VictorJuiz/thesis huggingface dataset:
Transcriptional control of differentiation in cerebellar granule neurons and medulloblastoma
Keywords: Developmental Biology.

Cerebellar granule neurons (GN), the most numerous neurons in the brain (~5 x 1010 in humans) mediate critical steps in motor control and motor learning. They arise from symmetric division of progenitors known as granule neuron precursor cells (GNPs). GNP terminal differentiation involves cell cycle exit, extension of processes, nuclear migration, and synapse formation with mossy fibers and Purkinje cells. Much remains to be learned about how gene regulation underlies neurogenesis steps like migration or neurite extension during GNP differentiation. Increasing, our understanding of GNP differentiation could have important therapeutic importance for children with brain tumors. Medulloblastoma is the most common malignant brain tumor in children and the SHH subtype of medulloblastoma arises from the cerebellar GN lineage. If we can identify what regulates differentiation in GNPs these processes could be targeted to induce differentiation of medulloblastoma cell. We have combined gene transcription data over the course of GN differentiation with measures of chromatin features such as histone marks, DNA methylation and DNA accessibility in proliferating GNPs. Of the genes that increase as GNPs terminally differentiate, more than half the genes are marked by H3K27me3 near their promoters, implying repression by the protein complex PRC2. Genetic inactivation of Ezh2, which encodes the enzyme that catalyzes formation of H3K27me3, resulted in GNPs leaving the external granule cell layer prematurely. while not affecting cell cycle exit. Ezh2 the catalytic methyltransferase of the repressive PRC2 complex shows the most substantial transcriptional decrease of the genes that are known to directly or indirectly effect H3K27me3. A normal role of Ezh2 is therefore to restrain GNP radial migration. Shh medulloblastoma tumors arise from cells within the GN lineage. Mice, which are heterozygous for Ptch1 will develop spontaneous medulloblastoma. In medulloblastoma cells from Ptch1+/- mice, ¾ of the H3K27me3 marked GN differentiation genes are persistently marked with H3K27me3 and the majority did not show an increase in transcription in MB compared to the dividing GNPs. In human SHH subtype medulloblastoma, the EZH2 transcript varies, with low EZH2 transcript being associated with higher expression of the differentiation genes and better survival. PRC2 mediated repression of differentiation genes seen in GNPs is ongoing in medulloblastoma. As with GNPs, Ezh2 inhibition in actively dividing Ptch1+/-MB cells did not induce differentiation. Combining a cell cycle inhibitor with the Ezh2 inhibitor, did allow differentiation of the tumor cells as measured by morphology and gene expression markers. Thus Ezh2 delays transcription of a set of differentiation genes in GNPs which, when depressed in MB cause differentiation preventing re-entry into cell cycle.
A transcriptional regulatory circuit regulates fat cell differentiation
Keywords: Chemical and Systems Biology.

Glucocorticoid and other adipogenic hormones are secreted in mammals in circadian oscillations. Loss of this circadian oscillation pattern correlates with obesity in humans, raising the intriguing question of how hormone secretion dynamics affect adipocyte differentiation. Using live, single-cell imaging of the key adipogenic transcription factors CEBPB and PPARG, endogenously tagged with fluorescent proteins, we show that pulsatile circadian hormone stimuli are rejected by the adipocyte differentiation control system. In striking contrast, equally strong persistent signals trigger maximal differentiation. We identify the mechanism of how hormone oscillations are filtered as a combination of slow and fast positive feedback centered on PPARG. Furthermore, we confirm in mice that flattening of daily glucocorticoid oscillations significantly increases the mass of subcutaneous and visceral fat pads. Together, our study provides a molecular mechanism for why stress, Cushing's disease, and other conditions for which glucocorticoid secretion loses its pulsatility may lead to obesity.
Transferable kinetic Monte Carlo models with thousands of reactions learned from molecular dynamics simulation of hydrocarbon chemistry
Keywords:  Department of Materials Science and Engineering
molecular dynamics
kinetic Monte Carlo
statistical learning
Text
Thesis

Molecular dynamics (MD) simulation of complex chemistry typically involves thousands of atoms propagating over millions of time steps, generating a wealth of data. Traditionally this data is used to calculate some aggregate properties of the system and then discarded, but we propose that this data can be reused to study related chemical systems. Using approximate chemical kinetic models and methods from statistical learning, we study hydrocarbon chemistries under extreme thermodynamic conditions. We discover that a single MD simulation can contain sufficient information about reactions and rates to predict the dynamics of related yet different chemical systems using kinetic Monte Carlo (KMC) simulation. Our learned KMC models identify thousands of reactions and run orders of magnitude faster than MD. The transferability of these models suggests that we can viably reuse data from existing MD simulations to accelerate future simulation studies and reduce the number of new MD simulations required.
Translation and its Potentials—A Discussion of World Literature through Han Kang’s "The Vegetarian" and its Translation
Keywords:  Stanford Global Studies
Stanford Global Studies
East Asian Studies
World Literature
National Literature
Translation
Thesis

In May 2016, Han Kang's novel "The Vegetarian" was the first translation ever to win the Man Booker International Prize, which also for the first time split the prestigious cash award between writer and translator. Following the announcement of the win, both Han Kang and the novel's translator Deborah Smith were drawn to the center of the media spotlight. The celebration within Korea, however, did not continue for long when Korean readers and critics began to accuse the novel of mistranslation. Who won the prize? Was it Han's original craft or Smith's translation? The debate over the novel's translation turned Han's novel and its prize-winning episode into a matter of controversy over literature and national identity. It also brings back to the discussion table, larger questions around the topic of world literature. What is the relationship between national and world literature? What kind of national literature can become successful world literature? What is the role of translation in world literature?
This thesis provides a comprehensive view of the origins of world literature and explains the controversies around how to read world literature today. Through the reading of "The Vegetarian" in Korean, English, and Chinese, I offer my own understanding of world literature as not a definable category but a methodology that readers can apply to work of literature written in a foreign language.
Transmission electron microscopy investigation of fuel cells related materials
Keywords: Materials Science and Engineering.

This dissertation will mainly deal with the TEM characterization on the fuel cell using a variety of different TEM techniques. The most of sample was prepared by site-specific lift-out technique using a focused ion beam (FIB). Subsequent TEM studies on these energy-related materials lead to have deep understanding of the relationship between the atomic scale structures with the other chemical/electronic properties. To provide a scientific establishment for break-out high-efficiency, cost-effective energy technologies, research activities have been focused on manipulation of materials at the nanometer scale to increase efficiency of energy conversion devices and exploitation of fundamental advances in charge transport, light absorption, and reaction thermodynamics and kinetics to improve performance and efficiency in energy conversion devices like fuel cell. To achieve these goals, we need to understand how nano-structuring modifies and governs the properties of materials, and how to control dimensionality and confinement to learn insights on model energy conversion materials, structures and devices. Transmission Electron Microscopy (TEM) with additional advanced functions enables us to approach profound understanding of the fundamental relationship between chemical / electronic properties of materials and crystal structure, composition, size, shape of them through the characterization at atomic or nano/micro scale.
Troubled waters : a political ecology of water scarcity in rural Colombia
Keywords: Anthropology.

Colombia has had a long, sordid history of conflicts over natural resource management, particularly among its Afro and indigenous populations in rural areas. Privatization of and development along major water sources continue to threaten communities' equitable access. Moreover, climate change is rapidly altering landscapes and water availability, putting more stress on both social and natural systems, further complicating how communities respond to these changes. While many studies focus on black communities in the Pacific region and Indigenous groups throughout other areas of Colombia, there is little attention given to black groups in the Caribbean, especially as it relates to social mobilization. This doctoral research addresses this gap by examining the ways in which Afro-indigenous communities, in two rural Caribbean villages of Colombia, mobilize amid several water development projects. When confronted with extreme water scarcity during a drought, the national government proposed projects to increase water services, but instead they became key sites of cultural and political contention. Throughout each chapter, I focus on the dynamics between community members, government officials, and private companies at two water sites—a marsh and municipal water plant. The goal is to identify how different members within these communities respond to environmental and development challenges through ethnocultural (identity) projects. This work contributes to broader understandings of identity, social movements, and environmental politics, which are particularly critical during times of rapid climate change. This study yields three primary findings. The first reveals that the water infrastructure projects were creating divisions within communities across different groups and further contributing to water inequity. This was largely a result of continued practices based on racially exclusive legislation and inefficient land tenure policies. The second finding identifies three social mobilization strategies employed by communities to resist their exclusion: 1) community-level engagements, 2) multi-level engagements, and 3) impromptu gatherings or protests. The final finding suggests that members who engage in community-level mobilizing, specifically around ethnocultural (Afro-indigenous) traditions were able to make a case for their inclusion in future development projects.
Twenty Months of Terror: Examining the Proliferation of Islamic-Related Terrorism in France during 2015 and 2016
Keywords:  Center for International Security and Cooperation
France
terrorism
Center for International Security and Cooperation
CISAC
Thesis

Between December 1996 and January 2015, France experienced only one Islamic-related terrorist attack. Then, starting in 2015, France experienced an acceleration of terrorism that shocked the country and the wider European community. Between the attack on the offices of Charlie Hebdo on January 7, 2015 and the assassination of Jacques Hamel, a Catholic priest in Normandy on July 26, 2016, 239 people of various nationalities and religious backgrounds were killed by Islamic terrorists on French soil. Existing literature has attempted to explain the phenomenon by analyzing changing French foreign policy and shifting domestic conditions. While helpful for shedding light on the driving forces behind the attacks, existing texts fail to explain the dramatic increase in the number and scope of the attacks during this time period. This thesis evaluates the acceleration from two opposing angles: the breakdown of counterterrorism operations and the evolution and adaptation of terrorist strategies and targets. French counterterrorism agencies had historically been extremely capable of adapting to new threats, but the dramatic change in the nature of the threat and inability to recognize precursor attacks lead to distinct challenges for law enforcement. On the other side, terrorists themselves perfected low sophistication strategies, such as stabbings and vehicle rammings, to perpetuate fear and persuade others of the ease of carrying out attacks within French borders. Ancillary factors, such as the high correlation between criminalization and terrorism, the deteriorating conditions in the banlieues, and the high numbers of foreign fighters further contributed to the dramatic acceleration.
Ultrafast-laser investigations of radiation damage in nuclear materials
Keywords: Geological Sciences.

Ionizing radiation—in the form of fission fragments, gamma rays, and alpha particles—is a major source of damage in nuclear materials. Energy from sources of ionizing radiation is deposited primarily into the electronic subsystem of a material over timescales shorter than that required for electron-phonon coupling. This induces highly non-equilibrium conditions that causes damage on femtosecond-to-nanosecond timescales. These short timescales have, thus far, made the direct observation of ionizing radiation damage impossible. Furthermore, the non-equilibrium conditions intrinsic to the damage process are difficult to model. This dissertation reports on the use of ultrafast lasers to better understand the process of ionizing radiation damage in nuclear materials. Studies of nuclear materials subjected to static high-pressure conditions were also conducted in order to better understand the interplay between induced defects and material properties and behavior. Structural phase transformations driven by ultrafast laser irradiation in ZrO2 and Gd2O3 were compared to previous results from swift heavy ion irradiation. Identical phase transformations were induced by the two irradiation techniques. This observation served as an experimental proof-of-concept for the use of ultrafast lasers to investigate ionizing radiation damage. The separation of thermal- and pressure-affected zones in ultrafast laser-irradiated materials provided the basis for understanding the phase transformation mechanism in Ln2O3 (Ln = Er-Lu). Although all investigated Ln2O3 compositions underwent the same transformation, their transformation mechanisms were found to differ. The transformation was pressure-driven for Ln = Tm--Lu, consistent with the material's phase behavior under equilibrium conditions. However, the transformation was thermally driven for Ln = Er, revealing that the non-equilibrium conditions of ionizing radiation can lead to unexpected transformation pathways. The use of ultrafast lasers also allowed time-resolved experiments to be performed, permitting the process of ionizing radiation damage to be observed in real-time. Investigations into the response of UO2 revealed a long-lived GHz-scale mode, which had not been observed under equilibrium conditions. This mode was attributed to the production of a photogenerated species. This species was found to originate in the dynamical magnetic structure of UO2. Investigation of the pressure-dependent mode behavior revealed coupling to the electronic structure of UO2. This non-equilibrium mode provides the basis for understanding the anomalously high resistance of UO2 to ionizing radiation damage.
Uncovering the Hidden Role of the Ribosome in Mammalian Development
Keywords:  Department of Biology
Biology
Development
Ribosome
Translation
Thesis

The ribosome, far from being a constitutive molecular machine, exerts
developmental control as apparent in the prevalence of ribosomopathies that manifest in remarkably specific developmental defects. However, much is unknown regarding the mechanism of how the ribosome affects and interacts with developmental processes. In order to further understand this role of the ribosome, we investigated a specific ribosomal protein, RPS6, deficient mouse model that presented with limb defects. Using skeletal staining and in situ hybridization with cartilage markers, we first characterized the defect as exhibiting radial underdevelopment (hypoplasia and aplasia). In order to assess if ribosomal protein reduction led to a perturbation of patterning, we explored candidate pathways and genes involved with proximal distal and anterior posterior patterning by performing in situ hybridization with candidate genes.
We identified perturbations in two genes important for limb patterning and development, namely Gli1 and Shh, indicating that ribosomal protein reduction may be interacting with these pathways. Finally, we sought to establish, beyond merely correlation, if candidate genes and pathways genetically interact with the phenotype of radial hypoplasia and aplasia. In order to do this, we reduced Shh expression and assessed if the phenotype is rescued or amplified. We found that reducing Shh expression resulted in a more severe mutant phenotype in the RPS6 deficient mouse, ascertaining the genetic interaction of RPS6 reduction and the Shh pathway. Thus, we concluded that ribosomes play a role in limb development, indicating that ribosomes are involved with the general process of patterning and development. We investigated the unknown mechanisms through which ribosomes regulate development, thus providing a potential foundation for understanding how ribosomal defects can manifest in tissue specific phenotypes.
Understanding and improving the energy efficiency of DRAM
Keywords: Electrical Engineering.

Human created data has been growing exponentially for decades and there are many reports stating 90% of all data were created in the past couple of years [1]. Moreover, this exceptionally high data growth rate is predicted to continue in the future. Increased data volume then drives storage capacity growth, and also places high demands on high bandwidth and large capacity DRAM [2]. However, growing capacity and memory performing also grows memory power making DRAM power consumption one of the most important component to optimize in power limited modern computer systems. This power issue led to the development of specialized DRAMs, such as Low Power Double Data Rate (LPDDR) and High Bandwidth Memory (HBM), that are much more energy efficient than conventional DDR DRAM. While minimizing memory power is a popular research topic, the DRAM design space is highly constrained by the heavy cost-per-bit optimization done in DRAM. Surprisingly, these constraints are difficult to find as those information are known only within the small community of DRAM circuit designers. To address this issue, we worked with former and current DRAM designers to build an open-sourced DRAM modeling framework named DramDSE, short for DRAM Design Space Exploration. The modeling framework incorporates crucial design constraints posed by modern DRAM and provides the area, detailed power breakdown, and current values that are needed to explore the design space of DRAM efficiently. We used DramDSE to create the first public domain models of two state-of-the-art DRAMs, LPDDR4 and HBM, for the first time in public domain and validated the correctness of our model using measured data collected from mass-produced LPDDR4 and HBM DRAMs. With a better understanding of DRAM gained from DramDSE, we propose three DRAM energy reduction schemes. The first two are built on top of a unique cell array design that can access only half of the page. Half Page DRAM reduces the row energy due to the row buffer overfetch problem in multi-core systems, which yields 38% row energy savings without any bandwidth loss. Charge Recycling Refresh reduces up to 32% of refresh energy by recycling charges from fully refreshed half page rows to the other half page rows that are to be refreshed. Each of them can be implemented in a modern DRAM with less than 1.5% area overhead and when both schemes are used together, the total power consumption is reduced by 15% on average across various workload. This is equivalent to the power savings achieved by scaling the DRAM technology node from 20 nm to a 10 nm class [3]. Finally, we propose Smart Refresh to further reduce refresh energy with negligible area overheads by utilizing the retention time distribution of the cells. Reducing refresh energy becomes more important as DRAM technology scales and memory density increases. Our two refresh energy reduction schemes also work in self-refresh mode, where refresh energy consumption is even more significant.
Understanding degradation and improving stability of solution-processed organic and perovskite solar cells
Keywords: Materials Science and Engineering.

The sun provides the most abundant source of clean energy and has the potential to provide three orders of magnitude more energy than the world energy demand. However, while state of the art commercial technology is capable of harvesting solar energy with 25% power conversion efficiency (PCE), it does so at a high cost. In order to incentivize the use of solar generated electricity and thus reduce our global carbon footprint, it is therefore necessary to develop more affordable and comparably efficient technologies. Organic bulk-heterojunction and perovskite solar cells are two promising solution-processed technologies with single junction record efficiencies of 14% and 22.7%, respectively. Nevertheless, stability is the biggest concern limiting commercialization of these technologies. The first part involves developing new design criteria for stabilizing organic solar cells. Solution-processed small molecules were used as a model system because of their narrow polydispersity index, ease of purification, and PCE exceeding 10%. The operational stability of six different high performance small molecule solar cells were assessed under 1 sun intensity at maximum power in an inert environment. Two types of degradation typically seen in organic solar cells -- burn-in and linear -- were observed and resulted in a TS80 stabilized lifetime of 2-3 years. Burn-in degradation was induced by heat and light, while linear degradation was caused only by heat. From these results, we concluded that the stability of small molecule solar cells can be improved by designing molecules with higher molecular weight for thermal stability and higher crystallinity for photostability. The second part covers optimization of perovskite solar cell encapsulation for environmental stability. While perovskite solar cells are efficient, they are known to decompose in the presence of heat and moisture. They are also mechanically fragile because of mismatches in the thermal expansion coefficients between multiple layers. I will provide my insights on a holistic design of glass-glass encapsulation utilizing commercially available materials, which for the first time enabled perovskite solar cells to pass the IEC standard's damp heat, temperature cycling, and UV-exposure tests. Having demonstrated that properly packaged perovskite solar cells can be environmentally stable, I pave the way for long-term stability of perovskites in the field and bring solution-processed perovskite solar cells one step closer to commercialization.