Academic literature on the topic 'Philip McLaren'

Aside from being part of a vibrant corpus of Indigenous futurism, Claire G. Coleman’s novel Terra Nullius (2017) can also be analysed as an eco-crime novel. Indigenous Australian authors of this genre (e.g., Philip McLaren, Steven McCarthy, Nicole Watson) often anchor the source of criminal acts in the theft, loss and devastation of traditional lands, which provides their crime novels with a heightened awareness of environmental issues. The same applies to Terra Nullius. This is, however, a novel that successfully conceals its futuristic framework until halfway through. Equally, this successfully disrupts the usual postulates of crime fiction by shifting the reader’s attention from the usual “whodunnit” to the more elusive “whoizzit” mode of crime fiction. This, as the discussion reveals, means that the criminal acts in Terra Nullius are rendered unpunishable. This paradox, as it is argued, is strengthened by introducing the so-called “noir detective” (Timothy Morton) in the character of Father Grark, who cannot investigate that which constitutes the crime and the alibi shaping the world of Coleman’s futuristic novel.

Background75% of diagnosed bladder tumors are non-muscle-invasive (NMIBC)[1, 2]. Most require intravesical instillation of M.bovis Bacillus Calmette-Guérin (BCG). Recurrence after immunotherapy occurs in ~50% patients. Development of treatments for BCG-resistant disease has lagged partly because few studies have attempted to understand the relationship between timing of tumor recurrence, reasoning for the recurrence, and the state of immune system at the time of recurrence.Immune exhaustion is observed following microbial infections, cancers and chronic inflammation [3–5]. Natural Killer (NK) cells are among the earliest responders[6–8] and undergo a similar program of exhaustion as T cells[9]. HLA-E strongly inhibits NKG2A-expressing NK and CD8+T cells and is commonly upregulated on tumors[10]. We evaluated the potential restorative capacity of NKG2A and PD-L1-blockade for reinvigorating NK and CD8+T cell antitumor functions in in BCG-resistant bladder cancer.Methods mRNA analysis of 2,892 genes was performed on tumor tissue of NMIBC patients before and after BCG therapy (n=35). Immunostaining (serial-IHC,immunofluorescence,imaging-mass cytometry) was performed on consecutive tissue sections. Single-cell-RNA-sequencing (scRNAseq) was performed on fresh bladder tumors (NMIBC,n=4; MIBC,n=9). OLink Proteomics (”Inflammation” panel) was performed longitudinally on plasma/urine from a prospective cohort of NMIBC patients. Patient tumors (n=3) were expanded as organoids and co-cultured with autologous tumor-derived NK and CD8+T cells in presence/absence of anti-PD-L1/NKG2A antibodies.ResultsWe demonstrate a robust local TME and systemic response to BCG that correlates with chronic inflammation and adaptive resistance rather than with preventing tumor recurrence. This resistance is mediated through IFN-γ-production by tumor-infiltrating NKG2A+NK and NKG2A+PD-1+CD8+T cells and results in increased HLA-E and PD-L1 on recurring tumors. Co-culture of treatment-naïve NMIBC tumors with recombinant IFN-gamma directly enhanced expression of PD-L1 and HLA-E. Longitudinal analysis of plasma before and during BCG immunotherapy revealed an inflammatory signature, including but not limited to IFN-gamma, that is maintained throughout treatment.Immunostaining and scRNAseq of NMIBC specimens revealed highly enriched infiltration by NKG2A+NK and NKG2A+CD8+T cells in HLA-EBrightPD-L1+ tumors and were spatially organized relative to tumors in a manner suggesting direct inhibition. Tumor-derived NK and CD8+T cells from BCG-resistant patients were co-cultured with autologous tumor organoids. Preliminary analyses demonstrated an improved anti-tumor response in presence of NKG2A/PD-L1-blockade.ConclusionsOur data support a model of BCG-resistance that points to a novel checkpoint axis that contributes to BCG-resistance: HLA-E/NKG2A. New insights into this axis in NMIBC and how it is altered with repeated BCG exposure will enable us to explore combination therapies (PD-L1/NKG2A-blockade) that may reduce BCG-resistance and provide durable response.ReferencesEidinger D, Morales A: Discussion paper: treatment of superficial bladder cancer in man. Ann N Y Acad Sci 1976, 277:239–240.Morales A, Eidinger D, Bruce AW: Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976, 116:180–183.Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP et al: Defining ‘T cell exhaustion’. Nat Rev Immunol 2019, 19:665–674.Hashimoto M, Kamphorst AO, Im SJ, Kissick HT, Pillai RN, Ramalingam SS, Araki K, Ahmed R: CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions. Annu Rev Med 2018, 69:301–318.McLane LM, Abdel-Hakeem MS, Wherry EJ: CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. Annu Rev Immunol 2019, 37:457–495.Lanier LL: NK cell receptors. Annu Rev Immunol 1998, 16:359–393.Biron CA, Gazzinelli RT: Effects of IL-12 on immune responses to microbial infections: a key mediator in regulating disease outcome. Curr Opin Immunol 1995, 7:485–496.Welsh RM, Jr.: Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. I. Characterization of natural killer cell induction. J Exp Med 1978, 148:163–181.da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, Osman I, Bhardwaj N: Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res 2014, 2:410–422.van Hall T, Andre P, Horowitz A, Ruan DF, Borst L, Zerbib R, Narni-Mancinelli E, van der Burg SH, Vivier E: Monalizumab: inhibiting the novel immune checkpoint NKG2A. J Immunother Cancer 2019, 7:263.Ethics ApprovalPrimary urothelial bladder cancer tumor tissue was obtained after obtaining informed consent in the context of an Institutional Review Board (IRB)-approved genitourinary cancer clinical database and specimen collection protocol (IRB #10-1180) at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (New York, NY).

The recognition by translation theorists that literary translation has the ability to perform a culture for a target readership has led to intense debate surrounding the difficulties posed by the translation of cultural specificity. This is now referred to as “the cultural turn in Translation Studies”. Theorists supporting a “foreignisation” strategy in translation argue that this facilitates understanding of the source culture by highlighting cultural difference. The staging of difference thus paradoxically serves to draw cultures closer together. Theorists supporting a “domestication” strategy, however, suggest that the goal should be to create equivalence – adapting the source text to provide understanding for the target culture by neutralising, naturalising or even eliminating cultural difference. In order to explore the ramifications of the strategies adopted by translators, this project will undertake a comparative textual analysis of four crime fiction novels by two Australian authors, Richard Flanagan and Philip McLaren, in which both authors have consciously set out to construct a distinctive sense of Australian cultural identity. The micro-textual analysis of the original texts and their translations aims to identify the ways in which peculiarly Australian features of these novels are conveyed to the French target readership. This will allow conclusions to be drawn on the influence that translation practices can have on the intercultural transcreation that takes place in the transportation of texts between cultures. The emergence of two other phenomena during the same period as the “cultural turn” in Translation Studies provides further scaffolding for this case study. First, there has been a renewed focus in the last thirty years or so on representations of Australian identity in the nation’s cultural productions and this has increased the visibility of that identity on the world stage. Secondly, there has been a growing acceptance by scholars that crime fiction narratives serve as a vehicle for authors to portray a sense of “self-identification”, while also offering a means for informing readers from other cultures about a particular cultural identity in a specific place and at a specific time. The longstanding respect that has been given to the genre of crime fiction by French readers and the notable increase in the production of this genre in Australia in the last thirty years have led to large numbers of “home-grown” narratives being selected for translation and publication in France. If reading crime fiction texts can become a way of viewing representations of Australian cultural identity, then the substantial case study proposed here will highlight the potential perils inherent in the process of “translating” that identity into the realms of the Francophone world.
Thesis (Ph.D.) -- University of Adelaide, School of Humanities, 2015

Indigenous voices emerged within Australian detective fiction with the greatest clarity in the 1990s. This chapter examines the figure of the Indigenous Aboriginal detective created by Indigenous writers as an underrepresented character and speaking subject within Australian detective fiction that both traverses and disrupts conventional elements of literary style. Certainly, the conventional characteristic elements of crime genre are present within detective fiction written by Indigenous writers, but this literary post-colonialist analysis explores how Indigenous writers such as Mudrooroo (“The Westralian,” “The Healer,” and “Home on the Range”), Philip McLaren (Scream Black Murder), and Sally Morgan (My Place) juxtaposed elements of style to both highlight constructs of reality in Australian detective fiction while simultaneously providing fresh perspectives on both the Indigenous detective as a figure of political interest and Australian Indigenous detective fiction as political writing.

Sydney is most well known internationally for its spectacular harbour, opera house and stunning Northern Beaches. But the history of the city includes an avant-garde underbelly. In 1965 Sydney was a fertile breeding ground for counter-cultural, underground cinema. and one of Australia’s first avant-garde independent film-making, distribution and exhibition groups, ‘Ubu’, was established. The name, from Alfred Jarry’s 1896 subversive play, Ubu Roi, signposted their revolutionary aims. Ubu’s members experimented with film form and pushed the boundaries of cultural conventions. They screened their own work and that of international and local avant-garde film-makers like Bruce Connor, Norman McLaren, Paul Winkler and Dusan Marek. They lobbied against censorship and built a creative community. Numerous members later became important to the revival of the Australian feature film industry in the 1970s, including Bruce Beresford, Yoram Gross, Phillip Noyce and Peter Weir.