VictorJuiz/thesis huggingface dataset:
Autism mutations in ProSAP2/Shank3 disrupt zinc-dependent dynamics and transsynaptic signaling [electronic resource]
Keywords: Neurosciences.

Autism spectrum disorders (ASDs) are a pervasive set of neurodevelopmental disorders that are characterized by deficits in social interaction and communication. ASDs are diagnosed in 1 out of 88 children and are more common in males. ASDs are thought to be highly heritable and a wide variety of genetic mutations have been identified, including mutations in several synaptic proteins. This dissertation research explores convergent synaptic mechanisms underlying ASDs, specifically exploring several aspects of synaptic biology that are disrupted by autism-associated mutations in the ProSAP/Shank family of postsynaptic scaffolding proteins, focusing primarily on one family member, ProSAP2/Shank3, for which the genetic data is strongest. Data collected for this thesis demonstrate that ProSAP/Shank proteins act within dendritic spines to coordinate pre- and postsynaptic changes in synaptic function by regulating the activation of Neurexin-Neuroligin signaling complexes. Intriguingly, autism mutations in ProSAP2/Shank3 were found to disrupt this transsynaptic signaling, thereby functionally linking several synaptic proteins implicated in ASDs. Mechanistic experiments revealed that ProSAP2/Shank3 activation and scaffold stability within postsynaptic densities (PSDs) are zinc-sensitive and that zinc supplementation can reactivate ProSAP2/Shank3 carrying an ASD mutations, partially or fully rescuing transsynaptic signaling. Importantly, zinc deficiencies are linked to mental retardation and thus may be a risk factor for autism by contributing to synaptic dysfunction within neuronal networks.
Automatic hole-cutting in overset grids using the X-rays approach [electronic resource]
Keywords: Mechanical Engineering

Overset grids resolve complicated geometries by creating high quality structured grids that are independently built for each component. This simplifies the process of grid generation, but domain connectivity must be performed so that adjacent grids share information. Currently available domain connectivity tools tend to be computationally expensive or require extensive user input. The X-rays approach is a robust and computationally efficient method, but it requires considerable user input and iteration. Shortcomings of the current X-rays method are explored to automate and improve the algorithm. Significant user time is saved by identifying and eliminating the manual bottlenecks of the X-rays approach. In addition, automation of the hole boundary adjustment helps to improve the accuracy of the solution. It is now possible to solve relative motion problems with significantly less user inputs, considerably reducing the design cycle time in engineering CFD analysis.
Bayesian analysis for reversible time series with applications to molecular dynamics simulation [electronic resource]
Keywords: Structural Biology.

A host of sequential models in probability and statistics are characterized by time reversibility, from Markov chain Monte Carlo samplers to queueing networks. In physics, this property arises naturally from Hamiltonian mechanics. Molecular dynamics simulations are computer experiments which approximate classical mechanics in a system of interacting particles; in consequence, they are frequently reversible. Recent technical progress has made it possible to investigate the dynamics of biological macromolecules in silico using molecular dynamics simulations. An active area of research within this field is concerned with modeling the output of a simulation stochastically. This dissertation deals with the problem of incorporating knowledge of reversibility into the estimation and testing of stochastic models. We define a range of Bayesian inference algorithms, which are motivated by specific problems in the analysis of molecular dynamics simulations.
Behavior modeling in smart environments using camera networks [electronic resource]
Keywords: Electrical Engineering

The goal of smart environments is to support people in their daily life by being sensitive and responsive to their presence and activities. The key challenges in achieving such a vision are the ability to robustly extract useful information from the sensors, and to utilize the extracted data to generate and reinforce a model representing the user's pattern of behavior so adaptive, personalized or even predictive responses can be provided. In the first part of the dissertation, we discuss how information about people in an environment can be obtained using a network of cameras. We propose efficient visual processing algorithms to track multiple people in real-time, to determine their pose and to estimate their head orientation. A discriminative classifier is trained to detect interactions between occupants of a space based on their locations and head orientations. We also describe methods to fuse information at different levels in a multi-camera scenario. In the second part of the dissertation, we discuss how behavior models can be constructed from observations obtained by cameras or other sensors. We propose a probabilistic model that takes into account the inherent hierarchical structure of human activities, as well as contextual information related to the user or the environment. Our model also allows for variations in the duration of different activities, and considers the uncertainty of the measurements reported by the sensors. To evaluate our visual processing algorithms and illustrate the benefits of our proposed behavior modeling approach, we study three use cases. In the first use case, we study the daily routine of an office worker, and derive the user's pattern of work. In the second use case, our proposed method is applied to a smart home to adaptively optimize energy consumption and user comfort by learning user preferences and habits. Finally, we consider a scenario where the built-in webcam on a personal computer is used to analyze the user's posture and gaze while working on the computer. Personalized ergonomic recommendations tailored to the user's behavior pattern are then provided. Experimental results are presented in each of the use cases to demonstrate the performance of our proposed methods.
Behind a veil of smoke [electronic resource] : big tobacco and the hidden world of research and development at Philip Morris, 1950-1985
Keywords: History

In 1952, the largest manufacturer of cigarettes, Philip Morris, founded a Department of Research and Development (R& D) that would ultimately elevate the company to its dominating role in the tobacco landscape. As revealed through internal industry documents available online and released through litigation, this study highlights both the role of scientific research in a controversial industry, and the role of individual researchers in the unbridled growth of Big Tobacco during the second half of the twentieth century. Despite extensive research, industry results were rarely published and never without extensive scrutiny by industry executives and lawyers. This scientific silence is in stark contrast to the industry's public stance of denying the health hazards of smoking. The extent to which the tobacco men understood the hazards of their products—and the specific details of several research projects on the dangers of smoking—are discussed. The history of the Department of Research at Philip Morris demonstrates that just as public concern was growing that smoking might be dangerous, the tobacco industry was actively pursuing research proving the very thing they were trying to convince the public was a non-issue: that smoking is harmful.
Biochemical, electrical, and optogenetic control of human pluripotent stem cell-derived cardiomyocytes [electronic resource]
Keywords: Bioengineering.

Cardiovascular disease affects more than 70 million Americans and is the number one cause of mortality in the United States. Because the regenerative capacity of cardiac tissue is limited, human pluripotent stem cells (hPSC) have emerged as a potential source for cellular-based therapies. However, for these therapies to be effective, sufficient amounts of differentiated cells must be produced, these cells must be identified and sorted, and, upon implantation, arrhythmias must be avoided. In this dissertation, I describe the biochemical control of hPSC for their directed differentiation into cardiomyocytes, electrical control for electrophysiology-based cell sorting, and optogenetic control for temporal synchronization. For future therapy, the in vivo application of optical stimulation could allow immediate, precise, and specific synchronization of efficiently derived and purified hPSC-CM with patient cardiac rates and rhythms. This, in turn, would significantly reduce the chance of arrhythmias arising from implanted hPSC-CM, and, therefore, contribute towards establishing a safe and effective cell-based therapy.
Biofilm formation and its interaction with surfactants and solvents [electronic resource] : a physico-biological approach
Keywords: Chemical Engineering

Bacteria tend to aggregate on surfaces and form biofilms that are characterized by an extracellular polymeric matrix consisting of proteins and polysaccharides. The unique structure of biofilms prevents bacteria from harsh environmental conditions so they can survive in a broad range of conditions. While this ability is beneficial to the bacteria's survival, biofilms are implicated in most infectious diseases such as catheter infections, cystic fibrosis, endocarditis, and urinary tract infections. Successful treatments of these diseases require thorough understanding of the biochemical and physico-chemical properties of biofilms that relate to function. In this thesis, we combined conventional biofilm research methods with interfacial science techniques including interfacial rheometry and tensiometry to study air-liquid interface biofilm (pellicle) formation by uropathogenic E. coli, which produces an amyloid-fiber called "curli" to develop a biofilm network. We analyzed the bacteria cell growth, adhesion ability, and curli expression, and relate them to the interfacial viscoelasticity during biofilm formation. Our results showed that over-expressed curli content leads to more robust biofilms with higher tenacity. Nonionic surfactant-biofilm interaction was also studied, and the results showed that biofilm formation was very sensitive to surfactant concentration. Below the critical micelle concentration (CMC), the surface was dominated by bacteria-degradable proteins from the nutrient broth, and pellicle formation was observed with delayed inception at increasing surfactant concentration. Above the CMC, the surface was dominated by surfactants, and biofilm formation was inhibited. Our studies demonstrated a unique approach to comprehensively examine air-liquid interface biofilm formation and investigated the influence of curli content and surfactants on amyloid-integrated biofilm formation. The application of this approach is extensible to studies of amyloid-integrated biofilm formation among other microorganisms as well as interactions of surfactant-protein and surfactant-polymer at air-liquid and oil-liquid interfaces.
Broken rotational symmetry in iron based superconductors [electronic resource]
Keywords: Applied Physics

High-temperature superconductivity often emerges in the proximity of a symmetry-breaking ground state in strongly interacting electronic materials. In the case of the superconducting iron pnictides, in addition to the antiferromagnetic ground state of the parent compounds, a ubiquitous but small structural distortion breaks the crystal C4 rotational symmetry in the underdoped part of the phase diagram. It has been proposed that this structural transition is driven by an electronic nematic phase transition, below which the electronic system spontaneously organizes with an orientational order without developing additional spatial periodic order. In this thesis I show how the effects of this electronic nematic order can be explicitly revealed by observing the response of the system to in-plane uniaxial stress. I present transport measurements of single crystal samples of various iron-based superconductors held under an in-situ tunable strain at temperatures above the phase transition, which explicitly confirm that the structural transition is fundamentally driven by a thermodynamic instability in the electronic part of the free energy. I will also discuss the nematic fluctuations prevailing throughout the overdoped part of the phase diagram, which suggests that a quantum phase transition occurs at the optimal doped composition. Finally, I will describe the in-plane resistivity anisotropy measurements of detwinned samples at temperatures below phase transition, which potentially reveals an intriguing interplay between topological protected Dirac pockets and spin/orbital ordering.
Building a creative community [electronic resource] : emergent practices and learning at a seven-week innovation camp
Keywords: Education.

Supporting creativity and innovation has emerged as a top priority across fields from Education to Environmental Sciences and even the Humanities. Accordingly, there has been a recent surge of experimental contexts to spark and sustain creativity and innovation. The Globul5 innovation camp, an extreme example of such an exploration, provided an unstructured context for twenty-eight young adults as they lived and worked together in a factory for seven weeks to redesign "the future of work." Through analysis of field notes, video records, photographs, and interviews, I investigated the conditions of the camp design, the community's emergent collaborative practices, and the residents' learning processes. The research questions guiding this study are: 1) What were the incoming conditions of the innovation camp? 2) How did collaborative teams address challenges that arose at the camp? 3) How did participants forge individual learning pathways at the camp? 4) What insights about creative collaboration did participants articulate after the camp? Results of this research suggest that the relational intensity and lack of structure at the camp posed challenges to team project work; however, a significant factor of the residents' learning may be attributable to these challenges and the resultant need to invent ways to manage them. Residents learned through observation, experimentation, critical reflection, and reflective discourse; ultimately, they described the camp as a transformative learning experience (Mezirow, 1991). Residents adapted, adopted, and developed practices at the camp to manage their collaborative work, including a ritual for abandoning projects that were failing due to attempts at consensus, methods for differentiating idea generation and idea evaluation, and implicitly designated spaces for open and informal communication. Based on post-camp interviews, residents came away from the Globul5 experience feeling increased confidence and having convictions about how to best support creative collaboration. The residents articulated insights related to: 1) how to support critique while maintaining group cohesion, 2) how to structure teams in order to foster autonomy and productivity, 3) how to find a common vision while valuing multiple perspectives, and 4) how to simultaneously achieve a sense of flexibility and clear direction. Results indicate that residents may have developed repertoires of collaborative practice (Barron et al., 2009), or adaptive understandings of how to apply practices and insights to future collaborations.
Capacitive micromachined ultrasonic transducer (CMUT) chemical sensor and its interface circuits [electronic resource]
Keywords: Electrical Engineering

Miniaturized chemical sensors based on microelectromechanical-systems (MEMS) offer competitive advantages over existing bench-top chemical analyzers, such as small size, low power consumption, low cost due to batch fabrication, and CMOS compatibility. The potential for system integration of these chemical sensors with on-chip CMOS circuitry expands the spectrum of use, including consumer, industrial, and homeland security applications. This thesis introduces a miniaturized resonant chemical sensor based on a 50-MHz capacitive micromachined ultrasonic transducer (CMUT). With a high mass sensitivity of 4.3 ag/Hz, this CMUT-based chemical sensor achieves excellent volume sensitivity of 21.2 ppt/Hz to dimethyl methylphosphonate (DMMP), a common simulant for Sarin gas. In addition, a direct application of a mesoporous silica thin-film on a CMUT for relative humidity and carbon dioxide detection is presented. Using a mesoporous silica thin-film with a pore size of ~11 nm, this sensor achieves one of the lowest volume resolutions and a sensitive detection of 5.1 × 10-4%RH/Hz to water vapor in nitrogen. In addition, a mesoporous thin-film that is functionalized with an amino-group is directly applied on the resonant sensor, which exhibits a volume sensitivity of 1.6 × 10-4%/Hz and a volume resolution of 1.82 × 10-4% to carbon dioxide in nitrogen. Lastly, this thesis describes the sensor interface circuitry for CMUT and discusses the frequency noise analysis of CMUT-based oscillators. Specifically, a multi-channel interface integrated circuit (IC) implemented using 0.18-um CMOS technology, which results in reduced area and power consumption for each channel is presented. Two-channel detection of relative humidity is demonstrated using this circuit.
Carbon nanotube containing electrodes for organic electronics applications [electronic resource]
Keywords: Applied Physics

Flexible transparent electrodes are critical for use in large-area or flexible touch screens, solar cells, and flat panel displays. An ideal material should be inexpensive, nontoxic, flexible, solution processable, thin and uniform, with a sheet resistance of less than 50 ohms per square at 90% transmission. No current material satisfies this set of specifications. One promising candidate is the carbon nanotube (CNT) network. There are two key challenges in making CNT electrodes. Firstly, in dispersion, van der Waals forces drive CNT aggregation into bundles, which are less efficient conductors than single tubes. Secondly, transport through a CNT network is typically dominated by large intertube resistances. The work in this thesis develops and studies composite materials addressing each of these challenges. In the first part of this thesis, we develop a method for making four-probe conductivity measurements on CNT bundles in networks, and compare these with data taken via electrostatic force microscopy. We confirm that bundles are less efficient at charge transport than single tubes, and that intertube rather than interbundle junctions limit transport in bundled networks. We then explore the use of poly-3-hexylthiophene (P3HT), as a dispersing agent for CNTs. While P3HT debundles CNTs, improves film morphology considerably and facilitates processing immensely, we find that too much P3HT can still substantially reduce the overall conductivity of the films. To improve this, and to address the tube junction resistance problem in general, the second part of the thesis focuses on p-type doping of CNTs, which increases free carrier concentration and lowers or eliminates intertube Schottky barriers. Known CNT dopants, including nitric acid and thionyl chloride, are toxic, corrosive, and/or ephemeral. We develop a new mild, stable and competitive process to dope CNT networks with molybdenum oxide, and explore the doping mechanism. We then compare this process with doping by thionyl chloride and by tetrafluorotetracyano-p-quinodimethane, a known mild molecular dopant. Lastly, to affirm the utility of these CNT composites as electrodes for organic semiconductor devices, we optimize methods to pattern them with high fidelity on dielectric surfaces and show that they can drive organic thin film transistors, in some cases better than can typical Au bottom contact electrodes.
Causes and consequences of fungal disease in cottonwoods [electronic resource]
Keywords: Biology.

Plant pathogens are microorganisms that cause disease and are therefore of great economic and ecological importance. Tremendous effort has been devoted to understanding plant genetic resistance to individual pathogens. Yet we know less about how natural genotypic variation in host plants affects the structure of pathogen communities. Here I test how both plant genotype and the environment influence the structure of fungal leaf pathogen communities, and how pathogens in turn affect plant herbivores. First, I test how the evolutionary history of plants affects their pathogen communities. I show that the pathogens of Populus angustifolia, the narrow leaf cottonwood of the Rocky Mountains, are consistent with a hypothesis of Beringian migration into North America by the ancestor of P. angustifolia. Second, in common garden studies and in the wild, I test how inter- and intraspecific genetic variation in Populus affects the structure of pathogen communities. I found that pathogen communities varied both among Populus species and genotypes within species, mostly in the severities of damage inflicted by constituent pathogens rather than in composition. These results suggest that quantitative genetic resistance, which is neither complete nor pathogen-specific, is affecting these communities. Third, I test how environmental variation affects both pathogen communities, and genetic resistance to pathogens. I found that the influence of plant genotype on pathogen communities attenuates as spatial scale and environmental heterogeneity increase, and that plant genetic resistance to pathogens is correlated to the level of disease risk within the environment where the plant occurs. Finally, I test how plant genotypic variation in pathogen severity influences pathogens' indirect effects on herbivores. I found that pathogens reduce the richness and abundance of herbivores most strongly on severely infected Populus species. Pathogens also reduced herbivory, but this effect was modulated by genotypic variation in herbivore resistance. Pathogens most strongly deterred herbivores on herbivore-susceptible genotypes, suggesting that they induce defenses. Overall, this thesis demonstrates that the genetic-based interactions of relatively few species (e.g., a plant and a pathogen) can be fundamental to understanding community structure.