VictorJuiz/thesis huggingface dataset:
Sub-Nyquist receiver for digital predistortion of RF power amplifiers
Keywords: Electrical Engineering.

Digital predistortion (DPD) is an essential building block of modern wireless base stations: it linearizes the radio frequency (RF) power amplifier (PA) such that the transmitter can be operated efficiently. A crucial ingredient to a DPD system is the feedback receiver which includes an analog-to-digital converter (ADC) which digitizes the PA output signal. Ever increasing signal bandwidths push conventional DPD receivers sampling at the Nyquist rate to their practical and economical limits. This issue is exacerbated in emerging technologies like 5G and beyond where the trend towards a denser grid of pico- and femto cells demands efficient and inexpensive components. Furthermore, DPD systems employing conventional Nyquist-rate feedback receivers do not allow efficient implementation of transmitter arrays (massive MIMO) due to the enormous bit rates. This thesis presents a framework for nonlinear system identification which allows to obtain the PA model with fewer samples than conventional methods. Furthermore, it is shown that the sampling rate as well as the ADC acquisition bandwidth is irrelevant for obtaining the PA model. To my knowledge, this is the first method which decouples the requirements of the feedback ADC from the input signal bandwidth. The presented framework is then used to implement a feedback receiver prototype for DPD of RF PAs. In contrast to conventional architectures, the receiver samples in the frequency domain. By randomly selecting a frequency bin in each sampling interval, the PA model is identified with substantially lower acquisition bandwidth and sampling rate. The receiver prototype is implemented in 28nm FD-SOI technology and samples at 4MS/s instead of the full Nyquist rate of 168MS/s for a 20MHz Long Term Evolution (LTE) signal with spectral regrowth. The prototype is shown to linearize a 4W small base station power amplifier from an adjacent channel leakage ratio (ACLR) of −35dBc to −47.7dBc after processing only about 250 samples. It is to my knowledge the first sub-Nyquist DPD feedback receiver implemented on an integrated circuit (IC).
Supply impacting synthesis of bryostatin 1 and the design, synthesis, and evaluation of bryostatin 1 analogs
Keywords: Chemistry.

The marine derived natural product bryostatin 1 has been investigated in preclinical studies for a wide range of indications (cancer, Alzheimer's disease, HIV/AIDS eradication, multiple sclerosis, fragile X syndrome, and others). Bryostatin 1 has been evaluated in more than 40 clinical trials for three of these highly impactful indications: cancer, Alzheimer's disease, and HIV eradication. The trials in Alzheimer's disease and the eradication of HIV are ongoing, and there is a planned trial in which bryostatin 1 will act as an adjuvant to enhance CAR T cell therapy used to treat cancer. Unfortunately, the isolation of bryostatin 1 from its source organism is not economically or environmentally sustainable, placing the supply of bryostatin 1 for clinical evaluation in jeopardy. Additionally, although bryostatin 1 has impressive biologic activity, it was not evolved for human use. Bryostatin 1 has been heavily studied, but significantly less preclinical evaluation has been performed on designed bryostatin 1 analogs. These analogs have the potential to be more efficacious and have fewer off target side effects relative to the parent natural product. Prior research indicates that the putative pathway for the activity of bryostatin 1 is exogenous regulation of protein kinase C (PKC) activity. The PKC family of enzymes plays a central and complex role in both normal and diseased states. Structurally different PKC modulators have exhibited drastically different biologic activities. Further understanding how the subtle structural elements of the bryostatin 1 scaffold affect its multiple PKC mediated activities, potentially through isoform specificity or differential protein ligand orientation, could aid in the development of analog compounds with improved functional activity. This thesis details of the collaborative team effort to solve the bryostatin 1 supply problem through a step-economical and scalable total synthesis (19 longest linear sequence, 29 total steps, 4.8% yield). To reduce the number of steps in the longest linear sequence, this total synthesis convergently constructs bryostatin 1 by bringing together two similarly complex fragments late in the synthesis. This thesis focuses on the synthetic route to one of those fragments, the C-ring fragment, and the final steps in the total synthesis of bryostatin 1. The scalable nature of the bryostatin 1 total synthesis provided access to unprecedented amounts of highly complex intermediates with many of the key structural features of bryostatin 1. This thesis also describes how those intermediates were leveraged to produce a library of "close-in" analogs to bryostatin 1. These analogs were used to test hypotheses about which molecular interactions between bryostatin 1, PKC, and cellular membranes contribute to the amazing phenotypic activity of bryostatin 1. A subset of these bryostatin 1 analogs have been advanced to more complex functional assays to determine if the analogs have superior efficacy or tolerability relative to bryostatin 1.
A supply-impacting synthesis of clinical lead bryostatin 1 and the design, synthesis and evaluation of novel protein kinase C modulators as preclinical leads
Keywords: Chemistry.

Protein kinase C (PKC) modulators are currently in clinical or preclinical development for a wide range of diseases that represent major causes of mortality and morbidity worldwide. For example, the marine natural product bryostatin 1, a lead PKC modulator, is in clinical trials for HIV/AIDS eradication and Alzheimer's treatment, with a trial for its use in small molecule-enhanced CAR-T cell therapy slated for the near future. Preclinically, bryostatin 1 has been evaluated for its use in treating fragile X syndrome, multiple sclerosis, ischemic stroke and Charcot-Marie-Tooth disease, among others. Other highly active PKC modulating natural products under clinical or preclinical evaluation include the tigliane natural product prostratin and several ingenane natural products. While nature has provided bioactive compounds that, conveniently, offer solutions to hugely important problems of global health and wellness, these compounds and methods of obtaining them are by no means optimal for clinical use. Many of these natural products are extremely scarce and require one to process staggering quantities of host organism to access even milligram quantities of the natural product. This is well illustrated in the case of bryostatin 1, where 14 tons of its host organism -- a coastal marine sponge -- were processed to access only 18 grams of the natural product. Additionally, while these natural products are excellent clinical leads, nature has not optimized them for use in human medicine. These compounds can have narrow therapeutic windows, undesired on- and off-target toxicities, poor metabolic stability and problematic solubility properties. The work presented herein focuses on solving both problems presented above through design, synthesis and evaluation of natural product leads and derivatives thereof. This document should provide a clear example of the influence that synthetic chemistry can have in supporting and driving forward clinical research on some of the most challenging problems in human healthcare to-date.
Surviving in China’s Sharing Bike Business: A Five Forces Analysis of Hellobike’s Strategies
Keywords:  Stanford Global Studies
Stanford Global Studies
East Asian Studies
Chinese business
sharing economy
Internet bike rental
Five Forces
competition strategy
Thesis

Although named the “sharing bike” in China, the Internet bike rental industry does not belong to the classic sharing economy. But the misplaced name did not hinder the industry in becoming one of the most sought-after investing fields since 2014. Though countless entrepreneurs and investors tried to ride this wave, only a few found success. Given fierce competition in the industry, Hellobike, a late-coming, small Internet bike rental bike company, grew rapidly in 2018, while massive industry giants collapsed. Even when ofo and Mobike, the once leading competitors in the industry, struggled to sustain their business, Hellobike fostered the most potential to continue developing. Therefore, the critical question for this thesis is why did Hellobike survive while many other companies failed, especially when compared against the two Internet bike rental companies: ofo and Mobike? Based on Porter’s Five Forces Model, this thesis will analyze the causes of Hellobike’s success from five different perspectives, disclosing its strategies to survive fierce Internet bike rental competition and achieve strong, positive growth.
Synthesis and Use of Solvatochromic Dyes to Label the Mycobacterial Cell Wall
Keywords:  Department of Biology
Biology
chemistry
diagnostics
tuberculosis
Thesis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and is one of the top ten causes of death worldwide. Current diagnostic methods available in low resource settings take days to weeks to perform or suffer from poor sensitivity. Previously, members of the Bertozzi group attached a solvatochromic fluorophore, 4-N,N-dimethylamino-1,8-naphthalimide (DMN), to the sugar trehalose (Tre) for incorporation into the mycomembrane, a hydrophobic layer of the cell envelope formed by trehalose glycolipids unique to Mtb and closely related organisms. Solvatochromic dyes shift in color or intensity based on the electronic properties of the surrounding solvent; DMN is fluorescent in hydrophobic but not hydrophilic environments. Thus, DMN-Tre does not label bacterial species that lack trehalose glycolipids because the dye fluoresces strongly in the mycomembrane but not in the surrounding solution. For this honors research study, we synthesized and characterized new solvatochromic trehalose probes (3HC-2-Tre and 3HC-3-Tre) that improve upon the properties of DMN-Tre. We performed in vitro labeling studies of mycobacteria to determine specificity and found that 3HC-2-Tre and 3HC-3-Tre can be used at concentrations 10x lower than DMN-Tre, are much brighter with less background fluorescence, and, in the case of 3HC-3-Tre, can label bacteria within 1 minute without requiring a wash step. 3HC-2-Tre is highly selective for bacterial species with a mycomembrane. Pre-labeled mycobacteria injected into zebrafish are readily detected by microscopy. These probes have the potential for use in TB diagnostics and the study of the effect of drug treatment on cell wall dynamics.
Synthesis of polycyclic conjugated hydrocarbons containing cyclobutadienoids and investigation of their antiaromaticity
Keywords: Chemistry.

Polycyclic conjugated hydrocarbons (PCHs) containing four-membered cyclobutadienoids (CBDs) are of great fundamental and technical interest due to the antiaromaticity brought by CBD circuits. Synthetic accessibility of such molecules, however, has been challenging and limited in scope, thus hampering the exploration and understanding of such systems. In this thesis, a versatile and efficient synthetic strategy was developed to access a large variety of CBD-containing PCHs with variable carbon structures, electronics, and topologies via catalytic arene-(oxa)norbornene annulation (CANAL) from readily accessible aryl bromides and oxanorbornenes (oNBEs). This new synthetic capability opens a myriad of opportunities for systematic investigation into CBD antiaromaticity as well as the potential applications of CBD-PCHs. With this facile method, we proposed and synthesized a series of unprecedented [3]naphthylene regioisomers, and found the regioconnectivity of [3]naphthylenes strongly affects the degree of local antiaromaticity and aromaticity for the fused CBD and naphthalenoid, respectively. Further, the C-C bond activation of CBD units was demonstrated with unsubstituted V-shaped [3]naphthylene to yield helical structures. In addition, we designed and efficiently synthesized a novel CBD-containing acene analogues, dinaphthobenzo-[1,2:4,5]dicyclobutadiene (DNBDCs), with strong antiaromaticity of the CBD units. This design also features orthogonally tunable electronic properties and molecular packing, which resulted in good device performance in organic field effect transistors.
Synthetic studies on the bis-guanidinium toxins 11-saxitoxinethanoic acid and zetekitoxin AB
Keywords: Chemistry.

Zetekitoxin AB (ZTX) is a potent neurotoxin isolated from the endangered Panamanian golden frog, Atelopus zeteki. The tricyclic, bis-guanidinium core of ZTX is common to other toxins such as (+)-saxitoxin (STX) and 11-saxitoxinethanoic acid (11-SEA), but ZTX and 11-SEA are the only known congeners with a C11-alkyl substituent. An unusual guanidinium N, O-acetal and a bridging macrolactam structure composed of a 3,4-disubstituted isoxazolidine render ZTX considerably more complex than all other members in this family of natural products. Efforts to synthesize ZTX and 11-SEA from a common hydroxyketone intermediate were undertaken. A tricyclic core bearing a C11-ketone moiety was accessed through a previously described route utilizing a C11-silylated pyrrole. The development of chemistry to elaborate the hydroxyketone culminated in the successful total synthesis of 11-SEA. Key steps in the preparation of this toxin include an oxidative annulation of an N-guanidyl pyrrole to form a five-membered cyclic guanidine and a base-catalyzed redox isomerization reaction. The challenges in applying the hydroxyketone intermediate towards the synthesis of ZTX have resulted in the design and implementation of a new synthetic route towards this complex natural product. The use of a formylpyrrole starting material enables the selective installation of an iodide at the desired C11 position. A diastereoselective Mannich cyclization reaction installs the requisite C13 carboxylic acid and generates a key bicyclic intermediate; from this material, the tricyclic guanidinium core is formed through oxidative dearomatization of the pyrrole ring. The identification of cross-coupling conditions to install a suitable heterocyclic group at C11, followed by macrolactam formation with the C13 carboxylic acid should ultimately lead to the assembly of ZTX.
A systematic framework to analyze the design space of DNN accelerators
Keywords: Electrical Engineering.

Deep neural networks (DNNs) have been widely used to solve many modern machine intelligence problems. However, their outstanding accuracy comes at the cost of high computation complexity which limits their speed on conventional CPUs. This difficulty has encouraged researchers to create efficient DNN accelerators. Interestingly these designs use a variety of approaches, and have not converged over time. While each design states the advantages of its approach, without a comprehensive understanding of the global space, it is difficult to understand which design choices really matter. To address this issue, this thesis shows how the space of DNN hardware accelerators can be represented as scheduling choices, including computation orders, storage orders, etc. Different DNN micro-architectures and mappings represent specific choices of loop order and hardware parallelism for computing the seven nested loops of DNNs. This observation enables one to create a formal taxonomy of all existing dense DNN accelerators, and systematically analyze the design space, including dataflow choice. The loop transformations needed to create these hardware variants can be precisely and concisely represented by Halide's scheduling language. By modifying the Halide compiler to generate hardware, we create a system that can fairly compare these prior DNN accelerators, and show that many different dataflows yield similar energy efficiency with good performance. As long as properly choosing the memory sizes to accommodate the efficient blocking strategy, it can ensure that most data references stay on-chip with good locality and the function units have high resource utilization. Thus, the hardware dataflow choices become less critical, but how resources are allocated, especially in the memory system, has a large impact on energy and performance. By optimizing hardware resource allocation while keeping throughput constant, we achieve up to 4.2X energy improvement for Convolutional Neural Networks (CNNs), 1.6X and 1.8X improvement for Long Short-Term Memories (LSTMs) and multi-layer perceptrons (MLPs), respectively
Tales of wit and enlightenment : laughter and humor in Northern Song (960-1127) China
Keywords: East Asian Languages and Cultures.

This dissertation examines notions of play, wit, and cognate concepts that are broadly pertaining to laughter and humor in premodern China. The Northern Song (960-1127) period witnessed significant enrichment to Chinese literati culture brought by scholar-officials' adoption of laughter and humor in their writings. This dissertation aims to disambiguate the popularity of laughter and humor in the Northern Song literati culture by revealing two important factors. The first factor is the rise of miscellany writing (biji, shihua, and other anecdotal genres) as a new mode of literary expression. The second factor is that Buddhism, through the Chan movement, was more deeply integrated into Chinese society. This dissertation demonstrates how laughter and humor played important roles in negotiating literati's identities, precipitating intellectual breakthroughs, and reconciliating conflicting stances. I focus on two important topics—Chinese literary criticism and literati-Buddhist interaction—in which representations of laughter help define the Northern Song achievements in synthesizing torrents of socio-political and religious changes. The dialectic of laughter emerged in these contexts as an overarching theme: caught between contradicting ideas of elegance and vulgarity, subversion and reverence, friendship and enmity, literati recurrently resorted to laughter to harmonize their dilemmatic stances in their attitudes towards literary writing, associations with Buddhist monks, and social interactions with their bureaucratic peers.
Taming nicotine : big tobacco's quest to hide and harness addiction
Keywords: History.

Nicotine remains America's deadliest drug. By compelling smokers to reach for cigarettes day after day, it causes 480,000 deaths per year in the United States alone. And yet, nicotine is peculiar drug. Smoking a cigarette for pleasure or to stave off withdrawal is, at the end of the day, an off-label use of a powerful natural insecticide. How did this toxic and seductive alkaloid become America's drug of choice? Taming Nicotine: Big Tobacco's Quest to Hide and Harness Addiction draws on millions of formerly secret tobacco industry documents to argue that cigarette makers played a crucial role in 20th century American drug policy and addiction research. These secret documents show that nicotine has led two mutually reinforcing lives: in the first, hidden away in industry laboratories, it was a molecular entity, whose addictiveness industry scientists sought to understand in order to hook new generations of smokers. But nicotine also has had a second, more public, life as a carefully manipulated cultural object. Deploying an army of consultants, cigarette makers claimed that nicotine should not be considered a drug, because it didn't produce intoxication, and that smoking was a free choice (rather than an addiction) because smokers aren't "junkies." In combination, these efforts produced an unprecedented public health crisis that was predicated on both selling nicotine while keeping its addictive power hidden. This remains an unfinished history: even today nicotine has not relinquished its dual nature between the botany of murder and the neurochemistry of desire.
Target-based genome mining of natural products and heterologous expression in Escherichia coli : choosing and accessing the natural world's menu of potential antibiotics
Keywords: Biochemistry.

Expanding genomic databases show that many microorganisms harbor polyketide synthase (PKS) gene clusters, many of which encode natural products with valuable antibacterial properties. However, identifying and accessing novel and useful PKS activities remain challenging, as many host organisms are uncultivable or do not express PKS genes in laboratory conditions, and from sequence data alone it is difficult to ascertain which gene clusters are the most promising. Here I present efforts to address these challenges. We first aimed to improve Escherichia coli as a heterologous host for production of polyketides originating from other bacteria. We studied 13 homologs of propionyl-CoA carboxylase (PCC), an essential enzyme for many PKS gene clusters. We built 13 strains of E. coli, each harboring a different PCC homolog. We observed variability in polyketide production amongst the 13 strains and identified optimal PCC homologs. Next, we leveraged commercial gene synthesis and a recently developed large DNA assembly pipeline to synthesize DNA encoding four PKS gene clusters, ranging in length from 30-40 kB and expressed them in recombinant E. coli strains. Untargeted metabolomics revealed cluster-specific compound production in two of the four strains. Follow-up experiments suggested that these compounds resulted from activity of the tailoring genes in the cluster, not the core PKS genes, and could represent modified endogenous metabolites in E. coli. This result illustrates a need for larger datasets of heterologous expression of PKSs in E. coli to more rapidly identify gene clusters resulting in novel and cluster-specific molecules. To identify PKS genes encoding clinically relevant antibiotics, we developed an automated method to identify and catalog clusters that harbor potential self-resistance genes. These genes, which are modified targets of the produced compounds, provide the cluster-harboring microorganisms a defense against the antibiotics produced by the clusters. We mined all National Center for Biotechnology Information (NCBI) nucleotide databases for known and putative antibacterial target genes from manually curated lists. With this approach, we generated a non-redundant catalog of PKS clusters harboring putative self-resistance genes. This method can be used to prioritize gene clusters producing compounds with new mechanisms of action, as well as to identify putative novel antibacterial targets.
Teaching in a post-truth era : supporting students to reason about online information
Keywords: Education.

Although young people increasingly rely on the Internet as a source of information, the web's growing complexity has outpaced educational efforts. When asked to evaluate digital content, students often make judgements based on perceived usefulness, appearance, or relevance, or they outsource responsibility for judging reliability to something they assume does a better job—a search engine algorithm. Furthermore, disparities in technological access and learning experiences threaten to expand and determine who has opportunities to learn to evaluate online information. The articles in this dissertation outline the beginnings of an educational response. Taken together, they investigate how students reason about online information (and how schools may, purposefully or not, contribute to students' strategies), characterize skilled practice, and probe how core content area teachers might help students learn to evaluate digital content.