Articoli di riviste: "Nathaniel J"

1

Browne, Ray B. "Mayflower by Nathaniel Philbrick". Journal of American Culture 30, n. 2 (giugno 2007): 249–50. http://dx.doi.org/10.1111/j.1542-734x.2007.00532.x.

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2

Campbell, Gordon. "Nathaniel Tovey: Milton's Second Tutor". Milton Quarterly 21, n. 3 (ottobre 1987): 81–90. http://dx.doi.org/10.1111/j.1094-348x.1987.tb00719.x.

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3

Waite, James J. "Nathaniel Hawthorne and the Feminine Ethos". Journal of American Culture 11, n. 4 (dicembre 1988): 23–33. http://dx.doi.org/10.1111/j.1542-734x.1988.1104_23.x.

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4

McConnell, Anita. "Pen portraits of Presidents - Nathaniel Beardmore". Weather 55, n. 9 (settembre 2000): 325–27. http://dx.doi.org/10.1002/j.1477-8696.2000.tb04087.x.

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5

Golinelli, Paola. "Different Architectures of Creativity: Louis and Nathaniel Kahn". Psychoanalytic Quarterly 83, n. 2 (aprile 2014): 441–64. http://dx.doi.org/10.1002/j.2167-4086.2014.00098.x.

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MOORE, JUDGE EUGENE A. "Sentencing Opinion: People of the State of Michigan v Nathaniel Abraham". Juvenile and Family Court Journal 51, n. 2 (aprile 2000): 1–11. http://dx.doi.org/10.1111/j.1755-6988.2000.tb00017.x.

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Claudia, Kemfert. "Markets and the Environment by Nathaniel O. Keohane and Sheila M. Olmstead". Agricultural Economics 38, n. 3 (maggio 2008): 385–87. http://dx.doi.org/10.1111/j.1574-0862.2008.00308.x.

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McLaughlin, John L. "Images of Others: Iconic Politics in Ancient Israel - By Nathaniel B. Levtow". Religious Studies Review 37, n. 3 (settembre 2011): 204. http://dx.doi.org/10.1111/j.1748-0922.2011.01534_7.x.

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Labriola, Patrick. "Ludwig Tieck and Nathaniel Hawthorne: The Fairy Tale and the Popular Legend". Journal of Popular Culture 38, n. 2 (novembre 2004): 325–32. http://dx.doi.org/10.1111/j.0022-3840.2004.00115.x.

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Buol, Justin. "Death’s Dominion: Power, Identity, and Memory at the Fourth-Century Martyr Shrine by Nathaniel J. Morehouse". Journal of Early Christian Studies 26, n. 4 (2018): 674–75. http://dx.doi.org/10.1353/earl.2018.0062.

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Teufel, Thomas. "Review: Nathaniel J. Goldberg.Kantian Conceptual Geography. Oxford: Oxford University Press, 2015. 271 + xiii pages; $74/hardcover." Philosophical Forum 47, n. 1 (9 febbraio 2016): 79–82. http://dx.doi.org/10.1111/phil.12100.

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Black, Jeremy. "AN UNDERRATED JOURNALIST: NATHANIEL MIST AND THE OPPOSITION PRESS DURING THE WHIG ASCENDENCY*". Journal for Eighteenth-Century Studies 10, n. 1 (1 ottobre 2008): 27–41. http://dx.doi.org/10.1111/j.1754-0208.1987.tb00003.x.

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FARRELL, STEPHEN. "Nathaniel Clements: Government and the Governing Elite in Ireland, 1725-75 - By A.P.W. Malcomson". Parliamentary History 27, n. 2 (10 settembre 2008): 293–96. http://dx.doi.org/10.1111/j.1750-0206.2008.00041_12.x.

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Kirkland, Russell. "Selfless Offspring: Filial Children and Social Order in Medieval China ? By Keith Nathaniel Knapp". Religious Studies Review 33, n. 1 (gennaio 2007): 82. http://dx.doi.org/10.1111/j.1748-0922.2007.00156_1.x.

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MCGRAW, BRYAN T. "THE MORALITY OF SPIN: VIRTUE AND VICE IN POLITICAL RHETORIC AND THE CHRISTIAN RIGHT by Nathaniel J. Klemp". Journal for the Scientific Study of Religion 51, n. 4 (dicembre 2012): 822–24. http://dx.doi.org/10.1111/j.1468-5906.2012.01688.x.

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Urban, Nathaniel N., Darrell A. Henze e German Barrionuevo. "Amplification of Perforant-Path EPSPs in CA3 Pyramidal Cells by LVA Calcium and Sodium Channels". Journal of Neurophysiology 80, n. 3 (1 settembre 1998): 1558–61. http://dx.doi.org/10.1152/jn.1998.80.3.1558.

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Urban, Nathaniel N., Darrell A. Henze, and German Barrionuevo. Amplification of perforant-path EPSPs in CA3 pyramidal cells by LVA calcium and sodium channels. J. Neurophysiol. 80: 1558–1561, 1998. The perforant path forms a monosynaptic connection between the cells of layer II of the entorhinal cortex and the pyramidal cells in hippocampal area CA3. Although this projection is prominent anatomically, very little is known about the physiological properties of this input. The distal location of these synapses suggests that somatically recorded perforant-path excitatory postsynaptic potentials (EPSPs) may be influenced by the activation of voltage-dependent channels in CA3 cells. We observed that perforant-path EPSPs are reduced (by ∼25%) by blockade of postsynaptic low-voltage–activated calcium and sodium channels, indicating that perforant-path EPSPs are amplified by the activation of these channels. These data suggest that the perforant path may represent an important and highly modifiable direct connection between the entorhinal cortex and area CA3.

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Nisbet, Jack. "Forest Under Story: Creative Inquiry in an Old-Growth Forest by Nathaniel Brodie, Charles Goodrich, and Frederick J. Swanson". Oregon Historical Quarterly 119, n. 1 (2018): 140. http://dx.doi.org/10.1353/ohq.2018.0069.

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18

Petrosino, Anthony J. "Book Review : Rehabilitating Criminal Sexual Psychopaths: Legislative Mandates, Clinical Quandaries by Nathaniel J. Pallone New Brunswick, NJ: Transaction, 1990". Journal of Contemporary Criminal Justice 7, n. 3 (agosto 1991): 202–3. http://dx.doi.org/10.1177/104398629100700308.

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19

Kjellmer, Göran, Ann-Marie Svensson, Monica Malm, Paul Goulding, Ronald Paul, Nathaniel Chase, Alan McGee et al. "Reviews and notices". Moderna Språk 92, n. 1 (1 giugno 1998): 100–120. http://dx.doi.org/10.58221/mosp.v92i1.9847.

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Includes the following reviews:pp. 100-102. Göran Kjellmer. Hill, J. & Lewis, M. (eds), Dictionary of Selected Collocations. pp. 102-103. Ann-Marie Svensson. Lass, R., Historical linguistics and language change. p. 103. Monica Malm. Cixous, H. & Calle-Gruber, M., Rootprints: Memory and Life Writing. p. 104. Paul Goulding. Storry, M. & Childs, P. (ed.), British Cultural Identities. p. 105. Ronald Paul. Young, G., From Sea to Shining Sea: a present-day journey into America's past. pp. 105-106. Monica Malm. Coupe, L., Myth. pp. 106-107. Nathaniel Chase. Modiano, M., A Mid-Atlantic Handbook. American and British English. p. 107. Alan McGee. Bowen, T., Build Your Business Grammar. pp. 107-108. Alan McGee. Comfort, J., Effective Socializing. pp. 108. Alan McGee. Mackenzie, I., Management and Marketing. pp. 109-110. Edelgard Biedermann. Besch, W., Duzen, Siezen, Titulieren: Zur Anrede im Deutschen heute und gestern. pp. 110-111. Stefan Neuhaus. Cumart, N., Zwei Welten. Gedichte. pp. 112-113. Stefan Neuhaus. Fontane, T., Englischer Sommer. pp. 113-115. Hans-Roland Johnsson. Brown, F., Zola, A Life. pp. 115-118. Karl-Anders Arvidsson. Le Nouveau Petit Robert électronique. pp. 118-120. Gabriella Villagrán Backman. Foster, D.W., Mexican Literature: A History.

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20

Aman, Mohammed M. "Siege: Crisis Leadership The Survival of the U.S. Embassy Kuwait: Roberta Culbertson and W. Nathaniel Howell". Digest of Middle East Studies 10, n. 2 (gennaio 2001): 56–57. http://dx.doi.org/10.1111/j.1949-3606.2001.tb00424.x.

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21

Rapaport, David. "I seminari di David Rapaport del 1957 sulla metapsicologia". PSICOTERAPIA E SCIENZE UMANE, n. 3 (settembre 2020): 357–59. http://dx.doi.org/10.3280/pu2020-003001.

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Nel 1957 David Rapaport (1911-1960) tenne una serie di seminari sulla metapsicologia psicoanalitica agli allievi del primo anno del Western New England Institute for Psychoanalysis (New Haven, Connecticut). Questi seminari, trascritti verbatim, non furono mai pubblicati, ma solo dattiloscritti e divisi in sette volumi curati da Stuart C. Miller nel 1959, i primi tre di "metapsicologia elementare" e gli altri quattro di "metapsicologia avanzata", per un totale di circa 700 pagine. I partecipanti erano, oltre a Rapaport che era sempre presente, Helen G. Gilmore, Nathaniel J. London, Seymour L. Lustman, George F. Mahl, Stuart C. Miller, John P. Plunkett, Herbert S. Sacks, Roy Schafer, Virginia Suttenfield e Robert B. White (in alcuni casi erano presenti Paul E. Emery, Jean Schimek, David Shapiro, Eugene Talbot, Eugene E. Trunnel, Ess A. White Jr.). Qui, dopo una Nota redazionale, vengono pubblicati " per mostrare il metodo di lavoro di Rapaport " i programmi dettagliati dei seminari (con l'elenco dei riferimenti bibliografici da leggere e dei "compiti assegnati") e il testo di una parte di un seminario, le pagine iniziali del primo dei quattro volumi di metapsicologia avanzata.

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22

Sen, Piyal. "Tinder-box criminal aggression. By Nathaniel J. Pallone and James J. Hennessy. Transaction Publishers, New Brunswick, NJ 08903, USA, 1996, 389 pp. ISBN 1-56000-253-0". Criminal Behaviour and Mental Health 8, n. 2 (giugno 1998): 158–59. http://dx.doi.org/10.1002/cbm.236.

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23

McLoughlin, John Grant. "Solutions to Calendar". Mathematics Teacher 90, n. 3 (marzo 1997): 218–19. http://dx.doi.org/10.5951/mt.90.3.0218.

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Problems 1–5 were contributed by Michael A. Steuben, 4651 Brentleigh Court, Annandale, VA 22003. Problems 6–11 were prepared by Peter Booth of the Mathematics and Statistics Department of Memorial University of Newfoundland, StJohn's, NF A1C 5S7. Problems 15–12 (working backward) were offered by William H. Kraus, Wittenberg University, Springfield, OH 45501. Problems 16–18 represent the contribution of James E. Beamer and Bikkar S. Randhawa of the University of Saskatchewan. Saskatoon, SK S7N OWO, and Cheuk Ng of Athabaska University, Athebaska. Alberta. Problems 19, 20, and 22 were provided by Barry Scully, York Region Board of Education, Aurora, ON lAG 3H2. Problems 21 and 23–26 were prepared by students in Betty J. Thomson's History of Math class at the Community College of Rhode Island, Warwick, RI 02886. The students were Marg McLellan, Laurie Nayman, Christine Nye, Diane Pardini, Andre Sabo, and Rick Wilson. Problem 27 was taken from 101 Puzzle Problems by Nathaniel B. Bates and Sanderson M. Smith (Concord, Mass.: Bates Publishing Co., 1980). Problems 28–31 were originally prepared for the Hamilton Junior Mathematics Contest by Eileen Shannon, Westmount Secondary School, Hamilton, Ontario, who generously provided them for the Calendar.

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24

Dillard, Daniel C. "Inventing America's “Worst” Family: Eugenics, Islam, and the Fall and Rise of the Tribe of Ishmael - By Nathaniel Deutsch". Religious Studies Review 37, n. 3 (settembre 2011): 230. http://dx.doi.org/10.1111/j.1748-0922.2011.01542_5.x.

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25

VANDOME, ROBIN. "American Scientists and Their Fictions: Professional Authorship and Intellectual Identity, 1870–1900". Journal of American Studies 53, n. 2 (13 dicembre 2017): 478–506. http://dx.doi.org/10.1017/s0021875817001852.

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Writers and critics in the Gilded Age United States frequently debated the relations between literature and science. A common contemporary interpretation of this relationship held that these two ways of knowing and writing were fundamentally opposed and that the advancement of science in American culture came at the expense of literary sensibilities. Nevertheless, and often as an effort to challenge this supposed opposition, many scientists also cultivated reputations as literary figures, and produced or planned diverse works ranging from travel writing and novels to verse drama. Such authors as Clarence King, J. Peter Lesley, Simon Newcomb and Nathaniel Southgate Shaler sustained a hybrid literary–scientific culture in the late nineteenth century. This interdisciplinary cultural zone was fragile and increasingly fractured by around 1900, as the emergence and consolidation of new categories of intellectual labour became increasingly wedded to the images of the “professional author” and the “scientist” as mutually exclusive identities. This article seeks to contribute to recurrent debates about the “two cultures” of literature and science by foregrounding the differentiation of these new forms of professional and intellectual identity as a decisive factor which constrained the possibility of a shared literary–scientific culture by the turn of the twentieth century.

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Pritchett, Lant. "Robert William Fogel, Enid M. Fogel, Mark Guglielmo, and Nathaniel Grotte,Political Arithmetic: Simon Kuznets and the Empirical Tradition in Economics". Population and Development Review 40, n. 1 (marzo 2014): 170. http://dx.doi.org/10.1111/j.1728-4457.2014.00658.x.

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27

Berzhanskaya, Julia, Nathaniel N. Urban e German Barrionuevo. "Electrophysiological and Pharmacological Characterization of the Direct Perforant Path Input to Hippocampal Area CA3". Journal of Neurophysiology 79, n. 4 (1 aprile 1998): 2111–18. http://dx.doi.org/10.1152/jn.1998.79.4.2111.

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Berzhanskaya, Julia, Nathaniel N. Urban, and German Barrionuevo. Electrophysiological and pharmacological characterization of the direct perforant path input to hippocampal area CA3. J. Neurophysiol. 79: 2111–2118, 1998. Monosynaptic perforant path responses evoked by subicular stimulation were recorded from CA3 pyramidal cells of rat hippocampal slices. These monosynaptic responses were isolated by using low intensities of stimulation and by placing a cut through the mossy fibers. Perforant path–evoked responses consisted of both excitatory and inhibitory components. Excitatory postsynaptic currents (EPSCs) were mediated by both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidreceptors (AMPAR) and N-methyl-d-aspartate receptors (NMDAR).Inhibitory postsynaptic currents consisted of γ-aminobutyric acid-A (GABAA-) and -B (GABAB)-receptor–mediated components. At membrane potentials more positive than -60 mV and at physiological [Ca2+]/[Mg2+] ratios, >30% of perforant path evoked EPSC was mediated by NMDARs. This value varied as a function of the membrane voltage and external [Mg2+]. Two types of responses were observed after low-intensity stimulation of the perforant path. The first type of response showed paired-pulse facilitation and was reduced by 2-amino-4-phosphonobutyric acid (AP4). The second type of response showed paired-pulse depression and was reduced by baclofen. Electrophysiological and pharmacological characteristics of these two types of responses are similar to the properties of lateral and medial perforant path–evoked EPSPs in the dentate gyrus.

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28

Sopiarz, Josh. "Untapped: Exploring the Cultural Dimensions of Craft Beer Nathaniel G. Chapman, J. Slade Lellock, and Cameron D. Lippard, Editors. West Virginia University Press, 2017." Journal of American Culture 41, n. 3 (settembre 2018): 342–43. http://dx.doi.org/10.1111/jacc.12956.

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29

Roberts, Albert R. "Prologue and Introduction to Sex Offender Treatment and Research: A Tribute to Professor Nathaniel J. Pallone Including Testimonials from James Finckenauer and Irving Louis Horowitz". Victims & Offenders 3, n. 1 (15 gennaio 2008): 1–7. http://dx.doi.org/10.1080/15564880701810120.

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30

Buchanan, Alec. "Tinder-Box Criminal Aggression By Nathaniel J. Pallone and James Hennessy. New Jersey: Transaction Publishers. 1996. 401 pp. £39.95 (hb). ISBN 1-56 000253-0". British Journal of Psychiatry 171, n. 6 (dicembre 1997): 589. http://dx.doi.org/10.1192/s0007125000148883.

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31

Shtakser, Inna. "The Jewish Dark Continent: Life and Death in the Russian Pale of Settlement. By Nathaniel Deutsch. (Cambridge, MA: Harvard University Press, 2011. Pp. 374. $35.00.)". Historian 74, n. 4 (1 dicembre 2012): 872–74. http://dx.doi.org/10.1111/j.1540-6563.2012.00334_46.x.

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Bartels, Brandon L. "Public Opinion and Constitutional Controversy. Edited by Nathaniel Persily, Jack Citrin, and Patrick J. Egan. New York: Oxford University Press, 2008. 376p. $99.00 cloth, $29.95, paper." Perspectives on Politics 8, n. 3 (23 agosto 2010): 960–61. http://dx.doi.org/10.1017/s1537592710001751.

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33

Hart, Roderick P. "The Morality of Spin: Virtue and Vice in Political Rhetoric and the Christian Right. By Nathaniel J. Klemp. Lanham, MD: Rowman & Littlefield, 2012. 199p. $66.50." Perspectives on Politics 12, n. 2 (giugno 2014): 495–96. http://dx.doi.org/10.1017/s1537592714001200.

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34

Stampfer, Shaul. "The Jewish Dark Continent: Life and Death in the Russian Pale of Settlement. By Nathaniel Deutsch. Cambridge, MA: Harvard University Press, 2011. Pp. vii + 374; map. Cloth, $35.00." Religious Studies Review 38, n. 4 (dicembre 2012): 250. http://dx.doi.org/10.1111/j.1748-0922.2012.01657_3.x.

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Henze, Darrell A., Nathaniel N. Urban e German Barrionuevo. "Origin of the Apparent Asynchronous Activity of Hippocampal Mossy Fibers". Journal of Neurophysiology 78, n. 1 (1 luglio 1997): 24–30. http://dx.doi.org/10.1152/jn.1997.78.1.24.

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Henze, Darrell A., Nathaniel N. Urban, and German Barrionuevo. Origin of the apparent asynchronous activity of hippocampal mossy fibers. J. Neurophysiol. 78: 24–30, 1997. Fiber volleys (FVs) from the stratum lucidum of rat hippocampal area CA3 were recorded extracellularly from in vitro slices in the presence of 10 mM kynurenic acid. In agreement with previous work, bulk stimulation of the dentate gyrus (DG) near the hilar border leads to an asynchronous FV. Transection of the stratum lucidum between the DG stimulation site and the CA3 recording site reduced or eliminated the early components of the asynchronous FV, indicating that they are of mossy fiber (MF) origin. In contrast, moving the stimulating electrode away from the hilus toward the hippocampal fissure reduced or eliminated the late components of the FV. Subsequently, we found that bulk stimulation on the DG/hilar border induces an antidromic population spike in CA3 pyramidal cells. Finally, the MFs and associational collaterals have differentconduction velocities (0.51 and 0.37 m/s, respectively; temperature =33°C). From these data, we conclude that the late components of the asynchronous FV are due to antidromic activation of CA3 collaterals that have been shown to be present in the DG and hilus. A corollary of these findings is that bulk stimulation on the DG/hilar border can lead to at least two different monosynaptic inputs to CA3 pyramidal cells: the MFs and the antidromically activated associational collaterals. We suggest that when MF synaptic responses are being evoked with the use of bulk stimulation, stimulating electrodes should be placed in the outer molecular layer of the DG to prevent the activation of hilar-projecting associational collaterals. This procedure should be added to the previously proposed criteria for preventing polysynaptic contamination of the intracellularly recorded evoked MF synaptic response.

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Lim, Junghyun, Ryan Rodriguez, Katherine Williams, John Silva, Alan Gutierrez, Paul Tyler, Faezzah Baharom et al. "Abstract LB361: The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated anti-tumor immunity". Cancer Research 84, n. 7_Supplement (5 aprile 2024): LB361. http://dx.doi.org/10.1158/1538-7445.am2024-lb361.

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Abstract The DNA exonuclease TREX1 (Three-prime repair exonuclease 1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. Since tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here we show, that in tumor cells TREX1 indeed restricts the spontaneous activation of the cGAS/STING pathway and the subsequent induction of a type I IFN response. As a result, TREX1 deficiency compromised in vivo tumor growth in mice. This delay depended on a functional immune system, systemic type I IFN signaling, and tumor-intrinsic cGAS expression. Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion and remodeled an immunosuppressive myeloid compartment. Consequently, TREX1 deficiency synergized with T cell directed immune checkpoint blockade. Collectively, we conclude that TREX1 is essential to limit tumor immunogenicity, and that targeting this innate immune checkpoint remodels the tumor microenvironment and enhances anti-tumor immunity by itself and in combination with T cell-targeted therapies. Citation Format: Junghyun Lim, Ryan Rodriguez, Katherine Williams, John Silva, Alan Gutierrez, Paul Tyler, Faezzah Baharom, Tao Sun, Eva Lin, Scott Martin, Brandon Kayser, Robert J. Johnston, Ira Mellman, Lélia Delamarre, Nathaniel West, Sören Müller, Yan Qu, Klaus Heger. The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB361.

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Ferrara, Marianna. "Andrade, Nathanael J. (2018). The Journey of Christianity to India in Late Antiquity. Networks and the Movement of Culture". ARYS. Antigüedad: Religiones y Sociedades, n. 18 (14 dicembre 2020): 377. http://dx.doi.org/10.20318/arys.2020.5549.

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ANDRADE, NATHANAEL J. (2018). The Journey of Christianity to India in Late Antiquity. Networks and the Movement of Culture. Cambridge: Cambridge University Press. 312 pp., 64,46€ [ISBN 978-1-1082-9695-3] [Reseña]

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38

Yon, Jean-Baptiste. "Nathanael J. Andrade. Zenobia: Shooting Star of Palmyra." American Historical Review 125, n. 5 (dicembre 2020): 1943–44. http://dx.doi.org/10.1093/ahr/rhz1254.

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Drake, Justin M., Kaylee J. Kamalanathan, Catalina Galeano-Garces, Nathaniel Bristow, Nicholas Heller, Mahdi Ahmadi, Olivia Hedeen et al. "Abstract 6078: Circulating tumor cell-based early detection of breast cancer". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 6078. http://dx.doi.org/10.1158/1538-7445.am2024-6078.

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Abstract Although mammograms have been a useful tool since the first half of the 20th century and have an acceptable sensitivity (87%) in the general population, that drops to <50% in women with dense breasts making it an ineffective screening tool in this population. Cell free DNA (cfDNA) has proven to be an inadequate alternative in this population, and while MRI is acceptable, it is expensive. Astrin Biosciences has developed a blood-based assay that detects circulating tumor cells (CTCs) at a high sensitivity to serve as an alternative screening method to mammography in breast cancer early detection, specifically in women with high-density breasts. Astrin’s technology integrates holographic imaging, machine learning, and microfluidics to identify CTCs in the blood stream. Omics analysis can then be performed on the collected cells to further differentiate patients with cancer from matched healthy controls. Astrin has initiated a small cohort study to investigate the sensitivity and specificity of CTC detection in women with early-stage breast cancer. Astrin’s small cohort study, including patients with ductal carcinoma in situ, stage 1, and stage 2 breast cancer patients, demonstrated > 85% sensitivity and specificity. A large cohort study is being conducted to validate these preliminary results. The small cohort study demonstrates the ability of Astrin Bioscience’s platform to detect cancer cells at an early stage, particularly in breast cancer. This technology will drastically increase the effectiveness of breast cancer screening modalities available to patients. Additionally, since it is a blood-based assay, it can be performed at shorter intervals in high-risk populations than mammograms which require a full patient appointment. Citation Format: Justin M. Drake, Kaylee J. Kamalanathan, Catalina Galeano-Garces, Nathaniel Bristow, Nicholas Heller, Mahdi Ahmadi, Olivia Hedeen, Alexa Hesch, Grant Schaap, Joel Hapke, Jeff Miller, Ivo Babris, Tuan Le, Tony Clacko, Jiarong Hong, Badri Konety, Jayant Parthasarathy. Circulating tumor cell-based early detection of breast cancer [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 6078.

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Schor, Adam M. "Nathanael J. Andrade.Syrian Identity in the Greco-Roman World." American Historical Review 120, n. 5 (dicembre 2015): 1950–51. http://dx.doi.org/10.1093/ahr/120.5.1950.

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41

Roper, Brad L. "A Primer on Common Practices in Clinical Neuropsychology - Specialty Competencies in Clinical Neuropsychology: A Primer on Common Practices, by Gregory J. Lamberty & Nathaniel W. Nelson. 2012. New York: Oxford University Press, 194 pp., $49.99, (PB)." Journal of the International Neuropsychological Society 19, n. 2 (febbraio 2013): 227–28. http://dx.doi.org/10.1017/s1355617713000052.

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42

Sághy, Marianne. "Death's dominion. Power, identity and memory at the fourth-century martyr shrine. By Nathaniel J. Morehouse. (Studies in Ancient Religion Culture.) Pp. viii + 203. Sheffield–Bristol, Ct: Equinox Press, 2016. £22 (paper). 978 1 78179 082 3". Journal of Ecclesiastical History 69, n. 3 (luglio 2018): 614–16. http://dx.doi.org/10.1017/s0022046918000374.

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Goldberg, Zelanna, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou et al. "Abstract 2732: A self-replicating RNA precision medicine approach to therapeutic protein delivery of narrow therapeutic index biomolecules". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 2732. http://dx.doi.org/10.1158/1538-7445.am2023-2732.

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Abstract Protein drug replacement using nucleic acid technologies has been a sought-after solution for in situ production of proteins with poor half-lives and challenging manufacturability. Linear mRNA approaches have failed clinically in this technological use case due to low levels of protein expression and poor durability. Self-replicating RNA (srRNA) is a new technology for expression of biotherapeutics combining the advantages of fully synthetic drug products with higher peak levels of protein expression with active expression persisting out to 49 days. RBI-2000 is a novel srRNA encapsulated in a lipid nanoparticle and encoding two distinct proteins on the same strand of RNA. The first protein is a pro-inflammatory multimeric cytokine to promote de novo immune cell generation and infiltration. The second molecule is a single chain high affinity protein antagonist of downstream mediators of the inflammasome to prevent sterile inflammation, aberrant angiogenesis, and tumor invasiveness. We selected a novel alphaviral vector which demonstrated an enhanced peak level of protein expression vs. the prototypical vector that has been used in other RNA products. These encoded proteins elicited a pharmacodynamic response that had no evidence of decay in the first 7 days following a single treatment down to doses of 0.01 mcg. Using an implanted MC38 tumor model, tumor control was obtained at the lowest, single dose tested at 0.1 mcg of RBI-2000. When tested in combination with a checkpoint inhibitor (CPI), a single dose of the CPI and a single dose of RBI-2000 at 10 mcg resulted in 80% tumor control in the mice (8/10 mice). Tumor re-challenge of the mice at a site distal to the original implantation showed 100% protection. Collectively, these data demonstrate the feasibility of novel srRNA vectors as a protein drug replacement approach including for the expression of complex, multimeric cocktails of proteins. Citation Format: Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Christopher A. Rabiola, Erika J. Crosby, Zachary C. Hartman, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad. A self-replicating RNA precision medicine approach to therapeutic protein delivery of narrow therapeutic index biomolecules [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 2732.

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Goldberg, Zelanna, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou et al. "Abstract 6403: A self-replicating RNA precision medicine approach to overcoming resistance to endocrine therapy in ER+BC". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 6403. http://dx.doi.org/10.1158/1538-7445.am2023-6403.

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Abstract Drug resistance remains the major driving factor behind the clinical failure of targeted therapeutics. Current oncology precision medicine approaches rely on targeting known acquired resistance mutations, such as EGFR T790M or ALK/ROS mutations in NSCLC with 2nd and 3rd generation molecules designed to overcome or prevent resistance. These next generation targeted therapeutic approaches have increasingly long and complex drug development timelines and burdensome toxicities from off target effects (e.g. wild-type receptor targeting) or drug-drug interactions (DDI). The toxicities limit tolerability, compliance and combinability of different targeted therapeutics. RNA-based immunotherapy approaches offer an increasingly attractive alternative to next generation small molecule targeted therapeutics approaches: (1) RNA-based approaches only require a known acquired resistance sequence, (2) drug development timelines, cost and complexity can be meaningfully condensed, and (3) multiple acquired resistance mutations can be targeted with the same candidate. RBI-1000 is a candidate using a novel type of self-replicating RNA (srRNA) to generate robust immunity directed against acquired resistance mutations that develop in ER+ breast cancer (ER+ BC) in response to endocrine therapy. RBI-1000 includes on-target mutations within the estrogen receptor ligand binding domain, and bypass mutations either in the form of activating mutations in the PI3K kinase domain or amplifications of HER2/HER3. Here, we demonstrate that this srRNA encapsulated in a lipid nanoparticle primes polyfunctional CD4 and CD8 T cells leading to tumor growth inhibition and improved survival in a mouse model expressing the targeted acquired resistance mutation. Priming of T cells against acquired mutations is also confirmed in human HLA-transgenic mice. The immune cell-mediated elimination of clones expressing the acquired resistance mutations is predicted to prolong endocrine control of ER+BC, in an analogous manner to small molecule or monoclonal antibody targeted therapies, but with a more favorable dosing and adverse event profile due to precise immunologic targeting and no DDI. Citation Format: Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Zachary C. Hartman, Christopher A. Rabiola, Erika J. Crosby, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad. A self-replicating RNA precision medicine approach to overcoming resistance to endocrine therapy in ER+BC. [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 6403.

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Klomp, Jennifer E., Jeff A. Klomp, Nathaniel J. Diehl, Cole A. Edwards, Kristina Drizyte-Miller, Priya S. Hibshman, Runying Yang et al. "Abstract B034: Determination of KRAS- and ERK-regulated phosphoproteomes in KRAS-mutant cancers". Molecular Cancer Research 21, n. 5_Supplement (1 maggio 2023): B034. http://dx.doi.org/10.1158/1557-3125.ras23-b034.

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Abstract Direct inhibitors of mutationally activated KRAS are currently under intense preclinical and clinical development, with one KRASG12C mutant-selective inhibitor approved. However, treatment-associated resistance to KRASG12C inhibitors has been reported, with ~60% of relapsed patients acquiring mutations in signaling components both upstream and downstream, and at the level of RAS itself, that led to reactivation of RAF-MEK-ERK and PI3K-AKT effector pathways. Unexpectedly, we found that ectopic expression of constitutively activated MEK1, ERK1 or ERK2, but not AKT1, drove near-complete resistance to direct inhibitors of KRASG12C or KRASG12D in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). Despite comprehensive studies, how ERK supports KRAS-dependent cancer growth remains poorly understood. Therefore, we focused on delineating the ERK-dependent phosphoproteome. We treated a panel of six KRAS-mutant PDAC cell lines acutely (1 h) and long-term (24 h) with the highly selective ERK1/2 inhibitor SCH772984. Our proteomics analyses identified 5,117 phosphosites on 2,252 proteins significantly dysregulated by ERK inhibition. We first compared our PDAC ERK phosphoproteome with a recent compendium of published direct/indirect ERK substrates identified in non-PDAC cells and found, surprisingly, only 12% overlap. Thus, our dataset substaintially extends the complexity of ERK-regulated phosphoproteins, in part, reflecting a pancreatic cancer selective profile. To elucidate the kinase network that drives our PDAC ERK-dependent phosphoproteome, we utilized our newly described global atlas of kinase-substrate specificities and reported kinase-substrate interaction datasets. This revealed a highly dynamic kinome dominated by ERK at 1 h, then dominated by ERK-regulation of CDK1-6 cell cycle components and RHO GTPase signaling. Next, we established the subcellular distribution of the PDAC ERK phosphoproteome, then evaluated data from DepMap, and found enrichment of nuclear ERK substrates that displayed strong dependencies in PDAC. We also determined the KRASG12C-regulated phosphoproteome in pancreatic, lung, and colorectal cancer cells using the KRASG12C selective inhibitor MRTX1257. We used our global atlas of kinase-motif specificities and ERK-regulated phosphoproteome to determine KRAS-regulated signaling pathways in KRASG12C mutant cancers. We found a high correlation between KRAS- and ERK-regulated phosphorylations, primarily driven by CDK substrates. However, we also noted key differences, principally in DNA damage response pathways not identified in our ERK-regulated phosphoproteome. Finally, we performed a high-throughput drug sensitivity and resistance screen of (DSRT) comprised of >500 clinically actionable drugs in combination with a KRASG12C inhibitor, and found ERK inhibitors as top hits. In summary, our studies establish a comprehensive profile of KRAS-ERK signaling output that may define new therapeutic targets for targeting KRAS- and ERK-dependent cancer growth. Citation Format: Jennifer E. Klomp, Jeff A. Klomp, Nathaniel J. Diehl, Cole A. Edwards, Kristina Drizyte-Miller, Priya S. Hibshman, Runying Yang, Alexis J. Morales, Khalilah E. Taylor, Mariaelena Pierobon, Emanuel F. Petricoin III, Johnson L. Jared, Emily M. Huntsman, Tomer M. Yaron, Markus Vähä-Koskela, Laura E. Herring, Alex W. Prevatte, Natalie K. Barker, Lee M. Graves, Wennerberg Krister, Lewis C. Cantley, James G. Christensen, Adrienne D. Cox, Channing J. Der, Clint A. Stalnecker. Determination of KRAS- and ERK-regulated phosphoproteomes in KRAS-mutant cancers [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B034.

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Lee, Seyoung, Kai Zhang, Jeeyeon Lee, Peter Haseok Kim, Amogh Hiremath, Salie Lee, Monica Yadav et al. "Abstract 2595: Accelerated and precise tumor segmentation in NSCLC: A comparative analysis of automated ClickSeg and manual annotation for radiomics". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 2595. http://dx.doi.org/10.1158/1538-7445.am2024-2595.

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Abstract Background: Radiomics models utilizing artificial intelligence are being explored as a potential biomarker in the field of oncology. Radiomics analysis requires segmentations of radiographic imaging. However, manual segmentation is a labor-intensive process that is time consuming, and acts as a major rate-limiting step. Thus the development of automated segmentation tools presents an opportunity for innovation in regards to efficiency and precision. Our study aims to explore the feasibility of autosegmentation in comparison with manual segmentation. Methods: A cohort of 105 stage III-IV non-small cell lung cancer patients receiving immunotherapy was examined, with a total of 168 lesions. We conducted a comprehensive comparative analysis of manual versus automated segmentation in time efficiency and segmentation quality, utilizing CT scans from the patients. Manual segmentation was performed by three physicians annotating in consensus using LIFEx software v7.3.0 (IMIV/CEA, Orsay, France). For a subset of randomly selected patients, annotation time was recorded as a reference point for the automated segmentation. In addition, automated segmentation was performed on all 168 lesions using ClickSeg from PictureHealth, a click-based interactive segmentation algorithm optimized for NSCLC lesions. Segmentation quality was evaluated using the Dice similarity coefficient to measure the concordance between ClickSeg outputs and consensus expert annotations. Results: Average manual annotation time of the tumor region was 15min 34sec, and ranged from 1min 2sec to 53min 12sec.. Average prediction time for the automated segmentation model was 1.94 seconds, and ranged from 0.71 seconds to 4.39 seconds. The median Dice coefficient, reflecting segmentation accuracy, was 0.72, highlighting the robust performance of the automated method. Conclusion: Our study demonstrates the efficient and accurate nature of automated segmentation supporting its potential integration into routine radiomic analysis procedures, streamlining the assessment of treatment response and ultimately improving patient care. Citation Format: Seyoung Lee, Kai Zhang, Jeeyeon Lee, Peter Haseok Kim, Amogh Hiremath, Salie Lee, Monica Yadav, Maria J. Chuchuca, Taegyu Um, Myungwoo Nam, Liam Il-Young Chung, Hye Sung Kim, Jisang Yu, Trie Arni Djunadi, Leeseul Kim, Youjin Oh, Sungmi Yoon, Zunairah Shah, Yuchan Kim, Ilene Hong, Grace Kang, Jessica Jang, Amy Cho, Soowon Lee, Cecilia Nam, Timothy Hong, Yuri S. Velichko, Anant Madabhushi, Nathaniel Braman, Young Kwang Chae. Accelerated and precise tumor segmentation in NSCLC: A comparative analysis of automated ClickSeg and manual annotation for radiomics [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 2595.

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Kemper, Ryan M., Travis J. Nelson, Nathaniel A. Hathaway e Daniel J. Crona. "Abstract 5965: First-in-class chemical induced proximity system achieves dose-dependent control of TP53 activation in gastric cancer". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 5965. http://dx.doi.org/10.1158/1538-7445.am2024-5965.

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Abstract Background: Gastric cancer (GC) remains a common and deadly disease, and inactivating TP53 mutations occur in up to 68% of GC tumors. p53 is a master regulator of multiple cellular pathways, such as the cell cycle, apoptosis, and senescence. Previously, we demonstrated the ability to activate endogenous target gene expression using a novel chemical induced proximity system comprised of deactivated Cas9 (dCas9) and “chemical epigenetic modifiers” or “CEMs” (PMID: 31712774). In this study, we applied our dCas9-CEM system for the first time in oncology to activate TP53 gene expression and selectively kill targeted cells in a preclinical model of GC. Methods: AGS cells were derived from a gastric adenocarcinoma, and harbor wild-type TP53. They were transduced with our dCas9 system and either sgRNAs targeting TP53 or a non-targeting (NT) sgRNA. After 48 h CEM87 incubation (1-25 nM), expression of TP53 and downstream targets (CDKN1A and BBC3) were evaluated by RT-qPCR. After 48 h CEM87 incubation (0.1-25 nM), colony-forming potential was assessed by crystal violet staining after 10 days. After 24 h incubation (5-25 nM), cells were fixed and stained with propidium iodide (PI), and DNA content was assessed by flow cytometry to determine cell cycle fractions. After 48 h incubation (50-200 nM), cells were fixed and stained with Annexin V and PI, and apoptosis was assessed by flow cytometry. Last, cells were treated with nine ascending concentrations (10 pM-100 μM) for 48 h, and cell viability was measured using CellTiter-Glo™. IC50 values were calculated using four-parameter non-linear regression. Results: AGS-TP53 cells show significantly increased expression of TP53 and downstream target genes CDKN1A and BBC3 versus AGS-NT cells after 10 nM CEM87 (105%, 99%, and 43% increase, P=0.004, 0.002, and 0.03, respectively; n=3). Colony formation was significantly reduced in AGS-TP53 versus AGS-NT cells after 10 nM CEM87 (60.2% reduction, P=0.003; n=3). Treatment with 10 nM CEM87 also led to a G2/M stall after significantly reducing cells in both G1 (47.4% vs 38.9%, P<0.0001; n=3) and S-phase (25.1% vs 20.3%%, P<0.0001; n=3) in AGS-TP53 versus AGS-NT cells. Treatment with 200 nM CEM87 significantly increased early apoptosis in AGS-TP53 versus AGS-NT cells (28.7% vs 6.6%, respectively, P<0.0001; n=3). Last, CEM87 was 50 times more potent in AGS-TP53 cells than AGS-NT cells (IC50: 3 vs 146 nM; n=8). Conclusions: These data highlight how our innovative system upregulates TP53 expression and impacts downstream phenotypic effects of TP53 activation in a preclinical model of GC. Citation Format: Ryan M. Kemper, Travis J. Nelson, Nathaniel A. Hathaway, Daniel J. Crona. First-in-class chemical induced proximity system achieves dose-dependent control of TP53 activation in gastric cancer [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 5965.

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Mironyuk, Sergei A. "The Control Over the Trans-Siberian Railway as a Motive for Britain’s Participation in an Allied Intervention in the Far East and Siberia in 1917–1919 and Its Role in the Operation (Based on the Memorandum “Siberia” by George Nathaniel Curzon (December 20, 1919))". Vestnik Tomskogo gosudarstvennogo universiteta, n. 458 (2020): 153–59. http://dx.doi.org/10.17223/15617793/458/19.

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The article deals with the problem of control provision over the Trans-Siberian Railway as a motive for Britain’s participation in an Allied intervention in the Far East and Siberia and evaluates its role in this operation. The work is based on the facts and judgments contained in the memorandum “Siberia” by George Nathaniel Curzon, the Secretary of State for Foreign Affairs, dated December 20, 1919. The memorandum has not been previously described and researched in the domestic historiography. Besides the text of the memorandum, the source base includes the minutes of the meetings of the British War Cabinet, the memories of W. Graves, the commander of the American expeditionary force, and of J. Ward, the chief of the British expeditionary detachment, and some other sources of personal origin. Works by N.E. Bystrova, F.D. Volkova, R. Ullman, A.I. Utkin, N.A. Halfin and other researchers were also used. The main research methods were comparative and narrative. The comparative method made it possible to compare the memorandum with some other documents from the National Archives of the United Kingdom, as well as with the sources of personal origin important for the research topic, and confirm its analytical, resumptive nature. Since some of the documents, including the memorandum “Siberia”, have not been previously investigated and described in the domestic historiography, the narrative method was widely used in the study. First, the author examines the main issues: Curzon’s approaches to the Eastern policy of Britain; Russia’s place in the British Eastern policy; control over globally important railways as an element of Britain’s Eastern policy. Then the author reviews the provisions of the memorandum relating to the Trans-Siberian Railway and the motives for Britain’s participation in the intervention in the Far East and Siberia, as well as the data on the participation of the United States, Japan, and Britain in the operation, and, on this basis, investigates the specificity, forms of participation and role of Britain in the intervention in these regions. The author concludes that, in fact, Britain became the main political driving force that led to the Allied intervention in the Far East and Siberia. The active position of Britain regarding the intervention in the Far East and Siberia was based on the tasks to oppose Germany during the war and at the same time to form and maintain Britain’s long-term Eastern policy under the new conditions. The control over the Trans-Siberian Railway could be an effective instrument to overcome these challenges. A possibility to participate in the allied control over the Trans-Siberian Railway was a weighty motive for Britain to intervene in Eastern Russia. Its role in the operation was political and pragmatic.

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KITLV, Redactie. "Book reviews". New West Indian Guide / Nieuwe West-Indische Gids 85, n. 1-2 (1 gennaio 2011): 99–163. http://dx.doi.org/10.1163/13822373-90002439.

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Globalization and the Po st-Creole Imagination: Notes on Fleeing the Plantation,by Michaeline A. Crichlow with Patricia Northover (reviewed by Raquel Romberg)Afro-Caribbean Religions: An Introduction to their Historical, Cultural, and Sacred Traditions, by Nathaniel Samuel Murrell (reviewed by James Houk) Africas of the Americas: Beyond the Search for Origins in the Study of Afro-Atlantic Religions, edited by Stephan Palmié (reviewed by Aisha Khan) Òrìṣà Devotion as World Religion: The Globalization of Yorùbá Religious Culture, edited by Jacob K. Olupona & Terry Rey (reviewed by Brian Brazeal) Sacred Spaces and Religious Traditions in Oriente Cuba, by Jualynne E. Dodson (reviewed by Kristina Wirtz) The Coolie Speaks: Chinese Indentured Laborers and African Slaves of Cuba, by Lisa Yun (reviewed by W. Look Lai) Cuba and Western Intellectuals since 1959, by Kepa Artaraz (reviewed by Anthony P. Maingot) Inside El Barrio: A Bottom-Up View of Neighborhood Life in Castro’s Cuba, by Henry Louis Taylor, Jr. (reviewed by Mona Rosendahl) On Location in Cuba: Street Filmmaking During Times of Transition, by Ann Marie Stock (reviewed by Cristina Venegas) Cuba in The Special Period: Culture and Ideology in the 1990s, edited by Ariana Hernandez-Reguant (reviewed by Myrna García-Calderón) The Cubans of Union City: Immigrants and Exiles in a New Jersey Community. Yolanda Prieto (reviewed by Jorge Duany) Target Culebra: How 743 Islanders Took On the Entire U.S. Navy and Won, by Richard D. Copaken (reviewed by Jorge Rodríguez Beruff) The World of the Haitian Revolution, edited by David Patrick Geggus & Norman Fiering (reviewed by Yvonne Fabella) Bon Papa: Haiti’s Golden Years, by Bernard Diederich (reviewed by Robert Fatton, Jr.) 1959: The Year that Inflamed the Caribbean, by Bernard Diederich (reviewed by Landon Yarrington) Dominican Cultures: The Making of a Caribbean Society, edited by Bernardo Vega (reviewed by Anthony R. Stevens-Acevedo) Chanting Down the New Jerusalem: Calypso, Christianity, and Capitalism in the Caribbean, by Francio Guadeloupe (reviewed by Catherine Benoît) Once Jews: Stories of Caribbean Sephardim, by Josette Capriles Goldish (reviewed by Aviva Ben-Ur) Black and White Sands: A Bohemian Life in the Colonial Caribbean, by Elma Napier (reviewed by Peter Hulme) West Indian Slavery and British Abolition, 1783-1807, by David Beck Ryden (reviewed by Justin Roberts) The Children of Africa in the Colonies: Free People of Color in Barbados in the Age of Emancipation, by Melanie J. Newton (reviewed by Olwyn M. Blouet) Friends and Enemies: The Scribal Politics of Post/Colonial Literature, by Chris Bongie (reviewed by Jacqueline Couti) Nationalism and the Formation of Caribbean Literature, by Leah Reade Rosenberg (reviewed by Bénédicte Ledent) Signs of Dissent: Maryse Condé and Postcolonial Criticism, by Dawn Fulton (reviewed by Florence Ramond Jurney) The Archaeology of the Caribbean, by Samuel M. Wilson (reviewed by Frederick H. Smith) Crossing the Borders: New Methods and Techniques in the Study of Archaeological Materials from the Caribbean, edited by Corinne L. Hofman, Menno L.P. Hoogland & Annelou L. van Gijn (reviewed by Mark Kostro)

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Zhang, Tongwu, Wei Zhao, Christopher Wirth, Marcos Díaz-Gay, Jinhu Yin, Phuc H. Hoang, Jian Sang et al. "Abstract LB226: Deciphering lung adenocarcinoma evolution and the role of LINE-1 retrotransposition". Cancer Research 84, n. 7_Supplement (5 aprile 2024): LB226. http://dx.doi.org/10.1158/1538-7445.am2024-lb226.

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Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Understanding lung cancer evolutionary dynamics can help identify tools to intercept its growth and suggest strategies for treatment. Multiple factors can impact the tumors’ natural history and distinctly affect growth rate. However, research on the evolutionary trajectories of lung cancer across demographic or exposure scenarios remains inadequate. Additionally, the roles of mutational processes and complex genomic alterations on the evolution of lung cancer are still largely unexplored. In the largest genomic study of lung cancer to date, we analyzed deep whole-genome sequencing (~ 81x) and other omics data of 1217 lung cancers from the Sherlock-Lung study. To ensure adequate statistical power for identifying subclone architectures and constructing lung cancer evolutionary histories, we utilized a metric known as NRPCC (number of reads per tumor chromosomal copy) to select 542 lung adenocarcinoma (LUAD) samples for clonal evolution analyses, including 186 and 181 samples from never-smoker subjects of European and Asian ancestry, respectively, and 121 samples from smokers of European ancestry. We found that major driver genes and exogenous mutations contribute to tumor initiation, while copy number gains and endogenous processes appear later in tumor evolution. Tumors harboring EGFR mutations in never-smoker females of European descent show long latency, while tumors with KRAS mutations have shorter latency regardless of ancestry and sex. Notably, tumors harboring the mutational signature ID2 have short latency and aggressive phenotype, accompanied by increased genomic instability, elevated hypoxia scores, high CpG methylator phenotype, low neoantigen burden, and propensity to develop metastasis. We show that LINE-1 retrotransposition-induced mutagenesis contributes to the origin of ID2 mutations. The transcriptional factor ZNF695, a member of the KZFP family, up-regulated in LUAD, appears to contribute to LINE-1 retrotransposition through a dominant-negative effect and LINE-1 promoter demethylation. In a multivariate analysis of genomics, exposures and demographic factors, LUAD latency was most significantly associated with ID2, followed by EGFR mutations, KRAS mutations, and sex, suggesting an independent impact of these factors on LUAD evolution. Our findings underscore the complex interplay of ancestry, sex, exogenous mutagenesis, epigenetic regulation, and LINE-1 retrotransposition in shaping LUAD evolutionary trajectories, paving the way for potential targeted therapeutic interventions. Citation Format: Tongwu Zhang, Wei Zhao, Christopher Wirth, Marcos Díaz-Gay, Jinhu Yin, Phuc H. Hoang, Jian Sang, John McElderry, Alyssa Klein, Azhar Khandekar, Caleb Hartman, Jennifer Rosenbaum, Frank Colon-Matos, Kristine M. Jones, Neil E. Caporaso, Robert Homer, Angela C. Pesatori, Dario Consonni, Lixing Yang, Bin Zhu, Jianxin Shi, Kevin Brown, Nathaniel Rothman, Stephen J. Chanock, Ludmil B. Alexandrov, Jiyeon Choi, Maurizio Cardelli, Qing Lan, Martin A. Nowak, David C. Wedge, Maria Teresa Landi. Deciphering lung adenocarcinoma evolution and the role of LINE-1 retrotransposition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB226.

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