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Journal articles on the topic 'Acts of Christopher'

Author: Grafiati

Published: 22 February 2023

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1

Napier, Stephen. "Moral Justification and Human Acts: A Reply to Christopher Oleson." Linacre Quarterly 76, no. 2 (May 2009): 150–62. http://dx.doi.org/10.1179/002436309803889214.

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The paper is written in reply to Christopher Oleson's “Dignitas personae and the Question of Heterologous Embryo Transfer” in this issue. Oleson provides a very perceptive and comprehensive commentary on the key texts. This reply articulates my reasons for continued skepticism on whether Dignitas personae has settled the question on embryo rescue. The source of my skepticism concerns Oleson's key premise according to which heterologous embryo transfer for treating infertility and for rescue are the same moral acts. I argue that they are in fact different moral acts not merely in virtue of different intentions, but in virtue of their order. Embryo transfer is properly ordered to the end of rescue, but is inapposite for treating infertility—as this would replace the conjugal act. I conclude by offering several reductio ad absurdum arguments that argue in favor of embryo rescue.

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Kamalakshan, Krishnapriya, and Sumathy K. Swamy. "The Paradox of Gender Performativity in Winnie-the-Pooh." Boyhood Studies 15, no. 1-2 (December 1, 2022): 94–102. http://dx.doi.org/10.3167/bhs.2022.15010206.

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In a heteronormative society, boys and girls are trained to dress and act in ways regarded appropriate for their respective genders. Even during play, a boy is expected to indulge only in activities that are traditionally considered masculine. A. A. Milne was inspired by his son’s pretend play to write the Pooh books. From the illustrations in the book, which were modeled upon the real Christopher Robin and his toys, and various biographical material on the Pooh books, it can be discerned that the young boy was dressed in a gender-nonconforming fashion. This article probes this paradox of gender performativity in Christopher Robin’s character in Winnie-the-Pooh (1926), wherein the child performs acts considered masculine in his imaginative play, while going against gender norms in his real-life appearance.

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3

Snyder, Julia. "Book Review: The Acts of Philip, Now Available in English: François Bovon and Christopher R. Matthews (trans.), The Acts of Philip." Expository Times 125, no. 3 (November 18, 2013): 136. http://dx.doi.org/10.1177/0014524613494632.

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4

Kun Hariani, Agiel Gendis, Abdul Muhid, and Puspita Dewi. "Revealing the Form of Directive Speech in Ready or Not Movie." Humanitatis : Journal of Language and Literature 8, no. 1 (December 14, 2021): 1–12. http://dx.doi.org/10.30812/humanitatis.v8i1.1177.

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This research was done to reveal the dominant form of Directive Speech Act (DSA) usage in Ready or Not Movie by Guy Busick and R Christopher Murphy, which was released in 2019. To reveal the form of directive speech act used by some characters in the conversation, it was considered to use theory by Yule about the directive speech act, and the data were analyzed by using a qualitative descriptive method. This current research shows that there was 52 (fifty-two) form of directive speech act used in the movie. The detail forms were 29 (twenty-nine) or 55.7% command, 20 (twenty) or 38.4% requests, 5 (five) or 9.6% suggestions, and 3 (three) or 5.7% warnings. Therefore, it can be concluded that the dominant directive is the command. Keywords:Speech Acts, Directive Speech Acts,form of Directive, Movie

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5

Hollis, Dawn L. "Constructing the Classical Past: the Role of Landscape in Christopher Wordsworth’s Greece." Classical Receptions Journal 14, no. 2 (January 7, 2022): 159–77. http://dx.doi.org/10.1093/crj/clab015.

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Abstract This article examines the works of Christopher Wordsworth (1807–85), who has hitherto been neglected as an important and intriguing figure in the history of travel writing on Greece. His texts, which invite readers to ‘view’ the country from mountain-tops and to imagine its caves and quarries filled with ancient figures, highlight the importance of landscape as a frame for studying classical reception. Wordsworth ‘received’ ancient Greece through its visible, modern landscape in three ways: through a sense of the landscape as a container for memory, through the use of specific landscapes as springboard for ‘flights of fancy’ enabling a vivid engagement with the classical past, and as a tool for better interpreting and understanding the history and literature of the ancient Mediterranean. Christopher Wordsworth constructed a vision of ancient Greece for his readers through his description of the nineteenth-century landscape. As such he offers an important reminder to consider the role played by the embodied experience of space and place in analysing acts of classical reception.

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Stougaard Pedersen, Birgitte. "Lytning og læsning som kreative processer?" Peripeti 9, S4 (January 1, 2012): 43–51. http://dx.doi.org/10.7146/peri.v9is4.110574.

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Is it possible to understand the acts of listening and reading as creative processes and if so, which types of knowledge do these acts generate? By collocating the creativity thinkers Christopher Frayling and Niels Lehmann(and through him, Edward de Bono), the paper presents a phenomenologically inspired method that understands listening and reading as creative processes. One of the points of the paper is to investigate if and how creativity thinking is perhaps imbued with implicit dimensions like spatiality and non-linearity. Birgitte Stougaard Pedersen drøfter, hvordan kunstneriske og videnskabelige praksisformer kan relateres uden at medieres. Med artiklen indtager Stougaard Nielsen en fænomenologisk position, som bl.a. slår til lyd for, at lyttestrategier kan struktureres metodisk – med kreative greb – som ‘rand’semantiske, fænomenologiske dimensioner. Artiklen undersøger operative og teoretiske aspekter af kreative læse- og lyttestrategier og drøfter muligheden for at træde ind i og ud af rollen som fænomenologisk lyttende betragter.

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7

T. Casey, Walter. "Fixing a Faulty Thermostat: A Replication and re-Analysis of "The Public as Thermostat” Employing a Fixed-effects Model." Journal of Public Administration and Governance 2, no. 3 (July 28, 2012): 1. http://dx.doi.org/10.5296/jpag.v2i3.2004.

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In a 1995 AJPS article, Christopher Wlezien advanced the notion that the public acts in an Eastonian manner as a thermostat for shaping policy preferences. I assert Wleziens use of a GLS-ARMA approach may be a true mis-specification problem. I propose the use of a fixed-effects model. Using both the older version of MICROCRUNCH and the newer version of RATS, I test Wleziens models and his hypotheses. The results in MICROCRUNCH are somewhat different from the original, whilst the results from RATS suggest that the findings of Wlezien are not nearly as significant as assumed.

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8

Shepard, Alan. "Endless Sacks: Soldiers’ Desire in Tamburlaine*." Renaissance Quarterly 46, no. 4 (1993): 734–53. http://dx.doi.org/10.2307/3039021.

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Christopher Marlowe's two-part Tamburlaine the Great (published 1590) captures all of the spirit and something of the scope of legendary violence the historical Tamerlane levied against his enemies. In the course of ten acts Tamburlaine's armies roll over several nations and cultures, leaving thousands of civilians enslaved or worse. Marlowe's graphic representation of the trail of blood and brutality is itself notorious.In the interest of founding his own legend as the hypermasculine “Generall of the world” (1:5.1.451), Tamburlaine practices virtual genocide against his enemies and ethnocide against their cities, religions, and ways of life. By no means does he work alone. The soldier-males who serve in his armies eagerly follow his lead.

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9

Azarmandi, Mahdis. "Commemorating No-bodies – Christopher Columbus and the Violence of Social-forgetting." Somatechnics 6, no. 1 (March 2016): 56–71. http://dx.doi.org/10.3366/soma.2016.0174.

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The Columbus statue in Barcelona is visited by millions of tourists each year and is one of the most well-known memorials dedicated to the “discovery” of the Americas. By looking at the productive nature of memorialisation, this paper questions this narrative of discovery. It looks at the history of the conquest of America as a moment of violence and massacre. Following the idea of coloniality of power and coloniality of being, this paper seeks to explore the relationship between coloniality and commemoration by analysing the different meanings of the statue of Columbus in Barcelona. I problematize and reconceptualise the monument from a decolonial perspective that highlights the subjugated knowledge of colonial conquest. I utilise the notion of epistemologies of ignorance to highlight how the statue is a representation of the master narrative of colonialism and consequently how this narrative acts to silence counter narratives of Columbus and Spanish history. Colonial monuments such as the Columbus statue are a tribute to on-going coloniality and the continuation of violence against racial ‘Others’. Thus, what is presented as a normative tribute to discovery is re-presented in this paper as a memorial to war and genocide.

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10

Baldwin, Matthew C. "The Apocryphal Acts of the Apostles: Harvard Divinity School Studies. François Bovon , Ann Graham Brock , Christopher R. Matthews." Journal of Religion 82, no. 2 (April 2002): 272–73. http://dx.doi.org/10.1086/491054.

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11

Jason, Gary. "Does Virtue Epistemology Provide a Better Account of the Ad Hominem Argument? A Reply to Christopher Johnson." Philosophy 86, no. 1 (December 21, 2010): 95–119. http://dx.doi.org/10.1017/s0031819110000616.

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AbstractChristopher Johnson has put forward in this journal the view that ad hominem reasoning may be more generally reasonable than is allowed by writers such as myself, basing his view on virtue epistemology. I review his account, as well as the standard account, of ad hominem reasoning, and show how the standard account would handle the cases he sketches in defense of his own view. I then give four criticisms of his view generally: the problems of virtue conflict, vagueness, conflation of speech acts, and self-defeating counsel. I then discuss four reasons why the standard account is superior: it better fits legal reality, the account of other fallacies, psychological science, and political reality.

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MURPHY, SCOTT. "In the Beginning of Penderecki's Paradise Lost." Twentieth-Century Music 10, no. 2 (August 12, 2013): 231–48. http://dx.doi.org/10.1017/s1478572213000030.

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AbstractInstead of using Milton's famous opening lines, librettist Christopher Fry begins the text for Krzysztof Penderecki's opera Paradise Lost with the invocation that opens Book III, which alludes to acts of creation both biblical and literary. While the primordial effects of Penderecki's instrumental introduction to the opera parallel this allusion in easily discernible ways, his melodic lines used within this introduction also parallel this allusion in ways understood using recent theoretical perspectives on the composer's neo-Romantic style. These melodies exhibit a rare feature of paradoxicality, in that they are at once finite and infinite within stylistic constraints. This musical paradox corresponds to notions of paradox in accounts of cosmological creation, in a literary-operatic creation in which the author is character, and in the hypostatic union of the divine and human in Jesus Christ, a union foregrounded more in Fry's and Penderecki's opera than in Milton's original poem.

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13

Tunick, Mark. "Constitutional Self Government. By Christopher L. Eisgruber. Cambridge, MA: Harvard University Press, 2001. 260p. $45.00." American Political Science Review 96, no. 4 (December 2002): 802–3. http://dx.doi.org/10.1017/s000305540227046x.

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Christopher Eisgruber takes a pragmatic approach to judicial review. Most judges and scholars would decide whether a branch of government acts legitimately by asking whether its actions were authorized or prohibited by some provision in the Constitution. The common assumption is that during the constitutional convention, states agreed to give up some of their powers in order to establish a new federal government with enumerated powers, at the same time explicitly setting limits both to the federal government and to states. By turning to the terms of this agreement, Supreme Court Justices seek to answer whether Congress, the president, or the state or local government in question acted within its rights. Eisgruber regards such assumptions about state sovereignty as “mystical” (p. 186). Instead, he would have us question, in deciding whether, say, Congress should be permitted to regulate the possession of guns in school zones, that this is the sort of thing a national government can “do well” (p. 186). Whether it was the intention of those who wrote or ratified the Constitution to give Congress this power is, to Eisgruber, more or less irrelevant.

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14

Wood, Danielle. "Writing Tasmania’s “Different Soul”." Island Studies Journal 3, no. 2 (2008): 153–62. http://dx.doi.org/10.24043/isj.219.

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: The narrator of Christopher Koch's 1958 novel The Boys in the Island claims for Tasmania “a different soul”, distinct from that of the Australian mainland to the north, in the same breath in which he claims for the island “a different weather”. Observations of the distinctiveness of island geography and weather – and of the quality of the light – are recurrent in narratives set not only in Tasmania, but also on those islands to which Tasmania itself acts as a ‘mainland’. This paper surveys a range of texts, including Koch’s The Boys in the Island, Joanna Murray-Smith’s Truce, and my own The Alphabet of Light and Dark, in which a Tasmanian island functions both as a setting for the protagonist's idealized childhood and as a metaphor for the protagonist’s “true self”. It explores the representation of islands in these texts, examining how a specific tradition of writing about Tasmania intersects with a broader tradition of writing about islands.

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15

Morwood, James. "The Double Time Scheme in Antigone." Classical Quarterly 43, no. 1 (May 1993): 320–21. http://dx.doi.org/10.1017/s0009838800044384.

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In three articles published in Blackwood's Magazine (November 1849, April and May 1850), one Wilson, under the nom de guerre of Christopher North, propounded the view that Shakespeare's Othello operates on a double time scheme. The represented time in Cyprus (Acts II to V) is some thirty-three hours, lasting from about 4 p.m. on Saturday till the early hours of Monday morning. If we take this time scheme at face value, there has been no opportunity for Desdemona and Cassio to commit adultery: Iago's insinuations and Othello's suspicions are manifestly absurd. However, another time scheme is in operation as well. By its clock, the protagonists have been in Cyprus for more than a week. For example, we find Bianca, a local courtesan, complaining that it has been ‘seven days and nights, / Eight score eight hours’ (III.iv.171–2) since she last saw Cassio, who by the first time scheme had arrived in Cyprus only the day before.

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16

McCorkindale, Christopher, and Janet L. Hiebert. "Vetting Bills in the Scottish Parliament for Legislative Competence." Edinburgh Law Review 21, no. 3 (September 2017): 319–51. http://dx.doi.org/10.3366/elr.2017.0433.

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In this article, Christopher McCorkindale and Janet Hiebert present the first empirical examination of the process by which bills in the Scottish Parliament undergo vetting for legislative competence. Based on a series of interviews with officials in the Scottish Government, Scottish Parliament and UK Government the paper makes a two-fold argument. First, that – despite the susceptibility of Acts of the Scottish Parliament to strong-form judicial review – the statutory requirement that the responsible minister and the Presiding Officer report to parliament on the competence of every bill, and the discretion of the Scottish and UK Government Law Officers to refer any bill to the Supreme Court before Royal Assent, align the devolution scheme with an emerging family of systems that favour legislative to judicial constitutional review. Second, that the deference shown by political actors to the advice of officials on questions of competence at each stage supplants legislative review – and its aspiration to engender a new culture of constitutional engagement – with a more closed form of bureaucratic review.

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17

Sakina Shepia Maharani, Ainal Mardiyah, Nur Fatihah, Arita Destianingsih, and Ari Satria. "Representation of Racism in Antebellum Movie." Journal of Pedagogy and Education Science 1, no. 1 (August 3, 2022): 1–11. http://dx.doi.org/10.56741/jpes.v1i1.4.

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Racism is a problem that has existed throughout the world since ancient times. Indonesia also does not escape the issue of racism. From the small issues that we did not realize until the big problems involving many parties. This racism makes the atmosphere uncomfortable and conducive if it has to involve many parties. Therefore, many filmmakers who try to raise the theme of racism become a film. Analysis of racism in “Antebellum” movie written and diricted by Gerard Bush and Christopher Renz. This research discuses the discrimination by white people to black people in Antebellum Movie. Black people and white people is separated by many rules that makes black people is intimidate, so racism is still growing up until generations. Racismmostly still happens in many countries, especially the country with a lot of majoritiesand minority groups with very strict differences in characteristics such as in the UnitedStates of America or other European countries.This research used semiotic analysis with the descriptive qualitative methods. This study aims to find out the contents of the film Antebellum, especially those related to forms of acts of racism. The lastresult of analysis, the researcher also found the Struggle that does by the black people in Antebellum Movie.

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18

Pearson, Birger A. "The Acts of Philip: A New Translation. Translated by Francois Bovon and Christopher R. Matthews. Waco, TX: Baylor University Press, 2012. Pp. vii + 114. Paper, $26.95." Religious Studies Review 39, no. 4 (December 2013): 272. http://dx.doi.org/10.1111/rsr.12084_32.

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19

Quick, R. C., W. J. Sonnenstuhl, and H. M. Trice. "Educating the Employee Assistance Professional: Cornell University's Employee Assistance Education and Research Program." Public Personnel Management 16, no. 4 (December 1987): 333–43. http://dx.doi.org/10.1177/009102608701600406.

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This article outlines in considerable detail Cornell University's Employee Assistance Education and Research Program which is funded by the New York State Department of Alcoholism and Alcohol Abuse, in cooperation with the Christopher D. Smithers Foundation of Mill Neck, NY. It utilizes an academic curriculum in combination with field experience to further develop the EAP profession. It has been on-going since the Fall of 1985 in various New York State cities (Syracuse, New York, Rochester, and Albany) and will soon expand to include Buffalo and Long Island. The authors were assisted with implementation of the program by Bernard Flaherty, who acts as its co-director, and who is Director of the Central District of Cornell's Extension Division of the School of Industrial and Labor Relations. In addition, the article addresses a dilemma faced by personnel executives as they try to reach decisions about how to assure quality in the EAP programs, and in the personnel who staff them. On the one hand, they seek practical, applied programs that can be readily implemented and attractive to employees. On the other, there is a need to feel confident that the EAP personnel they employ are thoroughly acquainted with the workplace, and with the treatment place, and have a sound understanding of the emotional disturbances that cause troubled employees to be poor performers.

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20

Perelshtein, Roman. "Eldar Ryazanov’s Film Watch Out For the Automobile Through the Prism of Joseph Campbell’s “Hero-Adventure”." Scientific and analytical journal Burganov House. The space of culture 15, no. 3 (September 10, 2019): 169–81. http://dx.doi.org/10.36340/2071-6818-2019-15-3-169-181.

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We propose a universal methodology for analyzing scripted films based on the “hero’s journey” structure defined by Joseph Campbell. This methodology helps in identifying new meanings in a dramatic work, regardless of the genre of the film. Eldar Ryazanov’s tragicomedy Watch Out For the Automobile (also known as Uncommon Thief in the United States) is a classic example of Campbell’s monomyph. According to Campbell, the hero’s journey consists of three acts: “departure,” “initiation,” and “return.” Each act consists of six stages, if we amend the “departure” act to include the “ordinary world” stage, described by Christopher Vogler in The Writer’s Journey: Mythic Structure For Writers. There exists a correspondence between the stages of the hero’s journey and the compositional structure of drama, which has been pointed out by a number of researchers (mainly American authors like Syd Field, Linda Seger, Christopher Vogler, etc.) We, however, will attempt to prove that comedy films can also be analyzed from the standpoint of Campbell’s “hero-adventure”. Eldar Ryazanov’s film Watch Out For the Automobile (1966) is centered around the character of Yuri Detochkin. The climax of every episode of the film is focused on Detochkin, just as the climax of every stage of the hero’s journey is associated with the hero of the myth. However, this is not the primary similarity. The character of Detochkin, portrayed by Innokenty Smoktunovsky, having passed through a series of trials, acquires integrity and becomes transformed. As in a monomyth, we are dealing with the character arc of a hero who has completed his journey, and has thus fulfilled his mission. In the spirit of “hero-adventure”, Campbell’s allegories help interpret a variety of dramatic situations. This is because, in essence, all of these situations are archetypes. It is very important, however, to define their placement in the structure of the story. Most often this happens spontaneously, by way of the artist’s intuition, but the structure proposed by Campbell helps approach the creative process more deliberately. The goal of this research was to demonstrate the congeniality of the two methods: the intuitive method used by the authors of the film Watch Out For the Automobile, and the rational method used by the author of the book The Hero with a Thousand Faces based on a vast collection of legends and myths. Our hypothesis was entirely confirmed: Eldar Ryazanov and Emil Braginsky were using the same artistic logic for guidance as their predecessor Joseph Campbell.

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Döring, Karoline. "Christopher Toenjes, Islam, the Turks and the Making of the English Reformation. The History of the Ottoman Empire in John Foxe’s Acts and Monuments. Frankfurt am Main, Lang 2016." Historische Zeitschrift 306, no. 1 (February 6, 2018): 212–14. http://dx.doi.org/10.1515/hzhz-2018-1040.

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22

., Carissa, and Sulistiono . "Pengaruh The Flower Of Service dan Physical Evidence terhadap Loyalitas Konsumen pada Starbucks Coffe." Jurnal Ilmiah Manajemen Kesatuan 5, no. 1 (July 16, 2018): 1–8. http://dx.doi.org/10.37641/jimkes.v5i1.15.

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The concept of Flower of Service was first introduced by Christopher Lovelock, a British service marketing expert. According to this concept, value is constructed by core products and supplementary services. There are two identified supplementary service, first is a supplementary service that acts as deliverer of service or aid in the usage of core products. And second is a supplementary service that strengthens and adds value to the customers. Mean while, physical evidence is recognized as one of the many factors that influence the customers to buy or use the offered services, and customers’ loyalty is a chance for the buyers to become a loyal customers and /or clients. This research is aimed to (1) find out about the influence of flower of service on customers’ loyalty, (2) to examine the influence of physical evidence on customer loyalty, and (3) to find out the influence of flower of service and physical evidence on customer loyalty. The research show that the multiple linear regression equation Y=3,786+0,482 X1+0,348 X2 which means that if flower of service is represented with 1 then the level of customers’ loyalty will increase for an amount of 0,482 and if physical evidence is 1 then the level of customers’ loyalty will increase for an amount of 0,348. The result of coefficient correlation analysis show that r = 0,642 which means that there is a significant relationships between flower of service and physical evidence on customers’ loyalty. The analysis for the coefficient determination proves that flower of service contributes 41,2% in creating customers’ loyalty and the rest of 58,8% was determined by other factors.

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23

Luptáková I., I. Dirgová, and J. Pospíchal. "How Random Is Spatiotemporal Chaos of Langton's Ant?" Journal of Applied Mathematics, Statistics and Informatics 11, no. 2 (December 1, 2015): 5–13. http://dx.doi.org/10.1515/jamsi-2015-0008.

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Abstract In recent years there have been numerous attempts to control chaotic behavior by evolutionary optimization. Most of these attempts were aimed at a study of chaotic systems defined by differential equations, but a few attempts were made also at evolutionary design of initial conditions or rules of cellular automata aimed at performing a specified task. We shall use a simple cellular automaton called Langton's ant after its designer, Christopher Langton. Generally, the ant acts on a 2D grid, where each it’s square can be either black or white. The ant is facing in one of four directions, and its behavior is described by 3 rules: (1) If ant is on a black square, it makes a left turn. (2) If ant is on a white square, it makes a right turn. (3) When ant moves to the next square, the one it was on reverses color. Despite simplicity of these rules, the ant produces extremely complex behavior, but after around 10000 steps the ant begins to construct a diagonal „highway“. This stable attractor has been always achieved regardless of the initial setting of black and white squares, but there is no proof, that it is always so. This behavior can be related to the undecidability of the halting problem. Our goal in this paper is to optimize initial conditions for the ant on a grid, so that it will be maximally “slowed down” in the sense that it should arrive at the preset boundary of the grid as late as possible. By a comparison of greedy stochastic optimization with an optimization by blind search are able to estimate, that is this chaotic system is not reasonably controllable and appears to have no regularity in the “optimal” initial conditions.

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Tu, Bo, Heather Wright T. Wright, Christopher C. Dufort, Martin C. Whittle, Libing Feng, Shelley M. Thorsen, and Sunil R. Hingorani. "Abstract A056: Epithelial hyaluronan synthase 2 expression promotes pancreas cancer metastasis." Cancer Research 82, no. 22_Supplement (November 15, 2022): A056. http://dx.doi.org/10.1158/1538-7445.panca22-a056.

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Abstract A defining characteristic of pancreatic ductal adenocarcinoma (PDA) is its robust desmoplastic reaction that promotes tumor progression and protects PDA from treatment. As a major component of the extreme microenvironment, hyaluronan (HA) is synthesized by the hyaluronan synthase (Has) family of enzymes and secreted in excess by both epithelial cells and cancer-associated fibroblasts (CAFs). We have previously described the role of HA in binding water and swelling to create vessel-crushing interstitial gel-fluid pressures and its function as a biophysical barrier. However, HA also acts by signaling through a wide range of specific receptors that can drive proliferation, migration and invasion. In an effort to understand the role of HA in PDA development and pathogenesis, we developed a KPC mouse model of autochthonous pancreas cancer in which Has2 is conditionally deleted in tumor epithelial cells (TECs). We demonstrate that Has2-deficient epithelial cells produce little to no HA and altered the dense microenvironment. We also found that deletion of Has2 leads to an increase in overall survival and a striking reduction in metastasis. We have further investigated the cell autonomous functions of Has2, associated with 3D invasion and activation of oncogenic signaling pathways in TECs. These data implicate a potential Achilles’ heel in PDA, whereby HAS2 is required to maintain a highly metastatic phenotype involving both non-cell and cell autonomous mechanisms. Citation Format: Bo Tu, Heather Wright T. Wright, Christopher C. Dufort, Martin C. Whittle, Libing Feng, Shelley M. Thorsen, Sunil R. Hingorani. Epithelial hyaluronan synthase 2 expression promotes pancreas cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A056.

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Anaraki, Cecily, Galloway Thurston, Nina G. Steele, Samuel A. Kerk, Hanna Hong, Peter Sajjakulnukit, Anthony Andren, et al. "Abstract B012: Differential stress responses drive asparagine exchange in pancreatic cancer." Cancer Research 82, no. 22_Supplement (November 15, 2022): B012. http://dx.doi.org/10.1158/1538-7445.panca22-b012.

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Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, contrasting a relatively low incidence rate. A principal barrier to the treatment of pancreatic cancer is the densely fibrotic tumor microenvironment and the high interstitial pressure which acts to collapse blood vessels, impairing the delivery of chemotherapy. This lack of functional vasculature limits nutrient availability within the tumor, causing cancer cells to develop numerous metabolic adaptations to allow for proliferation in hypoxic, austere conditions. Recent studies have demonstrated several clonal behaviors of cancer cells within individual pancreatic tumors, although it is unclear if this is true of metabolism. Exploring this, we found the metabolic profiles and sensitivities of a series of clonal cell lines derived from a single pancreatic tumor clustered into two distinct groups. These groups demonstrated differential sensitivities to inhibitors of mitochondrial metabolism; whereby the growth of the sensitive clones during impaired respiration can be rescued through co-culture with the insensitive cells. Profiling metabolites exchanged by the clonal populations, we identified this is mediated by asparagine released by insensitive cells. Mechanistically, the production of asparagine is driven by differential stress response pathway activation between clones. We further determined that exogenous asparagine supports the growth of both cancer and non-cancerous cells during limited respiration. Conversely, we found that the use of asparaginase to degrade asparagine sensitizes PDA tumors to mitochondrial inhibition. Collectively these data demonstrate distinct metabolic classes of cancer cells within single tumors and identify asparagine as a potential target to sensitize tumors to mitochondrial inhibition. Citation Format: Cecily Anaraki, Galloway Thurston, Nina G. Steele, Samuel A. Kerk, Hanna Hong, Peter Sajjakulnukit, Anthony Andren, Catherine Felton, Alica Beutel, Rima Singh, Heather R. Christofk, Andrea Viale, Howard Crawford, Marina Pasca di Magliano, Claus Jorgensen, Costas A. Lyssiotis, Christopher J. Halbrook. Differential stress responses drive asparagine exchange in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B012.

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MacDonald, Dennis R. "The Apocryphal Acts of the Apostles: Harvard Divinity School Studies. Edited by François Bovon, Ann Graham Brock, and Christopher R. Matthews. Religions of the World. Cambridge, Mass.: Harvard University Press, 1999. xxx + 394 pp. $24.95 paper." Church History 69, no. 3 (September 2000): 634–35. http://dx.doi.org/10.2307/3169401.

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Yocum, Sandra. "The Past as Pilgrimage: Narrative, Tradition & the Renewal of Catholic History by Christopher Shannon & Christopher O. Blum." American Catholic Studies 126, no. 4 (2015): 103–5. http://dx.doi.org/10.1353/acs.2015.0072.

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Bauer, Henry. "Unfathomed Dangers from Aluminum — Alzheimer’s? Autism? Multiple Sclerosis?" Journal of Scientific Exploration 35, no. 4 (January 15, 2022): 1095–102. http://dx.doi.org/10.31275/20212221.

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That aluminum is fatally toxic is beyond doubt, demonstrated by mass human poisoning at Camelford in Cornwall in Britain in 1988 (chapter 18) and by occasional fish kills (p. 49). Aluminum may also be a contributing factor in a number of human diseases, in particular those involving brain and nerves (p. 124) — autism, Alzheimer’s disease (AD) (chapter 14), Parkinson’s disease, multiple sclerosis. Aluminum salts used in kidney dialysis may be responsible for dialysis-related encephalopathy (pp. 38, 79). Aluminum adjuvants in vaccine can cause macrophagic myofasciitis (MMF: inflammation and associated microscopic muscle necrosis at the injection site) as well as such whole-body ailments as chronic fatigue syndrome and marked cognitive deficits (Rigolet et al. 2014); one middle-aged individual injected with five aluminum-adjuvanted vaccines within 4 weeks became work-disabled (pp. 72-73). Studying the possible dangers associated with aluminum adjuvants in vaccines is complicated by the fact that aluminum acts as an antigen as well as an adjuvant — the immune system generates antibodies against aluminum itself, so that later exposures to aluminum might produce an antibody cascade capable of damaging any of the tissues in which aluminum had accumulated (pp. 73-76). Christopher Exley has studied aluminum in relation to human health for some 35 years. This book summarizes his work and cites the pertinent primary publications (some 200) in appropriate peer-reviewed journals. The book also offers quite convincing evidence of the determined efforts by a variety of vested interests to disparage and suppress Exley’s work and findings. In my opinion, the published work summarized in this book makes a plausible case based on empirical evidence that aluminum may be a contributing causative factor in neurological and nerve diseases. Further, Exley suggests fully detailed mechanisms and quite plausible for how that comes about. Beyond that, he points to a quite fundamental a priori reason why aluminum, among all the other elements and metals, might be so uniquely dangerous. It is the third most abundant element in the Earth’s crust (after oxygen and silicon), yet there are no known biological uses of aluminum. By contrast, several other metals and non-metals are essential components of some biological systems, for example, iron in hemoglobin in blood (pp. 5-6, 11). Those two facts make it far from implausible that absorption of aluminum could be biologically harmful, by competing with or replacing other metals, or perhaps just because of its chemically oxidative properties. But if all that is so, how has the Earth’s biosphere flourished for billions of years without succumbing to the toxicity of the super-abundant aluminum?

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Cramer, Zvi, Xin Wang, Nicolae Adrian Leu, Keara Monaghan, Joshua H. Rhoades, Yuhua Tian, Joshua Rico, et al. "Abstract PR004: In vitro and in vivo CRISPR screens in colorectal cancer organoids identify suppressors of metastasis." Cancer Research 82, no. 23_Supplement_1 (December 1, 2022): PR004. http://dx.doi.org/10.1158/1538-7445.crc22-pr004.

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Abstract Colorectal cancer (CRC) is the 2nd-leading cause of cancer-related deaths worldwide and metastatic disease remains a major unmet clinical need. Nevertheless, the molecular underpinnings of metastatic spread and colonization of distant sites remain elusive. To systematically identify functional genes contributing to metastasis in a physiologically relevant model of CRC, we developed a novel platform enabling robust, pooled CRISPR/Cas9 screening in primary colonic organoids engineered with common CRC driver mutations in Apc, Kras, and Tp53. We performed parallel in vitro invasion and in vivo metastasis gain-of-function CRISPR/Cas9 knockout screens with high-content gRNA libraries to uncover novel suppressors of metastasis. We confirmed resulting hits as bona-fide metastatic suppressors using both pooled validation screens and single-gene approaches. Genes scoring in both in vitro and in vivo screens included previously identified regulators of migration and invasion, such as Ctnna1, and genes scoring only in the in vivo screen included novel negative regulators of metastasis such as Bcl2l13. These hits in the murine system were supported by human TCGA data, indicating that low expression of these genes is associated with worse 5-year survival in colon and rectal adenocarcinoma patients (COAD and READ). Utilizing transwell and live-imaging assays, we found that sgRNAs targeting Ctnna1 markedly enhanced invasion and migration of CRC organoids while sgRNAs targeting Bcl2l13 had no effect, an observation consistent with our in vitro screen. Therefore, while loss of Ctnna1 enhances metastasis by augmenting invasion and migration, loss of Bcl2l13 acts through alternative mechanisms. Single cell RNA sequencing of primary and metastatic lesions derived from Bcl2l13 knockout and control CRC tumors identified novel putative pathways promoting metastatic spread via migration-independent mechanisms, including upregulation of hypoxia signalling and recruitment of pro-tumorigenic macrophages. Thus, our CRISPR/Cas9 screening pipeline is a viable approach for the identification of novel regulators of CRC metastasis in vitro and in vivo, uncovering both motility and migration-dependent and independent paths to metastatic success. These findings will help untangle the complex web of molecular events underlying CRC metastasis and provide clinically-relevant insights into the process of human CRC metastasis. Citation Format: Zvi Cramer, Xin Wang, Nicolae Adrian Leu, Keara Monaghan, Joshua H. Rhoades, Yuhua Tian, Joshua Rico, Diego Mendez, Ricardo Petroni, Melissa S. Kim, Ning Li, Christopher J. Lengner, M. Andres Blanco. In vitro and in vivo CRISPR screens in colorectal cancer organoids identify suppressors of metastasis [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr PR004.

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Barrow, J. "English Episcopal Acta, XXXII: Norwich 1244-1266, ed. Christopher Harper-Bill." English Historical Review CXXVII, no. 525 (February 24, 2012): 426–27. http://dx.doi.org/10.1093/ehr/ces032.

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Tanner, N. "English Episcopal Acta. Volume 41: Norwich, 1289-1299, ed. Christopher Harper-Bill." English Historical Review 129, no. 539 (July 22, 2014): 949–50. http://dx.doi.org/10.1093/ehr/ceu181.

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Pucino, V., M. Nefla, V. Gauthier, S. A. Clayton, A. Filer, A. R. Clark, K. Raza, and C. D. Buckley. "OP0075 FIBROBLAST/MACROPHAGE CROSSTALK VIA LACTATE: NEW THERAPEUTIC TARGET IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 51–52. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2323.

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BackgroundThe synovial membrane is the principal site of inflammation in rheumatoid arthritis (RA) and distinct subsets of fibroblasts and macrophages, with different effector functions, have been described within it1,2,3. Inflammation renders the RA synovial microenvironment hypoxic and acidic, with increased levels of lactate, the end product of glycolysis. Lactate acts as an immunomodulatory molecule within the synovium4, interacting with lactate transporters present on fibroblasts and macrophages to regulate their function, movement and metabolism.ObjectivesTo test whether dysfunctional crosstalk between fibroblasts and macrophages, driven by lactate, promotes the persistence of synovial inflammation.MethodsSynovial tissues (n = 8) from patients fulfilling the 2010 ACR/EULAR RA criteria were obtained by ultrasound-guided synovial biopsy. Osteoarthritis (OA) synovial tissues of subjects undergoing joint replacement were used as control group. Monocarboxylate transporter 1 (MCT)1 and MCT4 expression on fibroblasts and macrophages was assessed via confocal microscopy. We used RA synovial fibroblasts and monocyte-derived macrophages to test the effect of lactate in vitro. Migration was assessed in trans-well plates or via scratch test assays. Seahorse was used to evaluate metabolic pathways. IL6 production was measured by ELISA. Bioinformatic data were confirmed on publicly available scRNAseq datasets.ResultsWe showed that: i) The expression of MCT1 and MCT4 which regulate lactate import and export respectively, is up-regulated upon inflammation. ii) Fibroblasts preferentially express MCT1, while MCT4 is more highly expressed by macrophages. iii) Lactate, at the concentration found in RA synovial fluid (10 mM), has divergent effects on the effector functions of these two cell types. In fibroblasts, lactate promotes IL6 production and cell motility; these effects are reduced by pre-treatment with a pan-lactate transporter inhibitor. In contrast macrophages respond to lactate by reducing migration, IL6 secretion and glycolysis.ConclusionThe contrasting effects of lactate on macrophage and fibroblast migration, IL6 production and metabolism suggest that lactate represents a key metabolite ensuring linked choreography between fibroblast and macrophage movement in the synovium which may become uncoupled in disease. We propose that dysfunctional crosstalk between these two cell types due to high lactate levels, promotes inflammation and the establishment of persistent disease in RA. Targeting lactate/MCTs pathway may provide a novel therapeutic strategy, to restore cellular crosstalk and to reduce inflammation in RA patients.References[1]Croft et al, Nature 2019;570:246-251[2]Culemann et al, Nature 2019;572:670-675[3]Alivernini et al, Nat Med 2020;26:1295-1306[4]Pucino et al, Cell Metab 2019;30:1055-1074.e8Disclosure of InterestsValentina Pucino: None declared, Meriam Nefla: None declared, Vincent Gauthier: None declared, Sally A Clayton: None declared, Andrew Filer Consultant of: Abbvie, Roche, Janssen, Grant/research support from: Roche, UCB, Nascient, Mestag, GSK, Janssen, Andy R Clark: None declared, Karim Raza: None declared, Christopher D Buckley Consultant of: GSK, Astra-Zenica, Roche, Pfizer, Lilly, Janssen Mestag, Grant/research support from: GSK, Roche, Pfizer, Janssen Mestag.

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Anastasiou, Panayiotis, Edurne Mugarza, Jesse Boumelha, Sareena Rana, Christopher Moore, Miriam Molina-Arcas, and Julian Downward. "Abstract 4029: Combination of KRASG12C(ON) and SHP2 inhibitors overcomes adaptive resistance and enhances anti-tumor immunity." Cancer Research 82, no. 12_Supplement (June 15, 2022): 4029. http://dx.doi.org/10.1158/1538-7445.am2022-4029.

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Abstract Oncogenic mutations in KRAS are frequent in non-small cell lung cancer and have been associated with poor prognosis. The recent development and approval of KRASG12C mutant-specific inhibitors could change the clinical practice of lung cancer patients harboring KRASG12C mutations. However, early clinical data indicate the development of acquired resistance after initial responses. All of the KRASG12C inhibitors being tested in clinical trials to date target GDP-bound KRAS (OFF state), which makes them vulnerable to upstream pathway reactivation, as this will increase KRAS in a GTP-bound (ON) state and therefore reduce drug efficacy. In this study we use a covalent tri-complex KRASG12C(ON) inhibitor which targets KRASG12C in the active state. In vitro, the KRASG12C(ON) inhibitor RM-029 exhibited higher efficacy than the KRASG12C(OFF) inhibitor MRTX849 (adagrasib). However, treatment with RM-029 also showed adaptive RAS pathway reactivation after 24 hours of treatment, which can be blocked using the SHP2 inhibitor RMC-4550, suggesting that pathway reactivation is mediated by signaling from RTKs to RAS proteins. In vivo, KRASG12C(ON) treatment led to strong regression of KRASG12C tumors and addition of a SHP2 inhibitor significantly increased anti-tumor responses. Single treatments with KRASG12C(ON) or SHP2 inhibitors led to complete responses in some animals and immunological memory in an immune responsive KRASG12C lung tumor model, with all tumors showing complete responses when the inhibitors were combined. Consistent with this finding, both KRASG12C(ON) and SHP2 inhibition resulted in a profound remodeling of the lung tumor microenvironment (TME), with increased infiltration and activation of T cells accompanied by a reduction of tumor-promoting myeloid cells. Interestingly, similar changes were obtained in an immune evasive KRASG12C lung cancer model. Besides acting upstream RAS, SHP2 has also specific roles in immune cells, including regulation of T cell function. As comparison, responses to SOS1 inhibition, which acts only upstream RAS, have also been analyzed. Overall, our preclinical results show that the anti-tumor activity of the combination of KRASG12C(ON) with SHP2 inhibition is the result of different mechanisms. First, a KRASG12C(ON) inhibitor potently inhibits oncogenic RAS and addition of a SHP2 inhibitor blocks RAS pathway reactivation increasing tumor responses. Second, both inhibitors have beneficial effects in the TME which can be potentiated when combined. Finally, addition of a SHP2 inhibitor could potentially overcome intrinsic resistant populations by directly targeting cells resistant to G12C inhibition and/or by increasing anti-tumor immunity. Citation Format: Panayiotis Anastasiou, Edurne Mugarza, Jesse Boumelha, Sareena Rana, Christopher Moore, Miriam Molina-Arcas, Julian Downward. Combination of KRASG12C(ON) and SHP2 inhibitors overcomes adaptive resistance and enhances anti-tumor immunity [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 4029.

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Isa, Deswita Davi, Ninuk Lustyantie, and Ratna Dewanti. "DIRECTIVE SPEECH ACT IN TOUS SUPER HÉROS COMIC BY JEAN-CHRISTOPHE CAMUS, LILIAN THURAM AND BENJAMIN CHAUD." IJLECR - INTERNATIONAL JOURNAL OF LANGUAGE EDUCATION AND CULTURE REVIEW 6, no. 1 (June 30, 2020): 42–49. http://dx.doi.org/10.21009/ijlecr.061.05.

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The objective of this study is to understand comprehensively the directive speech acts contained in the comic Tous Super-Héros by Jean-Christophe Camus, Lilian Thuram and Benjamin Chaud which includes forms, meanings and functions. The data analysed were dialogues between the characters in the Tous Super-Héros comic that were found in the dialogue balloon. The data, hereafter processed through a content analysis method with a qualitative approach. Qualitative approach used here is an approach that investigates a social phenomenon and human problems which the data collected consists of words (or text) from the expressions between speakers and interlocutors in the dialogue. Analysis of the findings shows that literal direct speech acts as a form of directive speech act has the highest intensity of 65.12%, the context of commands and warnings as the meaning of directive speech acts has the highest intensity of 20.93%, and advisories as a directive speech act function has the highest intensity of 24.41% . The findings in this study have implications for general French language insights, and for understanding the social and cultural of French expressions.

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Nault, François. "Sur la vocation acéphale du théologien." Laval théologique et philosophique 68, no. 2 (January 8, 2013): 293–309. http://dx.doi.org/10.7202/1013422ar.

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Résumé Cet article porte sur la question de la « vocation du théologien », comme « appel existentiel », mais aussi comme acte d’inscription ecclésiale et universitaire. Il cherche à montrer comment la réflexion de Christoph Theobald apporte un éclairage sur ces questions.

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Steltenkamp, Michael F. "Native Footsteps: Along the Path of Saint Kateri Tekakwitha ed. by Mark G. Thiel, Christopher Vecsey." American Catholic Studies 124, no. 4 (2013): 66–67. http://dx.doi.org/10.1353/acs.2013.0057.

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Garoutte, Alexander. "God's Quad: Small Faith Communities on Campus and Beyond ed. by Kevin Ahern and Christopher Derige Malano." American Catholic Studies 130, no. 3 (2019): 104–6. http://dx.doi.org/10.1353/acs.2019.0037.

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Quinn, Rhonda L. "Mission Cemeteries, Mission Peoples: Historical and Evolutionary Dimensions of Intracemetery Bioarchaeology in Spanish Florida by Christopher M. Stojanowski." American Catholic Studies 125, no. 2 (2014): 83–85. http://dx.doi.org/10.1353/acs.2014.0051.

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Kawentel, Linda. "Renewal: How a Generation of Faithful Priests and Bishops is Revitalizing the Catholic Church by Anne Hendershott, Christopher White." American Catholic Studies 125, no. 4 (2014): 77–78. http://dx.doi.org/10.1353/acs.2014.0074.

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van der Haven, Cornelis. "Patriotism and Bellicism in German and Dutch Epics of the Enlightenment." Arcadia 47, no. 1 (July 2012): 54–77. http://dx.doi.org/10.1515/arcadia-2011-0001.

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AbstractThe German and Dutch historiography of eighteenth-century patriotism defines two different forms of patriotism. It is either presented as an enlightened and virtuous-eudemonic form of ʻlove for the fatherlandʼ based on reason, or as an ideology that foreshadows nineteenth-century emphatic forms of aggressive nationalism. A critical reading of the mid-eighteenth-century epics Cyrus by Christoph Martin Wieland and De Gevallen van Friso by Willem van Haren shows that the discourses are strongly intertwined. Heroism in these epics is based on a personal experience of war acts and no longer on distanced and ʻtheatricalʼ experiences of the military spectacle. It confronts us with aggressive war fantasies related to early bellicism, as well as with pacifist statements. In Cyrus, for instance, the sentimental warrior inspires his fellow-soldiers to offer their blood in the struggle against the enemy, but he has doubts about the war and shows compassion with the enemy. Explorations of the effects of individual emotions on the battlefield, prepared both further idealisations of patriotic war acts and a more critical literary approach to war and fatherland.

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Mahlev, Haim. "A Philosophy of the Patriarchs?: The Agenda behind Christoph August Heumann’s Acta Philosophorum." Journal of the History of Ideas 76, no. 4 (2015): 517–39. http://dx.doi.org/10.1353/jhi.2015.0033.

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Kelly, Timothy. "Empowering the People of God: Catholic Action before and after Vatican II ed. by Jeremy Bonner, Christopher D. Denny, Mary Beth Fraser Connolly." American Catholic Studies 126, no. 3 (2015): 78–80. http://dx.doi.org/10.1353/acs.2015.0051.

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Doherty, H. F. "English Episcopal Acta. XXXIV: Worcester 1186-1218, ed. Mary G. Cheney, David Smith, Christopher Brooke, and Philippa Hoskin." English Historical Review CXXVI, no. 520 (June 1, 2011): 640–43. http://dx.doi.org/10.1093/ehr/cer122.

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Bartusis, Mark C. "Actes de Vatopédi, 2: De 1330 à 1376. Jacques Lefort , Vassiliki Kravari , Christophe Giros , Kostis Smyrlis." Speculum 82, no. 4 (October 2007): 1012–14. http://dx.doi.org/10.1017/s0038713400011726.

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Bartusis, Mark C. "Actes de Vatopédi, 1: Des origines à 1329. Jacques Bompaire , Jacques Lefort , Vassiliki Kravari , Christophe Giros." Speculum 78, no. 2 (April 2003): 468–70. http://dx.doi.org/10.1017/s0038713400168745.

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Jeffrey, Denis. "Mimésis et rituels dans l’anthropologie historique de Gunter Gebauer et de Christoph Wulf." Cahiers de recherche sociologique, no. 51 (March 26, 2013): 27–45. http://dx.doi.org/10.7202/1014996ar.

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Gunter Gebauer et Christoph Wulf ont cofondé avec leurs collègues allemands l’anthropologie historique. Leur perspective transdisciplinaire ambitionne de connaître la multiplicité historique et culturelle de la vie humaine. Nous présentons ici les fondements théoriques de cette anthropologie à travers les concepts de mimésis et de rituels. Pour ces chercheurs allemands, l’agir mimétique est à la base des diverses formes de vie sociales et culturelles. Par ailleurs, selon l’hypothèse qu’ils défendent, les rituels sont des actes corporels et symboliques acquis par mimétisme.

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Dempsey, Fiona C., Hussein Al-Ali, Scott J. Crichton, Charlene Fabian, Chris Pepper, and Christopher N. Parris. "Abstract P5-08-06: MDX-124, a novel annexin-A1 antibody, shows anti-tumor efficacy in several preclinical models of triple-negative breast cancer." Cancer Research 82, no. 4_Supplement (February 15, 2022): P5–08–06—P5–08–06. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-08-06.

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Abstract Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancer cases and is a particularly aggressive form of the disease, with poorer prognosis compared to other breast cancer subtypes. Advances in TNBC treatment have been made with the introduction of checkpoint inhibitors, PARP inhibitors and antibody drug conjugates. However, these therapies still have several limitations including low patient response rates, treatment resistance or relapse, and considerable side effects. Therefore, a significant unmet clinical need remains to develop novel targeted agents to treat TNBC. Annexin-A1 (ANXA1) is a phospholipid binding protein secreted in response to several physiological stimuli where it activates formyl peptide receptors (FPR1/2) triggering multiple oncogenic cell signaling pathways. Overexpression of ANXA1 by TNBC cells has been shown to influence several cancer-related processes including cell growth, cell cycle progression, angiogenesis, migration and invasion. In addition, ANXA1 has been shown to have immunomodulatory effects on T-cells, macrophages and dendritic cells. High ANXA1 expression in TNBC patients correlates with both poor overall survival and progression-free survival, indicating ANXA1 is a therapeutic target in TNBC. MDX-124 is a novel humanized antibody targeting ANXA1, and we have previously demonstrated its significant anti-proliferative activity. Here we present additional data showing the efficacy of MDX-124 in preclinical models of TNBC. Methods: The impact of MDX-124 on cell cycle progression was evaluated by measuring changes in DNA content using flow cytometry and analyzed with FlowJo™ software.The modulation of key oncogenic cell signalling pathways by MDX-124 was assessed using human phospho-kinase and XL Oncology Proteome Profiler™ antibody arrays. The effect of MDX-124 in combination therapy with chemotherapy was studied in-vitro using MTT cell proliferation assays, whilst synergy with anti-PD-1 therapy was evaluated using the EMT6 syngeneic mouse model of TNBC. Results: MDX-124 treatment dramatically decreased the proportion of HCC1806 TNBC cells in S-phase by 29.1% with a concomitant increase in G1 of 33.5% versus untreated cells. This occurred in a dose-dependent manner and is consistent with an MDX-124 mediated increase in cell cycle arrest.Treatment of HCC1806 TNBC cells with MDX-124 altered the expression of key oncogenic proteins and the phosphorylation of several kinases that regulate cell signaling pathways involved in proliferation, survival and migration. Notably, MDX-124 substantially reduced ERK and AKT phosphorylation by 84% and 72% respectively versus untreated control cells. In the HCC1806 TNBC cell line, proliferation was significantly reduced after 72 h treatment with MDX-124 and chemotherapy versus control.In the EMT6 syngeneic mouse model of TNBC, the murine analogue of MDX-124 (MDX-001) potentiated mean tumor growth inhibition of single agent anti-PD-1 treatment by 15%. Additionally, 30% of treated mice showed tumor regression in the MDX-001 combination therapy group versus 10% in the single agent anti-PD-1 group. This suggest that anti-ANXA1 antibody therapy acts synergistically with anti-PD-1 immunotherapy.Conclusion: MDX-124 binds to secreted and extracellular ANXA1 disrupting interactions with FPR1/2. This results in altered expression levels of several key cancer-related proteins preventing the activation of oncogenic signaling pathways that promote cancer progression. MDX-124 has demonstrated anti-cancer activity in several TNBC cell line and mouse models, as both a single agent and in combination with other drugs, including anti-PD-1 immunotherapy. Medannex plan to initiate a First-In-Human study in Q4 2021 to evaluate MDX-124 in solid malignancies, including TNBC. Citation Format: Fiona C Dempsey, Hussein Al-Ali, Scott J Crichton, Charlene Fabian, Chris Pepper, Christopher N Parris. MDX-124, a novel annexin-A1 antibody, shows anti-tumor efficacy in several preclinical models of triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-06.

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Supakorndej, Teerawit, Mahil Rao, and Daniel Link. "Myeloid Dendritic Cells Contribute to Hematopoietic Progenitor Mobilization by G-CSF." Blood 120, no. 21 (November 16, 2012): 2319. http://dx.doi.org/10.1182/blood.v120.21.2319.2319.

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Abstract Abstract 2319 Granulocyte-colony stimulating factor (G-CSF) is the prototypic agent used to mobilize hematopoietic stem and progenitor cells (HSPCs) into the blood where they can then be harvested for stem cell transplantation. G-CSF acts in a non-cell-intrinsic fashion to induce HSPC mobilization. We recently showed that G-CSF signaling in a CD68+ monocyte/macrophage lineage cell within the bone marrow initiates the HSPC mobilization cascade (Christopher et al., 2011). Consistent with this finding, two other groups showed that ablation of monocytes/macrophages induces HSPC mobilization (Winkler et al., 2010; Chow et al., 2011). CD68 marks a heterogeneous cell population that includes monocytes, macrophages, myeloid dendritic cells, and osteoclasts. To further define the relevant cell population(s) for HSPC mobilization by G-CSF, we first examined the role of osteoclasts. Receptor activator of NF-kappaB (RANK) signaling is required for osteoclast development. Osteoprotegerin (OPG) is a decoy receptor for RANK ligand, and treatment with OPG-Fc (a stabilized form of OPG) results in osteoclast ablation in mice. We treated mice with 100 μg of OPG-Fc and documented complete osteoclast ablation by histomorphometry. Osteoclast ablation did not result in constitutive HSPC mobilization, nor did it affect G-CSF-induced HSPC mobilization. To further assess the role of osteoclasts, we transplanted RANK−/− fetal liver cells into irradiated Csf3r−/− (G-CSF receptor deficient) recipients. Since RANK is required for osteoclast development, the osteoclasts in these bone marrow chimeras lack the G-CSFR, while other hematopoietic cells (including monocytes/macrophages) are G-CSFR sufficient. Again, G-CSF-induced HSPC mobilization in these mice was normal. Based on these data, we conclude that osteoclasts are dispensable for HSPC mobilization by G-CSF. We next quantified changes in monocytic/macrophage cell populations in the bone marrow after G-CSF treatment (250 μg/kg per day for 5 days) using a novel multi-color flow cytometry assay that includes CD115, F4/80, MHC class II, Gr-1, B220, and CD11c. Using this assay, we observed a significant decrease in macrophages (11.8 ± 3.6-fold) and, surprisingly, myeloid dendritic cells (MDCs; 5.5 ± 1.2-fold) in the bone marrow with G-CSF treatment. To further assess the role of MDCs, we used transgenic mice expressing the diphtheria toxin receptor under the control of the CD11c promoter (CD11c-DTR) to conditionally ablate MDCs. To avoid systemic toxicity, we transplanted CD11c-DTR bone marrow into congenic wild type recipients prior to MDC ablation. The resulting bone marrow chimeras were treated with diphtheria toxin (DT; 400 ng per day for 6 days), which resulted in a 92% reduction in MDCs. Ablation of MDCs resulted in a significant increase in colony-forming cells in the blood and spleen (figure 1A). Moreover, MDC ablation significantly increased mobilization of colony-forming cells and c-Kit+lineage−Sca-1+ (KLS) cells by G-CSF (figures 1B and 1C). Taken together, these data suggest that myeloid dendritic cells, but not osteoclasts, contribute to HSPC mobilization by G-CSF. Figure 1. HSPC mobilization in CD11c-DTR mice. CD11c-DTR bone marrow chimeras were treated with diphtheria toxin (DT) alone, G-CSF alone, or DT plus G-CSF. The number of CFU-C (A & B) or KLS cells (C) in the blood and spleen are shown. Data represent the mean ± SEM of 10–11 mice pooled from two independent experiments. *p < 0.05; **p < 0.001; ***p < 0.0001. Figure 1. HSPC mobilization in CD11c-DTR mice. CD11c-DTR bone marrow chimeras were treated with diphtheria toxin (DT) alone, G-CSF alone, or DT plus G-CSF. The number of CFU-C (A & B) or KLS cells (C) in the blood and spleen are shown. Data represent the mean ± SEM of 10–11 mice pooled from two independent experiments. *p < 0.05; **p < 0.001; ***p < 0.0001. Disclosures: No relevant conflicts of interest to declare.

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Taliadoros, Jason. "English Episcopal Acta 33: Worcester 1062-1185 - Edited by Mary Cheney, David Smith, Christopher Brooke and Philippa M. Hoskin." Journal of Religious History 34, no. 4 (November 15, 2010): 492–93. http://dx.doi.org/10.1111/j.1467-9809.2010.00963.x.

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TALIADOROS, JASON. "English Episcopal Acta 34: Worcester 1186-1218 - Edited by Mary Cheney, David Smith, Christopher Brooke, and Philippa M. Hoskin." Journal of Religious History 35, no. 3 (August 17, 2011): 460–61. http://dx.doi.org/10.1111/j.1467-9809.2010.01072.x.

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