Liberation Kitchen: Annotating Intergenerational Conversations Among Black Women in Art and Education

In this essay, we, four Black women art educators, draw from Black feminisms and Afrofemcentrism. Our practice considers nuanced ways that Black women curate spaces of communal care, which position forms of dialogic encounters with one another. We put forward aspects of Black life, as lived in and through sharing intimacies of the geospatial and as continuation of Black radical traditions. We argue that a kitchenspace indexes a Black praxis, centering intergenerational knowledge-sharing and methodology toward liberation. We think with Black feminist scholar/artists and insist a method of self-annotating, indexing our lives into the otherwise absences of Black women’s narratives in the field of art education. We practice the theorization and method of using images of personal artwork and our dialogues. These annotations realign new centers of knowledge and refuse cannibalization by Euro-dominant narratives

Development and Validation of an Attitudinal-Profiling Tool for Patients With Asthma

published_or_final_versio

Eco city development in China: addressing the policy implementation challenge

Over the last few decades, China has seen a steep rise in diverse eco city and low carbon city policies. Recently, attention has begun to focus on the perceived shortcomings in the practical delivery of related initiatives, with several publications suggesting a gap between ambitious policy goals and the emerging realities of the newly built environment. To probe this further, in this article we examine – based on the policy network approach – how the gap between high-level national policies and local practice implementation can be explained in the current Chinese context. We develop a four-pronged typology of eco city projects based on differential involvement of key (policy) actor groups, followed by a mapping of what are salient policy network relations among these actors in each type. Our analysis suggests that, within the overall framework of national policy, a core axis in the network relations is that between local government and land developers. In some cases, central government agencies– often with buy-in from international architecture, engineering and consulting firms – seek to influence local government planning through various incentives aimed at rendering sustainability a serious consideration. However, this is mostly done in a top-down manner, which overemphasizes a rational, technocratic planning mode while underemphasizing interrelationships among actors. This makes the emergence of a substantial implementation gap in eco city practice an almost predictable outcome. Consequently, we argue that special attention be paid in particular to the close interdependency between the interests of local government actors and those of land and real estate developers. Factoring in this aspect of the policy network is essential if eco city implementation is to gain proper traction on the ground

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

Metastatic disease is responsible for the majority of cancer-related deaths1. 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 relaps

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

Effects of Road Dust on the Pollination and Reproduction of Wildflowers

Premise of research. Dust particles and pollen grains are similar in size. Dust deposition might therefore influence the pollination and reproduction of flowering plants. Little is known about such effects, however, despite more general interest in ecological effects of dust. Methodology. We used observational and experimental methods to explore whether dust generated by traffic on unpaved roads affects the amounts of pollen received and numbers of seeds produced by four species of native wildflowers in the western United States. Pivotal results. Flowers of Nuttall's larkspur (Delphinium nuttallianum), scarlet gilia (Ipomopsis aggregata), Lewis flax (Linumlewisii), and sulphur paintbrush (Castilleja sulphurea) growing 1-2mfrom a road received substantially more dust and less pollen than those growing 40-50 m away. We observed the same pattern when we transplanted individuals of the first two species into pots and placed pots near to compared with far from a road. Experimental "hand dusting" of scarlet gilia and Lewis flax plants also reduced stigma pollen loads to a degree that resembled the average effect of road proximity for those species. On the other hand, numbers of seeds per flower ("seed set") did not vary consistently for any species as a function of road proximity or hand-dusting treatment. Conclusions. Several mechanisms might contribute to the different effects of dust on pollen loads and seed set. Wediscuss four possible mechanisms, which we refer to as pollen excess, pollen quality, resource limitation, and compensatory herbivory. These mechanisms suggest avenues for further study of dust, pollination, and plant reproduction with this and other systems.Rocky Mountain Biological Laboratory (RMBL); US National Science Foundation12 month embargo; ONLINE: Nov 23, 2016This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]