VictorJuiz/thesis huggingface dataset:
Photon shot noise limits on optical detection of neuronal spikes and estimation of spike timing [electronic resource]
Keywords: Applied Physics

Optical approaches for tracking neural dynamics are of widespread interest, but a theoretical framework quantifying the physical limits of these techniques has been lacking. We formulate such a framework by using signal detection and estimation theory to obtain physical bounds on the detection of neural spikes and the estimation of their occurrence times set by photon statistics (shot noise). These bounds are succinctly expressed via a discriminability index that depends on the kinetics of the optical indicator and the relative fluxes of signal and background photons. This approach facilitates quantitative evaluations of different indicators, detector technologies, and data analyses. We compare various types of Ca-2+ indicators and show that background photons are a chief impediment to voltage sensing. Thus, voltage indicators that change color in response to membrane depolarization may offer a key advantage over those that change intensity. We also identify the regimes in which commonplace ratiometric analysis of signals from fluorescence resonance energy transfer (FRET) indicators is sub-optimal and describe new, optimal filtering techniques. Overall, our treatment offers a valuable guide to experimental design, by showing how different optical factors interact to affect signal quality, and provides measures of confidence to assess optically extracted traces of neural activity.
Photovoltaic retinal prosthesis [electronic resource]
Keywords: Electrical Engineering

Degenerative retinal diseases are among the leading causes of vision loss in the developed world. In these diseases, the "image capturing" photoreceptor layer slowly dies while the "image processing" inner retinal layers are preserved to large extent. One approach to restore vision of patients suffering from the selective photoreceptor loss is to deliver information to the visual system by patterned electrical stimulation of the remaining retinal circuitry. Several retinal prosthetic systems have achieved promising results in clinical studies, with the most successful prostheses allowing blind people to read large letters. However, the current retinal prosthetic designs require a trans-scleral cable to deliver power or data to the retinal stimulating array. We designed a photovoltaic prosthetic system with a silicon photodiode array placed behind the retina, in which each pixel of the array photovoltaically converts patterned pulsed near-infrared light projected from video goggles into pulses of bi-phasic electric current to stimulate the nearby retinal neurons. The light-powered 30-µm thick photodiode array does not require any wired power connections, which greatly simplifies the surgical procedure and reduces chances of infection. Several arrays could be juxtaposed to tile a larger area on the retina and thereby expand the visual field. The local return electrodes in each pixel help to reduce the spatial spread of electric current, thereby reducing the cross-talk between pixels and improving the spatial resolution of the implant. Each pixel contains three photodiodes connected in series to increase charge injection levels. Deep reactive-ion etched trenches are used to isolate the three photodiodes in each pixel. Trenches between the pixels are open to allow perfusion of nutrient, which is essential for in-vitro electrophysiological experiments, and may also help with the in-vivo integration of the implant with the retina. We fabricated 1 and 2 mm wide arrays of photodiode for implantation in small and large animals. Three sizes of pixels (280 µm, 140 µm and 70 µm) were fabricated to explore the resolution that could be achieved by the implant. The development of the fabrication process for the silicon photodiode array is presented, which involves eight mask layers, including deep isolation trench etch, n+ region predeposition, p+ region ion implantation, first via etching, first metal deposition and liftoff, second via etching, polysilicon etching in selected trenches, second metal deposition and liftoff. A detailed optoelectronic characterization of the fabricated photodiode array is also presented. The initial electrophysiological results of retinal stimulation in-vitro and in-vivo show that the fabricated devices are able to reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space.
Phylogenetic patterns and ecological determinants of adaptive radiation [electronic resource]
Keywords: Biology.

It is well recognized that much of the biodiversity on Earth is the result of adaptive radiation, which is the process by which one biological lineage gives rise to many descendant lineages, all adapted to the various ecological roles they fill. However, it remains unclear why some lineages diversify greatly by adaptive radiation while others diversify little or not at all. The classic view is that "ecological opportunity" (where organisms find themselves in an area with abundant or under-utilized resources) allows the lineage to interact with the environment in novel ways and this promotes adaptive radiation. Here I utilize three taxonomically disparate systems (microbes, plants, and fishes) to examine patterns of diversification and identify possible ecological factors that promote or suppress adaptive radiation. In a laboratory experiment with bacteria and phage, I show that the prior evolutionary history of immigrants may determine their subsequent diversification dynamics after arrival to a new habitat. In another study, using molecular phylogenetics to investigate the rate of diversification of an adaptive radiation of flowering plants in Hawaii, I show that this radiation is among the most rapid yet studied in plants, on a per-unit-area basis, and suggest that the relative scale of habitable area available for the organisms under study is necessary to understand both the rate and the extent of diversification. Lastly, I utilize a radiation of marine fishes along the west coast of North America and show that morphological adaptations can facilitate habitat shifts leading to further evolutionary diversification not only in terrestrial and freshwater systems, but in marine systems as well, confirming the idea that general evolutionary principles apply across systems. One common theme that emerges from these studies is that the "ecological opportunity" hypothesis is supported, but that it may not fully explain diversification patterns. Overall, these studies suggest that explicit consideration of the prior evolution of immigrants, the relative scale of habitable area, and adaptive morphological shifts to novel habitats are necessary to fully understand patterns and drivers of adaptive radiation.
Physical constraints on the size and shape of microalgae [electronic resource]
Keywords: Biological Sciences

Scaling laws provide a link between biology and physics. They provide a means by which patterns in biology can be quantified and an explanation from physics can be correlated with such patterns. In this thesis, I use scaling laws to look for connections between biology and physics in two systems, diatom frustules and coralline algal reproduction. In Part I, I investigate diatom sinking speeds, a system for which a biologically derived scaling law has been known for some time, but is yet to be explained by a physically derived correlate (Chapter 1). Once I solve this discrepancy between the physical and biological scaling laws, I then spend the rest of the Part I deriving several other related scaling laws, from physical (Chapters 2 and 4) and biological (Chapter 3) perspectives. Part II works with an entirely new system for which few scaling laws have been derived, the spores of red algae and their attachment ability. This second part of my thesis works primarily from a biological perspective, as I empirically derive scaling laws and try to make sense of a new system.
Physical modeling of the harpsichord plectrum-string interaction [electronic resource]
Keywords: Physics

The harpsichord is a plucked string keyboard instrument which was prominent during the 16th through 18th centuries. In this thesis, we set out to physically model the complex interaction between the harpsichord plectrum and string during the plucking event. The modeling efforts are aided by various experimental work, and the model is later extended with additional digital filters with a focus on sound synthesis.
The physics of target-site search and DNA supercoiling in the cell [electronic resource]
Keywords: Chemical Engineering

Protein-DNA interactions within the confines of the crowded cellular space control critical biological processes such as genome regulation, replication, and compaction. In turn, protein activity on the genome is susceptible to the structure and dynamics of the DNA itself, a complex relationship whose study falls within the realm of polymer physics. Using analytical theory and numerical simulations, we present a systematic study of the relationship between DNA structure and dynamics and cellular processes mediated by DNA-binding proteins, in particular those involving a search for a target-site on the chromosome. We build a theoretical description of the transport of DNA-binding proteins along linear DNA modeled as a wormlike chain and delineate the resulting dynamic strategies employed by the cell in order to maximize translocation speed and efficiency. We extend this model to address the otherwise imperceptible molecular events present during effective protein diffusion along a stretched DNA strand during single-molecule experiments. In an effort to address the genome's higher-order structural effects, we explore the structure and dynamics of supercoiled DNA both as a free molecule in solution and under confinement in the cell, as in the case of Caulobacter crescentus. Our investigation of supercoiled DNA in confinement highlights dynamic consequences of vital importance to the cell's genome regulatory strategies. Finally, we synthesize our study of DNA-binding protein transport with our investigation of supercoiling dynamics to address the effect of DNA superstructure on the target-site search process, and we identify the search enhancement wrought by supercoiling of the chromosome.
Precursor-directed biosynthesis of macrolide antibiotics [electronic resource]
Keywords: Chemistry

Macrolides have long been among the most widely used antibiotics. Despite this utility, development of new macrolides through traditional synthetic and semisynthetic approaches has been greatly hindered by the inherent structural complexity of these compounds. Precursor-directed biosynthesis is a technique which circumvents this difficulty by incorporating simple synthetic precursors into a biosynthetic pathway, allowing the bulk of the molecule to be constructed enzymatically. This dissertation describes the evolution and application of a system for the facile production of new macrolides through precursor-directed biosynthesis. The results of this work are the discovery of an unexpected macrolide structure-activity relationship and the ultimate discovery of a promising new lead for macrolide development.
Preschoolers' use of communicative cues to guide inductive inference [electronic resource]
Keywords: Psychology

In constructing a conceptual understanding of the world, children must actively evaluate what information is idiosyncratic or superficial, and what represents generalizable, essential information about kinds and categories. In six experiments (N = 312), preschoolers observed identical evidence about a novel object's function produced in subtly different manners: accidentally, intentionally, or demonstrated communicatively and pedagogically. This subtle distinction had a powerful impact on children's inductive inferences. In Part One, this distinction influenced not only the strength of children's inferences about generalizability, but resulted in a fundamentally different conception of a novel kinds as defined not by superficial appearances but by deeper, functional properties. In Part Two, children showed surprising sophistication in navigating pedagogical interactions, judiciously identifying which specific actions in an ongoing interaction were meant as communicative demonstrations for their benefit. Taken together, these experiments illustrate a powerful learning mechanism for facilitating children's conceptual development.
Pricing options for acquiring a complete set of land [electronic resource]
Keywords: Management Science and Engineering

Whenever an entrepreneur wishes to acquire unique, complementary assets which are all required to complete a project, the entrepreneur faces the risk of one of the asset owners refusing to sell his asset. This risk is the holdout problem. If the entrepreneur proceeds with buying the assets as he completes negotiations he faces the possibility that one of the remaining owners refuses to sell or demands more than he is willing to pay. Because of this, the entrepreneur faces the prospect of sinking a lot of unrecoverable money into the project only to find out he cannot complete the project. This prospect can diminish the value of the project to the point where the entrepreneur would chose not to attempt it. As a solution to the holdout problem, this thesis proposes the use of options to secure assets for which negotiations have been completed. After negotiations are completed, the entrepreneur pays the owner a small fee up front for the right, but not the obligation, to purchase the asset at a later time. The entrepreneur will then only exercise the option and purchase the asset if he has secured all the assets. This thesis develops a way to price these options so that the entrepreneur can maximize her value by incorporating the outcome of past negotiations and her beliefs about future negotiations. This model allows for the consideration of multiple sets of assets so that the developer has alternatives for completing the project. After the basic model is developed, it is extended to allow for the analysis of more situations.
Probabilistic and statistical modeling of fixed income assets [electronic resource]
Keywords: Statistics

Fix income market is a very dynamic field in the eyes of finance modelers. There have been many models in the extant literatures trying to describe the dynamics of the short rate and default intensity as realistically as possible so that some of the most important credit assets can be better priced and have their risk better understood. Here we are going to propose first of all two Monte Carlo algorithms for simulating the default times of the financial entities in a certain portfolio. The first algorithm is unbiased but more computationally expensive than the second one, which introduces some bias as tradeoff. We also show that the bias introduced in the second algorithm can be controlled by a prespecified small constant. Moreover, we present a method based on measure change to solve the pricing and risk management of these credit assets that can accommodate many different model settings, and at the same time extend the computational tractability of some well understood models to more complicated ones. In particular, by applying our measure change one can allow the company defaults to be self- and cross-excited, as well as correlated with interest rate and recovery rate. These features have been observed in empirical studies and they are quite essential in pricing multi-name credit portfolios. Another part of this thesis work focuses on predicting the trade prices of corporate bonds with benchmark prices coming from some probabilistic models given. The discrepancy between the actual trade prices and theoretical benchmarks is determined more by the market microstructures trade information so a statistical approach might be more useful here. We have tried some models based on supervised learning techniques on a certain dataset and compared their performance in bond trade price prediction.
Probabilistic models for warning of national security crises [electronic resource]
Keywords: Management Science and Engineering

Intelligence analysts have experimented with static forms of Bayesian inference since the late 1960's. However, their static probabilistic approaches have proven unsuitable for warning analysis. In this dissertation, I develop an analytic framework for crisis early warning that addresses four challenges: (i) it has the flexibility to incorporate geographical variation; (ii) it reflects the dynamics of a crisis in order to enable lead time estimation; (iii) it incorporates conditional dependencies among signals and data; (iv) it treats an analyst's decision of when to warn, and type of warning to give, in decision-theoretic terms. The framework is rooted in a general warning system developed by Paté-Cornell and expands on the work of Schrodt. The models comprising the framework are illustrated using a historical example, the lead up to Japan's attack on Pearl Harbor in 1941. They are then demonstrated through a contemporary case study, the warning of violence against civilians in Guatemala being perpetrated by a transnational criminal organization. From the Pearl Harbor illustration, using parameters that are entirely illustrative, the model would have issued an alert for an attack on Oahu on December 2, 1941. Despite the illustrative nature of the results, the exercise highlights the importance of incorporating decision analytic techniques in the warning process. It also demonstrates the process of entity tracking through the inference of signals, which is broadly applicable. From the transnational criminal organization case study, I demonstrate how one's belief regarding the likelihood of violence in particular municipalities, distributed over time, changes with the observation of successive signals of organizational activities. I also identify two routes spanning the width of Guatemala, which, over the period February 1 to August 31, 2012, are consistently the most secure smuggling routes.
Probing mechanisms of myosin motors using single molecule techniques [electronic resource]
Keywords: Applied Physics

Members of the myosin family of molecular motors perform a variety of essential functions in the cell, including powering muscle contraction and cell division, transporting cargo, and serving as anchors and tension generators. Myosins accomplish these tasks by transforming chemical energy from ATP hydrolysis into mechanical work, as they either move along their actin filament tracks, or power the movement of the actin filaments. Single molecule techniques have proven especially useful for understanding the biophysical mechanisms that myosins employ in order to perform their functions. In this thesis, I discuss my application of quantitative, single molecule level approaches to remaining questions about the mechanisms of myosins II, V and VI. In the first section, I describe our analysis of myosin VI processivity via structurally engineered mutant constructs, which we examined using single molecule fluorescence. Myosin VI is both structurally and functionally unusual among myosins. In order to probe our understanding of its mechanism, we replaced its lever arm with a variety of engineered artificial lever arms, and tested whether it responded as we would expect. As part of this work, I also developed a quantitative model of processivity of myosin VI, which I used to analyze the expected effects of decreasing intramolecular communication between the heads of a processive myosin. This model has implications not only for myosin VI, but for other two headed processive motors, including processive myosins, kinesins, and dyneins. In this work, I found that processivity is markedly robust to decreased inter-head communication. In order to further characterize intramolecular communication in processive myosins V and VI, I hoped to directly visualize ATP molecules binding and releasing from myosin molecules as they walked along actin filaments. This required the development of techniques to allow the resolution of single fluorescent molecules at higher concentrations of fluorophore than has previously been possible. I approached this challenge using two technological approaches: linear zero mode waveguides (ZMW) and convex lens induced confinement (CLIC). While the direct visualization of nucleotide gating remains a challenge, I made significant progress toward applying these techniques to that outstanding question. Finally, in the last section of my thesis, I discuss work on characterizing mutations in the human cardiac myosin II protein that cause hypertrophic and dilated cardiomyopathy. While many mutations that cause these diseases have been identified, their mechanism(s) of action are not understood. Characterizing these effects requires precise quantification, since the changes in myosin behavior caused by the mutations are likely to be subtle. Toward that end, I have refined our approach to the gliding filament assay to increase its precision and reproducibility, and have begun to characterize the effects of several disease-causing mutations in this motor.
Probing the atomic limit of forces and engineered electronic structure with single molecules [electronic resource]
Keywords: Electrical Engineering

We use the atomic manipulation capabilities of a custom-built scanning tunneling microscope (STM) to manipulate individual molecules to study the limits of force sensing and electronic structure engineering. The system studied is CO molecules adsorbed on the Cu(111) surface. Both the molecular vibrational modes and the electron wave scattering properties of the CO molecules are used in these studies. First, the evolution of the molecular vibrational modes of a single CO molecule adsorbed on the surface are studied during the formation of a single molecule junction through isotopic labeling. Electrical contact to the molecule is made for point contact measurements. Second, the vibron virtualization experiment illustrates the non-local detection of the vibrational properties of the CO molecule through inelastic scattering by engineering the electronic states of a quantum corral. Third, a novel molecular cantilever is created by functionalizing the STM tip with a CO molecule. The molecular cantilever is used as a non-contact atomic force microscope probe by detecting the shifts in vibrational mode energy of the attached CO molecule through inelastic tunneling spectroscopy. Lastly, CO molecules are used as a periodic potential to pattern a two-dimensional electron gas to create the electronic band structure of graphene, realizing Dirac quasiparticles. Control over the hopping texture is exercised to open an energy gap at the Dirac point and to impart a pseudo-magnetic field on the lattice. The molecular cantilever experiment and artificial graphene experiment both represent techniques and concepts that can be extended upon in the future by using different molecules and building different lattices, respectively. These experiments show that one can use single molecules to study and make new materials and devices.