VictorJuiz/thesis huggingface dataset:
Elucidating in vitro activation of [FeFe] hydrogenase [electronic resource]

The sustainable production of hydrogen for use as a renewable energy source is a promising alternative to current fossil fuel-based technologies. We seek to exploit nature's prolific biological catalysts, hydrogenases, to replace fossil fuel-based hydrogen production with a carbon-neutral process. [FeFe] hydrogenases are specific and productive enzymes for hydrogen evolution, but the application of these complex proteins is limited by inefficient production methods. Here, we present progress towards a fully defined in vitro hydrogenase maturation system by elucidating the assembly requirements for producing fully active [FeFe] hydrogenase. The in vitro [FeFe] hydrogenase maturation system activates purified Clostridium pasteurianum CpI apoprotein using recombinant Shewanella oneidensis HydE, HydF, and HydG maturases, and exogenous small molecules. However, activation can only be achieved in the presence of a crude and undefined E. coli cell extract. In order to identify the protein(s) in the crude cell extract responsible for maturing the hydrogenase, various fractionation and protein separation techniques were implemented, and candidate proteins were evaluated for apo hydrogenase activation. For instance, prokaryotic frataxin, CyaY, interacts with iron sulfur cluster (isc) proteins and, when complexed with ferric iron fully enables activation of the hydrogenase while reducing the required amount of crude extract from 20% to 2% (v/v). Protease treatments were pursued to further separate protein fractions that retained hydrogenase-activating functionality. A 1hr, 60°C papain treatment was effective in significantly reducing proteomic content while maintaining the protein(s) responsible for activating the hydrogenase. After combining papain treatment with chromatography and LC-MS/MS analysis, the identified proteins suggested that oxidoreductases to play an essential role in donating electrons to the maturases. We present a thioredoxin based electron delivery system to active the first fully defined hydrogenase maturation system, requiring super-physiological thioredoxin concentrations. Finally, Ferrous transporter protein A, FeoA, was determined to be a promising candidate for fully maturing the hydrogenase by providing an electron delivery mechanism for H-cluster assembly and installation at physiological FeoA concentrations. In addition to its putative role as a ferrous iron trafficking protein, we propose a new functionality as an electron donor to satisfy the reduction requirements for the [FeFe] hydrogenase active site. These findings provide a deeper understanding of the mechanism for [FeFe] hydrogenase maturation. Further, this knowledge now enables genetic engineering of E. coli and photosynthetic organisms for the biological production of hydrogen as a clean and renewable alternative fuel.

Keywords: Chemical Engineering.
Advisor: Swartz James R. primary advisor. Thesis advisor
Dunn Alexander Robert advisor. Thesis advisor
Khosla Chaitan
"Elucidating the role of Casein Kinase 2 in regulating Glioblastoma Metastatic Potential"

Glioblastoma (GBM) is the most common malignant primary brain tumor comprising 40-50% of all adult cases. Despite standard treatment of care involving surgical resection followed by radiotherapy with chemotherapy, the median overall survival rate remains dismal at 14-15 months. The major barrier to effective treatment is GBM tumor metastasis, which enables tumors cells to have enhanced migratory and invasive potential. Recent work has demonstrated a link between Casein Kinase 2 and GBM tumorigenesis, indicating that CK2 modulation could be a promising therapeutic target for GBM. However, no one has studied the role of CK2 in GBM tumor metastatic potential, or the molecular mechanisms underlying tumor cell invasion and migration characteristic of the epithelial to mesenchymal transition (EMT). Here, we investigate the role of CK2 in GBM migration and invasion by using the wound-healing assay, trans well assay, and western blot analysis. We show that CK2 inhibition via CX-4945, a CK2 specific kinase inhibitor, decreases cell invasive potential, and this finding is recapitulated in two immortalized GBM cell lines. Additionally, we show that CK2 upregulation increases expression of mesenchymal markers, suggesting a potential role between CK2 expression, GBM invasiveness, and the EMT pathway. Furthermore, the data represent a major step in elucidating the molecular mechanisms of tumor metastasis, and help identify CK2 as a promising therapeutic target to more effectively treat GBM tumor recurrence.

Keywords:  Department of Biology
biology
cancer
glioblastoma
CK2
Thesis
Advisor: Li Gordon
Shen Kang
Embedded entropy concept for fluid dynamic simulations with discontinuous Galerkin scheme [electronic resource]

The Discontinuous Galerkin (DG) method represents an attractive simulation technique for computational fluid dynamics. Compared to conventional finite-difference and finite-volume methods, the DG method enables the high-order discretization on unstructured meshes, utilizes a compact discretization, and is well suited for advanced refinement strategies. However, it has been recognized that high-order DG approximations suffer robustness when applied to solving nonlinear conservation laws. These nonlinear numerical instabilities arise at physical discontinuities and numerically under-resolved flow-field features. By addressing these issues, this thesis work is concerned with the development of a realizable and stable high-order DG method for application to complex flows, involving discontinuities, shocks, and chemical reaction. An entropy-bounded discontinuous Galerkin (EBDG) scheme is developed, and the scheme is proven to preserve physical realizability of flow variables, such as the positivity of pressure and density, the boundedness of transported scalars and the boundedness of minimum entropy. In numerical tests, the EBDG scheme shows superb numerical stability and capability of capturing strong shock waves, as well as preservation of high-order accuracy for smooth solutions. The EBDG scheme is further augmented with a shock indicator and an artificial viscosity method to eliminate the Gibbs phenomenon triggered around shock discontinuities. The numerical framework developed based on the EBDG scheme is applied to study detonation initiation by shock-wall interaction. Specific focus of this study is on characterizing the role of Mach shock reflection on ignition and initiation processes. Furthermore, the accuracy and computational cost of the DG solver is assessed against a state-of-the-art finite volume solver in the applications to direct numerical simulations and large-eddy simulations of decaying turbulence. The comparison shows that on regular hexahedral meshes the finite volume scheme only requires one third of flops needed for the DG scheme at the same level of accuracy, while on tetrahedral meshes the DG scheme outperforms the finite volume scheme due to its capability of preserving the higher-order accuracy on unstructured and irregular meshes.

Keywords: Mechanical Engineering.
Advisor: Ihme Matthias
Lele Sanjiva K. (Sanjiva Keshava)
Moin Parviz advisor. Thesis advisor
Emerging electronic states at boundaries and domain walls in quantum materials [electronic resource]

Boundaries and domain walls in condensed matter often host unique electronic states that are distinct from those living inside the bulk. Their intriguing physics and diverse application potentials have attracted growing research effort on codifying the relevant emergent laws, whereas their complex and low-dimensional nature constantly calls for novel characterization techniques. Scanning Microwave Impedance Microscopy (MIM) characterizes local electrical response (complex permittivity) by probing microwave tip-sample admittance in the meso- to microscopic scale. It has matured in the past decade and has become a powerful tool for studying these emerging electronic states in real space, highly complementary to existing tools working in atomic scale or momentum space. In this dissertation I will first give a scientific overview of the field (Chapter 1), followed by a brief introduction to MIM, with a focus on the fundamental principles and recent developments (Chapter 2). I will then present five scientific studies made possible by MIM, which can be grouped into two categories, namely 1D edge states at solid-vacuum boundaries in 2D systems (Chapter 3), and order-parameter domain walls embedded in a 3D solid (Chapter 4). Chapter 3 contains the discovery of unexpected edge conduction in HgTe/CdTe quantum wells in the presence of a strong magnetic field, an unconventional correlation between quantum Hall transport quantization and bulk Landau level filling in gated graphene devices, and edge-bulk conductivity contrast in magnetic modulation doped Cr-(Bi, Sb)Te films in the quantum anomalous Hall regime. Chapter 4 includes the signature of charge-order domain walls with enhanced conductivity in a layered magnanite, and the establishment of neodymium iridate as the first experimental realization of a magnetic insulator with metallic magnetic domain walls.

Keywords: Applied Physics.
Advisor: Shen Zhi-Xun primary advisor. Thesis advisor
Goldhaber-Gordon David
Moler Kathryn A. advisor. Thesis advisor
Empirical models of analyst forecasts [electronic resource]

This dissertation is comprised of two studies on analyst forecasts. The first study provides empirical evidence about the objective function underlying analysts' choice of forecasts. Assumptions about sell-side analysts' objective function are critical to empirical researchers' understanding of their incentives and resulting behavior. In contrast to approaches used in previous papers which rely exclusively on statistical properties of forecasts, I compare theoretical models with alternate objective functions based on their ability to explain observed forecasts. A linear loss objective function which incorporates the effect future analysts' actions on analysts' deviation from peer forecasts is best rationalized by the data. I find that assumptions about the objective function have a substantial impact on the conclusions from empirical tests about analysts' incentives and behavior. The second study provides empirical estimates of uncertainty and disagreement about future earnings that underly analyst forecast dispersion. A parsimonious model which assumes that analysts' payoffs are jointly determined by forecast error and deviation from consensus reproduces many of the descriptive facts observed about forecast dispersion in the data. The strategic behavior that arises from the model distorts both the levels of forecast dispersion and the sensitivity of the measure with respect to cross-sectional variation in uncertainty. The estimated parameters perform better at predicting forecast dispersion out-of-sample than approaches based solely on regressions that use firm characteristics. Counterfactual simulations indicate that analysts' strategic incentives, together with the sequential forecast setting, plays a first-order role in determining forecast dispersion relative to the firm's information environment. The model-implied estimates of earnings uncertainty exhibit a substantially less negative association with future returns relative to the association generated by forecast dispersion. This finding partially reconciles the findings from previous studies with theories about the asset pricing implications of uncertainty and disagreement.

Keywords: Business.
Advisor: Larcker David F. primary advisor. Thesis advisor
Reiss Peter C. (Peter Clemens) primary advisor. Thesis advisor
Barth Mary E. advisor. Thesis advisor
Empirical studies in mobile security and privacy [electronic resource]

Mobile devices have become a dominant way that consumers interact with computing. Alongside the growth of mobile computing has been the popularization of a new software distribution method: the "app store''. In addition to representing a major shift in the distribution model of consumer software, app stores are a major opportunity for improving the measurement of the security and privacy properties of mobile computing. App stores provide uniform access to massive datasets of apps and include valuable app metadata that cannot be obtained by examining app code. This property makes it possible to obtain extremely highly quality samples of the entire mobile app ecosystem, study security threats at a population-level scale, and understand non-technical trends and correlates in security vulnerabilities in a manner that is difficult or impossible in other software domains. App stores also provide a platform to collect data about mobile devices and their users through the distribution of mobile apps. Because of the ubiquity of mobile computing, this approach allows for the easy collection of rich datasets of user information. In this dissertation I leverage datasets obtained using app stores to perform three large scale experiments in mobile security and privacy. I collect a massive dataset of Android apps from the Google Play app store spanning nearly four years and study the threat of Target Fragmentation in Android apps as well as the prevalence of security vulnerabilities related to unsafely embedding web content in Android apps. I also study the privacy properties of telephone metadata using a dataset crowdsourced through a mobile app. Each of these studies has serious practical implications. The experiments studying security vulnerabilities in Android apps demonstrate the widespread and continued existence of serious vulnerabilities in the Android ecosystem and the experiment studying the privacy properties of telephone metadata has been cited in legal cases opposing surveillance programs operated by the United States government.

Advisor: Mitchell John C. primary advisor. Thesis advisor
Aiken Alexander advisor. Thesis advisor
Boneh Dan
Empirical studies in operations management and pricing with customers [electronic resource]

This dissertation studies problems in operations management that arise in settings characterized by rich interactions with customers, especially online. We first study the pricing and inventory strategies of a retailer whose customers can monitor its offered prices over time through an online channel, where they incur heterogeneous costs to monitor. We then study the growth and customer loyalty of online services in the app economy from an operational perspective. We describe each of these settings and empirical inquiries in turn. Online retail reduces the costs of obtaining information about a product's price and availability and of flexibly timing a purchase. Consequently, consumers can strategically time their purchases, weighing the costs of monitoring and the risk of inventory depletion against prospectively lower prices. At the same time, firms can observe and exploit their customers' monitoring behavior. Using a dataset tracking customers of a North American specialty retail brand, we present empirical evidence that monitoring products online is associated with successfully obtaining discounts. We develop a structural model of consumers' dynamic monitoring to find substantial heterogeneity, with consumers' opportunity costs for an online visit ranging from

Keywords: Business.
Advisor: Bimpikis Kostas primary advisor. Thesis advisor
Mendelson Haim primary advisor. Thesis advisor
Nair Harikesh S. (Harikesh Sasikumar)
Enabling more sustainable affordable housing [electronic resource] : utilizing early design stage life cycle assessment to reduce life cycle costs and environmental impacts

Residential building structures contribute significantly to social, environmental, and economic impacts throughout their life cycle. Sustainability, is broadly concerned with these impacts and how they relate to complex social, environmental, and economic systems such as those that drive the residential built environment. This thesis presents a methodology for promoting more sustainable housing development by introducing environmental and economic impact feedback into the early design stage. The social dimension is addressed by focusing this research on affordable housing for low-income households. The environmental and economic impacts are addressed by integrating life cycle assessment and life cycle costing techniques into an automated, parametric analysis framework. This framework is applied to two low-income, affordable housing design spaces in the contrasting environments of San Francisco, California and Las Vegas, Nevada. The thesis illustrates how this methodology can aid design stakeholders in reducing the long-term environmental impacts and costs of low-income, affordable housing developments. The results are also compared to industry design preferences, collected through a survey of low-income, affordable housing practitioners. This comparison reveals potential gains in life cycle environmental impact and cost reductions that are not currently realized by prevailing industry design preferences. This thesis concludes by offering direction for future work and by highlighting the potential for this framework to inform housing development trends and regulatory decision-making.

Keywords: Civil and Environmental Engineering.
Advisor: Lepech Michael advisor. Thesis advisor
Enacting perception [electronic resource] : the contemporary lyrical novel

My dissertation studies the hybrid genre of the lyrical novel primarily in the post-1980 period. Considering lyrical novels a potential praxis, it argues that lyricism in narrative can result in a reader's experience resembling a process of perception that is enactive. I discuss Julio Llamazares' La lluvia amarilla, Horacio Castellanos Moya's El asco, Yoko Tawada's Wo Europe Anfängt?, W.G. Sebald's Austerlitz, and Abdelkébir Khatibi's Amour bilingue as contemporary lyrical novels that inquire into the limits of reality and fiction, into memory, self, and poetic language.

Keywords: Comparative Literature.
Advisor: Greene Roland
Gumbrecht Hans Ulrich primary advisor. Thesis advisor
Saldívar Ramón
An energy harvested ultra-low power wireless transceiver for biomedical implants [electronic resource]

Biomedical implants have been used to treat a variety of medical conditions as well as to monitor vital physiological information in the body. Advances in manufacturing technology for bio-materials and electronics have expanded the prospect of widespread use for these implants. Significant hurdles have to be overcome before these devices go mainstream. Power delivery to the implant is one of the major challenges faced by these systems. Although it is possible for batteries to supply uninterrupted power to certain kinds of implants, e.g. pacemakers, other implant applications need to be powered remotely from outside the body. RF powering is a widely used method among remote powering techniques for implants. Reducing the size of these devices is also highly desirable such that they could be implanted using less invasive surgical procedures. A wireless communication link enables information exchange with the implant using two sets of transceivers: one outside and one inside the body. The transceiver which is embedded in the implant has to be designed meeting stringent power, size, and data-rate requirements. In this thesis, an energy harvested ultra-low power wireless transceiver for biomedical implants is demonstrated. The transceiver is fully RF-powered at low gigahertz carrier frequencies suited for optimal power delivery using the midfield wireless powering technique. It demonstrates megabits-per-second data rates aimed at neuro-modulation and recording applications with large number of channels. The transceiver supports full duplex operation via frequency-division (FDD) or time-division (TDD) duplexing methods with a high energy efficiency. In FDD mode, the transceiver achieves maximum data rates of 58 Mbps in TX, and 2.5 Mbps in RX. The average power consumption of the transmitter is 93 μW at 58 Mbps while that of the receiver is 7.2 μW at 2.5 Mbps. This corresponds to an energy-per-bit metric of 2.9 pJ/bit for the RX and 1.6 pJ/bit for the TX. In TDD mode, data rates of 7.2 Mbps for the TX and 1.8 Mbps for the RX have been demonstrated. In this mode, The TX consumes 54 μW, while the RX consumes 9.4 μW. The transceiver, therefore, achieves energy efficiency of 7.5 pJ/bit for the TX and 5.2 pJ/bit for the RX. This radio was fabricated in 40 nm CMOS LP process and has a small silicon area of 0.8 mm2.

Keywords: Electrical Engineering.
Advisor: Poon Ada Shuk Yan
Howe Roger Thomas advisor. Thesis advisor
Wong S. Simon advisor. Thesis advisor
Engineering bivalency and bispecificity in protein therapeutics and protein scaffold development [electronic resource]

Multivalent and multifunctional proteins are abundant in nature. The avidity effect, a core principle of multivalent molecules, allows these proteins to tune biological functions and responses across a large dynamic range with varying specificity. Many protein therapeutics also take advantage of this evolvable tunability, the canonical example being the antibody. This thesis consists of two separate sections. Section One: I focus on the avidity effect of multivalent proteins and its therapeutic uses. As an illustrative case, our lab had previously created a protein variant that monomerically binds the c-MET tyrosine kinase. By dimerizing this variant, we find that we greatly increase its efficacy through increased apparent affinity to cell surface c-MET. Section Two: I focus on multispecific proteins and their uses in medical applications. Most current therapeutic protein scaffolds are single protein domains with monomeric binding and function. Combining these scaffolds to create multispecific functionality presents manufacturing challenges. Here the vascular endothelial growth factor (VEGF) protein is used as a stable, naturally bivalent scaffold for engineering bispecific proteins.

Keywords: Chemical Engineering.
Advisor: Cochran Jennifer R. primary advisor. Thesis advisor
Dunn Alexander Robert primary advisor. Thesis advisor
Khosla Chaitan