Parallel Adaptive Collapsed Gibbs Sampling

Rao-Blackwellisation is a technique that provably improves the performance of Gibbs sampling by summing-out variables from the PGM. However, collapsing variables is computationally expensive, since it changes the PGM structure introducing factors whose size is dependent upon the Markov blanket of the variable. Therefore, collapsing out several variables jointly is typically intractable in arbitrary PGM structures. This thesis proposes an adaptive approach for Rao-Blackwellisation, where additional parallel Markov chains are defined over different collapsed PGM structures. The collapsed variables are chosen based on their convergence diagnostics. Adding chains requires re-burn-in the chain, thus wasting samples. To address this, new chains are initialized from a mean field approximation for the distribution, that improves over time, thus reducing the burn-in period. The experiments on several UAI benchmarks shows that this approach is more accurate than state-of-the-art inference systems such as Merlin which have previously won the UAI inference challenge

Archaeological investigations along the Ruby Pipeline.

405 pages : illustrations (some color), maps ; 26 cm.The Ruby Pipeline originates in Opal, Wyoming, travels westward across Utah and Nevada, and terminates in Malin, Oregon. Almost 360 miles of the line is in Nevada, where it crosses through some of the most remote, sparsely populated land in the lower 48 states. Despite the remote nature of this corridor, it has produced a rich archaeological record reflecting a dynamic history of land-use pattern changes over a period of at least 13,000 years. Archaeological excavations were conducted at 578 prehistoric sites prior to construction of the pipeline. The sites were distributed across four ecological regions, including (from west to east): the High Rock Country, Upper Lahontan Basin, Upper Humboldt Plains, and Thousand Springs Valley. First evidence of human occupation dates to the Paleoindian (14,500-12,800 cal b.p.) and Paleoarchaic (12,800-7800 cal b.p.) periods, when people spent most of their time in the High Rock Country where important economic resources reached their highest densities. Paleoindian findings are limited to a series of Great Basin Concave Base projectile points and small obsidian flaked stone concentrations. Paleoarchaic sites are much more common, and tend to be represented by Great Basin Stemmed projectile points, bifaces, and a limited number of other flaked stone tools. Most of these assemblages reflect small groups of hunters refurbishing their tool kits as they traveled through the area. An important exception to this pattern was found at Five Mile Flat along the west end of pluvial Lake Parman where two significant habitation sites dating to 11,180 cal b.p. were discovered. One of these sites includes a house floor, which is the oldest ever found in the Great Basin. Despite the warm-dry conditions that characterized much of the middle Holocene, it appears that human populations nearly doubled during the Post-Mazama Period (7800-5700 cal b.p.). Most activity remained concentrated in the High Rock Country, but evidence for occupation begins to trickle out into the Upper Lahontan Basin and Upper Humboldt Plains regions as well. Most of the artifact assemblages remain rather narrow, often composed of Northern Side-notched and Humboldt Concave Base points, bifaces, and debitage, and reflect use of the region by mobile groups of hunters. Major changes took place with the arrival of the Early Archaic (5700-3800 cal b.p.) and continued forward into the Middle Archaic Period (3800-1300 cal b.p.). Early Archaic projectile points are largely represented by Humboldt and Gatecliff forms. It appears that population densities increased almost fourfold from the preceding interval, and all four regions experienced significant occupation for the first time. Simultaneous to this population increase and dispersal, a full complement of site types began to emerge, with large-scale residential areas becoming significant for the first time. This trend continued forward into the Middle Archaic Period where the relative frequency of residential sites almost doubled compared with the Early Archaic interval. Plant macrofossil and archaeofaunal assemblages also become more abundant and diversified at this time, probably marking a broadening of the diet breadth. This general trajectory extends into the Late Archaic (1300-600 cal b.p.) and Terminal Prehistoric periods, as people continued to expand into a wider range of habitats. This was particularly case for the latter interval, as the habitat preferences that made sense for over 12,000 years were upended, with population densities highest in the Upper Humboldt Plains and Thousand Springs Valley. This reorientation corresponds to the arrival of Numic speaking populations, especially the Western Shoshone who appear to have reached northern Nevada much earlier than the Northern Paiute, and is probably linked to a greater emphasis on small-seeded plants that are abundantly present in their territory. Although low ranked compared to many other foods, with the proper technology and work organization, small seeds could support higher population densities than was the case earlier in time. Finally, the discovery of obsidian in multiple Terminal Prehistoric sites from sources located much further away than any other time in the past may signal the earliest use of horses in northern Nevada

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Plasma Proteome Profiles Associated with Inflammation, Angiogenesis, and Cancer

Tumor development is accompanied by a complex host systemic response, which includes inflammatory and angiogenic reactions. Both tumor-derived and systemic response proteins are detected in plasma from cancer patients. However, given their non-specific nature, systemic response proteins can confound the detection or diagnosis of neoplasia. Here, we have applied an in-depth quantitative proteomic approach to analyze plasma protein changes in mouse models of subacute irritant-driven inflammation, autoreactive inflammation, and matrix associated angiogenesis and compared results to previously described findings from mouse models of polyoma middle T-driven breast cancer and Pdx1-Cre KrasG12D Ink4a/Arf lox/lox -induced pancreatic cancer. Among the confounding models, approximately 1/3 of all quantified plasma proteins exhibited a significant change in abundance compared to control mice. Of the proteins that changed in abundance, the majority were unique to each model. Altered proteins included those involved in acute phase response, inflammation, extracellular matrix remodeling, angiogenesis, and TGFβ signaling. Comparison of changes in plasma proteins between the confounder models and the two cancer models revealed proteins that were restricted to the cancer-bearing mice, reflecting the known biology of these tumors. This approach provides a basis for distinguishing between protein changes in plasma that are cancer-related and those that are part of a non-specific host response

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment