Journal articles on the topic 'Weinell, William E'

Tekst dotyczy filmu The Flicker (1966), kinematograficznego debiutu zmarłego niedawno Tony’ego Conrada – wybitnego muzyka, odważnego reżysera, głównej postaci nowojorskiego undergroundu lat 60. Autor przedstawia kluczowy film amerykańskiej awangardy lat 60. na szerokim tle kultury epoki: od ówczesnych zjawisk w sztukach wizualnych, przez wątki amerykańskiej kultury masowej, po tendencje nowojorskiej sceny muzyki eksperymentalnej. Szeroka panorama kulturowych zjawisk układa się estetykę nowego, bezpośredniego oddziaływania dzieła sztuki na odbiorcę, oddziaływania, dla którego modelem staje się działanie substancji psychoaktywnych. Estetyka ta rodzi się pomiędzy koncepcjami Johna Cage’a, Norberta Weinera oraz Williama Burroughsa. Autor w końcowej części tekstu zestawia The Flicker z innymi filmami eksperymentalnymi z tego okresu, kładąc nacisk na te powstające w środowisku Fluxusu.

A. K. Dickinson, P. J. Lee, and P. J. Rogers. Learning History. London: Heinemann Educational Books, Ltd., 1984. Pp. x, 230. Paper, $14.00; Donald W. Whisenhunt. A Student's Introduction to History. Boston: American Press, 1984. Pp. 31. Paper, $2.95. Review by Robert A. Calvert of Texas A&M University. Ronald J. Grele. Envelopes of Sound: The Art of Oral History. Chicago: Precendent Publishing, Inc. 1985. Second Edition. Pp. xii, 283. Cloth, $20.95. Review by Marsha Frey of Kansas State University. Reginald Horsman. The Diplomacy of the New Republic, 1776-1815. Arlington Heights, Illinois: Harlan Davidson., 1985. Pp. vii, 153. Paper, $7.95. Review by William Preston Vaughn of North Texas State University. Lynn Y. Weiner. From Working Girl to Working Mother: The Female Labor Force in the United States, 1820-1980. Chapel Hill and London: The University of North Carolina Press, 1985. Pp. xii, 187. Cloth, $17.95. Review by E. Dale Odom of North Texas State University. Mary Custis Lee de Butts, ed. Growing Up in the 1850s: The Journal of Agnes Lee. Chapel Hill and London: University of North Carolina Press, 1984. Pp. xx, 151. Cloth, $11.95. Review by Clarence L. Mohr of Tulane University. Raymond A. Mohl. The New City: Urban America in the Inudstrial Age, 1860-1920. Arlington Heights, Illinois: Harlan Davidson, Inc., 1985. Pp. 242. Paper, $8.95; Melvyn Dubofsky. Industrialism and the American Worker, 1865-1920 (Second Edition). Arlington Heights, Illinois: Harlan Davidson, Inc., 1985. Pp. 167. Paper, $8.95. Review by Richard L. Means of Mountain View College. David D. Lee. Sergeant York: An American Hero. Lexington, Kentucky: University Press of Kentucky, 1985. Pp. 162. Cloth, $18.00. Review by Richard Selcer of Mountain View College. Studs Terkel. "The Good War": An Oral History of World War Two. New York: Pantheon Books, 1984. Pp. xv, 589. Cloth, $19.95. Review by William Vance Trollinger of The School of the Ozarks. David W. Reinhard. The Republican Right Since 1945. Lexington: The University Press of Kentucky, 1983. Pp. ix, 294. Cloth, $25.00. Review by James C. Williams of Gavilan College. Christina Larner. Witchcraft and Religion: The Politics of Popular Belief. New York: Basil Blackwell, 1984. Pp. xi, 172. Cloth, $24.95. Review by K. Gird Romer of Kennesaw College. F. R. H. DuBoulay. Germany in the Later Middle Ages. New York: St. Martin's Press, Inc., 1984. Pp. xii, 260. Cloth, $30.00; Joseph Dahmus. Seven Decisive Battles of the Middle Ages. Chicago: Nelson Hall, 1984. Pp. viii, 244. Cloth, $23.95. Review by Robert H. Welborn of Clayton College. Gerald Fleming. Hitler and the Final Solution. With an Introduction by Saul Friedlaender. Berkeley: University of California Press, 1984 (German, 1982). Pp. xxxvi, 219. Cloth, $15.95; Sarah Gordon. Hitler, Germans, and the "Jewish Question." Princeton: Princeton University Press, 1984. Pp. xiv, 412. Cloth, $40.00; Limited Paper Edition, $14.50. Review by Thomas T. Lewis of Mount Senario College. Alan Cassels. Fascist Italy. Arlington Heights, Illinois: Harlan Davidson, Inc., 1985. Second Edition. Pp. x, 146. Paper, $8.95. Review by Lawrence S. Rines of Quincy Junior College; Additional response by Lawrence S. Rines of Quincy Junior College.

RÉSUMÉLa maladie de Parkinson est une affection chronique neurologique dégénérative qui affecte environ un million de personnes en Amérique du Nord. Or, tous les patients atteints de la maladie doivent être bien informés; ils ont surtout besoin d'en comprendre les symptômes et la progression pour être en mesure de l'affronter efficacement. Parkinsons disease: A complete guide for patients and families par Weiner, Shulman et Lang (2001) constitue une ressource précieuse pour les patients, leurs familles et les soignants qui travaillent auprès de cette population. Le livre fournit une bonne quantité d'information biomédicale sur la maladie. Les données sont communiquées selon un modèle élémentaire qui éduque le lecteur mais qui lui permet aussi de s'assumer et qui lui aide éventuellement à faire face à sa maladie. Le livre présente toutefois certaines faiblesses qu'il faut signaler, dont entre autres, le fait que l'approche biomédicale écarte les questions psychosociales reliées à la maladie. Une autre faiblesse porte sur l'absence de mention des efforts scientifiques récents dans d'autres secteurs que la médecine clinique. Enfin, il porte peu d'attention aux interventions thérapeutiques qui ne sont pas du domaine médical ou pharmacologique. Les auteurs renvoient à d'autres sources les lecteurs qui souhaitent se renseigner sur ces éléments.

Abstract The transcription factor NRF2 is a master regulator of cellular responses to oxidative stress, contributing to the pathogenesis of autoimmunity, metabolic disorders, and neurodegeneration. Somatic alterations in the NRF2 pathway also contribute to the growth and metastasis of many cancer types including ~30% of lung cancers. Still, the activation of NRF2 has frequently been observed in the absence of known genomic alterations, indicating that other pathways may drive its dysregulation. Further, approaches to target NRF2 pharmacologically have remained elusive. Here, we conducted a screen that identified a small molecule, ML329, exhibiting selective cytotoxicity in cells exhibiting NRF2 dependency and synthetic lethality to NRF2 pathway mutations across 489 cell lines. Surprisingly, we find that melanomas—which rarely have somatic mutations in the NRF2 pathway—were commonly sensitive to ML329. Melanomas were seen to exhibit NRF2-dependent metabolomic and transcriptional programs through the transcriptional activation of the adaptor protein p62/SQSTM1 by the melanocyte master regulator and oncoprotein MITF. This pathway was found to be conserved among all cancers characterized by genomic alterations of the MiT family (MITF, TFEB and TFE3) including subsets of renal cell carcinomas, pediatric sarcomas, and uveal and cutaneous melanomas. Our data identify a previously unrecognized, non-canonical mechanism of NRF2 activation by the MiT family, clarifying the regulation of NRF2 in pathologic and physiologic contexts. Pharmacologic inhibition of NRF2 could be valuable in the treatment of conditions with MITF family dysregulation. Citation Format: Xinbo Luo, Bart Lutterbach, Priya Pancholi, Yeon Sook Choi, Xiao Liu, Phillip Munson, Saqib Faisal, David A. Whipple, Robert A. Smith, Warren S. Weiner, David K. Johnson, Myriam Boukhali, Nicole S. Persky, Matthew G. Rees, Shunsuke Kitajima, David Barbie, Anuradha Roy, Michael Baltezor, Lian Rajewski, William McGuinness, John Haslam, Ananthan Sadagopan, Charles H. Yoon, Cory M. Johannessen, Christine G. Lian, Jason L. Hornick, Srinivas R. Viswanathan, David Liu, Vicki Nienaber, Wilhelm Haas, Frank J. Schoenen, David E. Fisher, Rizwan Haq. A non-canonical MiT/TFE-dependent NRF2 program is a druggable vulnerability in multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1706.

J. Lennart Berggren and Alexander Jones, Ptolemy's Geography: An Annotated Translation of the Theoretical Chapters. By Karin Tybjerg 194Natalia Lozovsky, ‘The Earth is Our Book’: Geographical Knowledge in the Latin West ca. 400–1000. By Evelyn Edson 196David Cantor (ed.), Reinventing Hippocrates. By Daniel Brownstein 197Peter Dear, Revolutionizing the Sciences: European Knowledge and Its Ambitions, 1500–1700. By John Henry 199Paolo Rossi, Logic and the Art of Memory: The Quest for a Universal Language. By John Henry 200Marie Boas Hall, Henry Oldenburg: Shaping the Royal Society. By Christoph Lüthy 201Richard L. Hills, James Watt, Volume 1: His Time in Scotland, 1736–1774. By David Philip Miller 203René Sigrist (ed.), H.-B. de Saussure (1740–1799): Un Regard sur la terre, Albert V. Carozzi and John K. Newman (eds.), Lectures on Physical Geography given in 1775 by Horace-Bénédict de Saussure at the Academy of Geneva/Cours de géographie physique donné en 1775 par Horace-Bénédict de Saussure à l'Académie de Genève and Horace-Bénédict de Saussure, Voyages dans les Alpes: Augmentés des Voyages en Valais, au Mont Cervin et autour du Mont Rose. By Martin Rudwick 206Anke te Heesen, The World in a Box: The Story of an Eighteenth-Century Picture Encyclopedia. By Richard Yeo 208David Boyd Haycock, William Stukeley: Science, Religion and Archaeology in Eighteenth-Century England. By Geoffrey Cantor 209Jessica Riskin, Science in the Age of Sensibility: The Sentimental Empiricists of the French Enlightenment. By Dorinda Outram 210Michel Chaouli, The Laboratory of Poetry: Chemistry and Poetics in the Work of Friedrich Schlegel. By David Knight 211George Levine, Dying to Know: Scientific Epistemology and Narrative in Victorian England. By Michael H. Whitworth 212Agustí Nieto-Galan, Colouring Textiles: A History of Natural Dyestuffs in Industrial Europe. By Ursula Klein 214Stuart McCook, States of Nature: Science, Agriculture, and Environment in the Spanish Caribbean, 1760–1940. By Piers J. Hale 215Paola Govoni, Un pubblico per la scienza: La divulgazione scientifica nell'Italia in formazione. By Pietro Corsi 216R. W. Home, A. M. Lucas, Sara Maroske, D. M. Sinkora and J. H. Voigt (eds.), Regardfully Yours: Selected Correspondence of Ferdinand von Mueller. Volume II: 1860–1875. By Jim Endersby 217Douglas R. Weiner, Models of Nature: Ecology, Conservation and Cultural Revolution in Soviet Russia. With a New Afterword. By Piers J. Hale 219Helge Kragh, Quantum Generations: A History of Physics in the Twentieth Century. By Steven French 220Antony Kamm and Malcolm Baird, John Logie Baird: A Life. By Sean Johnston 221Robin L. Chazdon and T. C. Whitmore (eds.), Foundations of Tropical Forest Biology: Classic Papers with Commentaries. By Joel B. Hagen 223Stephen Jay Gould, I Have Landed: Splashes and Reflections in Natural History. By Peter J. Bowler 223Henry Harris, Things Come to Life: Spontaneous Generation Revisited. By Rainer Brömer 224Hélène Gispert (ed.), ‘Par la Science, pour la patrie’: L'Association française pour l'avancement des sciences (1872–1914), un projet politique pour une société savante. By Cristina Chimisso 225Henry Le Chatelier, Science et industrie: Les Débuts du taylorisme en France. By Robert Fox 227Margit Szöllösi-Janze (ed.), Science in the Third Reich. By Jonathan Harwood 227Vadim J. Birstein, The Perversion of Knowledge; The true Story of Soviet Science. By C. A. J. Chilvers 229Guy Hartcup, The Effect of Science on the Second World War. By David Edgerton 230Lillian Hoddeson and Vicki Daitch, True Genius: The Life and Science of John Bardeen, the Only Winner of Two Nobel Prizes in Physics. By Arne Hessenbruch 230Stephen B. Johnson, The Secret of Apollo: Systems Management in American and European Space Programs, John M. Logsdon (ed.), Exploring the Unknown: Selected Documents in the History of the U.S. Civil Space Program. Volume V: Exploring the Cosmos and Douglas J. Mudgway, Uplink-Downlink: A History of the Deep Space Network 1957–1997. By Jon Agar 231Helen Ross and Cornelis Plug, The Mystery of the Moon Illusion: Exploring Size Perception. By Klaus Hentschel 233Matthew R. Edwards (ed.), Pushing Gravity: New Perspectives on Le Sage's Theory of Gravitation. By Friedrich Steinle 234Ernest B. Hook (ed.), Prematurity in Scientific Discovery: On Resistance and Neglect. By Alex Dolby 235John Waller, Fabulous Science: Fact and Fiction in the History of Scientific Discovery. By Alex Dolby 236Rosalind Williams, Retooling: A Historian Confronts Technological Change. By Keith Vernon 237Colin Divall and Andrew Scott, Making Histories in Transport Museums. By Anthony Coulls 238

Abstract Background: The limitations of current biomarkers for predicting outcome to anti-PD1 therapy, such as measuring tumor PDL1, are well-known. Evaluation of the PD1-PDL1 interaction as a potential biomarker has not been explored because of the lack of a suitable assay. We previously reported on a novel technology called the LIRECAP (Ligand-Receptor Complex-binding Aptamer) assay that quantifies the fractional occupancy of a receptor by its ligand (PMID: 31383650). LIRECAP assay is based on two RNA aptamers with differential binding to the unoccupied receptor vs. the ligand-receptor complex, where the ratio of aptamer binding reflects fractional occupancy. Here, we report the generation of RNA aptamers for use in a LIRECAP assay to quantify PD1-PDL1 interactions in tumor. Methods: SELEX: RNA aptamers were enriched using a variation of SELEX that consisted of pre-clearing followed by a positive selection against human PD1, PDL or the PD1-PDL1 complex. Target-bound aptamers were extracted, amplified with SEL2 primers and transcribed. After eight rounds, enriched aptamers were sequenced and lead aptamers were identified. Assessing target binding: Dynabeads were coated with recombinant PD1 alone or PDL1 alone. Complex-coated beads were made by incubating PD1-bound beads with PDL1. Beads were formalin-fixed to mimic biospecimens and prevent PD1-PDL1 dissociation. Aptamers were added to beads, unbound aptamers washed off and bound aptamers extracted and quantified by SYBR green-based RT-qPCR using SEL2 primers. Binding of each aptamer was normalized to the binding of unselected aptamer library (Rd0). Results: (1) A progressive enrichment of unique sequences was seen in all the three SELEX (PD1, PDL1, Complex) with maximum enrichment reached between rounds 4 and 5. (2) Binding of aptamers: Most of the lead candidates showed predominant binding to the targets against which they were enriched. (a) Three out of four lead aptamers from the PD1 SELEX showed significantly higher binding to unoccupied PD1 than to PD1-PDL1 complex (p<0.05). (b) Two out of five lead aptamers from the PDL1 SELEX showed significantly higher binding to unoccupied PDL1 compared to the complex (p<0.05). (c) Four out of five lead aptamers from the Complex SELEX showed significantly higher binding to PD1-PDL1 complex than to unoccupied PD1 (p<0.05). None of these aptamers showed cross-reactivity to unoccupied PDL1. Conclusions and Significance: Novel RNA aptamers with differential specificity towards PD1, PDL1 or PD1-PDL1 complex have been successfully created for use in a LIRECAP assay that will be used to quantify the fractional occupancy of PD1 by PDL1 in tumor biospecimens. Studies assessing whether the resulting assay can predict response to anti-PD1 therapy are expected to begin shortly. Citation Format: Suresh Veeramani, Travis Fischer, William H. Thiel, George J. Weiner. Generation of RNA aptamers for measuring fractional occupancy of PD1 by PDL1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2804.

Abstract Introduction: In this study, we investigated the prognostic role of the immune cell state atlas in predicting therapeutic benefits of patients treated with immune checkpoint inhibitors (ICI) within the ORIEN network of 18 collaborating cancer centers under the Total Cancer Care protocol. Methods: We utilized RNA-seq data of 926 samples generated from 875 individuals. Gene expression data were deconvoluted for immune cell states using the Carcinoma EcoTyper software. We then conducted a series of survival analyses to test the association between survival outcomes and predicted cell types and states in five malignant tumors: Genitourinary (GU), Gastrointestinal (GI), Thoracic (THO), Cutaneous (CUT), Head & Neck (H&N). The regularized Cox regression model in R package ‘glmnet’ was then applied to select the complementary pathway signatures (including gene ontology and KEGG pathways) to the immune cell states in predicting survival outcomes. We also explored the immune-related long non-coding RNAs (lncRNA) as potential biomarkers for cell states and patient outcomes. Results: EcoTyper analysis revealed that 692 (~80%) of patients were assigned to the 10 pre-identified Carcinoma Ecotypes (CE1 to CE10) or cell state atlas group. Overall, two immune deficiency ecotype patient groups (CE1 and CE2) pre-identified based on the independent training data were linked to worse survival, while two proinflammatory ecotype groups (CE9 and CE10) were associated with favorable surxvival. Those ecotype groups showed strong prognostic significance in predicting OS in melanoma and H&N. Meanwhile, CE6, a non-neoplastic tissue enriched cell subtype, was also found to be highly associated with longer OS in H&N and GU. CE7, an age-related mutation patient subgroup, contributed to shorter survival in both melanoma and GI. We also found that a subset of activated B cell state and the exhausted/effector CD4 T cell state were significantly associated with patient survival in melanoma and GU, respectively. The penalized Cox regression model revealed that β-catenin signaling pathway, P53 pathway and heme metabolism in the MSigDB Hallmark gene sets are the most complementary pathways to the ecotype scores in multiple cancer types. In additional, multiple pathways in KEGG such as endocytosis were found to jointly contribute to the ecotype-pathway composite prognostic model. In anazlying immune-related lncRNA biomarkers, we highlighted the prognostic role of NKILA in our dataset, which has been studied to promote tumor immune evasion. Conclusion: Our analysis has successfully established the utility of immune cell state atlas in predicting therapeutic benefits with ICIs. We expect that the discovered complementary signatures in the cancer-cell compartment will also lead to a novel spectrum of tumor-based biomarkers to ICI. Citation Format: Tingyi Li, Vineeth Sukrithan, Aakrosh Ratan, Martin McCarter, John Carpten, Howard Colman, Alexandra P. Ikeguchi, Xuefeng Wang, Igor Puzanov, Susanne Dalton, Michelle Churchman, Patrick Hwu, Paulo C. Rodriguez, William S. Dalton, George J. Weiner, Ahmad Tarhini. The immune cell state atlas analysis predicts therapeutic benefits with immune checkpoint inhibitors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5703.

Abstract Background: Emerging literature has identified key immune cell populations that appear to significantly impact immune activation or suppression in patients with cancer. We investigated candidate populations and their differential infiltration within tumors as estimated from mRNA co-expression levels of corresponding cellular markers. Methods: We utilized clinical and transcriptomic data from patients with melanoma, urothelial, ovarian, and pancreatic carcinomas enrolled in the Total Cancer Care Protocol (NCT03977402) to which patients provided a written informed consent. We analyzed mRNA co-expression levels of biomarkers defining stem-like tumor-infiltrating lymphocytes (TILs) (TCF7, IL7R, CXCR5, CD28, and CD27), tissue-resident memory (TRM) T cells (CD69 and CD103), early dysfunctional T cells (PD1+, CCR5+, TCF7+, TIM3-), late dysfunctional T cells (PD1+, CD38+, CD39+, CD101+, TIM3+), activated-potentially anti-tumor (APA) T cells (PD1+, CD27+, CD28+, CD137+, GITR+), and Butyrophilin 3 A (BTN3A) isoforms (BTN3A1, BTN3A2, BTN3A3). Mann-Whitney U or Kruskal-Wallis H tests were used to compare median gene expression signature scores between immunotherapy (IO) responders (> 2 years survival) and non-responders (< 2 years survival). Cox regression was used to assess 2-year survival outcomes following immunotherapy. Results: We found a significant difference in the estimated infiltration of APA T-cells in melanoma (P = 4.67 Χ10−12 and P = 5.80 Χ10−12) and in urothelial carcinoma (P = 1.86 Χ10−09 and P = 1.38 Χ10−09) as compared to ovarian and pancreatic tumors, respectively. There was less TRM T-cell infiltration in ovarian compared to melanoma (P = 2.23 Χ10−8), urothelial (P = 3.86 Χ10−28) and pancreatic (P = 7.85 Χ10−9). A similar trend was seen with stem-like T-cells, early dysfunctional T cells, and late dysfunctional T cells. Differences in the expression of BTN3A isoforms were less apparent between the different tumors, with a trend towards higher expression in melanoma. In melanoma, a higher density of stem-like TIL, TRM, early dysfunctional T cells, late dysfunctional T cells, activated-potentially anti-tumor T cells, and BTN3A isoforms were associated with improved survival (P = 0.0075, 0.00059, 0.013, 0.005, 0.0016 and 0.041, respectively). A higher density of stem-like TIL was associated with improved survival in the urothelial cohort (P = 0.028). TRM gene signature had the best AUCROC as a moderate predictor of survival in our melanoma cohort (AUROC = 0.65); Examining the 6 signatures in public datasets of IO treated melanoma patients, they were similarly predictive of survival (AUROC of 0.61 - 0.64). Conclusions: Our results support a higher infiltration of key cellular elements related to immune activation within immunogenic versus non-immunogenic tumors supporting a central role in anti-tumor immune response. Citation Format: Ahmad A. Tarhini, Islam Eljilany, Sam Coleman, Dale J. Hedges, Martin McCarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle Churchman, Patrick Hwu, William S. Dalton, George J. Weiner, Aik Choon Tan, Jose R. Conejo-Garcia, Paulo C. Rodriguez. Differential infiltration of key immune cell populations across malignancies varying by immunogenic potential and likelihood of response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 71.

Abstract Background: Neoantigen-based personalized cancer vaccines carry significant promise in treating solid malignancies. However, there are uncertainties regarding the choice between the primary or the metastatic tumor for neoantigen prediction in individual patients. Here, we conducted a thorough examination of somatic variations in 676 patients who had paired primary and metastatic solid tumors. Methods: Patients were enrolled in the Total Cancer Care protocol (NCT03977402) to which patients provided an IRB-approved written informed consent within the Oncology Research Information Exchange Network (ORIEN). Whole-exome sequencing of 756 primary and metastatic tumor pairs was performed (N = 676 patients). These included Genitourinary (n=83), Gynecological (n=97), Gastrointestinal (n=213), Thoracic (n=33), Cutaneous (n=24), Breast (n=108), Endometrial (n=49), Sarcoma (n=35), Head-and-Neck (n=106) and others (n=8). The data was analyzed through the ORIEN AVATAR Molecular Analysis Pipeline for somatic mutation variant detection and variant annotation. In this analysis, we focused on somatic events that result in an in-frame alteration (such as missense, in-frame deletion and in-frame insertion) and out-of-frame protein-altering mutations (such as frameshifts, de novo start, out-of-frame, and nonstop gain). Clonal population structure was determined based on pyclone-vi. Results: For in-frame events, bladder cancer, melanoma, and gynecological cancers shared close to 75% of the mutations between paired primary and metastatic cases. In contrast, sarcoma and thyroid cancer had a low overlap (~ 25%) of variants. For out-of-frame events, these events tend to have a lower proportion of shared somatic variants between primary and metastasis than in-frame variants. Oncogenic drivers (e.g., BRAF V600E, KRAS G12A, and TP53 loss-of-function) were highly likely to be present in both paired primary and metastatic tumors. Next, we performed additional analysis on evolutionary selection of protein-coding variants via dN/dS calculation. We found no significant global shift in dN/dS ratio between paired primary and metastatic tumors across malignancies. However, we found increased selection of protein-coding variants in brain and liver metastatic sites, which correlated with increased homologous recombination deficiency within these sites. Conclusions: Our analysis demonstrates genetic variations that exist when comparing paired primary and metastatic tumors that appear to vary by histology. Variants are potentially undergoing negative selection supported by the preferential loss of out-of-frame events in metastatic tumors and positive selection in specific metastatic sites. Overall, understanding the clonal structure will be key to neoantigen prediction for effective neoantigen-based vaccines. Citation Format: Alyssa Obermayer, Timothy Shaw, Darwin Chang, Joshua Davis, Jamie K. Teer, Xiaoqing Yu, Xuefeng Wang, Dale Hedges, Aik Choon Tan, Robert Rounbehler, Abdul Rafeh Naqash, Margaret Gatti-Mays, Aakrosh Ratan, Martin McCarter, Howard Colman, Igor Puzanov, Susanne Arnold, Michelle Churchman, Patrick Hwu, William Dalton, George Weiner, Jose Conejo-Garcia, Paulo C. Rodriguez, Bodour Salhia, Ahmad A. Tarhini. Analysis of clonal heterogeneity within paired primary and metastatic tumor samples of patients with solid tumors and implications for neoantigen-based personalized cancer vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3886.

Abstract Background: DNA replication and cell cycle regulation are frequently disrupted as part of a cancer’s progression toward uncontrolled proliferation, generating somatic copy number alterations (CNAs) and producing intratumoral heterogeneity that drives subsequent evolution. Structural variation and CNAs have been shown to impact epigenetic and chromatin states, but our ability to assess their impact on DNA replication timing (RT) and cell proliferation rates remains limited. Single-cell whole genome sequencing (scWGS) is a powerful method for studying clonal heterogeneity and CNAs, and has the potential to provide greater insight into DNA replication dynamics in aneuploid populations. However, computational identification of S-phase cells and distinguishing inherited somatic CNAs from transient DNA replication changes remain challenging. Methods: We present a new method, PERT, which uses a Bayesian framework to model read depth as a combination of somatic copy number, replication, and sequencing bias, enabling estimation of DNA replication profiles and cell cycle phase from scWGS data. Unlike previous approaches, PERT provides unbiased estimates of RT and cell cycle phase which allows for analysis of previously uncharacterized cell types using any scWGS platform. These unique properties enable PERT to perform novel analysis such as estimating clone-specific proliferation rates and studying the interplay between RT and somatic CNAs during tumor evolution. We applied PERT to a cohort of >50,000 scWGS cells obtained from a collection of genomically unstable breast and ovarian cell lines, xenografts and primary cancer tissues. Results: Clone RT profiles correlated with future copy number changes in serially passaged cell lines. Cell type was the strongest determinant of RT heterogeneity, while whole genome doubling (WGD) and mutational signature had weaker RT associations but were associated with accumulation of late S-phase cells. Recurrent CNAs affecting chromosome X had striking impact on RT, with loss of the inactive X allele shifting replication earlier, and loss of inactive Xq resulting in reactivation of Xp. Analysis of time series xenografts illustrated that cell cycle distributions approximate clone proliferation. This relationship enabled us to observe that highly proliferative clones were the most chemosensitive in cisplatin-treated xenografts and, separately, present novel evidence that WGD leads to slower proliferation. Conclusions: Our analysis implicates cell type as the strongest determinant of RT with chrX being the locus of highest RT variation due to X-inactivation. Separately, quantification of S-phase cells enables interrogation of the on- and off-treatment fitness of genetically distinct subclones. This work leads to better understanding of how DNA replication dynamics drive and are further modulated by genomic instability. Citation Format: Adam C. Weiner, Marc Williams, Hongyu Shi, Ignacio Vazquez-Garcia, Sohrab Salehi, Nicole Rusk, Sohrab P. Shah, Andrew McPherson. Single-cell DNA replication dynamics in genomically unstable cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 869.

Abstract Background: PD-L1 expression evaluated by immunohistochemistry (IHC) is a well-established predictor of anti-PD-L1/PD-1 cancer immunotherapy (CIT). The Phase II LCMC3 (NCT02927301) study evaluated pre-operative treatment (tx) with atezolizumab (anti-PD-L1) in pts with untreated early stage resectable NSCLC, achieving a 20% major pathologic response (MPR) rate (primary efficacy pts, n=143). A digital PD-L1 scoring method was developed to assess PD-L1 expression as a potential predictive marker for MPR in squamous and non-squamous tumor samples from LCMC3. Methods: Manual scoring was used to determine PD-L1 status on pre-tx biopsy samples using the tumor proportion score (TPS) with a positive threshold of TPS≥50 (22C3). Binary results were correlated with MPR and stratified by squamous/non-squamous histology. A digital pathology workflow for automated PD-L1 scoring was developed to yield a precise continuous PD-L1 TPS. Deep convolutional neural networks trained using pathologist annotations were used to detect individual cells within the tumor and tumor microenvironment and quantify their PD-L1 expression. These cell type predictions were used to compute a digital PD-L1 TPS. LCMC3 pts with available digital and manual PD-L1 scores were then used to assess the role of PD-L1 expression in predicting MPR. Results: PD-L1 scores were available for pre-tx biopsies from 108 pts. No significant difference in scores was seen between histological subtypes. At cutoff (Oct 15, 2021), TPS≥50 was seen in 41 (non-squamous, n=26 [39%]; squamous, n=15 [36%]) of 108 pts and was associated with MPR in non-squamous (odds ratio [OR], 28.6; P<0.001; Fisher’s exact test) but not squamous histology (OR, 1.3; P=1.0). Continuous digital PD-L1 scores (range: 0-100) were highly correlated with local manual PD-L1 scores (range: 0-100) for squamous (n=42, Pearson r=0.90, P<0.001) and non-squamous stained histology slides (n=66, Pearson r=0.90, P<0.001). Continuous digital and manual PD-L1 TPS on pre-tx biopsies (n=108) were predictive of MPR (digital: area under the receiver operating curve (AUROC)=0.678, logistic regression [LR] P=0.01; manual: AUROC=0.675, LR P=0.003). Strikingly, when pts were stratified by histology, PD-L1 scores were predictive of MPR from pre-tx biopsies for non-squamous samples (n=66; digital: AUROC=0.821, LR P=0.002; manual: AUROC=0.819, LR P=0.001) but not for squamous samples (n=42; digital: AUROC=0.519, LR P=0.93; manual: AUROC=0.506, LR P=0.90), despite no significant difference in MPR rate between the 2 groups. Conclusions: These findings support using digitally assessed PD-L1 IHC as a centralized and standardized scoring system and suggest that tumor histological subtype could be an important factor in the utility of PD-L1 as a predictive biomarker for neoadjuvant CIT in early stage NSCLC. Citation Format: John Abel, Christopher Rivard, Filip Kos, Guillaume Chhor, Yi Liu, Jennifer Giltnane, Sara Hoffman, Murray Resnick, Cyrus Hedvat, Amaro Taylor-Weiner, Farah Khalil, Alan Nicholas, Gregory A. Fishbein, Lynette M. Sholl, Natasha Rekhtman, Stephanie Hennek, Ilan Wapinski, Ann Johnson, Michael Montalto, Katja Schulze, Bruce E. Johnson, David P. Carbone, Konstantin Shilo, Andrew H. Beck, Sanja Dacic, William D. Travis, Ignacio Wistuba. AI-powered and manual assessment of PD-L1 are comparable in predicting response to neoadjuvant atezolizumab in patients (pts) with resectable non-squamous, non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT112.

Abstract Background: HER2 expression level is a key factor in determining the optimal treatment course for breast cancer patients. Roughly 15% of breast cancers are HER2(+), and determination of HER2 status is routinely assessed by immunohistochemistry (IHC). Accurate assessment of the HER2 IHC score (0, 1+, 2+, 3+) by pathologists is therefore critical, especially in light of novel therapeutic approaches demonstrating efficacy in the HER2-low setting (IHC scores 1+, and 2+/FISH-)1,2. To assist pathologists with the consistent provision of reproducible and accurate scores across the entire HER2 scoring range, we developed a machine-learning model (“AIM-HER2”) to generate accurate, slide-level HER2 scores aligned with ASCO-CAP guidelines in clinical breast cancer HER2 IHC specimens. Methods: AIM-HER2 was developed using whole-slide images (WSI; N=4261) from clinical and commercial sources. WSI were split into training (N=2694, 63%) and optimization (N=1567, 37%) sets. An additive multiple instance learning (aMIL) model3 was trained to predict HER2 scores directly from WSI and create interpretable heatmaps that depict HER2 predictions in tissue images. Image artifacts and in situ carcinomas were identified using previously trained artifact and tissue segmentation models and were excluded, leaving only regions of invasive carcinoma to be analyzed. AIM-HER2 performance was assessed on additional slides obtained from five academic or commercial sources (N=804 total, 770 evaluable) on which HER2 IHC was performed. Board-certified pathologists (N=52) with relevant experience provided manual HER2 scores based on ASCO-CAP guidelines. Nested pairwise non-inferiority analysis4 was used to compare model performance to that of pathologists (N=3 pathologists per slide). In the nested pairwise framework, agreement among pathologists was compared to agreement between AIM-HER2 and pathologists via linear kappa, so that summary metrics account for inter-pathologist variability. Results: High concordance was observed between AIM-HER2-predicted and pathologist-labeled slide-level HER2 scores, both overall and for each scoring level. Similar results were observed when assessing AIM-HER2 performance on multiple slide scanners and after IHC with multiple HER2 IHC antibody clones. Results are summarized in Table 1. Conclusions: We developed AIM-HER2, a novel aMIL-based approach for predicting slide-level HER2 IHC scores. AIM-HER2 has similar levels of agreement with pathologists as pathologists have with each other for determining HER2 score. This result is upheld when slides imaged using multiple scanning platforms and stained using multiple HER2 antibody clones. The performance of AIM-HER2 on multiple scanners and after multiple assays supports broad applicability of this algorithm in clinical laboratories, including for the identification of HER2-low cases. Work is ongoing to perform similar analyses in an independent, real-world dataset. References: 1Fernandez, AI, et al. JAMA Oncol. 2022 8(4):1-4. 2Modi, S et al. N Engl J Med. 2022 387:9-20. 3Javed, SA, et al. Adv Neural Inf Process Syst. 2022 35: 20689-702. 4Gerardin, Y, et al. 2023 arXiv:2306.04709 Table 1. Agreement between AIM-HER2 and pathologists compared to agreement among pathologists. Linearly weighted kappa values and 95% confidence intervals are shown. Citation Format: Zahil Shanis, Ryan Cabeen, Shreya Chakraborty, John Shamshoian, Marc Thibault, Harshith Padigela, Dinkar Juyal, Syed Ashar Javed, William Qian, Juhyun Kim, Beckett Rucker, Jacqueline Brosnan-Cashman, Harsha Pokkalla, Jimish Mehta, Amaro Taylor-Weiner, Ben Glass, Santhosh Balasubramanian. Accurate quantification of slide-level HER2 scores in breast cancer using a machine-learning model, AIM-HER2 Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-12.

Self-regulation in children is an important thing that needs to be prepared from an early age. Besides affecting children's school readiness, this also makes it easier for children to have good academic achievements. This study aims to determine the influence of moving to the beat of early childhood self-regulation. This research was conducted on kindergarten group B students in East Jakarta. The research method used is a quasi-experiment method with a sample of 20 students. The data collection technique uses observations by analysing paired t-test statistical data. The results of the study explained that there was a significant effect of moving to the beat of early childhood self-regulation. The significance level is 0.000 < 0.05, which means that H0 is rejected and H1 is accepted, this indicates a significant difference between the pre-test and post-test. For further research, it is recommended to look at the influence of other factors on early childhood self-regulation. 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Abstract The Society gratefully acknowledges the time and effort of the following individuals who served as reviewers of abstracts for this meeting: ASH ABSTRACTS COORDINATING REVIEWERS Blanche P. Alter Stephen M. Ansell Ralph B. Arlinghaus Scott Armstrong Asad Bashey Philip Bierman Neil Blumberg Chiara Bonini Dominique Bonnet Jacqueline Boultwood Rena Buckstein John C. Byrd Marc Carrier Lucio H. Castilla Selina Chen-Kiang Nicholas Chiorazzi Jorge Cortes-Franco Claire E. Dearden Mary C. Dinauer Harry Paul Erba Carolyn A. Felix Pierre Fenaux Debra L. Friedman Irene M. Ghobrial Jason R. Gotlib Brandon Hayes-Lattin Cheryl A. Hillery Achille Iolascon Jean-Pierre J. Issa Sundar Jagannath Diane F. Jelinek H. Phillip Koeffler John Koreth Robert J. Kreitman Robert B. Levy David Lillicrap Richard Lottenberg John D. McMannis Mark D. Minden Charles G. Mullighan Arnon Nagler Peter J. Newman Robert Z. Orlowski Antonio Palumbo Julie A. Panepinto Warren S. Pear Sibrand Poppema Barbara Pro Ching-Hon Pui A. Koneti Rao Aaron P. Rapoport Pieter H. Reitsma Douglas D. Ross J. Eric Russell Barbara Savoldo Kirk R. Schultz Radek C. Skoda Marilyn L. Slovak Susan Smyth Hugo ten Cate Herve Tilly John M. Timmerman Ivo Touw Amy J. Wagers Russell E. Ware Catherine J. Wu Virginia M. Zaleskas ASH ABSTRACTS REVIEWERS Camille Abboud Omar Abdel-Wahab Jeremy Abramson Suneet Agarwal Sikander Ailawadhi Onder Alpdogan Andrew Aprikyan Mary Armanios Aneel Ashrani Norio Asou Aglaia Athanassiadou Eyal Attar Mohammad Azam Maria Baer Jorg Baesecke Sarah Ball Karen Ballen Frederic Baron Shannon Bates Minoo Battiwalla Marie Bene Charles Bennett James Berenson Steven Bernstein Francesco Bertoni Monica Bessler Wolfgang Bethge Kapil Bhalla Deepa Bhojwani James Bieker Bruce R. Blazar Annemarie Block David Bodine Catherine Bollard Antonio Bonati Eric Bouhassira Benjamin Braun Christopher Bredeson Patrick Brown Ross Brown Jan Burger Dario Campana Jose Cancelas Paul Carpenter Andrew Carroll James Casella Rebecca Chan Roy Chemaly Benny Chen Jerry Cheng Linzhao Cheng Bruce Cheson Mark Chiang Athar Chishti Hearn Cho Magdalena Chrzanowska-Wodnicka Richard E. Clark Joseph Connors Kenneth Cooke Miguel Cruz Adam Cuker Sandeep Dave Janice Davis Sproul Lucia De Franceschi Philip De Groot Rodney DeKoter Richard Delarue Stephen Devereux Steven Devine Paola Jorge Di Don Diamond Meletios Dimopoulos John DiPersio Angela Dispenzieri Benjamin Djulbegovic Jing-fei Dong James Downing William Drobyski Rafael Duarte Charles Dumontet Kieron Dunleavy Brian Durie Dimitar Efremov Elizabeth Eklund Jonas Emsley Patricia Ernst Andrew Evens Chris Fegan Andrew Feldman Giuliana Ferrari Willem Fibbe Adele Fielding Thoas Fioretos Robert Flaumenhaft Rafael Fonseca James Foran Joseph Frank Janet Franklin Paul Frenette Alan Friedman Terry Fry Saghi Gaffari Naomi Galili Patrick Gallagher Anne Galy David Garcia Randy Gascoyne Cristina Gasparetto Norbert Gattermann Tobias Gedde-Dahl Alan Gewirtz Francis Giles Robert Godal Lucy Godley Ivana Gojo Norbert Gorin Andre Goy Eric Grabowski Steven Grant Timothy Graubert Elizabeth Griffiths H. Leighton Grimes Claudia Haferlach Corinne Haioun Parameswaran Hari Christine Harrison Robert Hasserjian Nyla Heerema Shelly Heimfeld Roland Herzog Elizabeth Hexner Teru Hideshima William H. Hildebrand Gerhard Hildebrandt Devendra Hiwase Karin Hoffmeister Donna Hogge Scott Howard Brian Huntly Hiroto Inaba Baba Inusa Shai Izraeli Suresh Jhanwar Amy Johnson Craig Jordan Joseph Jurcic Nina Kadan-Lottick Lawrence Kaplan Jonathan Kaufman Neil Kay Michelle Kelliher Craig Kessler H. Jean Khoury Allison King Joseph Kiss Issay Kitabayashi Robert Klaassen Christoph Klein Yoshihisa Kodera Alexander Kohlmann Barbara Konkle Michael Kovacs Robert Kralovics Amrita Krishnan Nicolaus Kroger Ashish Kumar Ralf Küppers Jeffery Kutok Ann LaCasce Raymond Lai David Lane Peter Lane Richard Larson Michelle Le Beau Gregoire Le Gal Ollivier Legrand Suzanne Lentzsch John Leonard John Levine Ross Levine Linheng Li Renhao Li Zhenyu Li Wendy Lim Charles Linker Jeffrey Lipton Per Ljungman John Lollar Philip Low David Lucas Selina Luger Leo Luznik Gary Lyman Jaroslaw Maciejewski Elizabeth MacIntyre Nigel Mackman Luca Malcovati Guido Marcucci Tomer Mark Susan Maroney Giovanni Martinelli Peter Maslak Alan Mast Grant McArthur Philip McCarthy Michael McDevitt Peter McLaughlin Bruno Medeiros Jules P.P. Meijerink Junia Melo Thomas Mercher Bradley Messmer Marco Mielcarek Ken Mills Shin Mineishi Arturo Molina Silvia Montoto Marie Joelle Mozziconacci Auayporn Nademanee Vesna Najfeld Eneida Nemecek Ellis Neufeld Peter Newburger Heyu Ni Charlotte Marie Niemeyer Yago Nieto Anne Novak Paul O\'Donnell Vivian Oehler Fritz Offner Johannes Oldenburg Rebecca Olin Richard J. O'Reilly Thomas Ortel Keiya Ozawa Rose Ann Padua Sung-Yun Pai James Palis Derwood Pamphilon Animesh Pardanani Farzana Pashankar Andrea Pellagatti Catherine Pellat-Deceunynck Louis Pelus Chris Pepper Melanie Percy Andrew Perkins Luke Peterson Andrew Pettitt Javier Pinilla-Ibarz Kimmo Porkka David Porter Amy Powers Claude Preudhomme Frederick Racke Margaret Ragni Thomas Raife Alessandro Rambaldi Mariusz Ratajczak Pavan Reddy Mary Relling Tannishtha Reya Lisa Rimsza Stefano Rivella Isabelle Riviere Pamela Robey Gail Roboz Aldo Roccaro Maria Alma Rodriguez Frank Rosenbauer Laura Rosinol Alan Rosmarin Giuseppe Saglio Jonathan Said Valeria Santini Ravindra Sarode Yogenthiran Saunthararajah Bipin Savani Alan Schechter Charles Schiffer Robert Schlossman Laurie Sehn Rita Selby Orhan Sezer Sadhna Shankar John Shaughnessy Jordan Shavit Kevin Sheehan Shalini Shenoy Colin Sieff Paul Simmons Seema Singhal Sonali Smith Gerard Socie Pieter Sonneveld Simona Soverini David Spaner Steven Spitalnik Kostas Stamatopoulos David Steensma Richard Stone Toshio Suda Perumal Thiagarajan Courtney Thornburg Rodger Tiedemann David Traver Guido Tricot Darrell Triulzi Suzanne Trudel Christel Van Geet Karin Vanderkerken David Varon Amit Verma Srdan Verstovsek Ravi Vij Dan Vogl Loren Walensky Edmund Waller George Weiner Daniel Weisdorf Karl Welte Peter Westervelt Adrian Wiestner P.W. Wijermans John Wingard Anne Woolfrey Mingjiang Xu Qing Yi Anas Younes Ryan Zarychanski Arthur Zelent Clive Zent Dong-Er Zhang Xianzheng Zhou James Zimring

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Introduction Mentors play a role in real life, just as they do in fiction. They also feature in reality television, which sits somewhere between the two. In fiction, mentors contribute to the narrative arc by providing guidance and assistance (Vogler 12) to a mentee in his or her life or professional pursuits. These exchanges are usually characterized by reciprocity, the need for mutual recognition (Gadamer 353) and involve some kind of moral question. They dramatise the possibilities of mentoring in reality, to provide us with a greater understanding of the world, and our human interaction within it. Reality television offers a different perspective. Like drama it uses the plot device of a mentor character to heighten the story arc, but instead of focusing on knowledge-based portrayals (Gadamer 112) of the mentor and mentee, the emphasis is instead on the mentee’s quest for ascension. In attempting to transcend their unknownness (Boorstin) contestants aim to penetrate an exclusive creative class (Florida). Populated by celebrity chefs, businessmen, entertainers, fashionistas, models, socialites and talent judges (to name a few), this class seemingly adds authenticity to ‘competitions’ and other formats. While the mentor’s role, on the surface, is to provide divine knowledge and facilitate the journey, a different agenda is evident in the ways carefully scripted (Booth) dialogue heightens the drama through effusive praise (New York Daily News) and “tactless” (Woodward), humiliating (Hirschorn; Winant 69; Woodward) and cruel sentiments. From a screen narrative point of view, this takes reality television as ‘storytelling’ (Aggarwal; Day; Hirschorn; “Reality Writer”; Rupel; Stradal) into very different territory. The contrived and later edited (Crouch; Papacharissi and Mendelson 367) communication between mentor and mentee not only renders the relationship disingenuous, it compounds the primary ethical concerns of associated Schadenfreude (Balasubramanian, Forstie and van den Scott 434; Cartwright), and the severe financial inequality (Andrejevic) underpinning a multi-billion dollar industry (Hamilton). As upward mobility and instability continue to be ubiquitously portrayed in 21st century reality entertainment under neoliberalism (Sender 4; Winant 67), it is with increasing frequency that we are seeing the systematic reinvention of the once significant cultural and historical role of the mentor. Mentor as Fictional Archetype and Communicator of ThemesDepictions of mentors can be found across the Western art canon. From the mythological characters of Telemachus’ Athena and Achilles’ Chiron, to King Arthur’s Merlin, Cinderella’s Fairy Godmother, Jim Hawkins’ Long John Silver, Frodo’s Gandalf, Batman’s Alfred and Marty McFly’s Doc Emmett Brown (among many more), the dramatic energy of the teacher, expert or supernatural aid (Vogler 39) has been timelessly powerful. Heroes, typically, engage with a mentor as part of their journey. Mentor types range extensively, from those who provide motivation, inspiration, training or gifts (Vogler), to those who may be dark or malevolent, or have fallen from grace (such as Michael Douglas’ Gordon Gekko in Wall Street 1987, or the ex-tribute Haymitch in The Hunger Games, 2012). A good drama usually complicates the relationship in some way, exploring initial reluctance from either party, or instances of tragedy (Vogler 11, 44) which may prevent the relationship achieving its potential. The intriguing twist of a fallen or malevolent mentor additionally invites the audience to morally analyze the ways the hero responds to what the mentor provides, and to question what our teachers or superiors tell us. In television particularly, long running series such as Mad Men have shown how a mentoring relationship can change over time, where “non-rational” characters (Buzzanell and D’Enbeau 707) do not necessarily maintain reciprocity or equality (703) but become subject to intimate, ambivalent and erotic aspects.As the mentor in fiction has deep cultural roots for audiences today, it is no wonder they are used, in a variety of archetypal capacities, in reality television. The dark Simon Cowell (of Pop Idol, American Idol, Britain’s Got Talent, America’s Got Talent and The X-Factor series) and the ‘villainous’ (Byrnes) Michelin-starred Marco Pierre White (Hell’s Kitchen, The Chopping Block, Marco Pierre White’s Kitchen Wars, MasterChef Australia, New Zealand, South Africa) provide reality writers with much needed antagonism (Rupel, Stradal). Those who have fallen from grace, or allowed their personal lives to play out in tabloid sagas such as Britney Spears (Marikar), or Caitlyn Jenner (Bissinger) provide different sources of conflict and intrigue. They are then counterbalanced with or repackaged as the good mentor. Examples of the nurturer who shows "compassion and empathy" include American Idol’s Paula Abdul (Marche), or the supportive Jennifer Hawkins in Next Top Model (Thompson). These distinctive characters help audiences to understand the ‘reality’ as a story (Crouch; Rupel; Stradal). But when we consider the great mentors of screen fiction, it becomes clear how reality television has changed the nature of story. The Karate Kid I (1984) and Good Will Hunting (1998) are two examples where mentoring is almost the exclusive focus, and where the experience of the characters differs greatly. In both films an initially reluctant mentor becomes deeply involved in the mentee’s project. They act as a special companion to the hero in the face of isolation, and, significantly, reveal a tragedy of their own, providing a nexus through which the mentee can access a deeper kind of truth. Not only are they flawed and ordinary people (they are not celebrities within the imagined worlds of the stories) who the mentee must challenge and learn to truly respect, they are “effecting and important” (Maslin) in reminding audiences of those hidden idiosyncrasies that open the barriers to friendship. Mentors in these stories, and many others, communicate themes of class, culture, talent, jealousy, love and loss which inform ideas about the ethical treatment of the ‘other’ (Gadamer). They ultimately prove pivotal to self worth, human confidence and growth. Very little of this thematic substance survives in reality television (see comparison of plots and contrasting modes of human engagement in the example of The Office and Dirty Jobs, Winant 70). Archetypally identifiable as they may be, mean judges and empathetic supermodels as characters are concerned mostly with the embodiment of perfection. They are flawless, untouchable and indeed most powerful when human welfare is at stake, and when the mentee before them faces isolation (see promise to a future ‘Rihanna’, X-Factor USA, Season 2, Episode 1 and Tyra Banks’ Next Top Model tirade at a contestant who had not lived up to her potential, West). If connecting with a mentor in fiction has long signified the importance of understanding of the past, of handing down tradition (Gadamer 354), and of our fascination with the elder, wiser other, then we can see a fundamental shift in narrative representation of mentors in reality television stories. In the past, as we have opened our hearts to such characters, as a facilitator to or companion of the hero, we have rehearsed a sacred respect for the knowledge and fulfillment mentors can provide. In reality television the ‘drama’ may evoke a fleeting rush of excitement at the hero’s success or failure, but the reality belies a pronounced distancing between mentor and mentee. The Creative Class: An Aspirational ParadigmThemes of ascension and potential fulfillment are also central to modern creativity discourse (Runco; Runco 672; United Nations). Seen as the driving force of the 21st century, creativity is now understood as much more than art, capable of bringing economic prosperity (United Nations) and social cohesion to its acme (United Nations xxiii). At the upper end of creative practice, is what Florida called “the creative class: a fast growing, highly educated, and well-paid segment of the workforce” (on whose expertise corporate profits depend), in industries ranging “from technology to entertainment, journalism to finance, high-end manufacturing to the arts” (Florida). Their common ethos is centered on individuality, diversity, and merit; eclipsing previous systems focused on ‘shopping’ and theme park consumerism and social conservatism (Eisinger). While doubts have since been raised about the size (Eisinger) and financial practices (Krätke 838) of the creative class (particularly in America), from an entertainment perspective at least, the class can be seen in full action. Extending to rich housewives, celebrity teen mothers and even eccentric duck hunters and swamp people, the creative class has caught up to the more traditional ‘star’ actor or music artist, and is increasingly marketable within world’s most sought after and expensive media spaces. Often reality celebrities make their mark for being the most outrageous, the cruelest (Peyser), or the weirdest (Gallagher; Peyser) personalities in the spotlight. Aspiring to the creative class thus, is a very public affair in television. Willing participants scamper for positions on shows, particularly those with long running, heavyweight titles such as Big Brother, The Bachelor, Survivor and the Idol series (Hill 35). The better known formats provide high visibility, with the opportunity to perform in front of millions around the globe (Frere-Jones, Day). Tapping into the deeply ingrained upward-mobility rhetoric of America, and of Western society, shows are aided in large part by 24-hour news, social media, the proliferation of celebrity gossip and the successful correlation between pop culture and an entertainment-style democratic ideal. As some have noted, dramatized reality is closely tied to the rise of individualization, and trans-national capitalism (Darling-Wolf 127). Its creative dynamism indeed delivers multi-lateral benefits: audiences believe the road to fame and fortune is always just within reach, consumerism thrives, and, politically, themes of liberty, egalitarianism and freedom ‘provide a cushioning comfort’ (Peyser; Pinter) from the domestic and international ills that would otherwise dispel such optimism. As the trials and tests within the reality genre heighten the seriousness of, and excitement about ascending toward the creative elite, show creators reproduce the same upward-mobility themed narrative across formats all over the world. The artifice is further supported by the festival-like (Grodin 46) symbology of the live audience, mass viewership and the online voting community, which in economic terms, speaks to the creative power of the material. Whether through careful manipulation of extra media space, ‘game strategy’, or other devices, those who break through are even more idolized for the achievement of metamorphosing into a creative hero. For the creative elite however, who wins ‘doesn’t matter much’. Vertical integration is the priority, where the process of making contestants famous is as lucrative as the profits they will earn thereafter; it’s a form of “one-stop shopping” as the makers of Idol put it according to Frere-Jones. Furthermore, as Florida’s measures and indicators suggested, the geographically mobile new creative class is driven by lifestyle values, recreation, participatory culture and diversity. Reality shows are the embodiment this idea of creativity, taking us beyond stale police procedural dramas (Hirschorn) and racially typecast family sitcoms, into a world of possibility. From a social equality perspective, while there has been a notable rise in gay and transgender visibility (Gamson) and stories about lower socio-economic groups – fast food workers and machinists for example – are told in a way they never were before, the extent to which shows actually unhinge traditional power structures is, as scholars have noted (Andrejevic and Colby 197; Schroeder) open to question. As boundaries are nonetheless crossed in the age of neoliberal creativity, the aspirational paradigm of joining a new elite in real life is as potent as ever. Reality Television’s Mentors: How to Understand Their ‘Role’Reality television narratives rely heavily on the juxtaposition between celebrity glamour and comfort, and financial instability. As mentees put it ‘all on the line’, storylines about personal suffering are hyped and molded for maximum emotional impact. In the best case scenarios mentors such as Caitlyn Jenner will help a trans mentee discover their true self by directing them in a celebrity-style photo shoot (see episode featuring Caitlyn and Zeam, Logo TV 2015). In more extreme cases the focus will be on an adopted contestant’s hopes that his birth mother will hear him sing (The X Factor USA, Season 2, Episode 11 Part 1), or on a postal clerk’s fear that elimination will mean she has to go back “to selling stamps” (The X Factor US - Season 2 Episode 11 Part 2). In the entrepreneurship format, as Woodward pointed out, it is not ‘help’ that mentees are given, but condescension. “I have to tell you, my friend, that this is the worst idea I’ve ever heard. You don’t have a clue about how to set up a business or market a product,” Woodward noted as the feedback given by one elite businessman on The Shark Tank (Woodward). “This is a five million dollar contract and I have to know that you can go the distance” (The X Factor US – Season 2 Episode 11, Part 1) Britney Spears warned to a thirteen-year-old contestant before accepting her as part of her team. In each instance the fictitious premise of being either an ‘enabler’ or destroyer of dreams is replayed and slightly adapted for ongoing consumer interest. This lack of shared experience and mutual recognition in reality television also highlights the overt, yet rarely analyzed focus on the wealth of mentors as contrasted with their unstable mentees. In the respective cases of The X Factor and I Am Cait, one of the wealthiest moguls in entertainment, Cowell, reportedly contracts mentors for up to $15 million per season (Nair); Jenner’s performance in I Am Cait was also set to significantly boost the Kardashian empire (reportedly already worth $300 million, Pavia). In both series, significant screen time has been dedicated to showing the mentors in luxurious beachside houses, where mentees may visit. Despite the important social messages embedded in Caitlyn’s story (which no doubt nourishes the Kardashian family’s generally more ersatz material), the question, from a moral point of view becomes: would these mentors still interact with that particular mentee without the money? Regardless, reality participants insist they are fulfilling their dreams when they appear. Despite the preplanning, possibility of distress (Australia Network News; Bleasby) and even suicide (Schuster), as well as the ferocity of opinion surrounding shows (Marche) the parade of a type of ‘road of trials’ (Vogler 189) is enough to keep a huge fan base interested, and hungry for their turn to experience the fortune of being touched by the creative elite; or in narrative terms, a supernatural aid. ConclusionThe key differences between reality television and artistic narrative portrayals of mentors can be found in the use of archetypes for narrative conflict and resolution, in the ways themes are explored and the ways dialogue is put to use, and in the focus on and visibility of material wealth (Frere-Jones; Peyser). These differences highlight the political, cultural and social implications of exchanging stories about potential fulfillment, for stories about ascension to the creative class. Rather than being based on genuine reciprocity, and understanding of human issues, reality shows create drama around the desperation to penetrate the inner sanctum of celebrity fame and fortune. In fiction we see themes based on becoming famous, on gender transformation, and wealth acquisition, such as in the films and series Almost Famous (2000), The Bill Silvers Show (1955-1959), Filthy Rich (1982-1983), and Tootsie (1982), but these stories at least attempt to address a moral question. Critically, in an artistic - rather than commercial context – the actors (who may play mentees) are not at risk of exploitation (Australia Network News; Bleasby; Crouch). Where actors are paid and recognized creatively for their contribution to an artistic work (Rupel), the mentee in reality television has no involvement in the ways action may be set up for maximum voyeuristic enjoyment, or manipulated to enhance scandalous and salacious content which will return show and media profits (“Reality Show Fights”; Skeggs and Wood 64). The emphasis, ironically, from a reality production point of view, is wholly on making the audience believe (Papacharissi and Mendelson 367) that the content is realistic. 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IntroductionThe debate about the responsibility of museums to respect Indigenous peoples’ rights (Kelly and Gordon; Butts) has caught our attention on the basis of our previous research experience with regard to the protection of the tangible and intangible heritage of the San (former hunter gatherers) in Southern Africa (Martin and Vermeylen; Vermeylen, Contextualising; Vermeylen, Life Force; Vermeylen et al.; Vermeylen, Land Rights). This paper contributes to the critical debate about curatorial practices and the recovery of Indigenous peoples’ cultural practices and explores how museums can be transformed into cultural centres that “decolonise” their objects while simultaneously providing social agency to marginalised groups such as the San. Indigenous MuseumTraditional methods of displaying Indigenous heritage are now regarded with deep suspicion and resentment by Indigenous peoples (Simpson). A number of related issues such as the appropriation, ownership and repatriation of culture together with the treatment of sensitive and sacred materials and the stereotyping of Indigenous peoples’ identity (Carter; Simpson) have been identified as the main problems in the debate about museum curatorship and Indigenous heritage. The poignant question remains whether the concept of a classical museum—in the sense of how it continues to classify, value and display non-Western artworks—will ever be able to provide agency to Indigenous peoples as long as “their lives are reduced to an abstract set of largely arbitrary material items displayed without much sense of meaning” (Stanley 3). Indeed, as Salvador has argued, no matter how much Indigenous peoples have been involved in the planning and implementation of an exhibition, some issues remain problematic. First, there is the problem of representation: who speaks for the group; who should make decisions and under what circumstances; when is it acceptable for “outsiders” to be involved? Furthermore, Salvador raises another area of contestation and that is the issue of intention. As we agree with Salvador, no matter how good the intention to include Indigenous peoples in the curatorial practices, the fact that Indigenous peoples may have a (political) perspective about the exhibition that differs from the ideological foundation of the museum enterprise, is, indeed, a challenge that must not be overlooked in the discussion of the inclusive museum. This relates to, arguably, one of the most important challenges in respect to the concept of an Indigenous museum: how to present the past and present without creating an essentialising “Other”? As Stanley summarises, the modernising agenda of the museum, including those museums that claim to be Indigenous museums, continues to be heavily embedded in the belief that traditional cultural beliefs, practices and material manifestations must be saved. In other words, exhibitions focusing on Indigenous peoples fail to show them as dynamic, living cultures (Simpson). This raises the issue that museums recreate the past (Sepúlveda dos Santos) while Indigenous peoples’ interests can be best described “in terms of contemporaneity” (Bolton qtd. in Stanley 7). According to Bolton, Indigenous peoples’ interest in museums can be best understood in terms of using these (historical) collections and institutions to address contemporary issues. Or, as Sepúlveda dos Santos argues, in order for museums to be a true place of memory—or indeed a true place of recovery—it is important that the museum makes the link between the past and contemporary issues or to use its objects in such a way that these objects emphasize “the persistence of lived experiences transmitted through generations” (29). Under pressure from Indigenous rights movements, the major aim of some museums is now reconciliation with Indigenous peoples which, ultimately, should result in the return of the cultural objects to the originators of these objects (Kelly and Gordon). Using the Native American Graves Protection and Repatriation Act of 1990 (NAGPRA) as an illustration, we argue that the whole debate of returning or recovering Indigenous peoples’ cultural objects to the original source is still embedded in a discourse that emphasises the mummified aspect of these materials. As Harding argues, NAGPRA is provoking an image of “native Americans as mere passive recipients of their cultural identity, beholden to their ancestors and the museum community for the re-creation of their cultures” (137) when it defines cultural patrimony as objects having ongoing historical, traditional or cultural importance, central to the Native American group or culture itself. According to Harding (2005) NAGPRA’s dominating narrative focuses on the loss, alienation and cultural genocide of the objects as long as these are not returned to their originators. The recovery or the return of the objects to their “original” culture has been applauded as one of the most liberating and emancipatory events in recent years for Indigenous peoples. However, as we have argued elsewhere, the process of recovery needs to do more than just smother the object in its past; recovery can only happen when heritage or tradition is connected to the experience of everyday life. One way of achieving this is to move away from the objectification of Indigenous peoples’ cultures. ObjectificationIn our exploratory enquiry about new museum practices our attention was drawn to a recent debate about ownership and personhood within the context of museology (Busse; Baker; Herle; Bell; Geismar). Busse, in particular, makes the point that in order to reformulate curatorial practices it is important to redefine the concept and meaning of objects. While the above authors do not question the importance of the objects, they all argue that the real importance does not lie in the objects themselves but in the way these objects embody the physical manifestation of social relations. The whole idea that objects matter because they have agency and efficacy, and as such become a kind of person, draws upon recent anthropological theorising by Gell and Strathern. Furthermore, we have not only been inspired by Gell’s and Strathern’s approaches that suggests that objects are social persons, we have also been influenced by Appadurai’s and Kopytoff’s defining of objects as biographical agents and therefore valued because of the associations they have acquired throughout time. We argue that by framing objects in a social network throughout its lifecycle we can avoid the recurrent pitfalls of essentialising objects in terms of their “primitive” or “traditional” (aesthetic) qualities and mystifying the identity of Indigenous peoples as “noble savages.” Focusing more on the social network that surrounds a particular object opens up new avenues of enquiry as to how, and to what extent, museums can become more inclusive vis-à-vis Indigenous peoples. It allows moving beyond the current discourse that approaches the history of the (ethnographic) museum from only one dominant perspective. By tracing an artwork throughout its lifecycle a new metaphor can be discovered; one that shows that Indigenous peoples have not always been victims, but maybe more importantly it allows us to show a more complex narrative of the object itself. It gives us the space to counterweight some of the discourses that have steeped Indigenous artworks in a “postcolonial” framework of sacredness and mythical meaning. This is not to argue that it is not important to be reminded of the dangers of appropriating other cultures’ heritage, but we would argue that it is equally important to show that approaching a story from a one-sided perspective will create a dualism (Bush) and reducing the differences between different cultures to a dualistic opposition fails to recognise the fundamental areas of agency (Morphy). In order for museums to enliven and engage with objects, they must become institutions that emphasise a relational approach towards displaying and curating objects. In the next part of this paper we will explore to what extent an online museum could progressively facilitate the process of providing agency to the social relations that link objects, persons, environments and memories. As Solanilla argues, what has been described as cybermuseology may further transform the museum landscape and provide an opportunity to challenge some of the problems identified above (e.g. essentialising practices). Or to quote the museologist Langlais: “The communication and interaction possibilities offered by the Web to layer information and to allow exploration of multiple meanings are only starting to be exploited. In this context, cybermuseology is known as a practice that is knowledge-driven rather than object-driven, and its main goal is to disseminate knowledge using the interaction possibilities of Information Communication Technologies” (Langlais qtd. in Solanilla 108). One thing which shows promise and merits further exploration is the idea of transforming the act of exhibiting ethnographic objects accompanied by texts and graphics into an act of cyber discourse that allows Indigenous peoples through their own voices and gestures to involve us in their own history. This is particularly the case since Indigenous peoples are using technologies, such as the Internet, as a new medium through which they can recuperate their histories, land rights, knowledge and cultural heritage (Zimmerman et al.). As such, new technology has played a significant role in the contestation and formation of Indigenous peoples’ current identity by creating new social and political spaces through visual and narrative cultural praxis (Ginsburg).Online MuseumsIt has been acknowledged for some time that a presence on the Web might mitigate the effects of what has been described as the “unassailable voice” in the recovery process undertaken by museums (Walsh 77). However, a museum’s online engagement with an Indigenous culture may have significance beyond undercutting the univocal authority of a museum. In the case of the South African National Gallery it was charged with challenging the extent to which it represents entrenched but unacceptable political ideologies. Online museums may provide opportunities in the conservation and dissemination of “life stories” that give an account of an Indigenous culture as it is experienced (Solanilla 105). We argue that in engaging with Indigenous cultural heritage a distinction needs to be drawn between data and the cognitive capacity to learn, “which enables us to extrapolate and learn new knowledge” (Langlois 74). The problem is that access to data about an Indigenous culture does not necessarily lead to an understanding of its knowledge. It has been argued that cybermuseology loses the essential interpersonal element that needs to be present if intangible heritage is understood as “the process of making sense that is generally transmitted orally and through face-to-face experience” (Langlois 78). We agree that the online museum does not enable a reality to be reproduced (Langlois 78).This does not mean that cybermuseology should be dismissed. Instead it provides the opportunity to construct a valuable, but completely new, experience of cultural knowledge (Langlois 78). The technology employed in cybermuseology provides the means by which control over meaning may, at least to some extent, be dispersed (Langlois 78). In this way online museums provide the opportunity for Indigenous peoples to challenge being subjected to manipulation by one authoritative museological voice. One of the ways this may be achieved is through interactivity by enabling the use of social tagging and folksonomy (Solanilla 110; Trant 2). In these processes keywords (tags) are supplied and shared by visitors as a means of accessing museum content. These tags in turn give rise to a classification system (folksonomy). In the context of an online museum engaging with an Indigenous culture we have reservations about the undifferentiated interactivity on the part of all visitors. This issue may be investigated further by examining how interactivity relates to communication. Arguably, an online museum is engaged in communicating Indigenous cultural heritage because it helps to keep it alive and pass it on to others (Langlois 77). However, enabling all visitors to structure online access to that culture may be detrimental to the communication of knowledge that might otherwise occur. The narratives by which Indigenous cultures, rather than visitors, order access to information about their cultures may lead to the communication of important knowledge. An illustration of the potential of this approach is the work Sharon Daniel has been involved with, which enables communities to “produce knowledge and interpret their own experience using media and information technologies” (Daniel, Palabras) partly by means of generating folksonomies. One way in which such issues may be engaged with in the context of online museums is through the argument that database and narrative in such new media objects are opposed to each other (Manovich, New Media 225). A new media work such as an online museum may be understood to be comprised of a database and an interface to that database. A visitor to an online museum may only move through the content of the database by following those paths that have been enabled by those who created the museum (Manovich, New Media 227). In short it is by means of the interface provided to the viewer that the content of the database is structured into a narrative (Manovich, New Media: 226). It is possible to understand online museums as constructions in which narrative and database aspects are emphasized to varying degrees for users. There are a variety of museum projects in which the importance of the interface in creating a narrative interface has been acknowledged. Goldblum et al. describe three examples of websites in which interfaces may be understood as, and explicitly designed for, carrying meaning as well as enabling interactivity: Life after the Holocaust; Ripples of Genocide; and Yearbook 2006.As with these examples, we suggest that it is important there be an explicit engagement with the significance of interface(s) for online museums about Indigenous peoples. The means by which visitors access content is important not only for the way in which visitors interact with material, but also as to what is communicated about, culture. It has been suggested that the curator’s role should be moved away from expertly representing knowledge toward that of assisting people outside the museum to make “authored statements” within it (Bennett 11). In this regard it seems to us that involvement of Indigenous peoples with the construction of the interface(s) to online museums is of considerable significance. Pieterse suggests that ethnographic museums should be guided by a process of self-representation by the “others” portrayed (Pieterse 133). Moreover it should not be forgotten that, because of the separation of content and interface, it is possible to have access to a database of material through more than one interface (Manovich, New Media 226-7). Online museums provide a means by which the artificial homogenization of Indigenous peoples may be challenged.We regard an important potential benefit of an online museum as the replacement of accessing material through the “unassailable voice” with the multiplicity of Indigenous voices. A number of ways to do this are suggested by a variety of new media artworks, including those that employ a database to rearrange information to reveal underlying cultural positions (Paul 100). Paul discusses the work of, amongst others, George Legrady. She describes how it engages with the archive and database as sites that record culture (104-6). Paul specifically discusses Legrady’s work Slippery Traces. This involved viewers navigating through more than 240 postcards. Viewers of work were invited to “first chose one of three quotes appearing on the screen, each of which embodies a different perspective—anthropological, colonialist, or media theory—and thus provides an interpretive angle for the experience of the projects” (104-5). In the same way visitors to an online museum could be provided with a choice of possible Indigenous voices by which its collection might be experienced. We are specifically interested in the implications that such approaches have for the way in which online museums could engage with film. Inspired by Basu’s work on reframing ethnographic film, we see the online museum as providing the possibility of a platform to experiment with new media art in order to expose the meta-narrative(s) about the politics of film making. As Basu argues, in order to provoke a feeling of involvement with the viewer, it is important that the viewer becomes aware “of the plurality of alternative readings/navigations that they might have made” (105). As Weinbren has observed, where a fixed narrative pathway has been constructed by a film, digital technology provides a particularly effective means to challenge it. It would be possible to reveal the way in which dominant political interests regarding Indigenous cultures have been asserted, such as for example in the popular film The Gods Must Be Crazy. New media art once again provides some interesting examples of the way ideology, that might otherwise remain unclear, may be exposed. Paul describes the example of Jennifer and Kevin McCoy’s project How I learned. The work restructures a television series Kung Fu by employing “categories such as ‘how I learned about blocking punches,’ ‘how I learned about exploiting workers,’ or ‘how I learned to love the land’” (Paul 103) to reveal in greater clarity, than otherwise might be possible, the cultural stereotypes used in the visual narratives of the program (Paul 102-4). We suggest that such examples suggest the ways in which online museums could work to reveal and explore the existence not only of meta-narratives expressed by museums as a whole, but also the means by which they are realised within existing items held in museum collections.ConclusionWe argue that the agency for such reflective moments between the San, who have been repeatedly misrepresented or underrepresented in exhibitions and films, and multiple audiences, may be enabled through the generation of multiple narratives within online museums. We would like to make the point that, first and foremost, the theory of representation must be fully understood and acknowledged in order to determine whether, and how, modes of online curating are censorious. As such we see online museums having the potential to play a significant role in illuminating for both the San and multiple audiences the way that any form of representation or displaying restricts the meanings that may be recovered about Indigenous peoples. ReferencesAppadurai, Arjun. The Social Life of Things: Commodities in Cultural Perspective. Cambridge: Harvard UP, 1986. Bal, Mieke. “Exhibition as Film.” Exhibition Experiments. Ed. Sharon Macdonald and Paul Basu. Malden: Blackwell Publishing 2007. 71-93. Basu, Paul. “Reframing Ethnographic Film.” Rethinking Documentary. Eds. Thomas Austin and Wilma de Jong. Maidenhead: Open U P, 2008. 94-106.Barringer, Tim, and Tom Flynn. Colonialism and the Object: Empire, Material Culture and the Museum. London: Routledge, 1998. 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In many ways, computers are becoming invisible and will continue to do so. When we reach into our pockets and pull out our cell phones to find a place to eat or message a friend on Facebook, we are no longer consciously aware that we are interacting with a user experience that has been consciously designed for our computer or device screen—but we are.— Andy Pratt and Jason Nunes, Interactive Design In theory, cell phones and other information and communication technologies (ICTs) are just a means for us to interact with people, businesses, and data sources. They have interfaces and, in a larger sense, are interfaces between their users and the networked world. Every day, people spend more time using them to perform more different tasks and find them more indispensable (Smith). As the epigraph above suggests, however, their omnipresence makes them practically invisible and has all but erased any feelings of awe or mystery that their power once generated. There is both a historical and functional dimension to this situation. In the historical advance of technology, it is part of what Kevin Kelly calls the “technium,” the ever-more complex interactions between advancing technology, our cognitive processes, and the cultural forces in which they are enmeshed; ICTs are measurably getting more powerful as time goes on and are, in this sense, worthy of our admiration (Kelly 11-17). In the functional dimension, on the other hand, many scholars and designers have observed how hard it is to hold on to this feeling of enchantment in our digital devices (Nye 185-226; McCarthy and Wright 192-97). As one study of human-computer interfaces observes “when people let the enchanting object [ICTs] do the emotional work of experience for them . . . what could be enchanting interactivity becomes a paradoxically detached interpassivity” (McCarthy et al. 377). ICTs can be ever more powerful, then, but this power will not necessarily be appreciated by their users. This paper analyzes recent narrative representations of ICT use in spy thrillers, with a particular focus on the canon of James Bond films (a sub-genre with a long-standing and overt fascination with advanced technology, especially ICTs), in order to explore how the banality of ICT technology has become the inescapable accompaniment of its power (Willis; Britton 99-123; 195-219). Among many possible recent examples: recall how Bond uses his ordinary cell phone camera to reveal the membership of the sinister Quantum group at an opera performance in Quantum of Solace; how world-wide video surveillance is depicted as inescapable (and amoral) in The Bourne Legacy; and how the anonymous protagonist of Roman Polanski’s Ghost Writer discovers the vital piece of top secret information that explains the entire film—by searching for it on his laptop via Google. In each of these cases, ICTs are represented as both incredibly powerful and tediously quotidian. More precisely, in each case human users are represented as interfaces between ICTs and their stored knowledge, rather than the reverse. Beginning with an account of how the naturalization of ICTs has changed the perceived relations between technology and its users, this essay argues that the promotional rhetoric of human empowerment and augmentation surrounding ICTs is opposed by a persistent cinematic theme of human subordination to technological needs. The question it seeks to open is why—why do the mainstream cinematic narratives of our culture depict the ICTs that enhance our capacities to know and communicate as something that diminishes rather than augments us? One answer (which can only be provisionally sketched here) is the loss of pleasure. It does not matter whether or not technology augments our capacities if it cannot sustain the fantasy of pleasure and/or enhancement at the same time. Without this fantasy, ICTs are represented as usurping position as the knowing subject and users, in turn, become the media connecting them– even when that user is James Bond. The Rhetoric of Augmentation Until the past five years or so, the technologization of the human mind was almost always represented in popular culture as a threat to humanity—whether it be Ira Levin’s robotic Stepford Wives as the debased expression of male wish-fulfillment (Levin), or Jonathan Demme’s brainwashed assassins with computer chip implants in his remake of The Manchurian Candidate. When Captain Picard, the leader and moral centre of the television series Star Trek: The Next Generation, is taken over by the Borg (an alien machine race that seeks to absorb other species into its technologized collective mind) in an episode from 1990, it is described as “assimilation” rather than an augmentation. The Borg version of Picard says to his former comrades that “we only wish to raise quality of life, for all species,” and it is a chilling, completely unemotional threat to the survival of our species (“Best of Both Worlds”). By 2012, on the other hand, the very same imagery is being used to sell smart phones by celebrating the technological enhancements that allegedly make us better human beings. In Verizon’s Droid DNA phone promotions, the product is depicted as an artificial heart for its user, one that enhances memory, “neural speed,” and “predictive intelligence” (thanks to Google Now). The tagline for the Verizon ad claims that “It’s not an upgrade to your phone; it’s an upgrade to yourself”, echoing Borg-Picard’s threat but this time as an aspirational promise (“Verizon Commercial”). The same technologization of the mind that was anathema just a few years ago, is now presented as both a desirable consumer goal and a professional necessity—the final close-up of the Verizon artificial heart shows that this 21st century cyborg has to be at his job in 26 minutes; the omnipresence of work in a networked world is here literally taken to heart. There is, notably, no promise of pleasure or liberation anywhere in this advertisement. We are meant to desire this product very much, but solely because it allows us to do more and better work. Not coincidentally, the period that witnessed this inversion in popular culture also saw an exponential increase in the quantity and variety of digitally networked devices in our lives (“Mobile Cellular”) and the emergence of serious cultural, scientific, and philosophical movements exploring the idea of “enhanced” human beings, whether through digital tool use, biomedical prostheses, drugs, or genetic modifications (Buchanan; Savulescu and Bostrom; “Humanity +”). As the material boundaries of the “human” have become more permeable and malleable, and as the technologies that make this possible become everyday objects, our resistance to this possibility has receded. The discourse of the transhuman and extropian is now firmly established as a philosophical possibility (Lilley). Personal augmentation with the promise of pleasure is still, of course, very much present in the presentation of ICTs. Launching the iPad 2 in 2011, the late Steve Jobs described his new product as a “magical and revolutionary device” with an “incredible magical user interface on a much larger canvas with more resources” and gushing that “it's technology married with liberal arts, married with the humanities, that yields us the result that makes our hearts sing” (“Apple Special Event”). This is the rhetoric of augmentation through technology and, as in the Verizon ad, it is very careful to position the consumer/user at the centre of the experience. The technology is described as wonderful not just in itself, but also precisely because it gives users “a larger canvas” with which to create. Likewise, the lifelogging movement (which encourages people to use small cameras to record every event of daily life) is at great pains to stress that “you, not your desktop’s hard drive, are the hub of your digital belongings” (Bell and Gemmell 10). But do users experience life with these devices as augmented? Is either the Verizon work cyborg or the iPad user’s singing heart representative of how these devices make us feel? It depends upon the context in which the question is asked. Extensive survey data on cell phone use shows that we are more attached than ever to our phones, that they allow us to be “productive” in otherwise dead times (such as while waiting in queues), and that only a minority of users worry about the negative effects of being “permanently connected” (Smith 9-10). Representations of technological augmentation in 21st century popular cinema, however, offer a very different perspective. Even in James Bond films, which (since Goldfinger in 1964) have been enraptured with technological devices as augmentations for its protagonists and as lures for audiences, digital devices have (in the three most recent films) lost their magic and become banal in the same way as they have in the lives of audience members (Nitins 2010; Nitins 2011; “List of James Bond Gadgets”). Rather than focusing on technological empowerment, the post 2006 Bond films emphasize (1) that ICTs “know” things and that human agents are just the media that connect them together; and (2) that the reciprocal nature of networked ICTs means that we are always visible when we use them; like Verizon phone users, our on-screen heroes have to learn that the same technology that empowers them simultaneously empowers others to know and/or control them. Using examples from the James Bond franchise, the remainder of this paper discusses the simultaneous disenchantment and power of ICT technology in the films as a representative sample of the cultural status of ICTs as a whole. “We don’t go in for that sort of thing any more...” From Goldfinger until the end of Pierce Brosnan’s tenure in 2002, technological devices were an important part of the audience’s pleasure in a Bond film (Willis; Nitins 2011). James Bond’s jetpack in Thunderball, to give one of many examples, is a quasi-magical aid for the hero with literary precursors going back to Aeneas’s golden bough; it is utterly enchanting and, equally importantly, fun. In the most recent Bond film, Skyfall, however, Q, the character who has historically made Bond’s technology, reappears after a two-film hiatus, but in the guise of a computer nerd who openly disdains the pleasures and possibilities of technological augmentation. When Bond complains about receiving only a gun and a radio from him, Q replies: “What did you expect? An exploding pen? We don’t really go in for that sort of thing any more.” Technology is henceforth to be banal and invisible albeit (as the film’s computer hacker villain Silva demonstrates) still incredibly powerful. The film’s pleasures must come from elsewhere. The post-credit sequence in Casino Royale, which involves the pursuit and eventual death of a terrorist bomb-maker, perfectly embodies the diminished importance of human agents as bearers of knowledge. It is bracketed at the beginning by the bomber looking at a text message while under surveillance by Bond and a colleague and at the end by Bond looking at the same message after having killed him. Significantly, the camera angle and setup of both shots make it impossible to distinguish between Bond’s hand and the bomber’s as they see the same piece of information on the same phone. The ideological, legal, racial, and other differences between the two men are erased in pursuit of the data (the name “Ellipsis” and a phone number) that they both covet. As digitally-transmitted data, it is there for anyone, completely unaffected by the moral or legal value attached to its users. Cell phones in these films are, in many ways, better sources of information than their owners—after killing a phone’s owner, his or her network traces can show exactly where s/he has been and to whom s/he has been talking, and this is how Bond proceeds. The bomber’s phone contacts lead Bond to the Bahamas, to the next villain in the chain, whom Bond kills and from whom he obtains another cell phone, which allows the next narrative location to be established (Miami Airport) and the next villain to be located (by calling his cell phone in a crowded room and seeing who answers) (Demetrios). There are no conventional interrogations needed here, because it is the digital devices that are the locus of knowledge rather than people. Even Bond’s lover Vesper Lynd sends her most important message to him (the name and cell phone number of the film’s arch villain) in a posthumous text, rather than in an actual conversation. Cell phones do not enable communication between people; people connect the important information that cell phones hold together. The second manifestation of the disenchantment of ICT technology is the disempowering omnipresence of surveillance. Bond and his colleague are noticed by the bomber when the colleague touches his supposedly invisible communication earpiece. With the audience’s point of view conflated with that of the secret agent, the technology of concealment becomes precisely what reveals the secret agent’s identity in the midst of a chaotic scene in which staying anonymous should be the easiest thing in the world; other villains identify Bond by the same means in a hotel hallway later in the film. While chasing the bomber, Bond is recorded by a surveillance camera in the act of killing him on the grounds of a foreign embassy. The secret agent is, as a result, made into an object of knowledge for the international media, prompting M (Bond’s boss) to exclaim that their political masters “don’t care what we do, they care what we get photographed doing.” Bond is henceforth part of the mediascape, so well known as a spy that he refuses to use the alias that MI6 provides for his climactic encounter with the main villain LeChiffre on the grounds that any well-connected master criminal will know who he is anyway. This can, of course, go both ways: Bond uses the omnipresence of surveillance to find another of his targets by using the security cameras of a casino. This one image contains many layers of reference—Bond the character has found his man; he has also found an iconic image from his own cultural past (the Aston Martin DB V car that is the only clearly delineated object in the frame) that he cannot understand as such because Casino Royale is a “reboot” and he has only just become 007. But the audience knows what it means and can insert this incarnation of James Bond in its historical sequence and enjoy the allusion to a past of which Bond is oblivious. The point is that surveillance is omnipresent, anonymity is impossible, and we are always being watched and interpreted by someone. This is true in the film’s narrative and also in the cultural/historical contexts in which the Bond films operate. It may be better to be the watcher rather than the watched, but we are always already both. By the end of the film, Bond is literally being framed by technological devices and becomes the organic connection between different pieces of technology. The literal centrality of the human agent in these images is not, in this disenchanted landscape, an indication of his importance. The cell phones to which Bond listens in these images connect him (and us) to the past, the back story or context provided by his masters that permits the audience to understand the complex plot that is unfolding before them. The devices at which he looks represent the future, the next situation or person that he must contain. He does not fully understand what is happening, but he is not there to understand – he is there to join the information held in the various devices together, which (in this film) usually means to kill someone. The third image in this sequence is from the final scene of the film, and the assault rifle marks this end—the chain of cell phone messages (direct and indirect) that has driven Casino Royale from its outset has been stopped. The narrative stops with it. Bond’s centrality amid these ICTS and their messages is simultaneously what allows him to complete his mission and what subjects him to their needs. This kind of technological power can be so banal precisely because it has been stripped of pleasure and of any kind of mystique. The conclusion of Skyfall reinforces this by inverting all of the norms that Bond films have created about their climaxes: instead of the technologically-empowered villain’s lair being destroyed, it is Bond’s childhood home that is blown up. Rather than beating the computer hacker at his own game, Bond kills him with a knife in a medieval Scottish church. It could hardly be less hi-tech if it tried, which is precisely the point. What the Bond franchise and the other films mentioned above have shown us, is that we do not rely on ICTs for enchantment any more because they are so powerfully connected to the everyday reality of work and to the loss of privacy that our digital devices exact as the price of their use. The advertising materials that sell them to us have to rely on the rhetoric of augmentation, but these films are signs that we do not experience them as empowering devices any more. The deeper irony is that (for once) the ICT consumer products being advertised to us today really do what their promotional materials claim: they are faster, more powerful, and more widely applicable in our lives than ever before. Without the user fantasy of augmentation, however, this truth has very little power to move us. We depict ourselves as the medium, and it is our digital devices that bear the message.References“Apple Special Event. March 2, 2011.” Apple Events. 21 Sep. 2013 ‹http://events.apple.com.edgesuite.net/1103pijanbdvaaj/event/index.html›. Bell, Gordon, and Jim Gemmell. Total Recall: How the E-Memory Revolution Will Change Everything. New York: Dutton, 2009.“The Best of Both Worlds: Part Two.” Star Trek: The Next Generation. Dir. Cliff Bole. Paramount, 2013. The Bourne Legacy. Dir. 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