VictorJuiz/thesis huggingface dataset:
Designing datacenter transports for low latency and high throughput

Recent trends in datacenter computing have created new operating conditions for network transport protocols. One of these trends is applications that operate at extreme low latency. Modern datacenter networking hardware offers the potential for very low latency communication; round-trip times of 5µs or less are now possible for short messages. A variety of applications have arisen that can utilize this low latency because their workloads are dominated by very short messages (a few hundred bytes or less); Facebook's Memcached and RAMCloud storage system are two instances of such low latency applications. Transport protocols, however, are traditionally designed to achieve high throughput rather than low latency. They sometimes even sacrifice low latency for the sake of achieving high throughput; TCP and TCP-like transports, which are the de facto transports used in most applications today are examples of high throughput transports. These transports are known to impose high latency for short messages when the network load is high. That's because their sender driven congestion control mechanism creates large queues in the network and short messages can experience long head-of-line blocking delays in these queues. So even though these large queues can bring high throughput and bandwidth utilization, they can extremely hurt short message latencies. In this thesis we postulate that low latency and high throughput are not mutually exclusive goals for transport protocols. In fact we design a new transport protocol named Homa that can achieve both of these goals in datacenter networks. Homa is a transport protocol for datacenter networks that provides exceptionally low latency, especially for workloads with a high volume of very short messages, and it also supports large messages and high network bandwidth utilization. Homa uses in-network priority queues to ensure low latency for short messages; priority allocation is managed dynamically by each receiver and integrated with a receiver-driven flow control mechanism. Homa also uses controlled overcommitment of receiver downlinks to ensure efficient bandwidth utilization at high load. We evaluate Homa in both simulations and a real system implementation. Our implementation of Homa delivers 99th percentile round-trip latencies less than 15 µs for short messages on a 10 Gbps network running at 80% network load. These latencies are almost 100x lower than the best published measurements of an implementation in prior works. In simulations, Homa's latency is roughly equal to pFabric and significantly better than pHost, PIAS, and NDP for almost all message sizes and workloads. Homa can also sustain higher network loads than pFabric, pHost, or PIAS.

Keywords: Electrical Engineering.
Advisor: Ousterhout John K. 
Kozyrakis Christoforos
Rosenblum Mendel
Designing idea generation protocols for consumers and firms

To jumpstart innovation and collect a diverse set of ideas for new product development, firms often organize events and activities exclusively dedicated to idea generation. For example, consumers partake in idea generation in online crowdsourced ideation contests and employees generate ideas in team meetings and during hackathons. How should marketers design these activities to maximize productivity? To answer this question, my dissertation examines how the structure of these ideation activities shape the cognitive mechanisms underlying idea generation and development. In my first essay, I investigate the efficacy of a frequently used ideation paradigm in consumer ideation contests, explicitly soliciting creative ideas, and uncover a creativity paradox— that encouraging creative ideas can backfire, leading to fewer novel ideas that firms can harvest. In my second essay, I examine the impact of virtual collaboration (i.e., videoconferencing) on the cognitive processes of idea generation and subsequent idea selection. Although videoconferencing closely mimics in-person conversation, I find that communication modality can meaningfully change new product development: virtual teams (vs. face-to-face teams) perform worse during idea generation but are better at identifying their best idea for further development. Finally, in my third essay, I explore when repeated practice can be leveraged to improve creative thinking. I find that while daily practice fosters creative problem-solving (i.e., convergent creativity), it does not facilitate, and may even undercut, ideation (i.e., divergent creativity). Taken together, these projects provide a deeper understanding of the psychological drivers of ideation and creativity as well as generate a rich set of tools for consumers and firms to increase creativity and fuel innovation.

Keywords: Business.
Advisor: Huang Szu-chi 
Levav Jonathan
Wheeler S. Christian
Designing languages for parallel portability of physical simulations, using relational algebraic abstractions

The desire to ever more efficiently simulate physical phenomena using computers produces a demand for increased specialization of physical models, geometric & numeric algorithms, and computing hardware/systems. This demand limits itself by trending towards unmanagable complexity; manifesting as an inability to separate disciplinary specialties via distinct parts of the simulation code. For parallelism in particular, the interface along which this separation happens must necessarily take the form of a language, separating compiler-programmers from simulation-programmers. Furthermore, such languages must exploit a more abstract and restricted data model than random-access-memory in order to enable performant portability across different parallel systems. I propose using a relational (algebraic) abstraction of simulation data in order to give compiler programmers both sufficient freedom and information to successfully port applications onto parallel hardware, while maintaining high performance (time and memory). I investigate three aspects of this problem, organized by the metric-topology distinction from geometry, and explored by constructing language prototypes: (1) Ebb, a language for local stencil computations on metric data; (2) Seam, a language for local modification of topological data (i.e. remeshing); and (3) Gong, a language for generation of topology from metric locality (i.e. collision detection). These languages use a common relational abstraction of data, including coupling of structured and unstructured mesh domains in a single program. Seam additionally leverages the concepts of transactions and views from databases, while Gong leverages the concepts of joins and indices. Database queries are extended by treating actions on queries using parallelizable lock-free effects beyond simple reading and writing. Experimental evaluation of prototype language implementations (with support for GPUs) shows that the performance of highly-tuned implementations can be matched to within a 1.25x overhead at worst (for an Ebb implementation of a super-computing benchmark; 1.15x for a Gong implementation of an industrial collision detection system). However, the ability to systematically port code to different platforms easily allows 2-9x accelerations of many simulation programs over the next best cpu/multi-core implementations available. Ebb programs are usually less than half as long, while automatic view maintenance in Seam yields 10x reductions in complex pointer manipulation code size.

Advisor: Hanrahan P. M. (Patrick Matthew) 
Aiken Alexander 
James Doug L.
Designing Sketch and Learn: Creating a Playful Sketching Experience that Helps Learners Build a Practice Toward Visual Notetaking (aka Sketchnotes)

Notetaking is an important practice in classrooms around the world and is useful for capturing information and forming connections between large amounts of information and ideas. However, traditional notetaking methods tend to follow a linear structure, and students are often trained to capture information in a verbose text-based format. Visual notetaking, also known as sketchnoting, is an under-recognized strategy that can enhance the practice of notetaking. Sketchnoting taps into both the verbal and visual processes of decoding and encoding information, allowing learners to use a combination of words and images to make meaning from verbal or text-based information. Not only do studies show the potential benefits of sketchnoting, educators who have taught sketchnotes in their classrooms have also reported that it opened up opportunities for minority students such as neurodiverse individuals and language learners, providing them with another means of expressing their ideas and showing their understanding of content.
To facilitate the learning of sketchnotes, we designed Sketch & Learn, a web-based game that engages learners in playful sketching quests that help them build a visual library and a dedicated practice toward sketchnoting. Drawing insights from learning theories on scaffolding, game design, and best practices from educators, Sketch & Learn uses a relevant narrative and short challenges to recruit interest from novice learners and support long-term engagement. Pedagogically, we used gameplay to establish a playful low-stakes learning environment and used worked examples to ease learners into sketchnoting.
Preliminary testing results showed that the narrative and quests sparked interest, promoted engagement from users, and elicited learning gain. Users expressed interest in further engagement, and a digital version of the visual library feature. With promising results from our design concept, we are one step closer to our mission to equip learners with tools that help them take control of the information around them, form connections, express ideas, and make their learning visible.

Keywords: sketchnotes notetaking learning design technology stanford education
Thesis
Detection & degradation of stalled nascent chains by ribosome-associated quality control

Cells invest an enormous portion of their resources into translation. This task involves tight coordination between hundreds of macromolecules, enabling the ribosome to decode mRNA and produce mRNA-encoded polypeptides. Complications during the translation cycle can cause translation to fail, leaving a potentially defective nascent polypeptide chain attached to a stalled ribosome. Organisms across all clades of life have evolved responses to detect these stalled ribosomes and degrade their associated nascent chains. I introduce the eukaryotic response, called "Ribosome-associated quality control" or RQC, in Chapter 1. Ribosomes can stall due to stochastic processes such as mRNA damage, so cells need to degrade any stalled nascent chain regardless of its identity. Two facets of RQC enable cells to meet this challenge. First, RQC initiates by recognizing a stereotyped state of stalled ribosomes rather than their attached nascent chains, which may vary in their properties. In Chapter 2, I discuss a pathway that detects stalled ribosomes and commits them to RQC. Second, RQC utilizes a non-templated form of protein synthesis (called "CATylation") to widen the spectrum of stalled nascent chains that RQC can degrade. Chapter 3 describes how CATylation enables RQC to degrade structured nascent chains as well as those that detach from the ribosome. In Chapter 4, I discuss how CATylation can also harm cells by forming aggregates. These aggregates exert proteotoxic stress and corrupt the function of CATylation as a degradation enhancer. While the complete picture of RQC is not yet in view, the work in this thesis illuminates key strategies that cells employ to degrade stalled nascent chains.

Keywords: Biochemistry.
Advisor: Brandman Onn
Kim Peter
Sarnow P. (Peter) 
Yeh Ellen
Developing angular intensity correlations of X-ray photons as a tool for studying structures of proteins in non-crystalline solutions

This dissertation offers lessons learned and tools developed as we attempt to apply correlated X-ray scattering (CXS) to non-crystalline proteins in solution. It builds on our previous work of extracting correlation signals from scattering intensities of ensembles of mental nanoparticles, which has led to three-dimensional (3D) structural insights not reflected in azimuthally averaged measurements. In his 1977 paper, Zvi Kam proposed the idea of correlating X-ray photons scattered by an ensemble of randomly oriented particles suspended in solution. He found that if the exposure time is much shorter than the diffusion timescale of Brownian motion, correlations between photons scattered into different angles encode 3D structural information of the particles not accessible via conventional small or wide-angle X-ray scattering. The advent of the X-ray free electron laser (XFEL) renders Kam's idea feasible for non-crystalline solutions of proteins. With femtosecond pulses and extremely high fluences, the XFEL is not only capable of probing ensembles of molecules essentially frozen in time but also delivering a large number of photons per pulse, a capability critical for enhancing angular intensity correlation signals. Meanwhile, probing proteins in solution removes the need for crystallization, allows measurements of mixtures of conformational states under physiological conditions, and broadens opportunities for time-resolved experiments. The body of work in this dissertation draws from scattering data collected with samples containing the G-protein Gi alpha subunit during two separate beam times conducted at the Linac Coherent Light Source. The Gi alpha subunit was chosen for these proof-of-principle experiments because of its important role in the G-protein coupled receptor signaling pathway. This dissertation has taken the first steps in developing and validating CXS as a tool for probing ensembles of biomolecules in solution. These first steps as well as ideas described in this dissertation to improve CXS towards a mature pipeline that yields reliable and detailed structural insights aim to inspire others in the solution scattering community to engage with the unique challenges and rewards of this technique.

Keywords: Physics.
Advisor: Doniach S. 
Brünger Axel T.
Weis William I.
Developing new expression parts and biosynthetic pathways for yeast synthetic biology

Baker's yeast (Saccharomyces cerevisiae) has been used in bioproduction for millenia. Current efforts in synthetic biology seek to further extend yeast's capabilities, enabling applications such as producing useful and valuable plant natural products in a cheaper and less resource-intensive manner than current methods, which rely on cultivation of the native producer plants. This dissertation opens with a review (Chapter 1) of current synthetic biology strategies for producing plant natural products in heterologous hosts: model plants, bacteria, and yeast. As a case study of heterologous phytochemical production, we describe a functional reconstitution of the dhurrin pathway from sorghum (Sorghum bicolor) in yeast (Chapter 2). We produced this plant defense compound at titers of over 80 mg/L, and demonstrated a workflow using our dhurrin-producing strain to explore the activities of other S. bicolor genes. Further, we developed a method for model-driven generation of artificial yeast promoters (Chapter 3). Promoters - DNA sequences that appear 5' to genes and modulate their expression - play a central role in controlling gene regulation; however, a small set of native promoters is used for most genetic construct design in S. cerevisiae, limiting engineers' ability to control gene expression in this organism. The ability to generate and utilize models that accurately predict protein expression from promoter sequence may enable rapid generation of novel useful promoters, facilitating synthetic biology efforts in yeast. We measured the activity of over 675,000 unique sequences in a constitutive promoter library, and over 327,000 sequences in a library of inducible promoters. Training an ensemble of convolutional neural networks jointly on the two datasets enabled very high predictive accuracies on multiple prediction tasks. We developed model-guided design strategies which yielded large, sequence-diverse sets of novel promoters exhibiting activities similar to current best-in-class sequences. In addition to providing large sets of new promoters, our results show the value of model-guided design as an approach for generating DNA parts. The final chapter discusses the outlook for the field and possible extensions to the work presented here (Chapter 4). Taken together, our work shows the value of yeast as a heterologous host for producing plant natural products, and offers a means to develop novel genetic parts to further expand its usefulness.

Keywords: Bioengineering.
Advisor: Smolke Christina D. 
Endy Andrew D. 
Zou James
Development and characterization of osteosarcoma patient-derived xenograph models and investigation into the pathogenesis of osteosarcoma metastasis

Osteosarcoma is the most common bone cancer of adolescents with 400 cases diagnosed annually in the United States. Early metastatic spread to the lungs is a hallmark feature of the disease, and is detrimental to overall survival of the patient. We used an approach to study osteosarcoma metastasis that involved the acquisition of patient tumors from both the primary site and metastatic site for whole genome and RNA sequencing, PDX production, and cell line production. Phenotypic characterization of the PDX and cell lines in vivo revealed that many will metastasize spontaneously and in a tail vein injection model. The function of ENPP1, a gene that is highly expressed in OS was also evaluated. ENPP1 expression correlated with metastatic capability in numerous OS cell lines. Gain and loss of function studies firmly established ENPP1's role in OS growth and metastasis. Our data described a role of ENPP1 in OS metastasis for the first time.

Advisor: Sweet-Cordero Eric 
Winslow Monte 
Bhutani Nidhi
Giaccia Amato J.
Development of a high-resolution fluorescent reporter system for clonal analysis

Lineage tracing techniques, which track cells and their progeny through development, are an essential tool to identify stem cells and characterize their regenerative capacities. The past decade has seen the emergence of lineage tracing tools that use 3-4 fluorescent proteins as labels. Such tools have been widely employed to characterize the regenerative capacity of mouse organs, including the brain, kidney, and liver. However, the small number of labels they employ limit their use in settings that exhibit cell migration, like early embryonic development, where the movement of cells makes it difficult to resolve whether certain cells share the same lineage. For the lineage tracing of these systems, a tool with a higher resolution is required.
This study demonstrates that multiple fluorescent labels can be used to mark a single cell by localizing fluorescent proteins to different cellular compartments. We then used these localized proteins to design a high-resolution reporter system that achieves 25 discernible labels by confocal microscopy. We derived and plan to validate a mouse line and mouse embryonic stem cell line that stably express the construct which we hope will be widely used for lineage tracing studies in the future.

Keywords:  Department of Biology
Biology
Developmental Biology
Stem Cell
Lineage Tracing
Clonal Analysis
Fluorescent Protein
GFP
Thesis
Advisor: Weissman Irving
Red-Horse Kristy
Development of a modular virus-like particle vaccine platform

Well-designed prophylaxis is always preferable to therapeutic treatment of a disease, and vaccines are second only to sanitation and clean drinking water in promoting global health. Despite their success, current vaccination strategies do not provide broad access to vaccines in the developing world largely due to the expense and cold-chain requirements. Finally, current development and production methods are poorly equipped to respond rapidly to emerging or altered pathogens. This thesis describes the use of the Swartz Lab engineered Hepatitis B core (HepBc) virus-like particle (VLP), a protein-based nanoparticle, as a vaccine platform which overcomes the concerns with current vaccines. Because of the T4 icosahedral assembly of the HepBc dimers, the engineered HepBc VLP scaffold provides 120 sites for the multivalent display of the relevant antigen in a manner that mimics presentation on the natural virus. Here we discuss the development of three antigens to be used in different vaccine candidates based on the HepBc VLP. The first antigen is derived from the Zika virus Protein E, Domain III. This antigen is difficult to produce using traditional protein production methods, but the flexibility of cell-free protein synthesis allows it to be produced with high yields and appropriate folding. The second antigen is derived from the Influenza virus Hemagglutinin Stem and has proven to require extensive protein engineering expertise to stabilize both the correct monomeric and trimeric conformations to provide broadly neutralizing protection against most strains of influenza. Finally, we have worked to produce an antigen derived from the gp41 protein of HIV. This antigen was originally developed in the Kim Lab at Merck Research Labs and had only been produced using peptide synthesis which is not practical for worldwide distribution. Ultimately, these antigens, together with the HepBc VLP scaffold will serve as novel vaccine candidates for Zika, Influenza, and HIV respectively.

Keywords: Chemical Engineering.
Advisor: Swartz James R. 
Dunn Alexander Robert 
Grimes Kevin
Kim Peter
Development of a quantum-based superconducting radio-frequency voltage standard

Metrology science is continuously transitioning toward a paradigm in which standard definitions of SI units are represented by systems that use quantum mechanical effects to relate measurement units to fundamental constants. This dissertation describes research efforts to achieve this transition for voltage and power metrology at frequencies above the audio range. In particular, this dissertation presents the design and experimental testing of a superconducting programmable radio-frequency waveform synthesizer intended for quantum-based metrology applications. The waveform synthesizer incorporates high-speed active superconducting circuit elements known as Josephson junctions and produces output waveforms with spectral power distributions that are traceable to the values of fundamental constants. This synthesizer has practical applications for calibration and characterization of communications-frequency electronics, and will supplement existing radio-frequency metrology tools that are not quantum-based.

Keywords: Electrical Engineering.
Advisor: Irwin Kent
Hopkins Peter (Peter Farrell)
Lee Thomas
Miller D. A. B.