Rebecca West and the Double Agent

This essay will explore the figure of the double agent as it tests notions of citizenship mid-century, specifically the clash or fusion of internationalist/nationalist definitions of citizen loyalty in the construction of the traitor ‘revolutionary’ citizen. It will be look at Kaminsky in Rebecca West's 1966 historical novel The Birds Fall Down as a late rewriting of the double agent, which West had theorized through her analyses of William Joyce (‘Lord Haw-Haw’)’s wartime propaganda and Stephen Ward in the Profumo Affair of the early 1960s. West's thinking draws on Hannah Arendt's writings on the double agent in Origins of Totalitarianism. The essay will explore both the political Cold War contexts that motivated West's return to Tsarist Russia and the double agent, and the feminist light cast on treacherous intelligence operations as forms of patriarchal control over women's bodies and minds. West is shown to be revising the double agent trope of spy fiction, reimagining the mole traitor as totalitarian fanatic revealing the extremes of hostile patriarchy and of male political desire.

561 Triple checkpoint blockade, but not anti-PD1 alone, enhances the efficacy of engineered adoptive T cell therapy in advanced ovarian cancer

BackgroundOver 20,000 women are diagnosed with ovarian cancer annually, and more than half will die within 5 years. This rate has changed little in the last 20 years, highlighting the need for therapy innovation. A promising new strategy with the potential to control tumor growth without toxicity to healthy tissues employs immune T cells engineered to target proteins uniquely overexpressed in tumors. Mesothelin (Msln) contributes to the malignant and invasive phenotype in ovarian cancer, and has limited expression in healthy cells, making it a candidate immunotherapy target in these tumors.MethodsThe ID8VEGF mouse cell line was used to evaluate if T cells engineered to express a mouse Msln-specific high-affinity T cell receptor (TCRMsln) can kill murine ovarian tumor cells in vitro and in vivo. Tumor-bearing mice were treated with TCRMsln T cells plus anti-PD-1, anti-Tim-3 or anti-Lag-3 checkpoint-blocking antibodies administered alone or in combination, ultimately allowing targeting up to three inhibitory receptors simultaneously. Single cell RNA sequencing was used to profile the impact of combination checkpoint blockade on both the engineered T cells and the tumor microenvironment.ResultsIn a disseminated ID8 tumor model, adoptively transferred TCRMsln T cells preferentially accumulated within established tumors, delayed ovarian tumor growth, and significantly prolonged mouse survival. However, our data also revealed that elements in the tumor microenvironment (TME) limited engineered T cell persistence and ability to kill cancer cells. Triple checkpoint blockade, but not single- or double-agent treatment, dramatically increased anti-tumor function by intratumoral TCRMsln T cells. Single cell RNA-sequencing revealed distinct transcriptome changes in engineered T cells and the TME following triple blockade compared to single- and double-agent treatment. Moreover, combining adoptive immunotherapy with triple checkpoint blockade prolonged survival in the cohort of treated tumor-bearing mice, relative to TCRMsln with or without anti-PD1, or double-agent treatments.ConclusionsInhibitory receptor/ligand interactions within the tumor microenvironment can dramatically reduce T cell function, suggesting tumor cells may evade T cell responses by upregulating the ligands for PD-1, Tim-3 and Lag-3. In a model of advanced ovarian cancer, triple checkpoint blockade significantly improved the function of transferred engineered T cells and improved outcomes in mice in a setting in which single checkpoint blockade had no significant activity. The results suggest that T cell therapy with triple blockade, which can ultimately be more safely pursed in a cell intrinsic form through T cell genetic engineering, may overcome barriers to achieving therapeutic efficacy in patients.Ethics ApprovalThe Institutional Animal Care and Use Committees of the University of Washington and the Fred Hutchinson Cancer Research Center approved all animal studies.

The double agent: aspects of literary translator affect as revealed in fictional work by translators

How do translator-authors represent translators and the translation act in fiction? What do such works indicate about the affective aspects of translation and literary translation in particular? This introductory survey of these issues analyses several fictional works written by translators, to show that certain emotional responses recur , and that while there is little research into affect and literary translation, there are elements commonly found in studies of bilingualism which are echoed in the works of fiction studied. Whether these echoes can be construed as constituting a psychological profile of the literary translator is a moot point; what does emerge clearly is a literary representation of a profession whose members are marginalised, trans gressive, even fraudulent or impostors; at the very least, prey to identity instability.

External knowledge transfer deployment inside a simple double agent Viterbi algorithm

We consider in this paper deploying external knowledge transfer inside a simple double agent Viterbi algorithm which is an algorithm firstly introduced by the author in his preprint "Hidden Markov Based Mathematical Model dedicated to Extract Ingredients from Recipe Text". The key challenge of this work lies in discovering the reason why our old model does have bad performances when it is confronted with estimating ingredient state for unknown words and see if deploying external knowledge transfer directly on calculating state matrix could be the solution instead of deploying it only on back propagating step.

Double agent indole-3-acetic acid (IAA): Mechanistic analysis of indole-3-acetaldehyde dehydrogenase AldA that synthesizes IAA, an auxin that aids bacterial virulence

The large diversity of organisms inhabiting various environmental niches on our planet are engaged in a lively exchange of biomolecules, including nutrients, hormones, and vitamins. In a quest to survive, organisms that we define as pathogens employ innovative methods to extract valuable resources from their host leading to an infection. One such instance is where plant-associated bacterial pathogens synthesize and deploy hormones or their molecular mimics to manipulate the physiology of the host plant. This commentary describes one such specific example - the mechanism of the enzyme AldA, an aldehyde dehydrogenase (ALDH) from the bacterial plant pathogen Pseudomonas syringae which produces the plant auxin hormone indole-3-acetic acid (IAA) by oxidizing the substrate indole-3-acetaldehyde (IAAld) using the cofactor NAD+ (Bioscience Reports, 2020, 40, https://doi.org/10.1042/BSR20202959). Using mutagenesis, enzyme kinetics, and structural analysis, Zhang K. et al., establish that the progress of the reaction hinges on the formation of two distinct conformations of NAD(H) during the reaction course. Additionally, a key mutation in the AldA active site ‘aromatic box’ changes the enzyme’s preference for an aromatic substrate to an aliphatic one. Our commentary concludes that such molecular level investigations help to establish the nature of the dynamics of NAD(H) in ALDH-catalysed reactions, and further show that key active site residues control substrate specificity. We also contemplate that insights from this study can be used to engineer novel ALDH enzymes for environmental, health and industrial applications.