Flow and use of information at the National Space Science Data Center

Information flow and dissemination at space science data cente

Cancer Epigenome Reprogramming

The identification of recurrent genetic mutations in cancer and their functionalcharacterization has provided a strong foundation for our understanding of tumorigenesis. The more recent observation of recurrent and specific epigenetic changes also present in cancer has widened this view, now establishing cancer as a disease of both genetic and epigenetic misregulation. Enhancers, genomic regions primarily responsible for tissue-specific gene expression, have been shown to be frequent targets of both genetic and epigenetic abnormalities. The observation that DNA methylation within regulatory regions has traditionally correlated with reduced gene expression, coupled with the known role of enhancers in regulating tissuespecific gene expression, suggests that cancer cells may lose their original cellular programming while also gaining expression for genes related to foreign cell types through altered DNA methylation within enhancers. Technological advancements allowing for genome-wide methylation profiling have vastly expanded our capacity to identify DNA methylation alterations present in enhancers, previously undetected in large comparative cancer studies. In Chapter 2, we compared global methylation alterations in two distinct cancer types, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM). We found that both cancer types displayed an increase in methylation over enhancers related to their cell type of origin. Recurrently hypermethylated enhancers in EAC clustered based on the presence of enriched transcription factor binding motifs. Enriched disease ontology pertaining to the majority of differentially methylated enhancer groups largely encompassed uterine-specific terms, suggesting that enhancers gaining methylation in EAC might contribute to the regulation of normal uterine function. Similarly, GBM hyperDMRs were shown to encompass a significantly greater number enhancers active in adult brain compared to those of developing brain. Further analysis of brain enhancer hyperDMRs revealed increased H3K27ac and H3K4me1 signal in adult brain compared to fetal brain, suggesting that the majority of enhancers being methylation were active in adult but not developing brain. In a second series of studies (Chapters 3 – 5), we sought to better understand the properties governing metastasis organotropism, specifically non-small cell lung cancer metastasis to brain. Reasoning that genomic, transcriptomic, and epigenomic changes might functionally contribute similar alterations, we profiled all three in a subset of 45 paired primary and metastasis samples. While few significantly mutated genes were private to metastasis, 75 genes displayed recurrent metastasis enriched variants (MEVs), largely implicated in focal adhesion and extracellular matrix receptor interactions. A similar analysis revealed increased variant allele frequencies (VAFs) in metastases over a wide range of epigenetic regulators, suggesting that epigenetic misregulation may be selected for, and possibly functionally contribute to, NSCLC metastasis to brain. Consistent with these observations, we observed widespread changes in DNA methylation as a function of disease progression, many losses of which were found within annotated brain-specific active enhancers and correlated with increased nearby gene expression. Transcriptional analyses corroborated these findings, revealing an overall increase in brain gene expression. Together these findings suggest that a potential contributor to NSCLC’s successful colonization of brain is the aberrant activation of brain transcriptional programs. To further understand how methylation changes might be contributing to metastasis, we examined DNA methylation differences across patients and found that the most recurrent and largest changes between primary and matched metastatic samples were within DNA methylation valleys (DMVs), large regions devoid of methylation in normal lung that primarily contain developmental genes. Further examination revealed that only a subset of DMVs, marked by high H3K9me3, H3K4me1, and H3K27me3 signal in normal lung, were undergoing progressive methylation gain. The known mutual exclusivity of H3K27me3 and DNA methylation within CpG islands prompted us to ask whether there was a loss of polycomb repressive complex 2 (PRC2), a multi-protein complex responsible for depositing H3K27me3, occupancy within DMVs accompanying the increased DNA methylation. The binding patterns of the PRC2 catalytic subunit, EZH2, in the non-small cell lung cancer lymph node-derived cell line, H1299, displayed a pervasive loss of EZH2 occupancy within DMVs, accompanying a large increase in DNA methylation. The mechanisms governing this epigenetic switch and its implications in metastasis are the topic of ongoing research, but may lead to the activation of encompassed developmental genes, shifting the tumor cells to a more stem-like state

Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated enhancers within EAC samples contain several transcription factor binding site clusters with enriched disease ontology terms highlighting uterine function, while hypermethylated enhancers in GBM are found to overlap active enhancer marks in adult brain. These findings suggest that loss of original cellular identity may be a shared step in tumorigenesis

Influence of oxygen ordering kinetics on Raman and optical response in YBa_2Cu_3O_{6.4}

Kinetics of the optical and Raman response in YBa_2Cu_3O_{6.4} were studied during room temperature annealing following heat treatment. The superconducting T_c, dc resistivity, and low-energy optical conductivity recover slowly, implying a long relaxation time for the carrier density. Short relaxation times are observed for the B_{1g} Raman scattering -- magnetic, continuum, and phonon -- and the charge transfer band. Monte Carlo simulations suggest that these two relaxation rates are related to two length scales corresponding to local oxygen ordering (fast) and long chain and twin formation (slow).Comment: REVTeX, 3 pages + 4 PostScript (compressed) figure

Doping Dependence of the Electronic Structure of Ba_{1-x}K_{x}BiO_{3} Studied by X-Ray Absorption Spectroscopy

We have performed x-ray absorption spectroscopy (XAS) and x-ray photoemission spectroscopy (XPS) studies of single crystal Ba_{1-x}K_{x}BiO_{3} (BKBO) covering the whole composition range $0 \leq x \leq 0.60$. Several features in the oxygen 1\textit{s} core XAS spectra show systematic changes with $x$. Spectral weight around the absorption threshold increases with hole doping and shows a finite jump between $x=0.30$ and 0.40, which signals the metal-insulator transition. We have compared the obtained results with band-structure calculations. Comparison with the XAS results of BaPb_{1-x}Bi_{x}O_{3} has revealed quite different doping dependences between BKBO and BPBO. We have also observed systematic core-level shifts in the XPS spectra as well as in the XAS threshold as functions of $x$, which can be attributed to a chemical potential shift accompanying the hole doping. The observed chemical potential shift is found to be slower than that predicted by the rigid band model based on the band-structure calculations.Comment: 8 pages, 8 figures include

Tradespace Investigation of a Telescope Architecture for Next-generation Space Astronomy and Exploration

Humanity’s endeavor to further its scientific understanding of the celestial heavens has led to the creation and evolution of increasingly powerful and complex space telescopes. Space telescopes provide a view of the solar system, galaxy, and universe unobstructed by Earth’s atmosphere and have profoundly changed the way people view space. In an effort to further advance space telescope capability and achieve the accompanying scientific understanding, the Massachusetts Institute of Technology (MIT), specifically, course 16.89 Space Systems Engineering, explored the tradespace of architectural enumerations encompassed within the design of an ultraviolet-optical-infrared (UVOIR) space telescope located at Sun-Earth Lagrangian Point Two (SE-L2). SE-L2 presents several advantages as an operating location for a UVOIR telescope such as a thermally stable environment and an orbit that allows the telescope to maintain a constant orientation with respect to all of the primary sources of heat and light. The main disadvantages associated with SE-L2 are caused by its relatively large distance from Earth, which marginalizes the effectiveness of real-time telerobotics because of latency and increases the cost of communications, launch, and servicing. Course 16.89 believes that, for this UVOIR application, the strengths of this operating location outweigh its weaknesses and therefore decided to explore the family of opportunities associated with SE-L2. This course used appropriate performance and system metrics to quantify the effectiveness of the aforementioned architectures and create a Pareto front of viable architectures. Evaluating the designs along the Pareto front allowed the course to characterize and group architectures and present these group-types to stakeholders for the selection of an optimal space telescope according to stakeholder requirements and resources. This course also developed sensitivity analysis, which allowed for a greater understanding of how architectural decisions affect the performance of the satellite. Segmentation, modularity, assembly, autonomy, and servicing were key aspects of this multidimensional analysis given the 16.8-meter class size and location of the telescope. Within the respective operating environment and for a spacecraft of similar characteristics, this model will allow stakeholders to predict the long-term operational effectiveness of different space telescope architectures and capture the synergistic effects of combining various architectural decisions into a spacecraft design. The following sections step through the aforesaid analysis and design efforts conducted in 16.89 beginning with Section III, which explicitly performs the stakeholder analysis and articulates the requirements of the mission. Section IV gives an overview of past designs and expands upon the architecture enumerations pertinent to this project, while Section V presents the methods and metrics by which those architectures will be evaluated and the system metrics which will be balanced and optimized in the creation of this space telescope. Section VI will present the model validation of this project and Section VII will discuss the results and analyses of the project. Finally, Section VIII will explore the future work opportunities of this project, while Section IX will present the conclusions and recommendations drawn from this project.MIT Department of Aeronautics and Astronautic

Electron-phonon coupling induced pseudogap and the superconducting transition in Ba0.67K0.33BiO3

We study the single particle density of states (DOS) across the superconducting transition (Tc = 31 K) in single-crystal Ba0.67K0.33BiO3 using ultrahigh resolution angle-integrated photoemission spectroscopy. The superconducting gap opens with a pile-up in the DOS, Delta(5.3 K) = 5.2 meV and 2Delta(0)/kBTc = 3.9. In addition, we observe a pseudogap below and above Tc, occurring as a suppression in intensity over an energy scale up to the breathing mode phonon(~ 70 meV). The results indicate electron-phonon coupling induces a pseudogap in Ba0.67K0.33BiO3.Comment: 5 pages with 4 figures, submitted to Phys. Rev. Let

Separating the Separatist Movements in Modern China: A Look at the Differing Situations of the Uighurs and the Hui

Mentor: Ewan Harrison From the Washington University Undergraduate Research Digest: WUURD, Volume 5, Issue 1, Fall 2009. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Co-editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor