which internal spin couples to velocity. By numerically verifying the Green-Kubo equation for odd viscosity, we provide support for the use of the Onsager regression hypothesis in its derivation, where this hypothesis is applied to fluctuations about a nonequilibrium steady state. I also study the canonical active system known as Active Brownian Particles via a coarse-graining analysis. This approach indicates that in such systems, activity manifests at the continuum level in the form of a body force, rather than as an addition to the stress tensor, as has been previously assumed in the literature. It also elucidates the connection between mass currents and inter-particle alignment interactions. Taken as a whole, these results provide guidance for the project of writing down continuum descriptions of active matter, and elucidate the connections between microscopic and macroscopic behavior for nonequilibrium systems.

Advisor: Mandadapu, Kranthi K
Pathway and organelle engineering for production of useful chemicals in yeast

Researchers in the field of metabolic engineering aim to develop processes to produce/nuseful chemicals, sustainably and responsibly, using biotechnology. These processes are/noften designed to replace products derived from fossil fuels, which are unsustainable and/ncontribute to climate change, or plant-based products, which compete with food/nproduction for scarce land and are subject to supply uncertainty due to weather, crop/ndisease, and climate change. Here, we present two research projects in metabolic/nengineering. First, we demonstrate microbial production of the red food dye betanin by/nengineering the betalain biosynthesis pathway into yeast. Betanin is currently/nmanufactured through extraction from red beets specifically grown for dye production./nWe achieved betanin production levels of 17 mg/L, which is equivalent to the amount of/nbetanin found in 10 g/L of beet extract. With further production improvements, this/nbioprocess may become cost-competitive with agricultural production and is likely to/nlead to a purer product. We also demonstrate the synthesis of a suite of non-natural/nbetalain dyes achieved through feeding of diverse amines to a yeast production host,/nincluding several which have never been reported. In the second research project, we/ndiscover that an enzyme that limits production levels of a drug family is toxic to the yeast/nproduction host. This enzyme, norcoclaurine synthase, is critical to the production of/nbenzylisoquinoline alkaloids, an important family of medicines that are extracted from/nplants like the opium poppy. We devised a novel subcellular compartmentalization/nstrategy, sequestering norcoclaurine synthase in the peroxisome to alleviate cytotoxicity/nwhile maintaining access to the enzyme’s substrates. By targeting norcoclaurine synthase/nfor organellar compartmentalization, we achieved improved cell growth, final titer, and/nculture productivity. These projects highlight the potential of engineering complex plant/npathways into microbial hosts for economical and sustainable chemical production.

Advisor: Dueber, John E
Clark, Douglas S
Lattice atom interferometry in an optical cavity

Atom interferometers are powerful tools for both measurements in fundamental physics and inertial sensing applications. Their performance, however, has been limited by the available interrogation time of freely falling atoms in a gravitational field. In this thesis, we realize an unprecedented interrogation time of 20 seconds by suspending the spatially separated atomic wavepackets in the resonant lattice of an optical cavity. Unlike traditional atom interferometers, our approach allows gravitational potentials to be measured by holding, rather than dropping, atoms. After seconds of hold time, gravitational potential energy differences from as little as microns of vertical separation generate megaradians of interferometer phase. This trapped geometry suppresses the phase variance due to vibrations by three to four orders of magnitude, overcoming the dominant noise source in atom-interferometric gravimeters.

Advisor: Müller, Holger