Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Time series analysis of summer hot spells in northeastern Illinois and southeastern Wisconsin : an application for utilities

Includes bibliographical references (pages [65]-67)Recent changes in the utility industry brought about by changes in government policy are promoting more efficient management. As a result, some utility managers now view climate analysis as a tool that may help them gain a competitive edge in the energy marketplace. This thesis used time series analysis to examine summer hot spells in northeastern Illinois and southeastern Wisconsin. The intent was to provide utility managers with useful information about summer hot spells that would allow for improved management decisions and strategies. The goals of this research are fourfold: (1) construct deterministic, dynamic-stochastic time series models of summer daily maximum air temperatures for twenty-two sites within the study region; (2) generate hot spell counts and duration probabilities for each site; (3) assess the accuracy of the models; and (4) examine summer hot spells geographically and temporally. The expectation is that the information from this hot spell analysis could be used in conjunction with long-range climate forecasts. It was found that Lake Michigan had a pronounced effect on the geography of summer hot spell frequencies and cumulative duration probabilities. Those sites closest to the lake experienced the highest total number of hot spells, but also had the lowest probabilities of a hot spell lasting for more than one day. This is probably due to the fact that lakeshore sites had lower over all average maximum temperatures and greater maximum temperature variance. Average frequencies of summer hot spell durations for warm, average, and cool summers were generated. The three summer types varied considerably. At inland sites, warm summers average 6.61 more hot spells and 19.5 more hot spell days than cool summers. It was found that the first-order autoregressive model which relied only on the autocorrelation coefficient and a random error term could not reproduce synthetic hot spells with the same frequency and magnitude that was exhibited in the empirical data. It is surmised that anticyclones or highs which may persist for days and cause hot spell conditions may not be modeled well by a firstorder autoregressive process.M.S. (Master of Science

From Musicology to Novel: Reassessing Robertson Davies’s Literary Representation of Peter Warlock

This article reconsiders the literary refiguring of the British composer Peter Warlock as the character Giles Revelstoke in Robertson Davies’s 1958 novel A Mixture of Frailties. Although several Davies scholars have highlighted the general nature of this portrait, a detailed consideration of how Cecil Gray’s 1934 study of Warlock was a catalyst for Davies has yet to be explored. Gray’s book allowed Davies to incorporate a plethora of details from Warlock’s biography (including his untimely death) and to draw upon Warlock’s work as a composer and critic, his reception, and his family background; however, Davies was also able to explore his own interpretative space. In comparing A Mixture of Frailties with other literary refigurings of Warlock in the early twentieth century, the detail of Davies’s portrayal is distinctive, particularly in terms of its discussion of music. Davies’s novel can therefore be identified as a significant contribution to musico-literary relations

Dutch influences on English literary culture in the early renaissance, 1470–1650

During the fifteenth, sixteenth and seventeenth centuries the Low Countries made a series of important contributions to English literature. Through such agents as the printers of Antwerp and Amsterdam, and the movements of Dutch scholars and Calvinist refugees, the Low Countries exerted a continuous impact on the literary culture of England. This article examines the scope of Dutch influence during the English Renaissance, indicates some of its key effects, and provides an overview of existing scholarship on the subject

Comprehensive molecular characterization of human colon and rectal cancer

To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.National Institutes of Health (U.S.) (Grant U24CA143799)National Institutes of Health (U.S.) (Grant U24CA143835)National Institutes of Health (U.S.) (Grant U24CA143840)National Institutes of Health (U.S.) (Grant U24CA143843)National Institutes of Health (U.S.) (Grant U24CA143845)National Institutes of Health (U.S.) (Grant U24CA143848)National Institutes of Health (U.S.) (Grant U24CA143858)National Institutes of Health (U.S.) (Grant U24CA143866)National Institutes of Health (U.S.) (Grant U24CA143867)National Institutes of Health (U.S.) (Grant U24CA143882)National Institutes of Health (U.S.) (Grant U24CA143883)National Institutes of Health (U.S.) (Grant U24CA144025)National Institutes of Health (U.S.) (Grant U54HG003067)National Institutes of Health (U.S.) (Grant U54HG003079)National Institutes of Health (U.S.) (Grant U54HG003273

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

© 2014 Elsevier Inc. Recent genomic analyses of pathologically defined tumor types identify 'within-a-tissue' disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-oforigin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pancancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies