VictorJuiz/thesis huggingface dataset:
Telomere extension using modified TERT mRNA to lengthen healthspan [electronic resource]

One of our long-term goals with this work is to extend the human health span, the period of life when humans are relatively free from age-related disease. Molecular mechanisms that limit the human health span include epigenetic drift, accumulation of cellular waste products, DNA damage, and telomere shortening, and here we demonstrate a method to address telomere shortening. Telomeres comprise DNA sequences that protect the ends of chromosomes but shorten over time due to oxidative damage and incomplete DNA replication during S phase of the cell cycle. Short telomeres can lead to activation of p53, cell cycle arrest or apoptosis, chromosome-chromosome fusions, or malignancy. Short telomeres are implicated not only in age-related diseases including cancer and heart disease, but in diseases in which cells are under high replicative demand, such as muscular dystrophy. The nucleoprotein telomerase comprising the protein component TERT and RNA component TERC extends telomeres, and several efforts at extending telomeres have focused on increasing the amount of telomerase in cells, which conveys proliferative capacity to cells in culture and can reverse phenotypes of aging in animal models. Currently small molecule activators of telomerase are in use by humans, but have no detectable effects on telomere length in many subjects. Adeno-associated viral delivery of TERT is another promising approach, one that extends rodent lifespan without increasing the incidence of cancer possibly because it is usually episomal and diluted out in fast-dividing cells, but risks genomic integration and resulting constitutive TERT expression which may not be acceptable in longer-lived species. Here we present an alternative method for telomere extension made possible by the recent discovery that delivery of mRNA comprising modified nucleotides such as pseudouridine modulates the Toll-like receptor mediated innate immune response that is activated in most cells in response to unmodified mRNA. Nucleoside modifications occur naturally in mammalian RNA and provide a means of distinguishing endogenous from exogenous RNA such as bacterial RNA which have fewer or no such modifications. We find that delivery of modified mRNA encoding TERT to fibroblasts and myoblasts results in transient elevation of telomerase activity, telomere extension, and increased proliferative capacity. All cells treated to date have eventually senesced and expressed markers of senescence to the same degree as untreated cells, important for the safety of our approach. Repeated treatment increases proliferative capacity further, suggesting that the approach may be useful over a prolonged period. We have taken initial steps at delivering mRNA in vivo and this work continues.

Advisor: Blau Helen M. primary advisor. Thesis advisor
Longaker Michael T.
Santiago Juan G. advisor. Thesis advisor
Sapolsky Robert M. advisor. Thesis advisor
Terra [electronic resource] : simplifying high-performance programming using multi-stage programming

Modern high-performance computers are heterogeneous machines that contain a mixture of multi-core CPUs, GPUs, interconnects, and other custom accelerators. The composition of individual machines varies and will change over time, so it is important that applications written for these machines are portable. One way to write portable high-performance applications is to abstract the problem at a higher-level and use approaches such as auto-tuners or domain-specific languages (DSLs) to compile the abstraction into high-performance code using domain knowledge. These approaches require that the application generate code programmatically. However, current state-of-the-art high-performance languages lack support for generating code, making it difficult to design these programs. This thesis presents a novel two-language design for generating high-performance code programmatically. We leverage a high-level language, Lua, to stage the execution of a new low-level language, Terra. Programmers can implement program analyses and transformations in Lua, but use built-in constructs to generate and run high-performance Terra code. This design reflects how programs like DSLs are often created in practice but applies principled techniques to make them easier to create. We adapt techniques from multi-stage programming to work within the two-language design. In particular, shared lexical scope makes it easy to generate code, but separate execution enables the programmer to control performance. Furthermore, we show how adding staged compilation to the typechecking process of Terra allows for the creation of high-performance types. This typechecking process combines meta-object protocols frequently used in dynamically-typed languages with staged programming to produce flexible but high-performance types. We evaluate the design presented in this thesis by implementing a number of example programs using Lua and Terra in areas where performance is critical such as linear algebra, image processing, probabilistic programming, serialization, and dynamic assembly. We show that these applications, which previously required many different languages and technologies, can be implemented concisely using just Lua and Terra. They perform as well as or better than their equivalents written using existing technologies. In some cases, we found that the added expressiveness of using our approach made it feasible to implement more aggressive optimizations, enabling the program to perform up to an order of magnitude better than existing approaches.

Advisor: Hanrahan P. M. (Patrick Matthew) primary advisor. Thesis advisor
Aiken Alexander advisor. Thesis advisor
Olukotun Oyekunle Ayinde advisor. Thesis advisor
Testing and characterization of superCDMS dark matter detectors [electronic resource]

The Cryogenic Dark Matter Search (SuperCDMS) relies on collection of phonons and charge carriers in semiconductors held at tens of milliKelvin as handles for detection of Weakly Interacting Massive Particles (WIMPs). This thesis begins with a brief overview of the direct dark matter search (Chapter 1) and SuperCDMS detectors (Chapter 2). In Chapter 3, a 3He evaporative refrigerator facility is described. Results from experiments performed in-house at Stanford to measure carrier transport in high-purity germanium (HPGe) crystals operated at sub-Kelvin temperatures are presented in Chapter 4. Finally, in Chapter 5 a new numerical model and a time-domain optimal filtering technique are presented, both developed for use with superconducting Transition Edge Sensors (TESs), that provide excellent event reconstruction for single particle interactions in detectors read out with superconducting W-TESs coupled to energy-collecting films of Al.

Keywords: Physics.
Advisor: Cabrera Blas primary advisor. Thesis advisor
Graham Peter (Peter Wickelgren) advisor. Thesis advisor
Osheroff Douglas D. advisor. Thesis advisor
Testing inflationary cosmology with BICEP2 and the Keck Array [electronic resource]

The BICEP2 and Keck Array experimental programs consist of arrays of microwave polarimeters located at the South Pole designed to measure the B-mode polarization of the Cosmic Microwave Background. B-mode polarization is a generic prediction of the theory of Inflation, which hypothesizes a period of exponential expansion preceding the Hot Big Bang. This inflation is hypothesized to have been driven by physics beyond the Standard Model, at energies of order the Planck scale. After three years of observations at 150GHz, BICEP2 reported a detection of B-mode polarization at degree angular scales. The Keck Array was deployed in 2010, with an instantaneous mapping speed a few times faster than that of BICEP2. The Keck Array is expected to improved upon the BICEP2 results by mapping the same region of sky at 100 and 150GHz. The analysis of BICEP2 utilized a new method for distinguishing E-mode polarization from B-mode polarization. In developing this method, we have produced a matrix operator which transforms an image of true sky into a map of the sky as seen by BICEP2.

Keywords: Physics.
Advisor: Kuo Chao-Lin (Physics professor) primary advisor. Thesis advisor
Cabrera Blas
Church Sarah Elizabeth advisor. Thesis advisor
Tethering Hawks: United States Restraints in the Cold War

The 2003 American invasion of Iraq broke the U.S.’s historic forbearance from pursuing a policy of preventive war. Recently, considerations of preventive war have come to the fore in the rhetoric of U.S. policymakers and academics. This thesis analyzes the U.S. restraints in historic considerations of preventive war. The period examined is the early Cold War. The cases analyzed are the American considerations of preventive war against the first and second Communist nations to develop nuclear weapons. The acquisition of nuclear weapons by each Communist state prompted the U.S. Departments of State and Defense to independently compile a litany of policy options which debated and weighed the political and military costs of preventive war. The primary source documents used in this thesis were recovered from a variety of sources, including the National Archives, where academically under-examined policy documents were recovered.
The documents examined reveal normative and theoretical restraints in each United States decision not to pursue a policy of preventive war. While the conventional narrative of the Cold War ascribes the phenomenon of peace to the dominant restraint of deterrence, this thesis proposes that each policy of restraint was instead created by several restraints, acting in concert. While current cases regarding considerations of preventive war are not examined, I hope this thesis elucidates how policies of restraint are formed. This thesis does not seek to replace the conventional narrative of deterrence, it seeks to augment it.

Keywords: restraints
preventive war
nuclear weapons
cold war
Center for International Security and Cooperation
Thesis
Advisor: Sagan Scott D.
Thaumatrope [electronic resource] : approaching East Asian aesthetic traditions in contemporary Latin American literature

In this dissertation, I study the use of East Asian aesthetic traditions in the works of several Latin American authors. I argue that these authors use East Asian traditions in their work as aesthetic and cognitive explorations, as social and political inquiry into the conditions and ideologies surrounding East Asians in Latin America and beyond. My intention is broadly twofold. On one level, I examine the authors' choices of aesthetic tradition and how these specific traditions advance what the texts seek to accomplish. On the other, I locate the choice of these traditions and their renovations in specific socio-historical contexts to analyze how through artistic negotiations, the authors explore the material conditions of certain historical moments, often in relation to how East Asian cultures are constructed in Latin America and other histories of marginalization.

Keywords: Iberian and Latin American Cultures.
Advisor: Rocha Marília Librandi primary advisor. Thesis advisor
Santana Cintia advisor. Thesis advisor
Sohn Stephen Hong advisor. Thesis advisor
Yarbro-Bejarano Yvonne
The Collaborative Filtering Effect of Netflix Ratings for Indie Films versus Blockbusters and Heavy Users versus Casual Users

Collaborative filtering algorithms, whose adoption by online recommendation engines has markedly increased in recent years, serve to match users with items based on what they have consumed in the past or the tastes of similar users. Meanwhile, Internet economists and marketing experts have cited a new phenomenon driven by online platforms called the "Long Tail," which is a distributional shift towards lesser-known niche products. In this paper, I test whether an online platform that uses a collaborative filtering algorithm can help match non-mass market goods with previously un-informed demanders and how this can affect user heterogeneity. I choose to examine movie ratings made publicly available in the Netflix Prize, an open source competition to improve the existing algorithm used for Netflix recommendations. Looking at demand across different movie categories, I find a stronger responsiveness of demand to early user ratings for indie films, relative to blockbusters. This effect is further magnified for "heavier" users with greater rating histories. As movie "buffs" with more variety in tastes, these users not only are greater influencers of demand, but are also more inclined to be influenced by others in their own demand, in contrast to what one observes on other online platforms.

Keywords:  Department of Economics
Long Tail
indie
collaborative filtering
recommendations
heavy users
Netflix
Stanford Department of Economics
Thesis
Advisor: Bresnahan Timothy
The Credibility of Extended Deterrence and Assurance: The US Commitment to Japan

Since the end of WW2-occupation and likely into the future, the US security commitment has been a critical component of Japanese security. Given this and the vital security issues Japan faces today, it is of the utmost importance to understand the extent of this security commitment. This thesis aims to determine what exactly the United States’ security commitment to Japan is and how the US has strengthened the credibility of that commitment by examining the key security agreements between the two states and recent US nuclear policy documents . This thesis finds that the US commitment has progressed from a weak commitment to a strong one, as the United States has agreed to firm, clearly articulated obligations and established procedures and practices to prepare for and carry out the defense of Japan against armed attack. US nuclear policy affirms the United States’ intention to pursue a world free of nuclear weapons but expresses general approaches to nonetheless maintain the US commitment to provide effective, credible nuclear deterrence for its allies. The finding have implications for important Japanese security issues and the understanding of extended deterrence and assurance.

Keywords: deterrence
assurance
security commitment
Center for International Security and Cooperation
Thesis
Advisor: Hellman Martin E.
The Devil You Know: The PRC's Strategic Calculus Regarding North Korea since the Korean War

“Close as lips and teeth,” “xuemeng”—meaning blood ties or shared blood—and “united in communist brotherhood,” are all phrases employed within Chinese rhetoric to describe the Sino-North Korean relationship. The relationship, as described through these phrases, is difficult for outsiders to comprehend. The policy-making processes of both of these governments are extraordinarily opaque, and as such, the relationship between the People’s Republic of China and the Democratic People’s Republic of Korea appears to exist within a black box, seemingly allowing foreign scholars to be able only to speculate about what shapes and drives the relationship.
This thesis presents analysis that challenges widely advanced explanations for China’s motivations behind its North Korea policy, which suggest that this policy has remained constant since the Korean War. This paper argues instead that China’s policies toward North Korea are based on an evolving strategic calculus, primarily influenced by what Beijing perceives to be the perils and possibilities offered by the international system and the constraints and requirements of China’s domestic politics. This paper employs international relations (IR) theory and foreign policy analysis (FPA) theory as analytical frameworks through which to review the sixty year-long relationship since the Korean War, in order to illuminate the “black box” of Sino-North Korean relations and provide some insight on the factors which have influenced and shaped China’s policy orientation toward North Korea.

Keywords: North Korea
China
Sino-North Korea relationship
Chinese policy
Chinese history
policy
Center for International Security and Cooperation
Thesis
Advisor: Fingar Thomas
The Effect of Selective Blockade of CD80 and CD86 on Immune Regulation in Cardiac Allograft Transplantation in Mice

The human immune system utilizes T lymphocytes to distinguish between self and non-self to protect the host against pathogens. This same process can lead to recognition of transplanted organs as foreign, and initiates an immune response against the graft. Thus, immunosuppression, which primarily targets cell-mediated immunity by T cells, becomes crucial for graft survival. Optimal T cell activation requires signal 1 that results from the ligation of antigen-specific T cell receptor (TCR) and cognate peptide bound to major histocompatibility complex (MHC) proteins on antigen presenting cells (APC), as well as signal 2, that can be either a negative or positive co-stimulatory signal from APC. Initiating positive co-stimulatory signals when bound by CD28 on naïve T cells, B7-1 (CD80) and B7-2 (CD86) on AOC are rapidly upregulated upon APC activation, even though their up-regulation timing and signaling mechanisms may differ. CTLA-4 is a B7 family member that competitively inhibits CD28 by binding to B7 with greater affinity, thus producing negative co-stimulatory signals and reducing the immune response.1,2 Abatacept is a is a CTLA4-Ig fusion protein that has been used to prolong graft survival by interfering with signal 2 delivered by the B7/CD28 interaction. However, previous work may have oversimplified the outcome of the CD28:B7 co-stimulatory pathway as binary (activate vs. inactivate) instead of combinatorial. In this study we address the quantitative and qualitative effects of the B7/CD28 pathway on regulatory T cells (Treg) development and maintenance by selective blockade of CD80 and CD86. We hypothesized that selective blockade of either CD80 or CD86 molecules can result in different degrees of immune regulation and Treg cells. Using a mouse heterotopic heart model of Treg-dependent long-term graft survival, we take immunomodulatory approaches that spare CD80 signaling to promote Treg development. After differentially treating mice with anti-CD80 and anti-CD86 blocking antibodies and CTLA4-Ig, we confirmed that CTLA4-Ig treatment results in accelerated graft rejection and a reduction in Helios+ Treg, a putative marker of natural Treg. We further show that combinatorial (anti-CD80+anti-CD86) approaches suppress both effector memory T cells and Tregs, while single monoclonal antibody (mAb) treatment of anti-CD86 mAb alone or anti-CD80 mAb alone results in a variable population of Treg and T effector cells, depending on the timing and the degree of surface molecule expression. Therefore, selective blockade of B7 molecules may be useful for promoting expansion of Treg cells in transplantation, although their optimal induction time and magnitude still needs further research.

Keywords:  Department of Biology
CD28:B7 co-stimulatory pathway
regular T cells development
immunosuppression
selective blockade of B7
preferential signaling
biology
adaptive immunity
Thesis
Advisor: Martinez Olivia
Jones Patricia
The Effects of Stress Inoculation on Stress-Coping Behavior in Mice

Adolescent stress is a common occurrence in most mammals’ lives, especially during weaning and the transition to independence. Early stress has often been linked to the development of psychiatric disorders later in life (Toledo-Rodriguez and Sandi, 2011; Ito et al., 2006; Lupien et al., 2009), but more recent studies have found that early stressful experiences that are not overwhelming may calibrate development and lead to increased resilience and arousal regulation in adulthood (Lyons et al., 2009; Kendig et al., 2011). The idea that mild early stress may be involved in developmental calibration is called stress inoculation, and it has been shown to have effects on both behavior and physiological changes in the brain. I use a mouse model to investigate whether early social stress in mice increases resilience and stress-coping behaviors later in life. Juvenile mice were exposed to eleven 10 minute sessions of social stress, and were subsequently tested for changes in stress-coping, novelty-seeking, reward-seeking, and risk-taking behaviors. Based on the results of the Tail Suspension, Open Field, Novel Object Exploration, and Sucrose Preference Tests, stress inoculation leads to an increase in indications of stress-coping and some novelty-seeking and risk-taking behaviors, but not reward-seeking.

Keywords:  Department of Biology
Biology
Stanford Biology
Stanford University
Stress
Stress Inoculation
Mice
Behavior
Thesis
Advisor: Lyons David
Heller H. Craig
The Empire Strikes Back: Postcolonialism and Colorism in Indian Women

Undergraduate Honors Thesis by Samra Adeni. This thesis considers the contemporary societal phenomenon of the fair skin bias in India, especially concentrated among Indian women. This colorism is reflected in matrimonial advertisements, commercial advertising and media, especially the 500 million dollar skin-lightening product industry, and Bollywood, the cinematic opium of the masses. This thesis examines the theory that this cultural mindset arises from the history of the subcontinent, namely the numerous invasions and imperial conquests that have occurred, where an imbalance of power has been created along the lines of light skin and dark skin. This power dynamic leads to a difference in socioeconomic status that over time became correlated with India’s caste system, and remains deeply entrenched in Indian society, even after the legalized prohibition of caste-based discrimination.

Keywords: Program in Feminist Gender and Sexuality Studies
India
Postcolonial Studies
skin color bias
socioeconomic status
Thesis
Advisor: Menon Jisha
The Impact of Rising Interest Rates on the Optimal Social Security Claim Age

Individuals are eligible to claim Social Security benefits between the ages of 62 and 70. While the actuarial present value of benefits for each individual is supposed to be unchanged, regardless of the age at which they are claimed, previous research has shown that this is not true. This paper aims to analyze the impact that interest rates have on the present value of the benefits and attempts to study how different interest rate expectations affect the optimal age at which to claim Social Security. The methodology used in this paper differs from that used in previous studies; I introduce a dynamic interest rate model based on forward rates under both a deterministic and stochastic approach to calculate the Net Present Value associated with different claim ages so as to identify the optimal claim age. The results of this paper display that under certain assumptions, it is advantageous for both men and women to begin claiming retirement benefits early – between the ages of 62 and 65. Moreover, the results indicate that there are significant losses associated with delaying claims beyond the optimal claim age.

Keywords:  Department of Economics
Social Security
Net Present Value
Retirement Benefits
Stanford Department of Economics
Thesis
Advisor: Goda Gopi Shah