VictorJuiz/thesis huggingface dataset:
An RNA-based framework for cellular dynamic controls - towards building a genetic operational amplifier [electronic resource]

Biological systems maintain functioning in dynamic environments by performing complex computations to determine proper responses. These "computation" processes can be decomposed and implemented by fundamental genetic controllers, such as amplifiers and differential sensors. Despite a growing number of examples of synthetic control systems, limited effort has been directed toward building a generalizable controller for such dynamic regulations. We proposed to design a genetic operational amplifier (gen-opamp), which can serve as a fundamental component for electronic circuit systems. This gen-opamp consists of three stages: a differential sensor, an amplifier, and an output stage. The differential sensor contains a molecular transducer that maps the inputs to mRNA levels, and an RNA antisense subtractor to perform differential calculation. The genetic differential signal is further amplified by a transcriptional device, which subsequently regulates the expression of an enzymatic output to form feedback loops. The non-feedback configuration of the gen-opamp functions simply as a comparator; whereas its feedback configuration acts as a level-setter that keeps the ratio of the inputs constant by actively adjusting one to the other. We designed a prototype gen-opamp in budding yeast, using theophylline and tetracycline as the inputs. The corresponding aptamer-coupled ribozymes (i.e., RNA switches) are used as molecular transducers to regulate mRNAs at 3' UTR, together with a mutual complementary sense-antisense pair (at 5' UTR) to achieve differential sensing. partially implemented this Two amplifiers are implemented using synthetic LexA- and TetR-based transcriptional devices, driving either an activator (caffeine demethylase) or deactivator (theophylline demethylase) to form enzymatic feedback loops targeting the theophylline level. We began by engineering and verifying biological parts in each stage of the gen-opamp, and further developed a model-facilitated approach to facilitate the assembly process of each stage (i.e., level-matching). We also built a multi-chamber chemostat that enables continuous growth and sampling for characterizing the dynamic regulations under closed-loop controls. We were able to partially assemble the gen-opamp (as an input-controlled amplifier) and achieved a gain on the order of 200. We further demonstrated how to this partially assembled amplifier to form closed-loop feedback, and were able to observe hysteresis effect on theophylline production (positive feedback) and relaxation effect (negative feedback). This thesis presented a strong groundwork for the full assembly of the designed gen-opamp, which is currently still in the process. Future work involves putting both feedback loops into a single system together with the RNA antisense to implement the gen-opamp.

Keywords: Bioengineering.
Advisor: Smolke Christina D. primary advisor. Thesis advisor
Das Rhiju
Riedel-Kruse Hans
Wooley Bruce A.
Robust market design [electronic resource] : information and computation

A fundamental problem in economics is how to allocate precious and scarce resources, such as radio spectrum or the attention of online consumers, to the benefit of society. The vibrant research area of market design, recognized by the 2012 Nobel Prize in economics, aims to develop an engineering science of allocation mechanisms based on sound theoretical foundations. Two central assumptions are at the heart of much of the classic theory on resource allocation: the common knowledge and substitutability assumptions. Relaxing these is a prerequisite for many real-life applications, but involves significant informational and computational challenges. The starting point of this dissertation is that the computational paradigm offers an ideal toolbox for overcoming these challenges in order to achieve a robust and applicable theory of market design. We use tools and techniques from combinatorial optimization, randomized algorithms and computational complexity to make contributions on both the informational and computational fronts: (I) We design simple mechanisms for maximizing seller revenue that do not rely on common knowledge of buyers' willingness to pay. First we show that across many different markets -- including notoriously challenging ones in which the goods are heterogeneous -- the optimal revenue benchmark can be surpassed or approximated by adding buyers or limiting supplies, and then applying the standard Vickrey (second-price) mechanism. We also show how, by removing the common knowledge assumption, the classic theory of revenue maximization expands to encompass the realistic but complex case in which buyers are interdependent in their willingness to pay. (II) We prove positive and negative results for maximizing social welfare without substitutability, i.e., without the convexity property known to drive economic efficiency. On the positive side, we design natural greedy mechanisms for two-sided markets with strong incentive properties, whose welfare performance depends on the market's distance from substitutability. On the negative side, we show how computational challenges related to complementarity lead to the economic failure of competitive markets, in the sense that there do not exist simple prices that guide such a market to an efficient allocation. These results carry implications for the practice of market design, both for revenue-maximizing sellers such as Internet companies running online auctions, and for welfare-maximizing policy makers such as governments running spectrum auctions.

Advisor: Roughgarden Tim primary advisor. Thesis advisor
Johari Ramesh
Milgrom Paul R. (Paul Robert)
The role of frontoparietal cortex in intertemporal choice [electronic resource]

We often have to make decisions in which we need to choose between immediate satisfaction and an objectively better but also more delayed benefit. These decisions are not only pervasive. They determine our well being in major aspects of life, including health, education and finance. The goal of this dissertation is to clarify the cognitive and neural mechanisms that enable us to make this kind of decisions. To this end, two fundamental questions are addressed. First, how can our behavior be influenced by the subjective values that we place on future outcomes? Second, how are we able to forgo temptations that may bring greater pleasure on the short run, but impede the receipt of greater future rewards? The overall thesis defended over six chapters is that the cognitive processes by which we solve both of these problems are implemented by a functionally integrated network of frontoparietal regions in the cerebral cortex.

Keywords: Psychology.
Advisor: McClure Samuel M. primary advisor. Thesis advisor
Knutson Brian advisor. Thesis advisor
Norcia Anthony Matthew
The role of joint visual attention in collaborative learning [electronic resource]

It is a well-known fact that increased levels of joint attention are associated with interactions of higher quality among individuals of all ages: for instance between babies and their caregivers (Stern, 1977), students (Barron, 2003) and adults (Richardson & Dale, 2005). In this dissertation, I describe three original contributions to the study of joint visual attention (JVA) using eye-tracking technology. In the first study (Schneider & Pea, 2013), I demonstrate that pairs of students who were able to see the gaze of their partner in real-time on a screen collaborated better and learned more than their peers in a control group (who could not see the gaze of their partner). By doing so, I show that levels of JVA can be manipulated and increased to support collaborative learning in dyads of students. In the second study (Schneider & Pea, 2014), I further analyze this eye-tracking dataset by building networks where nodes represent moments of JVA and edges saccades between regions of interest; I then show how features of those networks have predictive value for differentiating between productive and unproductive collaborative groups. Finally, in the third study (Schneider, Sharma, Cuendet, Zufferey, Dillenbourg & Pea, accepted) I extend those results to a more challenging setting and describe a methodology to extract JVA measures in an in-situ collaboration (i.e., when students interacted with a Tangible User Interface; TUI): half of the students worked with a 2D, abstract-looking interface while the other half used a 3D, realistic-looking system. I found that students who were looking at the 3D version of the system had more moments of JVA, and that JVA measures were correlated with outcomes of interest (students' learning gains, their task performance and quality of collaboration). These findings suggest features of a learning environment (i.e., 2D vs. 3D) can be manipulated to affect students' level of JVA. In the last section of this dissertation, I discuss the aforementioned results and mention implications for designing new technologies to support small group interactions.

Keywords: Education.
Advisor: Pea Roy D. primary advisor. Thesis advisor
Blikstein Paulo
Schwartz Dan
Role of the Brg bromodomain in BAF (mSWI/SNF) chromatin remodeling complex function and genomic targeting [electronic resource]

The mammalian SWI/SNF, or BAF, complex is a polymorphic ATP-dependent chromatin remodeler that is mutated in approximately 20% of human cancers and is necessary for many stages of development. BAF (Brg/Brm-associated factors) complexes are enriched at around thirty thousand genomic sites that vary depending on cellular context. We found that in embryonic stem cells (ESCs), which are dependent on BAF complex function for self-renewal and pluripotency, the majority of BAF complex sites align with gene promoters and enhancers. BAF complex targeting and function may be influenced by several of its ~6-13 putative chromatin binding domains, but the in vivo role of these domains has not been explored. We created a mutant Brg bromodomain (N1507A) ESC line to investigate this putative chromatin binding domain's role in BAF complex function during development. Surprisingly, the Brg bromodomain is dispensible for ESC derivation and self-renewal, in contrast to the essential role of the Brg ATPase. In a cell culture model, we found that the Brg bromodomain is necessary for differentiation of neural progenitors into glutamatergic neurons. In vivo, however, the BrgN1507A mutation causes peri-implantation lethality (E4.5-E6.5). Based on successful blastocyst hatching and outgrowth, we hypothesize that the Brg bromodomain may be necessary for the survival of the early or late epiblast, from which the three embryonic germ layers are formed. From biochemical studies of the BrgN1507A-containing BAF complex, we determined that the composition, size, and stability of the BAF complex seem unaffected. Under steady-state conditions, the mobility of the BAF complex in live cells was also unaffected, although mutant complexes were partially resistant to a hyperacetylation-mediated reduction in mobility. In order to gain insight into the essential role of the Brg bromodomain in early embryonic development, we examined genome-wide BAF complex binding and gene expression in a cell culture model of epiblast formation. While a number of developmentally regulated genes are mis-expressed in the BrgN1507A model, BAF complex targeting is minimally affected. While these subtle targeting defects may be biologically relevant, we hypothesize that the main role of the Brg bromodomain is to regulate the BAF complex or its binding partners through allosteric mechanisms. We hope to continue studies of the Brg bromodomain in order to fully understand how it influences overall BAF complex function.

Advisor: Crabtree Gerald R. primary advisor. Thesis advisor
Khavari Paul A. advisor. Thesis advisor
Wernig Marius advisor. Thesis advisor
Wysocka Joanna
The saw and the seed [electronic resource] : Japanese forestry in colonial Korea, 1895-1945

This dissertation examines Japanese efforts to understand, rehabilitate, exploit, modernize, and showcase Korea's forests during the period of colonial rule (1910-1945). As a source of natural resources, a space of habitation, and a repository of rural traditions, Korea's woodlands formed a dynamic and highly contentious site of colonial governance. And yet, save for Korean- and Japanese-language studies on forestry policy, Korea's mountains and forests, which comprise more than 70 percent of the peninsula, remain a historiographical hinterland. Building on the growing body of comparative literature on the tangled roots of colonialism, scientific forestry, and conservationism, I argue that the forestry enterprise in colonial Korea was as concerned with the seed as it was with the saw: it placed afforestation and forest conservation at the heart of the colonial project to reform the Korean landscape and the ecological sensibilities of its inhabitants. Driven by utilitarian concerns about resource scarcity, a growing empire-wide demand for Korea's forest products, and fears of cascading environmental degradation, Japanese foresters set out in Korea to reclaim a peninsula routinely described as "a land of bald mountains and red earth." But forest reclamation in Korea was far from benevolent or benign: it siphoned off forestland to Japanese corporations and capitalists, cut off local communities from woodlands that had long sustained them, and placed vast tracts of commercially viable forests (especially those in the Yalu and Tumen River basins) under state control. Afforestation, in other words, was a process rife with conflict and fraught with contradiction. By chronicling the vicissitudes of this intensive, contested, and largely forgotten forestry project, I offer a case study in the promise and perils of natural resource management as it took shape in Japan's empire. Three principle lines of inquiry sustain my analysis. First, by surveying how, where, and when Korea's forests (and the range of resources therein) were utilized during the colonial period, I examine the materiality of modernization and the ecological implications of colonial rule. Second, through an examination of the mechanics and implementation of forestry policy, I map the contours of the politics of sustainability: a term that connotes the often-conflicting interests inherent to forest management and the myriad forces shaping forestry reforms (including bureaucratic conflict, geopolitics, peasant protest, and global markets). Third, by drawing attention to the interpenetration of forestry and everyday life, I explore the emergence in Korea of colonial ecological modernity: a concept that highlights how colonial forestry was not simply a process of modernization, but a far reaching and contested public campaign that touched the lives, values, and sensory experiences of residents across the peninsula.

Keywords: History.
Advisor: Uchida Jun primary advisor. Thesis advisor
Moon Yumi advisor. Thesis advisor
White Richard
Wigen Kären
Scalable software tools and methods for smart grid modeling and optimization [electronic resource]

The electric grid in its current incarnation-- comprising utility companies, power system operators, market players and other agents-- is undergoing rapid change. Increasing adoption of distributed energy resources, electric vehicles, and demand response programs are adding further stress to the aging grid infrastructure. In order to realize the benefits of these new technologies, engineers need new tools to model and optimize the complex interactions. We address this need with GridSpice, a software framework with the computational scale and the modeling capability to represent diverse scenarios in large interconnected grid systems. GridSpice leverages existing best-in-class point tools and fuses them together in a modular architecture. The GridSpice framework is designed to run on the cloud, giving researchers and engineers the ability to elastically utilize many machines to perform complex simulations. After describing the GridSpice framework, we introduce a method to optimize centralized storage in wholesale markets. Specifically, this method maximizes the expected present value (PV) of an independently operated electric energy storage (EES) unit cooptimized to perform both energy arbitrage (EA) and regulation service (RS). The method is particularly suitable for fast-ramping EES units with a high power-to-capacity ratio, such as a grid-scale battery. The method is applied to two sample battery technologies using market data from the Independent Service Operator of New England (ISONE), illustrating how the cost and performance of storage technologies translates to financial returns. Next, we present a method for optimizing energy storage on a low voltage distribution grid with high penetrations of renewable distributed generation (RDGs). The method shows how intelligently storage can alleviate local volt/var violations, increase the maximum safe RDG penetration level, and simultaneously reduce the average cost of energy by shifting aggregate load from peak to off-peak hours (i.e., energy arbitrage). Finally, we show how to characterize the return on investment of storage and solar installations as a function of the technology parameters, penetration level, and limitations on the communication network.

Keywords: Electrical Engineering.
Advisor: El Gamal Abbas A. primary advisor. Thesis advisor
Narayan Amit
Rajagopal Ram advisor. Thesis advisor
Scalar transport in channel networks [electronic resource] : development of a particle tracking model to study the movement of scalars in the Sacramento - San Joaquin Delta

A three dimensional particle tracking model (PTM) is developed to study the transport of scalars in a branched network of channels. The PTM is used to quantify the effects of different transport mechanisms in the Sacramento-San Joaquin delta (henceforth, the Delta) for various hydrological conditions. The paths taken by scalars and crucial branching points are identified. The different transport and mixing mechanisms are quantified by successively applying the PTM with tidal and cross-sectional flow structure removed and computing the differences between the results. Channel junctions are implemented using a streamline following mechanism of particle movements. It is found that the bifurcating and recombining junctions are critical to the transport of scalars in the Delta. The streamline following junction model produces more accurate results than the randomizing model. Secondly, in-channel transport and mixing mechanisms, which are strongly influenced by the upstream history of mixing along transport pathways do not contribute significantly to the transport of scalars in the Delta. The most important transport mechanism in the Delta is found to be the significantly increased dispersion through the junctions. Thirdly, tides dominate throughout the West, Central and North Delta, and hence the tidal flows and the mixing mechanisms induced by the tides are at least as important as mean river flows and mixing mechanisms due to mean flows. Lastly, parameters which incorporate the transport pathways are better able to quantify bulk Delta processes. Scalar fate is quantified using by developing and using new parameters such as cloud volume growth, particle pathway based residence times and dispersion coefficients and Delta mass balance. The Delta is defined as a set of simply connected interacting geographic regions with dominant transport mechanisms. Applications of the project include pollution mitigation, ecosystem restoration and habitat management, and the design of water quality standards.

Keywords: Civil and Environmental Engineering.
Advisor: Monismith Stephen Gene primary advisor. Thesis advisor
Fong Derek advisor. Thesis advisor
Freyberg David L. advisor. Thesis advisor
Fringer Oliver B. (Oliver Bartlett) advisor. Thesis advisor
Koseff Jeffrey Russell advisor. Thesis advisor
Scaling up object detection [electronic resource]

Hundreds of billions of photographs are created on the web each year. An important step towards understanding the content of these photographs is to be able to understand all objects that are depicted. My research focuses on the problem of automatically naming and localizing objects in large collections of images. This is referred to as the task of object detection. The work in this thesis scales up object detection algorithms in both the number of images and the number of objects that can be recognized. I've developed efficient object detection algorithms which can be applied on large image collections and studied using shareable generic object attribute descriptions that can be used to effectively describe a variety of object classes without learning individual class appearance models. The key roadblock to scaling up object detection is that extensive manual annotation is required for training the models, which can be very time-consuming and expensive. To address this roadblock, my colleagues and I created the ImageNet Large Scale Visual Recognition Challenge (ILSVRC). ILSVRC serves as a benchmark large-scale object recognition for hundreds of international research teams. I led the effort to construct the object detection benchmark, scaling up by more than an order of magnitude compared to previous dataset (e.g., the PASCAL VOC). The construction of this dataset required developing novel crowd engineering techniques for reducing annotation cost. The availability of this large-scale data lead to a revolution in object detection algorithms. I performed a detailed analysis of the current state of the field of object recognition, providing insights for future research efforts. Thinking ahead about scaling up object detection even further, I developed a framework for bringing together the state-of-the-art automatic large-scale object detection with state-of-the-art crowd engineering techniques into a principled human-in-the-loop framework for accurately and efficiently localizing objects in images.

Advisor: Li Fei Fei
Bernstein Michael S.
Lin Yuanqing (Department Head of Media Analytics)