VictorJuiz/thesis huggingface dataset:
Interactive biology cloudlab system architecture and applications in large scale online education [electronic resource]

Experimentation in life science is necessary for academia, industry and education, but many access barriers exist due to professional training, operation cost, maintenance, and safety requirements. High-throughput experimental equipment combined with cloud computing infrastructure has the potential to alleviate these access barriers through abstraction and time-sharing. Recently, a few commercial cloudlabs such as Transcriptic and Emerald Cloudlab have emerged, where highly standardized experimentation protocols are outsourced and executed semi-automatically based on the instructions provided by the users ahead of time without any means to interrupt or interact with an ongoing experiment. Therefore, a truly interactive biology cloudlab does not yet exist, whereas interaction is the key to exploration based science. In this dissertation, we conceptualized an interactive biology cloudlab paradigm. The core of this conceptualization is a domain specific device, Biotic Processing Unit (BPU) that hosts a biological sample and allows interactive experimentation. Biological systems are particularly difficult to handle as they, unlike physical systems, may exhibit unpredictable natural variabilities. Therefore, to provide a better Quality of Service (QoS), we proposed a general method to automatically monitor an array of backend BPUs to check the underlying biological state. We implemented two different cloudlab architectures to support 1) nonreal-time chemotaxis experimentation with a slime mold, Physarum polycephalum and 2) real-time phototaxis experimentation with a single celled micro-swimmer Euglena gracilis. In the Physarum based cloudlab, users time-shared a set of pre-allocated BPUs for experiments that would last two days. In the Euglena based cloudlab, users were scheduled in a queue using an Automatic Call Distributor (ACD) system, where experiments would last ∼ 1 minute. We compared these two architectures to draw general design rules, and recommended future cloudlab implementations based on the time-scale of the underlying biology. We iteratively developed our cloudlab by deploying it in various educational settings with different interaction modalities: in graduate level university classes, middle and high school classes, and eventually through an MOOC course with over 300 students. To this end, we also implemented a modeling platform along with other HCI components to facilitate visual and data analytics to enable inquiry-based learning as mandated by the National Research Council. In conclusion, we have paved the way to make complex biology experimentation accessible to a broader audience - including researchers, citizen scientists, and learners alike - at low cost and scale.

Advisor: Dill David L.
Riedel-Kruse Hans
Bernstein Michael S.
Blikstein Paulo
Inter-colony variation in harvester ant foraging behavior in response to weather conditions

Individuals of the same species differ in reaction norms, responding to environmental cues in distinct ways. Reaction norms describe the range of phenotypes a single genotype can produce, depending on the environment. In this study, we investigate reaction norms in foraging behavior of red harvester ant colonies (Pogonomyrmex barbatus) in response to weather conditions. We aim to build on previous research that has suggested that both foraging intensity and foraging regulation are affected by weather (Gordon, Dektar, and Pinter-wollman 2013; Azc and Kovacs 2007). At a field site near Rodeo, NM, we compared data from 2 years on the foraging behavior of 4 colonies, and examined the relation of foraging behavior to temperature and humidity. We statistically examined the correlation between weather conditions and foraging rate by quantifying foraging behavior of each day using 4 metrics: average rate of outgoing foragers, maximum rate of outgoing foragers, total outgoing foragers, and the difference between outgoing and incoming foragers. We found that colonies varied in their foraging behavior relative to each other in the same weather conditions, and differed in their sensitivity to varying weather conditions. Exploring the behavioral plasticity of colonies as they integrate environmental cues helps us understand more about the regulation of collective behavior.

Keywords:  Department of Biology
reaction norms
collective behavior
Thesis
Advisor: Gordon Deborah
Peay Kabir
Interferon signaling in lupus-prone mice and systemic lupus erythematous [electronic resource]

The majority of SLE patients are symptomatically treated using glucocorticoids, NSAIDs or cytotoxic agents. In the last decade, the field has seen a large push for pathophysiologically founded therapeutics, which are currently in late-stage clinical trails. Included in this category, is multiple therapeutics targeting IFNα1 (a Type I interferon, IFN-1), a known key player in SLE. In fact, a robust approach to subset patients is by the presence or absence of an IFNα Bio-signature, increased expression of transcripts regulated by IFNα, which correlates with disease severity. Additional studies in patients and murine models have supported a pathogenic role of Fin (Type II interferon, IFN-II). Nonetheless the mechanism by which IFN-I and IFN-II perturb the immune system in SLE remains unclear, and studies have revealed conflicting roles in murine models. Here, we seek to understand how IFN signaling modulates disease through cellular and molecular mechanisms in both mouse models of SLE and patients. First, we discover the role of individual IFN signaling components in MRL/lpr mice. Second, we identify single cell differences in cellular phenotype, cytokine signaling and immune function between IFN-high (IFN-H) and IFN-low (IFN-L) patients. To dissect the individual contributions of Type Type II IFNs and I in lupus disease a spontaneous murine model of SLE. We show increased IL-17-producing CD4+ T cells in the spleens and kidneys of STAT1-/- mice via shunted phosphorylation of STAT3/4. A similarly contrasting relationship is seen in the autoantibody produce- tin from these mice where STAT1-/- mice exhibit decreased autoantibody reactivity to SLE-associated antigens, whereas IRF9-/- mice exhibit increased autoantibody re- activity limited to histones. These data strongly suggest that IFN-I/II signaling proteins play differing roles in T helper cell polarization, B cell autoantibody production and interstitial kidney disease. In human work, we identify single cell differences in cellular phenotype, cytokine signaling and immune function between IFN-H and IFN-L patients. First, we determined the IFN signatures for 80 patients in the Stanford Registry SLE cohort. Autoantibody production of these patients was profiled using multiplexed protein arrays and confirmed higher autoantibody production in IFN-H patients as compared to IFN-L. Lastly, we used cytometry by time-of-flight (CyTOF), to perform simultaneous and unprecedented single-cell proteomic analysis of surface markers and intracellular functional proteins in SLE patients. We find that IFN-H and SLE patients in general exhibit decreased global STAT phosphorylation at baseline. However, increasing IFN score was associated with increased stat levels downstream of IFNα, IFNγ and IL-21 in addition to relevant clinical criteria.

Advisor: Utz Paul primary advisor. Thesis advisor
Negrin Robert S. advisor. Thesis advisor
Nolan Garry P. advisor. Thesis advisor
Robinson William (William Hewitt) advisor. Thesis advisor
Interrogation of viscoelastic protein layers at bubble interfaces [electronic resource]

From a cup of creamed coffee to the salty spray of seawater, fluid-fluid interfaces exist everywhere in our lives. Simple fluid-fluid interfaces can be described by a scalar surface tension, but adherence of amphiphilic species such as small molecule surfactants, particles, and macromolecules, and the consequent formation of interfacial microstructures, results in the formation of a complex interface that is inadequately described by a simple surface tension. The scope of the thesis will wholly focus on complex air-aqueous solution interfaces, the presence of which can be undesirable, for example, in the form of isolated bubbles entrained in pharmaceutical processing flows, or desirable, as the foams for beverages and consumer products. Furthermore, the focus is on proteins at the air-aqueous solution interface which form a viscoelastic protein layer. The first project examines the aggregation of a proprietary monoclonal (mAb) molecule under interfacial deformations by investigating the mechanical response of mAb-adsorbed interfaces to dilatational strains and by characterizing particles ejected from dilatationally-compressed surfaces with spectroscopic and microscopic techniques. The project also introduces the interfacial dilatational rheometer that underpins much of the work and demonstrates its capabilities in studying the stability of product formulations. The second part of the thesis examines the influence of rheological surface elasticity on thin film entrainment within foams for bovine serum albumin (BSA) protein-adsorbed interfaces. The results of the latter study could be beneficial for industries interested in developing a framework for predicting bulk foam characteristics, such as liquid foam density, from interfacial and bulk liquid properties.

Keywords: Chemical Engineering.
Advisor: Fuller Gerald G.
Cegelski Lynette advisor. Thesis advisor
Dunn Alexander Robert advisor. Thesis advisor
Inventing an American political tradition [electronic resource] : how John Locke became "America's philosopher"

Inventing an American Political Tradition elucidates the trans-Atlantic influence of the seventeenth-century English philosopher John Locke on American thought and culture from before the American Revolution through the Civil Rights Movement. It tells the story of how and why Americans transformed Locke, best known to them in the eighteenth and nineteenth centuries as an epistemologist of the Scientific Revolution, into "America's Philosopher" in the twentieth century—the supposed founder in his Second Treatise of a distinctly American liberal democratic political tradition resting on property rights, individual liberty, freedom of religious practice, and representative government. This dissertation is the first study of Locke's place in American intellectual and political life across multiple centuries.

Keywords: History.
Advisor: Winterer Caroline
Burns Jennifer
Ober Josiah advisor. Thesis advisor
Investigating contemporary questions in climate science from a modern statistical perspective [electronic resource]

The recent "hiatus" in global warming has been the subject of much scrutiny and debate, both in the scientific community and in the public discourse. The implications of the alleged hiatus call into question the reliability of climate models and the need for mitigating anthropogenic contributions to warming. The observed change in the relationship between temperature and atmospheric carbon dioxide concentrations during the hiatus period has also raised questions regarding model-based estimates of climate sensitivity. The aim of this dissertation is to make sense of some of the current compelling questions in climate science in a rigorous way. An important component in this is to develop and apply modern statistical methodology, with the explicit goal of informing the scientific debate. We formally consider the hypothesis of a recent "hiatus" in global warming with the aid of quantitative statistical methods. We also investigate the related assertion that despite increase in greenhouse gas concentrations, temperatures have not followed suit. We develop a general methodology to test for a difference between two populations, even when one population has a fixed, small sample size. The method applies quite generally, as we are able to account for arbitrary temporal dependence in the data without explicitly modeling the temporal structure (under minimal stationarity assumptions). We additionally consider two scientific hypotheses that consider surface warming at a regional scale. Appropriate statistical methods are used to account for multiple hypothesis testing, temporal dependence, and spatial dependence.

Keywords: Environmental Earth System Science.
Advisor: Rajaratnam Balakanapathy primary advisor. Thesis advisor
Chamberlain C. Page advisor. Thesis advisor
Diffenbaugh Noah S. advisor. Thesis advisor
Romano Joseph P.
Investigating the biophysical mechanisms of integrin-based adhesion at the cellular and single-molecule level [electronic resource]

Integrins mediate cell adhesion to the extracellular matrix and enable the construction of complex, multicellular organisms, yet fundamental aspects of integrin-based adhesion remain poorly understood. Notably, recent estimates of the load experienced by integrins span two orders of magnitude, a discrepancy arising from limitations inherent to existing techniques. Thus, it is unclear if integrin-based adhesion, and by extension mechanotransduction, reflects a disproportionate contribution by only a few integrins bearing large forces, or is instead a collective phenomenon reflecting the cumulative output of many weaker interactions. We used FRET-based molecular tension sensors (MTSs) to directly measure the distribution of forces experienced by individual integrins in living cells. We find that the majority of integrins transmit relatively modest forces of less than 7 pN, and that a large proportion of these integrins bear minimal loads of less than 3 pN. This finding suggests that most integrins are tensioned to well below their load-bearing capacities. In addition, load-bearing integrins are not exclusively localized to adhesion structures; integrins exerting low forces outside of discernible adhesions contribute a significant fraction of the cell's total traction and are sufficient for maintaining adhesion. Further, we developed MTSs presenting the full fibronectin type III 9th and 10th domains which includes the synergy site, a secondary binding site thought to reinforce the fibronectin- α5β1 integrin bond. Our data indicate that the synergy site does not increase the force per integrin, but does increase the relative contribution of α5β1 integrin in mediating adhesion. Further, our data indicate that the synergy site is critical for the cell's ability to resist detachment when exposed to externally applied load. In total, these data suggest that a substantial population of bound but minimally tensioned integrins, aided by synergy site-mediated mechanical reinforcement, can provide cells and tissues with physical resiliency. Finally, we tested the hypothesis that loads are apportioned differently on distinct integrin types (here, α5β1 and αv-class). Surprisingly, our data indicate minimal differences in the amount of force transmitted by either α5β1 and αv-class integrins. Instead, our data are consistent with a model in which different integrin subtypes play distinct roles in organizing adhesion structure and dynamics.

Keywords: Chemical Engineering.
Advisor: Dunn Alexander Robert primary advisor. Thesis advisor
Lin Michael Z. advisor. Thesis advisor
Swartz James R. advisor. Thesis advisor
Investigating the effects of beta1-adrenergic receptor agonist and antagonist administration on microglia in a mouse model of Alzheimer’s disease

The beta1-adrenergic receptor agonist xamoterol has been shown to rescue cognitive deficits, downregulate pro-inflammatory cytokine production (TNF-α, CD74, and CD14) and decrease amyloid beta accumulation in Alzheimer’s disease (AD) mouse model. Nevertheless, given these previous results, the cellular mechanism of action and neuronal/glial correlates responsible for xamoterol’s AD-therapeutic effects are not well characterized. Furthermore, few studies have looked at microglia in the context of AD. In this study, a beta1-adrenergic receptor agonist (xamoterol) and antagonist (metoprolol) were separately administered to wildtype mice and amyloid precursor protein-overexpressing Alzheimer’s disease (AD) mouse model, and drug effects on microglial cellular density and Iba1 immunoreactivity (obtained through cell counts and immunohistochemical quantification of Iba1, a marker of activated microglia) were determined for hippocampal and cortical regions of the brain. Xamoterol was shown to have no significant effect on microglial density in either transgenic or wildtype animals. Furthermore, metoprolol administration mildly suppressed microglial cellular populations in dentate gyrus in both transgenic and wildtype animals, relative to saline-dosed controls. Altogether, these data suggest that beta1-adrenergic receptor antagonism leads to downregulated microglial populations for both wildtype and transgenic AD mice, while receptor agonism has no effect on microglial populations. Data from this study also do not support the role of a microglial-density-dependent mechanism of action in xamoterol’s activity as a therapeutic drug in AD mouse model.

Keywords:  Department of Biology
Biology
Neuroscience
Alzheimer's Disease
Alzheimer's
Microglia
Thesis
Advisor: Shamloo Mehrdad
Evans Andrew
Bergmann Dominique
Investigating the effects of chemical composition and surface structure of catalysts on the electrochemical reduction of carbon dioxide [electronic resource]

The elimination of our dependence on fossil fuel sources is strongly motivated by the non renewable nature of these resources and the mounting evidence of their connection to anthropogenic climate change. Such a shift away from the use of fossil fuels could be facilitated by the electrochemical reduction of CO2, as it could allow for a sustainable process by which renewable energy from wind and solar are used directly in the production of fuels and chemicals. However, one key barrier to its utilization is the lack of effective catalysts that make the process energy efficient and selective. In order to develop effective catalysts for the process, fundamental understanding of the catalytic reaction must be established. To this end, the relation between catalyst properties and catalytic performance was investigated in this thesis. In order to obtain fundamental insights into the chemical processes occurring at the catalyst surfaces during CO2 electroreduction, we first investigated a broad group of transition metals. The potential-dependent activity and selectivity of CO2 electroreduction on each metal were characterized, which allowed for the observation of trends across the metals investigated. Using these results and theory, key factors affecting the catalytic performance for CO2 electroreduction were elucidated along with insights for the design of better catalysts. The catalyst property-performance relation was further probed through surface modification schemes such as alloying and surface structure engineering. Key observations from these investigations include: the enhancement in the activity for CO2 electroreduction to further reduced products on a AgZn alloy compared to pure Ag and pure Zn, the composition dependence of the catalytic performance of a PdxIny alloy system, and the surface structure-dependence of the product selectivity among further reduced products on Cu thin films. These results highlight the importance of control over chemical composition and surface structure of the catalyst surface, and contribute toward the design of effective catalysts.

Keywords: Chemical Engineering.
Advisor: Jaramillo Thomas Francisco primary advisor. Thesis advisor
Bao Zhenan advisor. Thesis advisor
Nørskov Jens K.
Investigating the quantum properties of jets and the search for a supersymmetric top quark partner with the ATLAS detector [electronic resource]

Quarks and gluons are the fundamental building blocks of matter responsible for most of the visible energy density in the universe. However, they cannot be directly observed due to the confining nature of the strong force. The Large Hadron Collider (LHC) uses proton-proton collisions to probe the highest energy reactions involving quarks and gluons happening at the smallest distance scales ever studied in a terrestrial laboratory. The observable consequence of quark and gluon production in these reactions is the emergent phenomenon known as the jet: a collimated stream of particles traveling at nearly the speed of light. The quantum properties of the initiating quarks and gluons are encoded in the distribution of energy inside and around jets. These quantum properties of jets can be used to study the high energy nature of the strong force and provide a way to tag the hadronic decays of heavy boosted particles. The ATLAS detector at the LHC is well-suited to perform measurements of the internal structure of high energy jets. A variety of novel techniques utilizing the unique capabilities of the ATLAS calorimeter and tracking detectors are introduced in order to probe the experimental and theoretical limits of the quantum properties of jets. Studying quarks and gluons may also be the key to understanding the fundamental problems with the Standard Model (SM) of particle physics. In particular, the top quark has a unique relationship with the newly discovered Higgs boson and as such could be a portal to discovering new particles and new forces. In many extensions of the SM, the top quark has a partner with similar relationships to other SM particles. For example, a scalar top partner (stop) in Supersymmetry (SUSY) could solve the Higgs boson mass hierarchy problem. Miraculously, a SUSY neutralino could also account for the dark matter observed in the universe and may be copiously produced in stop decays. High-energy top quarks from stop decays result in jets with a rich structure that can be identified using the techniques developed in the study of the quantum properties of jets. While there is no significant evidence for stop production at the LHC, the stringent limits established by this search have important implications for SUSY and other models.

Keywords: Physics.
Advisor: Schwartzman Ariel G.
Su Dong
Peskin Michael Edward
Tompkins Lauren Alexandra advisor. Thesis advisor