VictorJuiz/thesis huggingface dataset:
Optogenetic studies of brain disease [electronic resource] : engineering light delivery into biological tissue

Optogenetic neuromodulation is giving scientists an unprecedented ability to modulate neural circuits, providing specificity with regards to location, cell type, as well as neuromodulatory effect. On the other hand, electrical stimulation and lesions, methods commonly used to study neural circuits, are lacking in specificity, often affecting both local cells and passing axons, as well as multiple cell types. Our laboratory has been at the forefront of the field of optogenetics, having developed, for use in mammalian systems, Channelrhodopsin-2 (ChR2), an algal light-activated cation channel that depolarizes neurons in response to blue light, and Natronomonas pharaonis halorhodopsin (eNpHR), a chloride pump that hyperpolarizes neurons in response to amber light. These proteins can control neuronal activity with millisecond timescale precision, and through promoters, they can be targeted to specific cell-types in heterogeneous tissue. Along with its specificity, light stimulation with optogenetic tools often allows the recording of neural activity without the artifact that obfuscates recordings with electrical stimulation. The advantages provided by optogenetics allowed us to make a breakthrough in determining the therapeutic mechanism of deep brain stimulation, a robust treatment for Parkinson's disease in which stimulating electrodes are implanted deep in the brain. Using optogenetics, we replicated the effect of deep brain stimulation by modulating cortical inputs into the region where the stimulating electrode is normally placed. Combined with other corroborating publications, a hypothesis is emerging that electrical stimulation deep in the brain actually produces its effect by modulating cortical projections to the deep brain region. Based on this concept, several clinical studies are being done to better understand the cortical role in Parkinson's disease and determine whether cortical stimulation (potentially non-invasive), could be an alternative to the invasive implants currently used. In order to perform these experiments, we studied the transmission of visible light in brain tissue to estimate the volume of activation produced by optogenetic stimulation and developed a device to measure fluorescence in awake, behaving animals, allowing the quantification of virally transfected gene expression over time, as well as the localization of expression along axon bundles. The knowledge gained from these experiments will have a significant impact on future experiments in the broader field of optogenetics.

Keywords: Bioengineering.
Advisor: Deisseroth Karl primary advisor. Thesis advisor
Graves Edward (Edward Elliot)
Henderson Jaimie (Jaimie M.) advisor. Thesis advisor
Palanker Daniel advisor. Thesis advisor
Shenoy Krishna V. (Krishna Vaughn) advisor. Thesis advisor
Organic transistors for flexible electronics [electronic resource] : fabrication and device physics

Organic semiconductors have shown promising potentials in flexible electronics. Because the materials can be directly fabricated on flexible plastic substrates at low temperatures, researchers envision development of novel flexible applications, such as flexible displays, flexible circuits, and conformal sensors. In order to develop these practical devices, organic transistor technologies should provide reliable fabrication processes and mature techniques to control the electrical characteristics of each device. In this dissertation, I will discuss several methods to overcome these issues. First, I have demonstrated high-capacitance gate dielectric using atomic layer deposition. This low-temperature process was used to fabricate low-voltage and high-performance flexible organic transistors and inverters. I will also present controlling current-voltage characteristics of organic transistors from the device physics point of view.

Keywords: Electrical Engineering
Advisor: Bao Zhenan primary advisor. Thesis advisor
Murmann Boris primary advisor. Thesis advisor
Nishi Yoshio
Orientability of moduli spaces and open Gromov-Witten invariants [electronic resource]

We show that the local system of orientations on the moduli space of J-holomorphic maps from a bordered Riemann surface is isomorphic to the pull-back of a local system defined on the product of the Lagrangian and its free loop space. The latter is defined using only the first and second Stiefel-Whitney classes of the Lagrangian. In the presence of an anti-symplectic involution, whose fixed locus is a relatively spin Lagrangian, we define open Gromov-Witten type invariants in genus zero.

Keywords: Mathematics
Advisor: Ionel Eleny primary advisor. Thesis advisor
Eliashberg Y.
Li Jun (Mathematician) advisor. Thesis advisor
The origin and evolution of alpha-catenin in epithelial cell polarity [electronic resource]

A fundamental characteristic of metazoans is the formation of a simple, polarized epithelium. In higher animals, the structural integrity and functional polarization of simple epithelia require a cell-cell adhesion complex containing a classical cadherin, the Wnt-signaling protein [Beta]-catenin and the actin-binding protein [Alpha]-catenin. I have investigated the evolutionary origins of epithelial cell polarity and of the cadherin-catenin complex. I show that the non-metazoan Dictyostelium discoideum forms a polarized epithelium that is essential for multicellular development. Although D. discoideum lacks a cadherin homolog, I have identified and characterized an [Alpha]-catenin ortholog that binds a [Beta]-catenin-related protein. Both proteins are essential for formation of the epithelium, polarized protein secretion and proper multicellular morphogenesis. Thus the organizational principles of metazoan multicellularity may be more ancient than previously recognized, and the role of the catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins.

Advisor: Weis William I. primary advisor. Thesis advisor
King Nicole
Oro Anthony
Spudich James A.
P53 transactivation-domain mutant mice reveal context-specific differences in P53's mechanism of action [electronic resource]

The p53 protein suppresses tumorigenesis by inducing cell cycle arrest, apoptosis, or cellular senescence. At the molecular level p53 plays a central role as a transcriptional activator, and p53 has two amino-terminal transactivation domains important for this role. However, the contribution of each of these domains to p53 activity has not been determined in vivo. To analyze transactivation domain requirements for p53 function, we have generated a series of p53 knock-in mouse models in which we replaced the endogenous p53 gene with transactivation mutants containing point mutations in the first (p53^25,26), second (p53^53,54), or both (p53^25,26,53,54) p53 transactivation domains. These experiments are the first to address the unique contribution of each of the p53 transactivation domains in vivo. By gene expression microarray, we determined that these mutants represent an allelic series of p53 transactivation mutants, whereby p53^53,54 retains wild-type p53 transactivation potential, p53^25,26,53,54 loses nearly all p53-dependent transactivation, and p53^25,26 exhibits a severely compromised transactivation phenotype. Experiments comparing all three transactivation domain mutants in cell culture and mouse models have unveiled important differences in the function of the two transactivation domains. Apoptosis or cell-cycle arrest downstream of acute DNA damage rely on the first transactivation domain and robust p53 transactivation, while senescence and tumor suppression in response to oncogene activation can occur without the full transactivation function of p53. These results implicate unique p53 transcriptional programs in acute DNA damage responses and tumor suppression, and mechanistically distinguish these two p53 response pathways. Further, we have uncovered striking differences in the developmental phenotypes of these different mutant mice, leading to conclusions about the activity of p53 tetramers.

Advisor: Attardi Laura primary advisor. Thesis advisor
Brunet Anne
Lipsick Joseph Steven
Sage Julien advisor. Thesis advisor
Pade-legendre method for uncertainty quantification with fluid dynamics applications [electronic resource]

Abstract: The Pade-Legendre (PL) method, a novel approach for uncertainty quantification is introduced. The proposed method uses a rational function expansion and is designed to effectively characterize uncertainties in strongly non-linear or discontinuous systems. The discontinuities can be either in the underlying functions (inherent discontinuities) or from lack of sufficient data resolution (multi-scale discontinuities). In the former case, PL method can produce an accurate response surface without spurious oscillations and does not require prior knowledge of the discontinuities. For the latter type of discontinuities, the PL method can help reduce the number of deterministic simulations required to accurately represent the response surface. If sufficient data resolution is achieved, the PL method degenerates to standard polynomial reconstruction. The present approach is illustrated in a number of applications as an uncertainty propagation technique. Moreover, the method is applied to an inference problem in which a sharp discontinuity in the system input is present. The PL method shows a considerable improvement over the traditional approach when discontinuities are present. In addition, an ongoing effort called the UQ Experiment in which we used the PL method to help design the experimental setup is discussed.

Keywords: Mechanical Engineering
Advisor: Iaccarino Gianluca primary advisor. Thesis advisor
Najm Habib (Habib Nasri) advisor. Thesis advisor
Papanicolaou George advisor. Thesis advisor
Part I, unnatural thymidine analogs and shape mimics as substrates for human thymidine kinases; Part II, fluorescent size-expanded DNA analogs as efficient substrates for a template-independent DNA polymerase. [electronic resource]

This thesis is composed of two separate studies involving unnatural nucleoside (DNA) analogs in two different types of enzymes: human thymidine kinases 1 and 2 and terminal deoxynucleotidyl transferase (TdT). The ability of two types of unnatural DNA analogs, nonpolar nucleoside analogs and expanded nucleoside analogs, to act as efficient substrates in enzymes will be described. Nonpolar nucleoside analogs lacking the ability to hydrogen bond were synthesized to systematically vary in size and shape, and then used to probe the ability of two types of human thymidine kinases (TK1 and TK2) to recognize and phosphorylate these analogs. The results establish that nucleoside recognition mechanisms for these two classes of thymidine kinase are very different. On the basis of this data, nonpolar nucleosides are likely to be active in the nucleotide salvage pathway in human cells, suggesting new designs for bioactive molecules. Another class of nucleoside analogs, expanded nucleoside (xDNA) analogs, maintain the ability to hydrogen-bond to their respective natural bases, but have enhanced pi-stacking due to their larger size, allowing the molecule to have greater stability in a DNA duplex, and unique fluorescent properties. It was found that terminal deoxynucleotidyl transferase (TdT), a template-independent DNA polymerase, can accept multiple xDNA nucleotide analogs as substrates with efficiencies close to that of natural nucleotides. In addition, the expanded adenine (xA) and cytosine (xC) analogs show a visible and spectral change in fluorescence when TdT incorporates multiple analogs. The ease of enzymatic synthesis of these analogs and their inherent fluorescence suggest their use in nucleic acid labeling and hybridization studies. The comparable efficiencies which nonpolar nucleoside analogs and xDNA nucleotide analogs have to natural bases in thymidine kinases and TdT give new information about the steric and electronic requirements of these enzymes, and will be useful for potential therapeutic and biotechnological applications.

Keywords: Chemistry
Advisor: Kool Eric T. primary advisor. Thesis advisor
Chen James Kenneth advisor. Thesis advisor
Waymouth Robert M. advisor. Thesis advisor
Path-policy compliant networking and a platform for heterogeneous IaaS management [electronic resource]

The dissertation is divided into two parts, each of which can stand independently of the other: ICING and Expedient. The ICING project aims to build a network architecture that empowers the end-points of a communication by giving them control over the path used for the communication. The challenge is providing this control without violating the policies of the providers carrying the communication's traffic and ensuring that the path is followed. ICING consists of a number of sub-projects: ICING-PVM, ICING-ON, and ICING-L3. Expedient is an answer to the following question: How can users manage resources across a federated set of Infrastructure-as-a-Service (IaaS) providers? These resources may be heterogeneous, consisting of different types of network, compute, or other resources, they may be sliced, virtualized, or fully delegated, and they may cross trust boundaries. Expedient provides a platform that gives users access to all resources using one set of credentials, does not require infrastructure developers to change their systems, and allows infrastructure providers to enforce their policies concerning the use of their resources. This dissertation discusses Expedient in the context of GENI, a federated set of IaaS providers with the goal of providing resources for experimental network research.

Keywords: Electrical Engineering
Advisor: Mazières David (David Folkman)
McKeown Nick primary advisor. Thesis advisor
Walfish Michael Howard advisor. Thesis advisor
Permutations with interval restrictions [electronic resource]

This thesis studies the problem of the random transposition walk on permutations with interval restrictions. The mixing time of this Markov chain is explored, and a number of different cases are considered. For the case of bounded interval restrictions, a polynomial bound for the mixing time is achieved. For a specific example of bounded interval restrictions called Fibonacci permutations, the correct order of the mixing time is derived. An example of a family of interval restriction matrices for which the random walk mixes in exponential time is provided, showing that the walk in general does not mix in polynomial time. The case of one-sided interval restrictions is also studied, and cut-off is shown for a large class of one-sided interval restriction matrices. Furthermore, examples are provided in which chi-squared cut-off occurs, while total variation mixing occurs significantly earlier without cut-off. Finally, a coupling argument showing the correct order mixing time for the random transposition walk on the whole symmetric group is presented. This is achieved via projection to conjugacy classes and then a path coupling argument.

Keywords: Mathematics
Advisor: Diaconis Persi primary advisor. Thesis advisor
Dembo Amir advisor. Thesis advisor
Wood Philip Matchett advisor. Thesis advisor
Phase fluctuations in microcavity exciton polariton condensation [electronic resource]

In a homogeneous two-dimensional system at non-zero temperature, although there can be no ordering of infinite range, an ordered superfluid phase is expected to occur for a Bose liquid. Theory predicts that, in this phase, the correlation function decays with distance as a power law, and quantum vortices are bound to antivortices to form molecular-like pairs. We study the relevance of this theory to microcavity exciton polaritons. These are two-dimensional bosonic quasiparticles formed as a superposition of a microcavity photon and a semiconductor quantum well exciton, and have been shown to condense at high enough densities. Because of the short lifetime, equilibrium is not established, but we instead probe the steady state of the system, in which particles are continuously injected from a pumping reservoir. We employ a Michelson interferometer setup to measure the first order spatial correlation function of such a condensate. The gaussian form of the short-distance decay allows us to define an effective thermal de Broglie wavelength, although the system is not in thermal equilibrium. The long-distance decay is measured to be a power law with an exponent in the range 0.9-1.2, larger than is possible in equilibrium. Our non-equilibrium theory suggests that this can be attributed to laser pumping noise. We also present our observation of a single vortex-antivortex pair in a condensate of the appropriate size. Pairs are generated due to pumping noise, and are formed sequentially at the same point due to the inhomogeneous pumping spot profile. They are revealed in the time-integrated phase maps acquired using Michelson interferometry. Our results suggest that vortex-antivortex pairs can be created in a two-dimensional condensate without rotation or stirring. The observed correlated motion of a vortex and antivortex imply that vortex-antivortex pairs do not dissociate, which is consistent with the measured power law decay of the spatial correlation function. These two experiments uniquely describe the condensate phase fluctuations and provide stringent tests to theories of nonequilibrium condensation. They also highlight the exciton polariton condensate as a very well characterized system showing mesoscopic coherence and deepen our understanding of fundamental two-dimensional bosonic physics. Progress in this field is expected to lead towards long-sought applications such as quantum simulation or low-threshold laser sources.

Keywords: Physics
Advisor: Yamamoto Yoshihisa primary advisor. Thesis advisor
Fetter Alexander L.
Kasevich Mark A. advisor. Thesis advisor
Photoacoustic molecular imaging and its biomedical applications [electronic resource]

Biomedical imaging has seen a tremendous shift over the past decades, moving to non-invasive and high spatial-resolution imaging, spanning multiple imaging modalities and applications. However, one common limitation of traditional medical imaging is its intrinsic inability to provide information on the molecular levels of various biomarkers. Molecular Imaging solves this limitation by introducing an exogenous imaging agent that upon administration to the subject, binds to or interacts with the molecular target(s) and produces an imaging signal. The agent can be designed to produce the imaging signal in the form of visible fluorescent light, gamma rays, ultrasound waves and other forms of energy. In this thesis, we summarize our work on Photoacoustic Molecular Imaging, a technique where short laser light pulses are converted into ultrasound waves by a nanoparticle that was molecularly targeted to a diseased site. We summarize the physical basis for the technique and its first demonstration -- highlighting angiogenesis markers in living subjects (Chapter 2). We then summarize the development of second generation photoacoustic imaging agents and demonstrate their utility in ultrahigh sensitivity molecular imaging of tumors (Chapter 3) as well as in multiplexing studies (Chapter 4). Next, we describe a novel application for Photoacoustic Imaging in visualizing the retina and the posterior eye segment with unprecedented depth of penetration, giving hope for early diagnosis of age-related macular degeneration and other retinal diseases (Chapter 5). We then describe a novel molecular imaging technology called Optical Coherence Contrast Imaging, and demonstrate it provides ultrahigh resolution and sensitivity images of gold nanoparticles in living mice eyes (Chapter 6). Finally, we conclude with various therapeutic and theranostic (therapy and diagnostic combined) concepts and highlight the synergy between them and the imaging methods presented in earlier chapters (Chapter 7).

Keywords: Electrical Engineering.
Advisor: Gambhir Sanjiv Sam primary advisor. Thesis advisor
Harris J. S. (James Stewart)
Wang Shan advisor. Thesis advisor
Photon management in hydrogenated amorphous silicon solar cells using periodic nanostructures [electronic resource]

Solar technology is a leading candidate for clean energy production. Silicon is an excellent material for photovoltaic (PV) applications due to its low toxicity, abundance, long term stability, and well developed processing technologies. Crystalline Si solar cells currently dominate the photovoltaic market despite requiring more material and more energy-intensive manufacturing processes than their thin-film counterparts. Thin-film silicon, e.g. amorphous silicon (a-Si:H), provides the advantage of decreasing material costs over crystalline silicon. Because the material is amorphous, there are many defects, which results in a small minority carrier diffusion length. Thus, a thinner absorber is required. However, thinner absorber layers do not absorb light effectively, resulting in poor cell performance. If the active material could be made to absorb all of the light in a film with a thickness approximately equal to the minority carrier diffusion length, the open-circuit voltage (Voc), short-circuit current (Jsc), and fill factor (FF) of the device would be greater than those of a thicker cell. My research is comprised of three parts: (1) developing a nanostructure fabrication process, (2) designing device geometries for alternative light trapping strategies in both substrate and superstrate configurations, and (3) investigating the effects of nanostructures' morphologies on the optical and electrical properties of devices. In contrast to the use of randomized surface texturing to improve the coupling of light into the active material, we employed periodic nanostructures to couple incident light into guided modes that propagate in the plane of the absorber. This approach can significantly increase the optical path length inside a thin absorber layer. To achieve this goal, I first developed a nanostructure fabrication process by combining self-assembly and reactive ion etching. We then employ these as-made nanostructures in a-Si:H solar cells. The periodic-nanostructure devices show an enhanced absorption and photocurrent generation in comparison with planar cells. We used FTDT studies to confirm that the increased photocurrent was indeed caused by enhanced absorption. We also systematically studied the effects of morphological parameters on light-trapping efficiency and electrical characteristics of the device. With my optical and electrical findings, we have achieved efficiencies up to 9.7% for devices with substrate configurations and 11.2 % for devices with superstrate configurations.

Keywords: Materials Science and Engineering
Advisor: Cui Yi
Fan Shanhui
Prinz F. B. advisor. Thesis advisor
Phylogenetic inference of the Tibeto-Burman languages or on the usefulness of lexicostatistics (and "megalo"-comparison) for the subgrouping of Tibeto-Burman [electronic resource]

It has been argued that lexicostatistical methods cannot be fruitfully applied to the Tibeto-Burman (or the larger Sino-Tibetan) language family. This dissertation first develops a statistical method for determining linguistic cognates (or sound correspondences) between arbitrarily many languages. This method is then applied to a subset of the Sino-Tibetan languages to infer the correspondences and further develops a method for lexicostatistical analysis for subgrouping those languages. The output of these methods agrees very well with that determined by the traditional comparative method. Furthermore, this method yields both greater resolution of the subgroupings, and provides statistical inference of the confidence in the various groupings.

Keywords: Anthropological Sciences
Advisor: Fox James primary advisor. Thesis advisor
Brown Melissa advisor. Thesis advisor
Sun Chao advisor. Thesis advisor