Bob Brown Research Articles

Saudades: Toward a Sociopoetics of Diaspora, Migration, & Exiled Writing

Unpacking the term saudades, this article weaves together Claude Lévi-Strauss's research in Brazil for Tristes Tropiques with both Oswald de Andrade's 1928 Manifesto Anthropofago, and Rose and Bob Brown's visual poetry, travel guides, cookbooks, and young adult history books about Brazil. One can consider these projects as decolonial theory, poetry, and sociopoetics seventy or eighty years before decolonial theory became a widely discussed term. Augusto de Campos of the Noigandres group and a leader of the International Concrete Poetry movement wrote introductions to facsimile editions of both Oswald de Andrade's manifesto and then later to Bob Brown's republished collection of visual poems, 1450-1950. Although almost completely unknown now, Rose herself authored three children’s books, Two Children of Brazil, Two Children and their Jungle Zoo, and Amazon Adventures of Two Children, one social geography, Land and People of Brazil, and one biographical history, American Emperor: Dom Pedro II of Brazil, all while living in Brazil. Rose and Bob together edited the Brazilian American business weekly in the early and mid-1920s. All of these people may have known each other in Brazil as they worked and lived among overlapping circles of friends and colleagues involved in the modernist avant-garde, but as-of-yet, whether they met or not remains a mystery.

1450–1950: The Gutenberg Galaxy According to Bob Brown

1450–1950:The Gutenberg Galaxy According to Bob Brown Ross Hair (bio) In 1929, the Paris-based Black Sun Press (formerly known as Editions Narcisse) run by Caresse and Harry Crosby published a slim volume of hand-drawn images and handwritten texts by a fellow American named Bob (Robert Carlton) Brown. Titled 1450–1950, and printed in a run of 150 copies, Brown's book is the very antitype of the high-end books that the press is known for.1 Printed by the Parisian "Maître-Imprimeur" Roger Lescaret and using only the optimum quality papers and inks, the Black Sun Press titles by, among others, James Joyce and Ezra Pound are notable for the quality of their production.2 Compared to these specimens of what Jerome McGann considers modernist extensions of "the late nineteenth-century Renaissance of Printing," Brown's manuscript is comparatively amateurish, and, at times, illegible.3 Brown's "whimsical, instinctively deconstructive picture poems in holograph," as Cary Nelson describes them, pay little heed to typographical propriety or bibliographical decorum.4 As a result, the "categories of high art, seriousness, representation, and literariness" are, Nelson suggests, "all at risk" in 1450–1950 (173). So too is the sanctity of the book itself. To use Brown's own trope, 1450–1950 is the distracting "FLY SPECK" on the "NEW" typeset page of modernism.5 But as well as questioning the dominance of typography in modernism's "Revolution of the Word," Brown's figurative fly speck also foregrounds a series of racialized and gendered assumptions that have not only tarnished (indelibly so) but also enabled what McGann calls "the visible language of modernism" (Black Riders). [End Page 457] Click for larger view View full resolution Fig 1. Bob Brown, "I LIKE LOOKING BACK," 1450–1950, ed. Craig Saper (1959, rpt. Baltimore, MD: Roving Eye Press, 2015). Permission to reprint "I LIKE LOOKING BACK" from Bob Brown's 1450–1950 in the 2015 edition granted by Craig J. Saper based on Jonathan Williams's Jargon edition of 1959 and with special acknowledgement of Bob Brown's great grand-, and grand-, children. [End Page 458] 1450–1950 therefore constitutes a prolegomenon to the new reading technologies that Brown would subsequently promote in The Readies.6 If, as Jessica Pressman claims, these later essays and books of Brown's "invite us to consider how reading has a medial history that is part of literature and literary history," then 1450–1950 is itself indexical of the prejudices and discriminations tacitly shaping this history.7 Building on Michael North's ideas regarding the utopic scope of Brown's visible language, and the way in which "race is intrinsic to his innovations," this essay examines how Brown's problematic representations of race and gender in 1450–1950 highlight a broader set of assumptions concerning otherness in the materiality of print.8 By reflecting on its own material processes of expression, and by subverting the typographic medium of print, 1450–1950 draws attention to some ideological biases that are deeply impressed in the medial history of Western literature. The "recursive relationship between literature and reading machines," including Brown's Readies, Pressman writes, "opens up new directions for writing literary history" (Digital Modernism, 77). Without contesting such a claim, the imbedded prejudices evident in 1450–1950's own medial history of the book reminds its reader that, in order to open up "new directions for writing literary history," the recursive relationship between literature and literacy also requires a level of re-medial intervention that will heed the errors and omissions in extant reading practices, technologies, and mediums. Colophon In 1959, two small presses associated with the New American poetry—Jargon in North Carolina and Corinth Books in New York City—copublished a new edition of Brown's book. The initiator of the new edition, Jonathan Williams, had recommenced Jargon while a student at Black Mountain College, publishing fellow Black Mountaineers such as Charles Olson. It was also at Black Mountain where Williams first encountered 1450–1950. Caresse Crosby, having published Olson's Y&X in 1950, brought with her a rare copy of Brown's book while visiting the campus. The scarcity of Brown's "utterly...

Law and Litigation for the Conservation of Forest Communities

Australia’s natural environment is in decline and under increasing threat. The extent and severity of biodiversity loss is highlighted by the second independent, 10-yearly review of the Environment Protection and Biodiversity Conservation Act 1999 (Cth) (‘EPBC Act’). The Review points to climate change as a critical compounding danger — one to which Australia and its unique flora and fauna are highly vulnerable. In this article, we discuss the role of law in protecting and extending the public interest in nature conservation, with special focus on the forest context. The term ‘public interest,’ while complex in meaning, typically refers to public or community values, as opposed to private interests such as those of property rights holders. We consider the recent judgments in Friends of Leadbeater’s Possum Inc v VicForests (No 4) [2020] FCA 704 (‘Leadbeater’s Possum’) and Bob Brown Foundation Inc v Commonwealth of Australia [2021] FCAFC 5 (‘Great Forest’) with respect to the ongoing function of the Regional Forest Agreements (‘RFAs’) in exempting the operation of the EPBC Act. In light of the Review’s comment that Australia’s federal environmental law is not fit for purpose, as well as the gaps and limitations in the law revealed by the two court cases, we conclude that legal reform is needed. Without legal reform, there can be no guarantee that cumulative threats to forest biodiversity will be adequately managed because although the relevant legislation appears to embody principles of ecologically sustainable development on its face, it also prevents key decision-makers and operators from being held to account. The inescapable dependency of humans on nature means the insufficiency of environmental laws fundamentally concern us all.

Women in Australian Politics: Maintaining the Rage against the Political Machine

Women in Australian Politics: Maintaining the Rage against the Political Machine

The Readies (from Bob Brown to dj readies)

I focused in this article on a precise example of a reading machine, a machine that probably never truly existed, but received however quite a lot of feedback, to the point that it became the center piece of a protest rhetoric. Those are Robert Carlton Brown’s Readies (1930). The desire to find new ways of capturing, preserving and transmitting texts has been a recurring feature throughout the 20th century. And the process intensified in the 21st century with the latest computer developments that have multiplied the reading surfaces, the touch pad and e-readers to more and more accurate screens of our computers. These new devices bring us into a culture of the screen that seems to sound the death knell of the book and its culture. However, this search for a technical device capable of competing with the codex was not done at once, it did not lead spontaneously to a functional model. The desire to renew the very instruments of reading has left many traces, projects of reading machines dead on the soap opera. These projects all concern a wish, that of renovating the techniques of conservation and dissemination of texts, as well as the very mechanisms of reading, which never evolves quickly enough. The careful examination of Brown's project, notably in it’s controversial resumption by Craig Saper, under the pseudonym dj readies, will make it possible to understand how reading machines, beyond their technical dimension, have important semiotic and symbolic implications.

Our Cows and Whales

Our Cows and Whales

Abstract 2925: Anti-tumor activity of a MYC-targeting dicer substrate siRNA in combination with BRD4/CDK7 inhibitors

Abstract MYC is a well-characterized driver of numerous tumor types. Since the protein encoded by this gene is challenging to target via conventional modalities, progress in new therapeutic agents has been slow despite decades of research. RNA interference technology has enabled the inhibition of previously-undruggable genetic targets at the mRNA level, and has advanced to clinical development for several indications. DCR-MYC, a lipid nanoparticle (LNP)-formulated Dicer substrate siRNA (DsiRNA) targeting MYC mRNA, is currently in Phase Ib/II clinical trials and showing promising results. In this study we used an improved EnCore LNP and MYC DsiRNA, which demonstrated MYC mRNA silencing activity and efficacy in mouse models of human hepatocellular carcinoma (HCC). Small molecule inhibitors that target BRD4; JQ1 and CDK7; THZ1 has previously reported anti-proliferative effects in various cancer types and efficacy in several tumor mouse models including HCC. Treatment with both JQ1 and THZ1 induced cell cycle arrest and apoptosis in various cancer cells by repressing MYC expression. Here we observed striking anti-proliferative effects in vitro when MYC-DsiRNA was combined with THZ1 in cancer cells. In addition, when mice bearing HCC tumors were treated with MYC-DsiRNA combined with either THZ1 or JQ1, the antitumor efficacy was additive or synergistic relative to either single agent alone. We observed significantly more MYC mRNA knockdown in the tumors that had the combination treatment compared to the tumors that received either of the single agent treatment. These preclinical data suggests the possibility of a significant and practical benefit of combining MYC-DsiRNA and small molecule inhibitors that target an epigenetic regulator BRD4 (JQ1) and a global gene regulator CDK7 (THZ1). Citation Format: Edmond Chipumuro, Zakir Siddiquee, Shanthi Ganesh, Serena Shui, Anee Shah, Boyoung Kim, Dongyu Chen, Purva Pandya, Rachel Storr, Weimin Wang, Hank Dudek, Cheng Lai, Marc Abrams, Bob Brown. Anti-tumor activity of a MYC-targeting dicer substrate siRNA in combination with BRD4/CDK7 inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2925.

Abstract 3827: Preclinical characterization of DCR-BCAT as a component of combination therapy

Abstract Dicer-substrate siRNAs (DsiRNAs) are a potent class of RNA interference (RNAi) triggers capable of silencing any expressed mRNA with high specificity. DCR-MYC, a first-in-class DsiRNA targeting the MYC oncogene is currently in Phase 1b/II clinical trials [ASCO 2015, abstract 11006]. DCR-BCAT is an advanced preclinical development candidate that targets CTNNB1, the gene which encodes β-catenin. The β-catenin/Wnt pathway is consistently activated in human tumors, including >50% of hepatocellular carcinomas (HCC) and >80% of colorectal cancers (CRC). Robust preclinical and genetic evidence strongly suggests that inhibiting β-catenin function would yield broad therapeutic benefit in oncology, but efforts to target it using conventional drug modalities have been unsuccessful to-date. We have previously reported extensive preclinical pharmacology for DCR-BCAT in mouse tumor models of diverse origin. Here, we explore DCR-BCAT as a monotherapy and in combination with both standard-of-care and experimental therapeutics. Interestingly, when mice bearing HCC tumors were treated with a combination of CTNNB1 and MYC DsiRNAs, the antitumor efficacy was additive or synergistic relative to either single agent alone. Additionally, since up to 50% of colorectal tumors have both activated Wnt signaling and mutant KRAS, we also explored combination therapy of DCR-BCAT and FDA-approved MEK inhibitors. A major advantage of DCR-BCAT is that the improved nanoparticle formulation is more selective for siRNA delivery to tumors over liver and other normal tissues. These data support continued development of DCR-BCAT as a first-in-class RNAi therapeutic, and highlight the potential for use in combination with other promising agents. Citation Format: Shanthi Ganesh, Wendy Cyr, Martin Koser, Girish Chopda, Edmond Chipumuro, Zakir Siddiquee, Kevin Craig, Serena Shui, Dongyu Chen, Cheng Lai, Hank Dudek, Weimin Wang, Bob Brown, Marc Abrams. Preclinical characterization of DCR-BCAT as a component of combination therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3827.

Pharmacists' responses to natural disasters: Insights into the soul of pharmacists and our role in society.

In this issue, we feature an article from Denise A. Epp, a Canadian now living in Japan (and obtaining her PhD in pharmacy). She tells the stories of how pharmacists in Japan and Canada have responded to major disasters. After the Tohoku earthquake-tsunami-nuclear disaster, Yoshirou Tanno, despite his significant personal losses, immediately helped to set up the emergency evacuation centre in the local school, coordinated pharmacist volunteers to get people their medications and set up a temporary pharmacy. She also tells the story of Anita and Bob Brown in Okotoks, Alberta, and the services they provided to patients from nearby High River, which had been particularly hard hit by the floods of June 2013. Ms. Brown was one of the first Alberta pharmacists to receive her prescribing authorization, and the overrun local health centre began to direct patients to see her. The Browns courageously mobilized their staff to provide care to the many displaced patients who needed their help. Read the article—it’s heartwarming and inspirational. As a follow-up to this story, on April 14 to 16 of this year, the Kumamoto area of Japan was struck with several earthquakes and aftershocks. Ms. Epp emailed me in May to tell me that Mr. Tanno was there—1600 km from his home—providing emergency pharmacy services. Because he has lived through such a disaster, he has a unique rapport with the latest earthquake victims. Mr. Tanno’s vest and helmet, which identify him as a pharmacist at the disaster sites (photo credit: Yoshirou Tanno). As I write this, the tragic wildfires in Fort McMurray and surrounding area are ongoing. The evacuation of Fort McMurray has resulted in 40,000 people temporarily relocating to Edmonton, often with nothing but the clothes on their backs. I spoke to Deb Van Haaften, Executive Director, Pharmacy, Edmonton Zone, Alberta Health Services, who, along with Sandra Leung (the pharmacist in charge of home care services), are providing administrative leadership during the crisis. When I spoke to her, Ms. Van Haaften had just completed a shift at the evacuation centre set up at the Northlands Expo complex. The centre has been providing food, clothing, shelter and health care support for evacuees. She got the call last week—Alberta Health Services wanted pharmacists to be there 24 hours a day. Interestingly, they didn’t want pharmacists to dispense drugs but rather to assess patients and prescribe their medications. I repeat, Alberta Health Services wanted pharmacists for their ability to prescribe, not dispense. Pharmacists are also helping assess patients’ coverage of medications. For those unable to pay, they have set up a partnership with a community pharmacy, and Alberta Health Services is covering the costs. And they have even set up a shuttle bus to take patients from the evacuation centre to the pharmacy. They have also been asked to help patients requiring methadone and tuberculosis therapies. One of Japan’s 3 mobile pharmacy vans arrived in the Kumamoto area the day after the second earthquake struck (photo credit: Denise A. Epp). Yesterday, the first pharmacist (from the Royal Alexandra Hospital in Edmonton) was sent to the field hospital set up in Fort MacMurray. Her mission will be to serve the first responders’ needs. And the challenges continue: as of today, they have noted acute diarrheal illnesses in many evacuees, likely a Norwalk or similar virus. This is the scene at the Northlands Expo Centre where pharmacists are busy assessing and prescribing for victims of the Fort McMurray disaster (photo credit: Deb Van Haaften). In all of this, hospital pharmacists have volunteered to help, 24/7. The Royal Alexandra Hospital pharmacy is busy restocking emergency medical supplies. Many community pharmacies have also stepped up to meet the needs of patients. These are all very different tragedies. But I note a few strong themes: courage, selflessness, and above all, patient-centredness. This is an inspiring demonstration (and recognition) of the role that we play in society. Indeed, the actions of these and other pharmacists in the face of disasters could be a defining moment for pharmacy. ■

Protect the Tasmanian wilderness

Australia's Tasmanian Wilderness World Heritage Area (TWWHA) is one of the three largest remaining temperate wilderness regions in the Southern Hemisphere ([ 1 ][1]). It covers about 1.6 million hectares, almost a quarter of Australia's State of Tasmania ([ 1 ][1]). Pristine wilderness is the most important core value of the region. In January 2014, to encourage local economic growth, the Australian federal government sought to remove 74,039 hectares of land from the TWWHA ([ 2 ][2]). Although the request was rejected by the World Heritage Committee in June 2014 ([ 3 ][3]), the Tasmanian state government still supports housing, airport, road, mining, and logging projects within the TWWHA. The World Heritage Committee urged the federal government to stop any such development within the property ([ 4 ][4]). It is unclear how the federal government will address the Committee's demand, which leaves the values and integrity of the TWWHA at risk. Australia is only the third country in the world, after Oman and Tanzania, to seek the delisting of its World Heritage areas ([ 5 ][5]). Australian governments, especially the federal one, should show leadership in implementing the World Heritage Convention. Local and national communities should also raise their voices to politicians and governments to make clear that the values and integrity of the TWWHA cannot be sacrificed by any socioeconomic development. ![Figure][6] Mount Pelion East in the Tasmanian Wilderness World Heritage Area. PHOTO: ©CHRISTIAN KOBER/ROBERTHARDING/CORBIS 1. [↵][7]Department of Primary Industries, Parks, Water and Environment, Tasmania, The 2014 Draft Tasmanian Wilderness World Heritage Area Management Plan (Hobart, 2014). 2. [↵][8]1. A. Darby , Abbott government to cut 74,000 ha of forest from World Heritage Zone, Sydney Morning Herald (31 January 2014). 3. [↵][9]The World Heritage Committee, Decisions Adopted by the World Heritage Committee at Its 38th Session (Doha, 2014). 4. [↵][10]The World Heritage Committee, Decisions Adopted by the World Heritage Committee at Its 39th Session (Bonn, 2015). 5. [↵][11]1. B. Williams , Bob Brown says UNESCO decision on Tasmanian World Heritage Forests is a bittersweet victory, Courier-Mail (24 June 2014). [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5 [6]: pending:yes [7]: #xref-ref-1-1 View reference 1 in text [8]: #xref-ref-2-1 View reference 2 in text [9]: #xref-ref-3-1 View reference 3 in text [10]: #xref-ref-4-1 View reference 4 in text [11]: #xref-ref-5-1 View reference 5 in text

Lotass och läsmaskinen

Lotass and the Reading Machine: on Reading Mechanisms in Lotta Lotass’ Fjärrskrift.
 The American modernist Bob Brown (1886–1959) had a vision of modernising the way we read by moving away from the traditional book medium. He proposed a reading machine to revolutionise the literary experience, in the same manner that the ”talkies” revolutionised the experience of film. In her work Fjärrskrift (”Distant Writing” or ”Teleprinter”) Lotta Lotass (1964–) creates a reading experience which resembles Brown’s vision. Fjärrskrift is a work that makes use of three different media – a 50-meter-long teleprinter strip, and two filmed versions distributed in cinemas and published online – portraying how the strip is made through a teleprinter.
 Utilising Lars Elleström’s theory of intermediality, this article investigates various connections between the three different media versions of Fjärrskrift and how the work distances itself from the traditional book medium. Most prominently, the article questions the effect the medial implications have on the reading process, and the mechanisms attached to it.
 I conclude that Fjärrskrift, rather than offering a revolutionary alternative to the book medium, creates an uncomfortable reading experience that put focus on the process of reading as such.

Abstract 3536: Targeting β-catenin with a Dicer-substrate siRNA (DsiRNA) in a sleeping beauty transposon-driven murine hepatoblastoma model

Abstract Hepatoblastoma (HB), the commonest pediatric liver tumor is frequently associated with an N-terminal deletion in the CTNNB1 gene, which encodes stable β-catenin and promotes nuclear localization and transactivation activity. In 80% of patients, nuclear localization of β-catenin and Yes Associated Protein (YAP), a Hippo-related transactivator, is seen together. Further, stable hepatic co-expression of Δ90-CTNNB1 and active-YAP in mice causes rapid and aggressive HB. Dicer-substrate siRNAs (DsiRNAs) are potent RNA interference (RNAi) triggers that that are efficacious in preclinical tumor models of diverse origin, and are currently under clinical evaluation. To determine if CTNNB1-targeting DsiRNAs have potential as a therapy in HB, we encapsulated this oligonucleotide payload into lipid nanoparticles (LNPs), and systemically administered into mice bearing CTNNB1/YAP-induced HB. The LNP platform used, termed EnCore (because of its specific Envelope and Core lipid components), enables high encapsulation efficiency, long-term stability, and consistent analytical criteria. Downstream of LNP-mediated DsiRNA delivery, both qPCR and in situ hybridization were used to visualize changes in CTNNB1 expression in both tumor and normal liver. Robust and specific silencing of CTNNB1 mRNA was achieved in the tumors. The distribution of mRNA knockdown within each tumor nodule suggests efficient extravasation and internalization of the LNP and its payload into the tumor parenchyma, in contrast to previous reports of vascular-channel limited nanoparticle accumulation in tumors. Intriguingly, a “liver-centric” LNP formulation, which delivers cargo efficiently to a normal liver due to rapid hepatic extraction and apolipoprotein-mediated internalization, was inactive in the tumors. Further evaluation demonstrated efficacy of β-catenin targeting in this model. In conclusion, we report a highly relevant modality of RNAi delivery in a mouse model of hepatoblastoma to target a classically-undruggable oncogene. Citation Format: Marc T. Abrams, Junyan Tao, Shanthi Ganesh, Wendy Cyr, Bo Ying, Martin Koser, Rokhand Arvan, Girish Chopda, Hank Dudek, Cheng Lai, Weimin Wang, Bob Brown, Satdarshan Monga. Targeting β-catenin with a Dicer-substrate siRNA (DsiRNA) in a sleeping beauty transposon-driven murine hepatoblastoma model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3536. doi:10.1158/1538-7445.AM2015-3536

Abstract 3533: Systemic delivery of CTNNB1 Dicer-substrate siRNAs (DsiRNAs) leads to efficient oncogene silencing in diverse tumor types of extra hepatic origin

Abstract The β-catenin/Wnt pathway is consistently activated in human tumors, including >50% of hepatocellular carcinomas (HCC) and >80% of colorectal cancers (CRC). This is often caused directly by tumorigenic mutations in the CTNNB1 gene, which encodes β-catenin protein. Preclinical evidence in genetic cancer models strongly suggests that inhibiting β-catenin function would yield therapeutic benefit to many cancer patients. Since β-catenin is very challenging to target via conventional modalities, no efficacious therapy targeting β-catenin has emerged despite decades of research. RNA interference (RNAi) technology has enabled the inhibition of previously undruggable targets at the mRNA level and has advanced to late-stage clinical development for several indications. However, the clinical application of RNAi has proven to be most successful for targeting mRNAs in the normal liver, and challenges remain with developing formulations that efficiently deliver to extra-hepatic tumors. Here we describe the development and characterization of a platform to treat tumors of diverse primary tissue origin and metastatic location with CTNNB1-targeting DsiRNA. Tumor types tested included xenograft tumors of colorectal origin (CRC), experimental melanoma lung metastases, and difficult-to-transfect leukemia cells which have infiltrated the spleen. In addition to strong silencing of CTNNB1 mRNA, >75% inhibition of tumor growth was observed for a CRC xenograft model. This was achieved by formulating the DisRNA payload in a lipid nanoparticle (LNP) platform termed EnCore (because of its specific Envelope and Core lipid components). EnCore activity against multiple tumors was further improved by optimizing critical cationic lipid and PEG-lipid components. Importantly, studies in knockout mice demonstrate that in vivo tumor activity is independent of Apolipoprotein E, which has been widely described as an essential endogenous ligand for internalization of LNPs into hepatocytes. This strongly suggests that Encore-mediated delivery to tumors in vivo is independent of the ApoE/LDLR system. DCR-MYC, an EnCore-delivered DsiRNA targeting MYC mRNA, is currently in Phase I clinical trials. Further evaluation of LNP-delivered DsiRNAs in PK/PD and efficacy models, including PDX and GEMM will guide a clinical development strategy for CTNNB1 DsiRNA. Citation Format: Shanthi Ganesh, Bo Ying, Martin Koser, Wendy Cyr, Girish Chopda, Hank Dudek, Cheng Lai, Weimin Wang, Bob Brown, Marc T. Abrams. Systemic delivery of CTNNB1 Dicer-substrate siRNAs (DsiRNAs) leads to efficient oncogene silencing in diverse tumor types of extra hepatic origin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2015-3533

Experiences of coming to law: An Interview with Bob Brown on the Tasmanian wilderness society as client in the Tasmanian Dam Case

While histories of law tend to examine the lawyers and judges involved through readings of the texts of transcripts and judgments, this contribution contextualises and presents a different and rarer artefact: the recollections of a client seeking to become part of a divisive, nationally significant case. The text here is a transcript that combines two interviews I conducted with Dr Bob Brown about his experience as head of the Tasmanian Wilderness Society when it sought to appear as amicus curiae before the High Court in the Tasmanian Dam Case. As an historical artefact, this interview tells a story of coming to law: Brown's recollections and explanation of the Wilderness Society's aims, expectations and experience before, during and after the matter. This contribution contextualises and presents the interview. To conclude, it suggests that among many readings of this text, it can be usefully read as a story about legalism; here, the encounter and disjuncture between environmental values and legal form.

Digital modernism: making it new in new media

Introduction Chapter 1 - Close Reading: Marshall McLuhan, From Modernism to Media Studies Chapter 2 - Reading Machines: Machine Poetry and Excavatory Reading in William Poundstone's Electronic Literature and Bob Brown's Readies Chapter 3 - Speed Reading: Super-Position and Simultaneity in Young-hae Chang Heavy Industries's Dakota and Ezra Pound's Cantos Chapter 4 - Reading the Database: Narrative, Database, and Stream of Consciousness Chapter 5 - Reading Code: The Hallucination of Universal Language from Modernism to Cyberspace Coda - Rereading: Digital Modernism in Print, Mark Z. Danielewski's Only Revolutions

Abstract B222: Dicer substrate siRNAs to MYC, B-catenin, and other target genes effectively induce in vivo target gene knockdown and tumor inhibition.

Abstract Although there are now multiple successful examples of targeted therapeutics in cancer, many key protein targets have remained largely ‘undruggable’, including transcription factors such as B-catenin (CTNNB1) and MYC. B-catenin mediates Wnt signaling, which is overactive in many cancers including hepatocarcinoma (HCC). RNAi offers a way to reach such undruggable targets by inhibiting their expression at the mRNA level. Dicer substrate siRNAs (“DsiRNAs”) can be particularly effective for gene silencing. DsiRNAs are longer than conventional siRNAs, and therefore are substrates for processing by Dicer, after which the product RNA duplexes are incorporated into RISC, leading to target mRNA knockdown. We have used DsiRNAs to target B-catenin, MYC, and other key genes in HCC and other cancers. Through large-scale DsiRNA screening, we have identified a series of high potency DsiRNAs with picomolar to sub-picomolar IC50 values for mRNA knockdown. Lead DsiRNAs fully tolerated extensive 2’-OMe modification, retaining high potency, and lacked detectable immunostimulatory activity. To test the effect of target gene knockdown on tumor growth in vivo, we used a lipid nanoparticle (LNP) delivery system. LNP/DsiRNA particles effectively delivered to tumors in mouse tumor models, leading to rapid knockdown of target gene mRNA and protein. Knockdown of B-catenin, MYC, and other target genes strongly inhibited tumor growth. B-catenin knockdown also strongly reduced expression of the B-catenin-regulated genes Axin2 and MYC, a potential mechanism for tumor inhibition. In summary, we have developed high potency DsiRNAs to cancer target genes, and effectively delivered these DsiRNAs to tumors in vivo, resulting in inhibition of target gene expression and inhibition of tumor growth. DsiRNA therapeutics show promise as novel agents for reaching traditionally undruggable target genes. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B222. Citation Format: Hank Dudek, Kathleen Wortham, Rokhand Arvan, Anee Shah, Bo Ying, Wendy Cyr, Hailin Yang, Wei Zhou, Utsav Saxena, Yi Zhou, Rohan Diwanji, Ben Holmes, Ruchir Farkiwala, Aalok Shah, Bob Brown. Dicer substrate siRNAs to MYC, B-catenin, and other target genes effectively induce in vivo target gene knockdown and tumor inhibition. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B222.

Some Thoughts on the Future of Stroke

David Blacker speaks to Simi Thankaraj, Assistant Commissioning Editor David Blacker was born in Bunbury, Western Australia, and studied medicine at the University of Western Australia (Perth, Australia), graduating in 1991. He undertook physician and neurology specialist training in Perth. He developed an interest in acute stroke therapies early in his career, and was involved with cases treated with intra-arterial techniques in the mid-1990s. Like many young Australian neurologists, he then undertook 2 years of fellowship training at the Mayo Clinic (MN, USA). There, Blacker was mentored by Professors Bob Brown and Eelco Wijdicks, and further developed interests in stroke and acute hospital-based neurology. His return to Australia in 2003 coincided with the approval of tissue plasminogen activator as a stroke therapy. He helped establish the acute stroke team at Sir Charles Gairdner Hospital (Perth, Australia), and has continued to work on the development of stroke services locally, and across the geoprahically enormous state of Western Australia ever since. In his role as a Clinical Associate Professor of Neurology at the University of Western Australia, he is actively involved in teaching, and has a wide range of research interests mainly in acute stroke, but also in neurorehabilitation. In this interview, he shares some thoughts on the future of stroke treatment and research.

Machine Poetics and Reading Machines: William Poundstone's Electronic Literature and Bob Brown's Readies

A recent essay in the New York Times Book Review titled “The Godfather of the E-Reader” suggests, “if you’re searching for a godfather of the reading machine, you might look past Jeff Bezo and Steve Jobs to a nearly forgotten early-twentieth-century writer and impresario named Bob Brown” (Schuessler 27). Robert Carlton (Bob) Brown, an American experimental writer of the modernist period, shared a social network with the likes of Williams Carlos Williams and Gertrude Stein, and planned to build a reading machine that would speed up the pace of reading literature and thereby change the kind of literature we read. He called his machine “The Readies.” “Revolutionize reading and a Revolution of the Word will be inkless achieved,” he writes (Readies 35). The Readies was never built and has been nearly forgotten by literary history; so too has Brown remained on the margins of literary history. But recent events in the evolution of digital reading machines prompt excavation of the Readies and reconsideration of it as a vital part of the genealogy of contemporary technopoetics and literary practices. The essay pursues such excavation by reading the Readies in relation to recent machine-informed poetics of electronic literature. I present Brown as godfather of a contemporary generation of writers experimenting with the newest reading machine, the digital computer. I claim

Bob Brown, ““Inforg””: The ““Readies”” at the Limits of Modernist Cosmopolitanism

Bob Brown’s 1930–1931 reading machine hyperbolically attempts to mradicate the difference between human and book, as well as between local reading and global reading. Brown could thus be described somewhat anachronistically as an example of what Luciano Floridi refers to as an “inforg,” an “interconnected organism . . . sharing with biological agents and engineered artifacts a global environment ultimately made of information, the infosphere.” Brown’s reading machine, I suggest most provocatively, fashions readers and writers as global word processors avant le lettre, or rather post le lettre. The reading machine implies that electronically transmitted language will alter the nature of literary form; at the same time, it parodies the Americanization of the wor(l)d brought about by new technologies of communication.

Growing Together? Land Rights and the Northern Territory Intervention

According to the Oxford English Dictionary, the term coalition comes from the Latin coalescere or ‘coalesce’, meaning “come or bring together to form one mass or whole”. Coalesce refers to the unity affirmed as something grows: co – “together”, alesce – “to grow up”. While coalition is commonly associated with formalised alliances and political strategy in the name of self-interest and common goals, this paper will draw as well on the broader etymological understanding of coalition as “growing together” in order to discuss the Australian government’s recent changes to land rights legislation, the 2007 Emergency Intervention into the Northern Territory, and its decision to use Indigenous land in the Northern Territory as a dumping ground for nuclear waste.