Book Review: Stepping Twice Into the River: Following Dakota Waters

During his year-long journey along North Dakota\u27s Sheyenne River, Robert King travels not merely for pleasure or personal fulfillment but to share local truth true in general, in the process discovering how North Dakota\u27s Nowhere becomes Everywhere. The book\u27s title and controlling metaphor come from Heraclitus, who insisted that one cannot step into the same river twice. King, however, seeks to do just that, claiming that he intends to step into the same river as did French geograpJoseph Nicollet, who crossed the Sheyenne in the 1830s while mapping the Mississippi waterway

Imagining the American West in Wharton’s Short Fiction

Dans ses romans, Wharton raconte parfois un voyage vers l’Ouest américain, ou de l’Ouest vers l’Est, pour évoquer la confrontation entre ses personnages féminins et les normes culturelles. Lily Bart part avec les Gormer en Alaska pour se dérober aux regards extérieurs. Undine Spragg part vers l’Ouest pour mettre fin à son mariage avec Ralph Marvell en divorçant à Reno, ce qui souligne le lien entre la liberté des territoires de l’Ouest américain et la liberté croissante des femmes. L’Ouest américain joue un rôle assez différent dans les nouvelles. Mon analyse, centrée sur « Bunner Sisters », s’appuie aussi sur d’autres nouvelles donnant de l’Ouest une image négative : c’est le domaine du matérialisme grossier des nouveaux riches, un monde ignorant totalement les usages de la société polie, un domaine en proie aux scandales et à l’illégalité. Dans « Bunner Sisters », l’Ouest est un monde où les possibilités semblent se restreindre, vision fort éloignée de l’image nostalgique de l’Ouest des contemporains de Wharton. On peut même dire que la nouvelliste prend le contrepied de cette vision en montrant que la liberté de l’espace culturel de l’Ouest constitue une menace pour la vie des femmes

Memorial Boxes and Guarded Interiors: Edith Wharton and Material Culture

Emily J. Orlando is a contributing author, “Picturing Lily: Body Art in The House of Mirth”. In Edith Wharton’s works, references to architecture, interior decoration, painting, sculpture, and fashion abound. As these essays demonstrate, art and objects are for Wharton evidence of cultural belief and reflect the values, assumptions, and customs of the burgeoning consumer culture in which she lived and about which she wrote. Furthermore, her meditations about issues of architecture, design, and decoration serve as important commentaries on her vision of the literary arts. In The Decoration of Houses she notes that furniture and bric-à-brac are often crowded into a room in order to compensate for a lack of architectural composition in the treatment of the walls, and that unless an ornamental object adequately expresses an artistic conception it is better removed from the room. These aesthetic standards apply equally to her construction of narratives and are evidence of a sensibility that counters typical understandings of Wharton as a novelist of manners and place her instead as an important figure in the development of American literary modernism. Essays in this collection address issues such as parallels between her characters and the houses they occupy; dress as a metaphor for the flux of critical fashion; the marketing of Wharton\u27s work to a growing female readership ; her relationship to mass culture industries such as advertising, theater, and cinema; the tableaux vivant both as set piece and as fictional strategy; the representation of female bodies as objets d’art; and her characters’ attempts at self-definition through the acquisition and consumption of material goods. All of Wharton’s major novels—The House of Mirth, The Fruit of the Tree, Ethan Frome, The Custom of the Country, Summer, The Age of Innocence, and Twilight Sleep—as well as her short stories, criticism, and essays are explored. --Publisher descriptionhttps://digitalcommons.fairfield.edu/english-books/1003/thumbnail.jp

Imagining the American West in Wharton’s Short Fiction

Dans ses romans, Wharton raconte parfois un voyage vers l’Ouest américain, ou de l’Ouest vers l’Est, pour évoquer la confrontation entre ses personnages féminins et les normes culturelles. Lily Bart part avec les Gormer en Alaska pour se dérober aux regards extérieurs. Undine Spragg part vers l’Ouest pour mettre fin à son mariage avec Ralph Marvell en divorçant à Reno, ce qui souligne le lien entre la liberté des territoires de l’Ouest américain et la liberté croissante des femmes. L’Ouest américain joue un rôle assez différent dans les nouvelles. Mon analyse, centrée sur « Bunner Sisters », s’appuie aussi sur d’autres nouvelles donnant de l’Ouest une image négative : c’est le domaine du matérialisme grossier des nouveaux riches, un monde ignorant totalement les usages de la société polie, un domaine en proie aux scandales et à l’illégalité. Dans « Bunner Sisters », l’Ouest est un monde où les possibilités semblent se restreindre, vision fort éloignée de l’image nostalgique de l’Ouest des contemporains de Wharton. On peut même dire que la nouvelliste prend le contrepied de cette vision en montrant que la liberté de l’espace culturel de l’Ouest constitue une menace pour la vie des femmes

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Introduction to African American Travel Narratives from Abroad: Mobility and Cultural Work in the Age of Jim Crow

Gary Totten, Introduction to African American Travel Narratives from Abroad: Mobility and Cultural Work in the Age of Jim Crow (Amherst: University of Massachusetts Press, 2015), 1-15