Articoli di riviste: "Shy hero"

1

Strizhko, Viktoria Aleksandrovna. "Features of dramaturgy and system of expressive means. Works by R. Schumann". Uchenyy Sovet (Academic Council), n. 7 (25 giugno 2022): 461–66. http://dx.doi.org/10.33920/nik-02-2207-04.

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It is safe to say that Schumann was a kind of personification of the "romantic hero": rather secretive and shy in his personal life, at the same time, he was in a constant flame of creative excitement. The composer's music is imbued with an amazing wealth of psychological nuances; it is rebellious and agitated, unconditionally rendering the heightened and subtle reactions experienced by the creator. The author analyzes the features of R. Schumann's creative body of works, reveals the specifics of his compositional writing, and shows the features of the performance of his works. The material presented in the article may be useful in the preparation of performing musicians.

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Moody, Jeana. "“Imaginative? More Like Normative”". Boyhood Studies 15, n. 1-2 (1 dicembre 2022): 123–31. http://dx.doi.org/10.3167/bhs.2022.15010208.

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Mune: Guardian of the Moon is a children’s animated film about a series of misadventures resulting in a lighthearted good-versus-evil plotline. This movie attempts to be imaginative and original, and succeeds in some ways, through positioning slight-figured, compassionate, shy Mune as the hero of the story and using dreams of transformation instead of fists to defeat evil. However, it falls short through its stereotypical depictions of masculinities and gendered dynamics. Rather than portraying diverse and alternate ways that masculinity can be performed, Mune utilizes normative gender roles and hegemonic masculinity to emphasize that even small, unassuming young men can adequately fulfill typical masculine leadership roles, so long as they are most powerful and ultimately win the girl.

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3

Wanamaker, Lynne. "Within a Room". Journal of Childhood Studies 42, n. 1 (30 maggio 2017): 45. http://dx.doi.org/10.18357/jcs.v42i1.16886.

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<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p><span>In the face of an injustice toward a child, what is the responsibility of an early childhood educator? What are the risks if we speak out? What are the risks if we remain silent, if we do nothing? “Courage, Hannah Arendt (1958/1998) suggests, which we often think of as a quality of the ‘hero,’ is already present in the willingness to act and speak, to insert oneself into the world and begin a story” (Berger, 2010, p. 73). </span></p><p><span>“Lynne is conscientious in her work but she is shy.” I find it quite interesting that this comment/label written about me on my report card </span><span>52 years ago by my kindergarten teacher entered my thoughts out of somewhere while I was contemplating how to tell this particular story about taking risks in my practice as an early childhood educator, and how I let go of normal. If indeed I am normally shy, I most </span><span>definitely let go of my personal and professional normal in a family drop-in program in which I am the only early childhood educator-facilitator. It happened one busy morning in front of parents, grandparents, care providers, and children from infancy to five years old. </span><span>People had been engaged in relation with each other and the mostly unconventional materials in the intentionally unstructured, untimed, and nontraditionally run program that is situated within a room in an urban elementary school. </span></p></div></div></div>

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4

Boucher, Robert L. "Toward Achieving a Focal Point for Sport Management: A Binocular Perspective". Journal of Sport Management 12, n. 1 (gennaio 1998): 76–85. http://dx.doi.org/10.1123/jsm.12.1.76.

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In the summer of 1941, Sergeant James Allen Ward was awarded the Victoria Cross for climbing onto the wing of his Wellington bomber 13,000 feet above the Zuider Zee in Holland to extinguish a fire in the starboard engine. Secured only by a rope around his waist, he managed not only to smother the fire but also to return along the wing to the aircraft's cabin. Churchill, an admirer as well as a performer of swashbuckling exploits, summoned the shy New Zealander to 10 Downing Street (for our American friends that's like the British White House). Ward was struck dumb with awe in Churchill's presence and was unable to answer the Prime Minister's simplest questions. Churchill surveyed the unhappy hero with some compassion. “You must feel very humble and awkward in my presence,” said Churchill. “Yes sir,” stammered the young flyer. “Then you can imagine how humble and awkward I feel in yours,” said Churchill. (Fadiman, 1985, pp. 122-23)

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5

Dubinina, Tatiana G. "THE MIRACLE OF PARENTAL LOVE: A.P. CHEKHOV`S SHORT STORY "THE BISHOP" AND I.S. TURGENEV'S NOVEL "FATHERS AND CHILDREN"". Proceedings of Southern Federal University. Philology 26, n. 4 (22 dicembre 2022): 119–26. http://dx.doi.org/10.18522/1995-0640-2022-4-119-126.

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The article considers the question of the influence of I.S. Turgenev's novel "Fathers and Children" on A.P. Chekhov's story "The Bishop". The relevance of the work lies in the perspective of the study, which assumes not just a comparison of the images of mothers in the works, but also allows us to talk about child-parent relations as an important problematic core of texts. Despite the fact that Chekhov's interest in this novel is known to everyone, the "Bishop" did not become an object of interest to the scientist in the proposed way. Common features in the "mother-son" collision are revealed. Mothers are similar in relation to their sons – they love children very much and are shy to show this love at the same time. Their affection is manifested in facial expressions, gestures, and eye expressions. The problem of tragic loneliness of heroes is touched upon. If in Turgenev's novel Bazarov opposes himself to the world, then in Chekhov's story the world seems to repel the hero, who has no one to talk to sincerely. Even the strong and sincere love of the mother does not save the hero from loneliness. The finales of the texts turn out to be fundamentally important. They find themselves converging on one thing – private death does not disrupt the general course of life. Both Turgenev and Chekhov avoid didactics. However, in the finale of the novel "Fathers and Children", the parents' funeral prayer for their son sounds. The idea of the saving power of parental love is affirmed. It will be the key to the hope of eternal life for their son. The finale of Chekhov's story is tragic. Despite his sincere faith in God, the hero is experiencing an existential catastrophe, and maternal love is not able to prevent it. There is no triumph of life over death.

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6

Dorri, Zari. "Holden Caulfield: A Marginal Player Made by Historical Context". International Letters of Social and Humanistic Sciences 80 (gennaio 2018): 1–6. http://dx.doi.org/10.18052/www.scipress.com/ilshs.80.1.

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Holden Caulfield, the major character in Jerome David Salinger’s most rewarded novel The Catcher in the Rye, long stood as the innovative and leading figure for such distinctive and revolutionary traits in a character he presented in 1959s’ America literary domain. Salinger media-shy and no interview policies led the public to spread out the idea of the author’s being the whole genius behind the sheer novelty of Holden Caulfield character by making a myth out of the author who turns down any kind of publicity and is finally lionized. This student-friendly hero who denigrate respectability and” phoniness” with his cynical attitude and obscene language, in one way or another, is kept being compared to such huge characters like Huckle Berry Finn whose universal popularity is barely deniable; but the question is that, could at any rate, J.D.Salinger be the sole innovator behind this genuineness? On the other hand, are there any other social and environmental factors, which came to pave the way for any kinds of Holden to be born and well liked? The main purpose of the paper is to answer these questions by a kind of critical theory as New Historicism and survey through the history as a discourse in this method. The results and findings indicate that, apparently, there was a specific social context for the emergence of this novel, with which the author had to interact. By opening up the environmental condition of those days and considering the facts, which affected Holden’s birth and popularity in that era. This essay will point out the fact that criticizing America’s 50s in such aforementioned ambience was inevitably and to some extent predictable.

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7

Sokolova, Marina G. "Realization of traditional images of comparative tropes with diminutive dendronyms in the Russian poetry of the 19–21st centuries". Izvestiya of Saratov University. Philology. Journalism 23, n. 2 (22 maggio 2023): 108–14. http://dx.doi.org/10.18500/1817-7115-2023-23-2-108-114.

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The article examines the traditional images of comparison, characterizing diminutive dendronyms in the language of the Russian poetry of the 19–21st centuries, from the perspective of the relationship of ‘cultural-stereotypical (traditional) – author’s individual’. The analysis of 725 fragments from the Russian poetic works of the 19–21st centuries reveals the ways of word formation and the composition of diminutive dendronyms, as well as the composition of folk poetic, general poetic and individual author’s images of comparative tropes representing these diminutives as subjects of comparison: girl; love attraction, longing; to cry (tears), to grieve, to yearn; fertility; separation; bitter, unhappy fate, orphanhood; gold, silver; emerald; smoke; clothing; fire; pattern, mesh product; infantas by Velasquez, ermine coat; calico; fidelity. The referencedenotative features of the corresponding realia, motivating the choice of figurative associations are determined: a thin trunk, flexible branches, serrated, heart-shaped leaves, flowering trees, fruit trees. The techniques that help make stereotypical images of comparison in the Russian poetic language individualized are established: the inclusion in the composition of an extended anthropomorphic metaphor; updating by means of occasional epithets, lexical variation of the components of the trope. The stable semantic connotations of diminutive dendronyms are singled out: ‘shy’, ‘timid’, ‘meek’, ‘slender’, ‘tall’, ‘gentle’, ‘curls’, ‘braids’, ‘thin figure’, ‘beauty’, ‘breasts’, ‘captivate’, ‘innocence’, as well as the ways of their representation in poetic contexts: extended metaphors ‘autumnal withering of a tree – withering of female beauty’; memories of the lyrical hero about close people; parallelism of the images of a tree and a human condition; conventional epithets (weeping, bitter); features of the situation of a literary text. The results of the study allow us to improve the understanding of how comparative tropes with diminutive dendronyms develop dynamically in the Russian poetic language.

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8

Levey, Hilary. "Here She is … and There she Goes?" Contexts 6, n. 3 (agosto 2007): 70–72. http://dx.doi.org/10.1525/ctx.2007.6.3.70.

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Little Miss Sunshine (20th Century Fox, 2006) Pageant School: Becoming Miss America (CMT and PB&J Television, original airdate January 26, 2007) 2006 and 2007 Miss America Pageant (CMT, original air-dates January 21, 2006, and January 29, 2007)

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9

HELLYER, Nathan J., Kunrong CHENG e John G. KOLAND. "ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase". Biochemical Journal 333, n. 3 (1 agosto 1998): 757–63. http://dx.doi.org/10.1042/bj3330757.

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ErbB3 (HER3), a unique member of the ErbB receptor family, lacks intrinsic protein tyrosine kinase activity and contains six Tyr-Xaa-Xaa-Met (YXXM) consensus binding sites for the SH2 domains of the p85 regulatory subunit of phosphoinositide 3-kinase. ErbB3 also has a proline-rich sequence that forms a consensus binding site for the SH3 domain of p85. Here we have investigated the interacting domains of ErbB3 and p85 by a unique application of the yeast two-hybrid system. A chimaeric ErbB3 molecule containing the epidermal growth factor receptor protein tyrosine kinase domain was developed so that the C-terminal domain of ErbB3 could become phosphorylated in the yeast system. We also generated several ErbB3 deletion and Tyr → Phe site-specific mutants, and observed that a single ErbB3 YXXM motif was necessary and sufficient for the association of ErbB3 with p85. The incorporation of multiple YXXM motifs into the ErbB3 C-terminus enabled a stronger ErbB3/p85 interaction. The proline-rich region of ErbB3 was not necessary for interaction with p85. However, either deletion or mutation of the p85 SH3 domain decreased the observed ErbB3/p85 association. Additionally an ErbB3/p85 SH3 domain interaction was detected by an assay in vitro. These results were consistent with a model in which pairs of phosphorylated ErbB3 YXXM motifs co-operate in binding to the tandem SH2 domains of p85. Although a contributing role for the p85 SH3 domain was suggested, the N- and C-terminal SH2 domains seemed to be primarily responsible for the high-affinity association of p85 and ErbB3.

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10

Ben-Ur, Aviva. "Moses Montefiore: Jewish Liberator, Imperial Hero (review)". Shofar: An Interdisciplinary Journal of Jewish Studies 29, n. 3 (2011): 171–73. http://dx.doi.org/10.1353/sho.2011.0180.

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11

Donawerth, Jane. "The Female Tragic Hero in English Renaissance Drama (review)". Shakespeare Quarterly 55, n. 2 (2004): 238–39. http://dx.doi.org/10.1353/shq.2004.0061.

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12

DAVIES, MALCOLM. "THE HERO AND HIS ARMS". Greece and Rome 54, n. 2 (3 settembre 2007): 145–55. http://dx.doi.org/10.1017/s0017383507000137.

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Arma virumque cano Virgil sang, or professed to sing, at the start of his epic, and one may reformulate the import of his programmatic words to fit a new context. Obtaining weapons he can call his own is very often a key moment near the start of the career of a folk-tale hero. And very often it is the hero's mother who equips him with them. Paradoxically, this truth may be confirmed, e contrario, by reference to the Welsh story of Lleu Llaw Gyffes from the Mabinogion, for, in that narrative, the hero's mother Aranhry seeks to thwart at its inception the career of her son – whom she had exposed, since his very existence causes her so much embarrassment – by placing a Destiny or interdiction upon him: he will never bear arms unless and until she herself bestows them. The ban is circumvented by a cunning ruse: the magician Gwydion disguises her son and himself as peripatetic bards, in which capacity they are entertained in Aranhry's castle. When Gwydion conjures up a phantom army and fleet to besiege the citadel, the alarmed Aranhry is all too ready to bestow weapon and armour on the younger of her two guests – only to find the army vanished and her own son in possession of the arms she had sworn he would not bear.

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13

Wolitz, Seth L. "Forging a Hero for a Jewish Stage: Goldfadn's Bar Kokhba". Shofar: An Interdisciplinary Journal of Jewish Studies 20, n. 3 (2002): 53–65. http://dx.doi.org/10.1353/sho.2002.0046.

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14

Kaouk, Theodore F. "Homo Faber, Action Hero Manqué: Crafting the State in Coriolanus". Shakespeare Quarterly 66, n. 4 (2015): 409–39. http://dx.doi.org/10.1353/shq.2015.0069.

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15

Dunda, Jessica Mae Scott. "We Don't Say “H” Here". Teaching Artist Journal 15, n. 1 (2 gennaio 2017): 17–27. http://dx.doi.org/10.1080/15411796.2017.1297614.

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16

Rana, Geeta, Alok Kumar Goel e Ajay Kumar Saini. "Knowledge transfer in Hero Motor Corp Ltd." Strategic HR Review 13, n. 6 (7 ottobre 2014): 260–63. http://dx.doi.org/10.1108/shr-08-2014-0046.

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Purpose – This paper aims to examine the issues of knowledge transfer in international strategic alliance within Hero Moto Corp. Ltd., an Indian multinational company. International Strategic alliances have been increasing in numbers in the past decades and transfer of knowledge and its transfer in multinational companies is wider debate. The case explores the complex issues involved in cross-organization and cross-country transfer of knowledge. The company has forged a strategic alliance with the US-based Erik Buell Racing for accessing technology and design inputs. Design/methodology/approach – It presents a structured case study that examines a wide range of knowledge transfer issues of international strategic alliance. Findings – It reveals that a major influencing factor is the national culture of the parents and that of the host country which provides the context with in which alliances are operate. It is also explored the ways in which the multi-parentage of strategic alliances influences their Human Resource Management (HRM) policies and practices. Originality/value – It provides plenty of useful information on an issue that affects virtually every employee and organization.

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O’Neill, Mark E., e Murray G. Phillips. "Sport, Film, and Australian Cultural Identity: Reading Hero to a Nation". Sport History Review 41, n. 1 (maggio 2010): 1–16. http://dx.doi.org/10.1123/shr.41.1.1.

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18

Jücker, Manfred, Charles A. Schiffer e Ricardo A. Feldman. "A Tyrosine-Phosphorylated Protein of 140 kD Is Constitutively Associated With the Phosphotyrosine Binding Domain of Shc and the SH3 Domains of Grb2 in Acute Myeloid Leukemia Cells". Blood 89, n. 6 (15 marzo 1997): 2024–35. http://dx.doi.org/10.1182/blood.v89.6.2024.

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Abstract The Shc gene encodes three proteins that have been implicated as mediators of signal transduction from growth factor receptors and nonreceptor tyrosine kinases to Ras. Overexpression of Shc in established murine fibroblasts results in oncogenic transformation, indicating that Shc has oncogenic potential. Shc proteins contain a carboxy terminal SH2 domain and a novel non-SH2 phosphotyrosine-binding (PTB) domain that specifically recognizes a phosphorylated NPXpY motif in target proteins such as the epidermal growth factor receptor. We show here that Shc is constitutively tyrosine-phosphorylated in all primary acute myeloid leukemias analyzed and that, in some of these leukemias, Shc is associated through its PTB domain with a tyrosinephosphorylated protein of 140 kD (p140) in vivo. In factor-dependent cells, this 140-kD protein can be tyrosine-phosphorylated in vitro in response to cytokines involved in myeloid proliferation and differentiation, ie, granulocyte-macrophage colony-stimulating factor and colony-stimulating factor-1. A similar or identical protein of 140 kD is constitutively bound to the C-terminal SH3 domain of Grb2 in the same acute myeloid leukemias. In addition to p140, other tyrosine-phosphorylated proteins of 61 and 200 kD are constitutively associated with Shc in some of the leukemias analyzed. Our results implicate Shc, Grb2, p140, and additional tyrosine-phosphorylated proteins of 61 and 200 kD in signalling of acute myeloid leukemia cells.

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Kohe, Geoffery Z. "Judging Jack: Rethinking Historical Agency and the Sport Hero". Sport History Review 45, n. 2 (novembre 2014): 200–219. http://dx.doi.org/10.1123/shr.2012-0022.

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20

Ungar, Sheldon, e Aysan Sev'er. ""Say It Ain't So, Ben": Attributions for a Fallen Hero". Social Psychology Quarterly 52, n. 3 (settembre 1989): 207. http://dx.doi.org/10.2307/2786715.

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21

Tymowski, Andrzej, e Mark Znidericz. "“…and She also is Not Here”". Dialogue and Universalism 14, n. 5 (2004): 117–22. http://dx.doi.org/10.5840/du2004145/628.

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22

Conway, Carr, e Robert W. Rouse. "Never Say,?It Can't Happen Here!?" Journal of Corporate Accounting & Finance 13, n. 1 (2001): 49–53. http://dx.doi.org/10.1002/jcaf.1207.

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23

Wisniewski, David, Annabel Strife, Steve Swendeman, Hediye Erdjument-Bromage, Scott Geromanos, W. Michael Kavanaugh, Paul Tempst e Bayard Clarkson. "A Novel SH2-Containing Phosphatidylinositol 3,4,5-Trisphosphate 5-Phosphatase (SHIP2) Is Constitutively Tyrosine Phosphorylated and Associated With src Homologous and Collagen Gene (SHC) in Chronic Myelogenous Leukemia Progenitor Cells". Blood 93, n. 8 (15 aprile 1999): 2707–20. http://dx.doi.org/10.1182/blood.v93.8.2707.408k17_2707_2720.

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Because of the probable causal relationship between constitutive p210bcr/abl protein tyrosine kinase activity and manifestations of chronic-phase chronic myelogenous leukemia (CML; myeloid expansion), a key goal is to identify relevant p210 substrates in primary chronic-phase CML hematopoietic progenitor cells. We describe here the purification and mass spectrometric identification of a 155-kD tyrosine phosphorylated protein associated with src homologous and collagen gene (SHC) from p210bcr/abl-expressing hematopoietic cells as SHIP2, a recently reported, unique SH2-domain–containing protein closely related to phosphatidylinositol polyphosphate 5-phosphatase SHIP. In addition to an N-terminal SH2 domain and a central catalytic region, SHIP2 (like SHIP1) possesses both potential PTB(NPXY) and SH3 domain (PXXP) binding motifs. Thus, two unique 5-ptases with striking structural homology are coexpressed in hematopoietic progenitor cells. Stimulation of human hematopoietic growth factor responsive cell lines with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrate the rapid tyrosine phosphorylation of SHIP2 and its resulting association with SHC. This finding suggests that SHIP2, like that reported for SHIP1 previously, is linked to downstream signaling events after activation of hematopoietic growth factor receptors. However, using antibodies specific to these two proteins, we demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3 in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4. Such an enzymatic difference raises the possibility that SHIP1 and SHIP2 may serve different functions. Preliminary binding studies using lysates from p210bcr/abl-expressing cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB domain of SHC but not to its SH2 domain. Interestingly, SHIP2 was found to selectively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the SH3 domain of Src. Furthermore, in contrast to SHIP1, SHIP2 did not bind to either the N-terminal or C-terminal SH3 domains of GRB2. These observations suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of binding SH3 containing proteins and therefore may modulate different signaling pathways and/or localize to different cellular compartments and (2) that they may be substrates for tyrosine phosphorylation by different tyrosine kinases. Because recent evidence has clearly implicated both PI(3,4,5)P3 and PI(3,4)P2 in growth factor-mediated signaling, our finding that both SHIP1 and SHIP2 are constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor cells may thus have important implications in p210bcr/abl-mediated myeloid expansion.

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Kidd, Colin. "On Heroes, Hero-Worship and Demonology in Scottish Historiography: A Reply to Dr. Ferguson". Scottish Historical Review 86, n. 1 (aprile 2007): 108–12. http://dx.doi.org/10.3366/shr.2007.0041.

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25

Szczuka, Kazimiera. "Bohater, spisek, śmierć: Wykłady żydowskie (Hero, Conspiracy, Death: The Jewish Lectures) (review)". Shofar: An Interdisciplinary Journal of Jewish Studies 29, n. 3 (2011): 122–28. http://dx.doi.org/10.1353/sho.2011.0167.

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Swara Thacker. "Sita: The Hero of Nandini Sahu’s Retelling of Ramayana". Creative Saplings 2, n. 1 (25 aprile 2023): 27–36. http://dx.doi.org/10.56062/gtrs.2023.2.01.251.

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Generation after generation has heard the story of Ramayana as the epic battle or dharmayudh between Rama and Ravana. Sita is mostly presented as the damsel in distress whose honour is protected by her husband and who is supposed to prove her chastity in order to find a place in society. However, her life before marriage, her natural gift, resilience, courage, and ability to detach from everything that is close to her are many times overlooked. The hero is Rama, and the villain is Ravana. Sita is the victim. Nandini Sahu’s Sita is not a victim. She is the true warrior of the epic Ramayana who deserves to be called the hero. She is the faithful daughter, wife, and mother who performs all the three roles with devotion and dedication. However, most importantly, she is a woman of substance who never loses hope in adverse circumstances and resiliently faces every challenge that life throws her way. This paper is an attempt to reconstruct Sita’s identity as the warrior of the epic instead of the victim by referring to Nandini Sahu’s rendering of the story of Ramayana from Sita’s perspective. This analysis will be done from the postcolonial perspective in which the story of the subaltern Sita will be the highlight, and her actual contribution to the action of the epic will be brought to the forefront to show that she is the hero and not the victim.

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27

Wisniewski, David, Annabel Strife, Steve Swendeman, Hediye Erdjument-Bromage, Scott Geromanos, W. Michael Kavanaugh, Paul Tempst e Bayard Clarkson. "A Novel SH2-Containing Phosphatidylinositol 3,4,5-Trisphosphate 5-Phosphatase (SHIP2) Is Constitutively Tyrosine Phosphorylated and Associated With src Homologous and Collagen Gene (SHC) in Chronic Myelogenous Leukemia Progenitor Cells". Blood 93, n. 8 (15 aprile 1999): 2707–20. http://dx.doi.org/10.1182/blood.v93.8.2707.

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Abstract (sommario):

Abstract Because of the probable causal relationship between constitutive p210bcr/abl protein tyrosine kinase activity and manifestations of chronic-phase chronic myelogenous leukemia (CML; myeloid expansion), a key goal is to identify relevant p210 substrates in primary chronic-phase CML hematopoietic progenitor cells. We describe here the purification and mass spectrometric identification of a 155-kD tyrosine phosphorylated protein associated with src homologous and collagen gene (SHC) from p210bcr/abl-expressing hematopoietic cells as SHIP2, a recently reported, unique SH2-domain–containing protein closely related to phosphatidylinositol polyphosphate 5-phosphatase SHIP. In addition to an N-terminal SH2 domain and a central catalytic region, SHIP2 (like SHIP1) possesses both potential PTB(NPXY) and SH3 domain (PXXP) binding motifs. Thus, two unique 5-ptases with striking structural homology are coexpressed in hematopoietic progenitor cells. Stimulation of human hematopoietic growth factor responsive cell lines with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrate the rapid tyrosine phosphorylation of SHIP2 and its resulting association with SHC. This finding suggests that SHIP2, like that reported for SHIP1 previously, is linked to downstream signaling events after activation of hematopoietic growth factor receptors. However, using antibodies specific to these two proteins, we demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3 in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4. Such an enzymatic difference raises the possibility that SHIP1 and SHIP2 may serve different functions. Preliminary binding studies using lysates from p210bcr/abl-expressing cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB domain of SHC but not to its SH2 domain. Interestingly, SHIP2 was found to selectively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the SH3 domain of Src. Furthermore, in contrast to SHIP1, SHIP2 did not bind to either the N-terminal or C-terminal SH3 domains of GRB2. These observations suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of binding SH3 containing proteins and therefore may modulate different signaling pathways and/or localize to different cellular compartments and (2) that they may be substrates for tyrosine phosphorylation by different tyrosine kinases. Because recent evidence has clearly implicated both PI(3,4,5)P3 and PI(3,4)P2 in growth factor-mediated signaling, our finding that both SHIP1 and SHIP2 are constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor cells may thus have important implications in p210bcr/abl-mediated myeloid expansion.

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Woodall, Denise. "Here She Comes: Women of Convict Criminology". Journal of Prisoners on Prisons 33, n. 1 (16 novembre 2023): 38–54. http://dx.doi.org/10.18192/jpp.v33i1.7017.

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In response to Joanne Belknap’s 2014 presidential address in which she critiqued the white male dominance of Convict Criminology, formerly incarcerated women formed the group’s first thematic panel on “Women of Convict Criminology” at the American Society of Criminology annual conference in 2016. This article reports the results of an analysis presented in the first session that illustrates the invisibility of directly impacted women contributors to our knowledgebase and recaps the inspiration, courage, and empiricism that sparked the presence of a new, more diverse group of directly impacted people fighting for recognition and inclusion in knowledge construction within ‘malestream’ criminology. Ways of conceptualizing carceral status as one axis of oppressions and directions for the future of Convict Criminology are discussed.

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Hussein, Ali, e Riyadh Hasan. "Thomas Hardy's Tess of the d'Urbervilles:The epresentative of a Tragic Hero". Kufa Journal of Arts 1, n. 18 (21 aprile 2014): 61–78. http://dx.doi.org/10.36317/kaj/2013/v1.i18.6422.

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Tess of the d'Urbervillesis Thomas Hardy's novel that tackles the story of Tess Durbeyfield, a working-woman in the farm of d'Urbervilles. She works so as to help her family in getting living. Jack Durbeyfield, Tess's father has no job. He spends his days in drinking wine. Tess looks like her mother, Joan Durbeyfield, in that both of them are uneducated and beautiful women. Alec d'Urbervilles forced Tess to be raped by him. She cannot oppose him because he is her master in work on one hand, and she is ignorant in the sexual relation-shipsbetween man and woman and the outcomes connecting from such arelationship. Hardy condemns the passivity of Tees. Being a passive person means to loose; means to be aimless, dependent, and having conforming to the fate without any resistance. Tess is passive in not attacking, defending herself from Alec's seduction at the beginning. She is passive in accepting Angel Clare's decision to leave her―at the night of confession―at the end. She had better counteract the outsider attacks. She is partly responsible for her tragic flaw and the other responsibility lies upon her mother, Joan. Her mother did not advice, and did not tell her how to guard herself. By tragic flaw, it is the destructive factor generated from the defects in the character that lead to destroy the charactertotally.

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Sipeki, Szabolcs, Kitti Koprivanacz, Tamás Takács, Anita Kurilla, Loretta László, Virag Vas e László Buday. "Novel Roles of SH2 and SH3 Domains in Lipid Binding". Cells 10, n. 5 (13 maggio 2021): 1191. http://dx.doi.org/10.3390/cells10051191.

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Signal transduction, the ability of cells to perceive information from the surroundings and alter behavior in response, is an essential property of life. Studies on tyrosine kinase action fundamentally changed our concept of cellular regulation. The induced assembly of subcellular hubs via the recognition of local protein or lipid modifications by modular protein interactions is now a central paradigm in signaling. Such molecular interactions are mediated by specific protein interaction domains. The first such domain identified was the SH2 domain, which was postulated to be a reader capable of finding and binding protein partners displaying phosphorylated tyrosine side chains. The SH3 domain was found to be involved in the formation of stable protein sub-complexes by constitutively attaching to proline-rich surfaces on its binding partners. The SH2 and SH3 domains have thus served as the prototypes for a diverse collection of interaction domains that recognize not only proteins but also lipids, nucleic acids, and small molecules. It has also been found that particular SH2 and SH3 domains themselves might also bind to and rely on lipids to modulate complex assembly. Some lipid-binding properties of SH2 and SH3 domains are reviewed here.

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31

Mckinlay, Judith E. "Rahab: a Hero/Ine?" Biblical Interpretation 7, n. 1 (1999): 44–57. http://dx.doi.org/10.1163/156851599x00236.

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AbstractCan Rahab be regarded as a hero/ine? I ask this question, aware that the context of my reading is that of twentieth-century Aotearoa New Zealand, and that different communities read textual dynamics in different ways, and that texts allow this. But if there is an interpretive open-endedness, so that in narrative terms one may ask whether Rahab is saviour, or traitor, or victim, the story as it is told appears to have been shaped for Israelite listeners, with Israel's interests encoded. For whose voice do we hear in Rahab's long speech to the spies? A Canaanite Rahab? Or a Rahab who is an Israelite construct? The text has led the reader to accept its assumptions that foreign/outsider women are sexually available and can be bought, just as their land lies there for the taking. The reader is provided with Rahab as the model in reading the situation as an Israelite, for she herself has read and entered Israel's ideological world. The making of Rahab the hero/ine is part of the "semiotic economy" of Israel. But if Rahab is a hero/ine, not only is there a danger here for ancient Canaanites, but other dominant cultures may identify with the voice of the text which justifies taking others' land, and those who have already lost to Christian invaders may be led to read against their history and identity. Such issues force me to face the costliness of such co-opting. If Rahab is a hero/ine, then let the reader read again.

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32

Tanaka, S., S. Hattori, T. Kurata, K. Nagashima, Y. Fukui, S. Nakamura e M. Matsuda. "Both the SH2 and SH3 domains of human CRK protein are required for neuronal differentiation of PC12 cells". Molecular and Cellular Biology 13, n. 7 (luglio 1993): 4409–15. http://dx.doi.org/10.1128/mcb.13.7.4409-4415.1993.

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Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that both SH2 and SH3 are required for signaling from CRK protein. Microinjection of the CRK protein induced neurite formation of rat pheochromocytoma cell line PC12. This activity was abolished by mutation of the CRK protein in either SH2 or SH3. The neuronal differentiation induced by the CRK protein was blocked by an excess amount of peptides containing CRK SH3. Moreover, we identified three proteins, of 118, 125, and 136 kDa, which bound specifically to CRK SH3. The CRK-induced neuronal differentiation was also suppressed by monoclonal antibodies against either CRK SH2 or p21ras. These results suggest that both SH2 and SH3 of the CRK protein mediate specific protein-protein binding and that the resulting multimolecular complex generates a signal for neurite differentiation through activation of p21ras.

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33

Tanaka, S., S. Hattori, T. Kurata, K. Nagashima, Y. Fukui, S. Nakamura e M. Matsuda. "Both the SH2 and SH3 domains of human CRK protein are required for neuronal differentiation of PC12 cells." Molecular and Cellular Biology 13, n. 7 (luglio 1993): 4409–15. http://dx.doi.org/10.1128/mcb.13.7.4409.

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Abstract (sommario):

Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that both SH2 and SH3 are required for signaling from CRK protein. Microinjection of the CRK protein induced neurite formation of rat pheochromocytoma cell line PC12. This activity was abolished by mutation of the CRK protein in either SH2 or SH3. The neuronal differentiation induced by the CRK protein was blocked by an excess amount of peptides containing CRK SH3. Moreover, we identified three proteins, of 118, 125, and 136 kDa, which bound specifically to CRK SH3. The CRK-induced neuronal differentiation was also suppressed by monoclonal antibodies against either CRK SH2 or p21ras. These results suggest that both SH2 and SH3 of the CRK protein mediate specific protein-protein binding and that the resulting multimolecular complex generates a signal for neurite differentiation through activation of p21ras.

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34

Panchamoorthy, G., T. Fukazawa, L. Stolz, G. Payne, K. Reedquist, S. Shoelson, Z. Songyang, L. Cantley, C. Walsh e H. Band. "Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn". Molecular and Cellular Biology 14, n. 9 (settembre 1994): 6372–85. http://dx.doi.org/10.1128/mcb.14.9.6372-6385.1994.

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Abstract (sommario):

The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The repression is mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain is required for this interaction. However, the biochemical basis of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3 domain was decreased. An interdomain communication was further revealed by occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain SH3-specific cellular polypeptides. Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did not require an intact phosphotyrosine binding pocket on the SH2 domain; however, perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating the enzymatic activity of Src kinases and their interactions with other proteins.

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35

Panchamoorthy, G., T. Fukazawa, L. Stolz, G. Payne, K. Reedquist, S. Shoelson, Z. Songyang, L. Cantley, C. Walsh e H. Band. "Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn." Molecular and Cellular Biology 14, n. 9 (settembre 1994): 6372–85. http://dx.doi.org/10.1128/mcb.14.9.6372.

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Abstract (sommario):

The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The repression is mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain is required for this interaction. However, the biochemical basis of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3 domain was decreased. An interdomain communication was further revealed by occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain SH3-specific cellular polypeptides. Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did not require an intact phosphotyrosine binding pocket on the SH2 domain; however, perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating the enzymatic activity of Src kinases and their interactions with other proteins.

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36

Gurock, Jeffrey S. "Hank Greenberg: The Hero Who Didn’t Want to Be One by Mark Kurlansky (review)". Shofar: An Interdisciplinary Journal of Jewish Studies 31, n. 3 (2013): 187–89. http://dx.doi.org/10.1353/sho.2013.0053.

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37

PO, RONALD C. "Hero or Villain? The evolving legacy of Shi Lang in China and Taiwan". Modern Asian Studies 53, n. 05 (15 maggio 2019): 1486–515. http://dx.doi.org/10.1017/s0026749x17000737.

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Abstract (sommario):

AbstractFor over two centuries, prominent officials, literary figures, and intellectuals in China have paid special attention to the legacy of Shi Lang. Compared to many other historical figures, Shi Lang remains essential to our understanding of the cross-strait tension and the murky outlook for its future. Although the image of Shi Lang continues to mean different things to different individuals, to some degree, his significance to one particular community is also communicated to other communities. By analysing most of the previous appraisals and examinations of Shi Lang, we can reveal the historical narratives of this man as being continually under construction in a shifting and mutually reinforcing process. This article aims to examine the ways in which the legacy of Shi Lang has percolated throughout Chinese history, since the Qing dynasty, and also how it continues to function in the present day. It is fascinating to not only delineate how the story of Shi Lang has evolved as a legacy, but also to explore the rich variety of ways in which an individual or a community has adapted the narratives that make up the story of Shi Lang to suit the demands of different historical settings and perspectives.

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38

Boldyreva, Elena M. "Rickshaw as a cultural hero in Russian and Chinese literature of the twentieth century". Yaroslavl Pedagogical Bulletin 1, n. 124 (2022): 234–47. http://dx.doi.org/10.20323/1813-145x-2022-1-124-234-247.

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Abstract (sommario):

The article is devoted to the consideration of the image of rickshaw in Russian (I. Bunin, V. Mayakovsky, N. Agnivtsev, E. Dolmatovsky, M. Sinelnikov) and Chinese literature of the twentieth century (Lu Xun, Lao She, Hu Shi, Shen Yinmo, Liu Bannong, Zheng Min). Particular attention is paid to the consideration of the principles of artistic representation of the image of rickshaw in the work of representatives of the Chinese «Movement for a New Culture», in the discourse of Soviet children's literature of the late 1920s and the «Chinese theme» in Soviet literature, as well as in the story of I. Bunin «Brothers» and the novel by Lao She «Ricksha» as detailed narratives about the life and existence of representatives of this class, common motives and plot-compositional constants are revealed for writers (ambivalent semantics of rickshaw physicality, deestetization motives reaching bodily destruction, the important role of the olfactor component, the motif of feverish non-stop running, the sacral status of the stroller as the equivalent of the hero's fate, the test of rickshaw love, etc.). The article concludes that, despite the relative small number of the rickshaw literary gallery, rickshaw gives rise to many different meanings in the literature of different countries and eras: the vivid image of the exotic East, the quintessence of stereotypes of public consciousness, the emblematic sign of Soviet literary and political discourse, one of the tragic variations of a small man, a catalyst for moral self-reflection of intelligentsia, the embodiment of the complex of her guilt and her conscience before the world of «humiliated and offended», cultural and historical portrait of the era and the «encyclopedia of Chinese life», personification of the ideas of Buddhism and the philosophy of «living life» and, finally, the universal symbolic image of the «marathon runner of life», pushing the horizons of space and time and forever running in an ongoing cycle of births and deaths in search of truth.

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Richard, S., D. Yu, K. J. Blumer, D. Hausladen, M. W. Olszowy, P. A. Connelly e A. S. Shaw. "Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1." Molecular and Cellular Biology 15, n. 1 (gennaio 1995): 186–97. http://dx.doi.org/10.1128/mcb.15.1.186.

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Abstract (sommario):

src family tyrosine kinases contain two noncatalytic domains termed src homology 3 (SH3) and SH2 domains. Although several other signal transduction molecules also contain tandemly occurring SH3 and SH2 domains, the function of these closely spaced domains is not well understood. To identify the role of the SH3 domains of src family tyrosine kinases, we sought to identify proteins that interacted with this domain. By using the yeast two-hybrid system, we identified p62, a tyrosine-phosphorylated protein that associates with p21ras GTPase-activating protein, as a src family kinase SH3-domain-binding protein. Reconstitution of complexes containing p62 and the src family kinase p59fyn in HeLa cells demonstrated that complex formation resulted in tyrosine phosphorylation of p62 and was mediated by both the SH3 and SH2 domains of p59fyn. The phosphorylation of p62 by p59fyn required an intact SH3 domain, demonstrating that one function of the src family kinase SH3 domains is to bind and present certain substrates to the kinase. As p62 contains at least five SH3-domain-binding motifs and multiple tyrosine phosphorylation sites, p62 may interact with other signalling molecules via SH3 and SH2 domain interactions. Here we show that the SH3 and/or SH2 domains of the signalling proteins Grb2 and phospholipase C gamma-1 can interact with p62 both in vitro and in vivo. Thus, we propose that one function of the tandemly occurring SH3 and SH2 domains of src family kinases is to bind p62, a multifunctional SH3 and SH2 domain adapter protein, linking src family kinases to downstream effector and regulatory molecules.

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40

Segal, Lester A. "The Image of Bar Kokhba in Traditional Jewish Literature: False Messiah and National Hero (review)". Shofar: An Interdisciplinary Journal of Jewish Studies 16, n. 3 (1998): 176–78. http://dx.doi.org/10.1353/sho.1998.0006.

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41

Girdler-Brown, B. V., e J. Murray. "Epidemic reproduction numbers and herd immunity". Southern African Journal of Public Health (incorporating Strengthening Health Systems) 4, n. 2 (14 agosto 2020): 59. http://dx.doi.org/10.7196/shs.2020.v4i2.121.

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42

Orsagh, Matthew. "Is Global “Say on Pay” Here to Stay?" CFA Institute Magazine 22, n. 6 (novembre 2011): 22–23. http://dx.doi.org/10.2469/cfm.v22.n6.13.

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43

Cyranoski, David. "Marie Curie doesn't live here, Japanese women say". Nature 419, n. 6909 (ottobre 2002): 768. http://dx.doi.org/10.1038/419768b.

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44

Kalina, Marc, e Dianne Scott. "“You have to say everything is nice here”". Qualitative Research Journal 19, n. 3 (24 luglio 2019): 307–23. http://dx.doi.org/10.1108/qrj-12-2018-0011.

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Abstract (sommario):

Purpose The purpose of this paper is to reflect on the author’s research experiences in northern Mozambique in order explore the multiplicity of gatekeeper relations that arose while seeking to arrange access to both “the field” and respondents, as well as the impacts that these relationships had on the research process. Although this dynamic has been thoroughly described within methodological literature, there exists a tendency to presume research–gatekeeper relations as static; once established, there is little discussion on how the relationships develop or can be managed, once access has (or has not) been achieved. Design/methodology/approach The paper draws upon qualitative fieldwork conducted predominantly in rural communities in northern Mozambique. The study analysed the development of the Nacala Development Corridor programme and the N13 Highway Rehabilitation Project in northern Mozambique in order to examine the impacts of the development on local citizens and examine the relationship between citizen and state within development processes. Fieldwork consisted of three different phases of semi-structured and open-ended interviews with key stakeholders and affected persons, spanning five different interview schedules, and a total of 77 individual interviews and 27 community focus groups conducted along the N13. Findings The study found that duality of Mozambican governance which includes both local officials and traditional leadership contributed to a multiplicity of local gatekeepers which impacted the research process in a multitude of ways. As a result, researcher–gatekeeper relations were not static, but had to be managed throughout the duration of the study. Originality/value This discussion provides a more dynamic representation of the challenges involved with establishing and managing gatekeeper relations in rural, developing, and in particular, southern African, contexts, while offering cautious practical advice to researchers working within rural or southern African contexts.

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45

Kerr, R. A. "Studies Say--Tentatively--That Greenhouse Warming Is Here". Science 268, n. 5217 (16 giugno 1995): 1567–68. http://dx.doi.org/10.1126/science.268.5217.1567.

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46

Rosenzweig, Robert M. "California, Here She Comes: Thatcherism and Higher Education". Change: The Magazine of Higher Learning 21, n. 5 (ottobre 1989): 40–42. http://dx.doi.org/10.1080/00091383.1989.9939179.

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47

Kobulova, Nodira Bakhodirovna. "THE ROLE OF THE BIOGRAPHICAL METHOD IN CHARACTERIZING THE CH TERIZING THE CHARACTER OF THE HERO". Scientific Reports of Bukhara State University 3, n. 2 (28 febbraio 2019): 159–64. http://dx.doi.org/10.52297/2181-1466/2019/3/2/9.

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The article deals with the role of biographical method in the lighting and analysis of the nature and creativity of the writer. It is safe to say that the inner human desire for freedom, courage, fear of evil and lies, the confusion of the paths of destiny, is an image that reflects the modern image. The characters in a work of art have a legal basis, not a random one, in which the writer's point of view is an important factor. This is evidenced by the analysis of the works of Erkin Azam, which we have seen above.

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48

Sloboda, Noel. "All the Devils Are Here: How Shakespeare Invented the Villain". Shakespeare Bulletin 39, n. 3 (2021): 519–22. http://dx.doi.org/10.1353/shb.2021.0053.

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49

Mayer, B. J., e D. Baltimore. "Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase". Molecular and Cellular Biology 14, n. 5 (maggio 1994): 2883–94. http://dx.doi.org/10.1128/mcb.14.5.2883-2894.1994.

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Abstract (sommario):

We have used in vitro mutagenesis to examine in detail the roles of two modular protein domains, SH2 and SH3, in the regulation of the Abl tyrosine kinase. As previously shown, the SH3 domain suppresses an intrinsic transforming activity of the normally nontransforming c-Abl product in vivo. We show here that this inhibitory activity is extremely position sensitive, because mutants in which the position of the SH3 domain within the protein is subtly altered are fully transforming. In contrast to the case in vivo, the SH3 domain has no effect on the in vitro kinase activity of the purified protein. These results are consistent with a model in which the SH3 domain binds a cellular inhibitory factor, which in turn must physically interact with other parts of the kinase. Unlike the SH3 domain, the SH2 domain is required for transforming activity of activated Abl alleles. We demonstrate that SH2 domains from other proteins (Ras-GTPase-activating protein, Src, p85 phosphatidylinositol 3-kinase subunit, and Crk) can complement the absence of the Abl SH2 domain and that mutants with heterologous SH2 domains induce altered patterns of tyrosine-phosphorylated proteins in vivo. The positive function of the SH2 domain is relatively position independent, and the effect of multiple SH2 domains appears to be additive. These results suggest a novel mechanism for regulation of tyrosine kinases in which the SH2 domain binds to, and thereby enhances the phosphorylation of, a subset of proteins phosphorylated by the catalytic domain. Our data also suggest that the roles of the SH2 and SH3 domains in the regulation of Abl are different in several respects from the roles proposed for these domains in the closely related Src family of tyrosine kinases.

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50

Mayer, B. J., e D. Baltimore. "Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase." Molecular and Cellular Biology 14, n. 5 (maggio 1994): 2883–94. http://dx.doi.org/10.1128/mcb.14.5.2883.

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Abstract (sommario):

We have used in vitro mutagenesis to examine in detail the roles of two modular protein domains, SH2 and SH3, in the regulation of the Abl tyrosine kinase. As previously shown, the SH3 domain suppresses an intrinsic transforming activity of the normally nontransforming c-Abl product in vivo. We show here that this inhibitory activity is extremely position sensitive, because mutants in which the position of the SH3 domain within the protein is subtly altered are fully transforming. In contrast to the case in vivo, the SH3 domain has no effect on the in vitro kinase activity of the purified protein. These results are consistent with a model in which the SH3 domain binds a cellular inhibitory factor, which in turn must physically interact with other parts of the kinase. Unlike the SH3 domain, the SH2 domain is required for transforming activity of activated Abl alleles. We demonstrate that SH2 domains from other proteins (Ras-GTPase-activating protein, Src, p85 phosphatidylinositol 3-kinase subunit, and Crk) can complement the absence of the Abl SH2 domain and that mutants with heterologous SH2 domains induce altered patterns of tyrosine-phosphorylated proteins in vivo. The positive function of the SH2 domain is relatively position independent, and the effect of multiple SH2 domains appears to be additive. These results suggest a novel mechanism for regulation of tyrosine kinases in which the SH2 domain binds to, and thereby enhances the phosphorylation of, a subset of proteins phosphorylated by the catalytic domain. Our data also suggest that the roles of the SH2 and SH3 domains in the regulation of Abl are different in several respects from the roles proposed for these domains in the closely related Src family of tyrosine kinases.

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