1,365 research outputs found
Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro.
No full textThe success of Imatinib (IM) therapy in chronic myeloid leukemia (CML) is compromised by the development of IM resistance and by a limited IM effect on hematopoietic stem cells. Danusertib (formerly PHA-739358) is a potent pan-aurora and ABL kinase inhibitor with activity against known BCR-ABL mutations, including T315I. Here, the individual contribution of both signaling pathways to the therapeutic effect of Danusertib as well as mechanisms underlying the development of resistance and, as a consequence, strategies to overcome resistance to Danusertib were investigated. Starting at low concentrations, a dose-dependent inhibition of BCR-ABL activity was observed, whereas inhibition of aurora kinase activity required higher concentrations, pointing to a therapeutic window between the two effects. Interestingly, the emergence of resistant clones during Danusertib exposure in vitro occurred considerably less frequently than with comparable concentrations of IM. In addition, Danusertib-resistant clones had no mutations in BCR-ABL or aurora kinase domains and remained IM-sensitive. Overexpression of Abcg2 efflux transporter was identified and functionally validated as the predominant mechanism of acquired Danusertib resistance <i>in vitro</i>. Finally, the combined treatment with IM and Danusertib significantly reduced the emergence of drug resistance <i>in vitro</i>, raising hope that this drug combination may also achieve more durable disease control <i>in vivo</i>
TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation
No full textThe interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3–ch-TOG onto spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule binding surface. Whether there is a pool of TACC3–ch-TOG that is independent of clathrin in human cells, and what is the function of this pool, are open questions. Here, we report that TACC3 is recruited to the plus-ends of microtubules by its association with ch-TOG and that this pool is independent of phosphorylation and binding to clathrin. The plus-end binding of TACC3–ch-TOG persists in interphase and we propose that one cellular function of TACC3–ch-TOG is to modulate cell migration. We also describe the distinct subcellular pools of TACC3, ch-TOG and clathrin. TACC3 is often described as a centrosomal protein, but we show that there is no significant population of TACC3 at centrosomes. The delineation of distinct protein pools reveals a simplified view of how these proteins are organized and controlled by post-translational modification
Methods of Desire: Language, Morality, and Affect in Neoliberal Indonesia.
No full textSince the Asian financial crisis of the late 1990s, Indonesia has undergone a radical program of administrative decentralization and neoliberal reforms. In Methods of Desire, author Aurora Donzelli explores these changes through an innovative perspective—one that locates the production of neoliberalism in novel patterns of language use and new styles of affect display. Building on almost two decades of fieldwork, Donzelli describes how the growing influence of transnational lending agencies is transforming the ways in which people desire and voice their expectations, intentions, and entitlements within the emergent participatory democracy and restructuring of Indonesia’s political economy. She argues that a largely overlooked aspect of the Era Reformasi concerns the transition from a moral regime centered on the expectation that desires should remain hidden to a new emphasis on the public expression of individuals’ aspirations.
The book examines how the large-scale institutional transformations that followed the collapse of the Suharto regime have impacted people’s lives and imaginations in the relatively remote and primarily rural Toraja highlands of Sulawesi. A novel concept of the individual as a bundle of audible and measurable desires has emerged, one that contrasts with the deep-rooted reticence toward the expression of personal preferences. The spreading of foreign discursive genres such as customer satisfaction surveys, training sessions, electoral mission statements, and fundraising auctions, and the diffusion of new textual artifacts such as checklists, flowcharts, and workflow diagrams are producing forms of citizenship, political participation, and moral agency that contrast with the longstanding epistemologies of secrecy typical of local styles of knowledge and power. Donzelli’s long-term ethnographic study examines how these foreign protocols are being received, absorbed, and readapted in a peripheral community of the Indonesian archipelago.
Combining a telescopic perspective on our contemporary moment with a microscopic analysis of conversational practices, the author argues that the managerial forms of political rationality and the entrepreneurial morality underwriting neoliberal apparatuses proliferate through the working of small cogs, that is, acts of speech. By examining these concrete communicative exchanges, she sheds light on both the coherence and inconsistency underlying the worldwide diffusion of market logic to all domains of life
The Aurora space launcher concept
No full textThis paper gives an overview about the Aurora reusable space launcher concept study that was initiated in late-2015/early-
2016. Within the Aurora study, several spaceplane-like vehicle configurations with different geometries, propulsion systems
and mission profiles will be designed, investigated and evaluated with respect to their technical and economic feasibility.
The first part of this paper will discuss the study logic and the current status of the Aurora studies and introduces the first
vehicle configurations and their system design status. As the identification of highly efficient structural designs is of particular
interest for Aurora, the structural design and analysis approach will be discussed in higher level of detail. A special
design feature of the Aurora vehicle configurations is the utilization of the novel thin-ply composite material technology for
structural mass reductions. Therefore, the second part of this paper will briefly discuss this technology and investigate the
application and potential mass savings on vehicle level within simplified structural analysis studies. The results indicate that
significant mass savings could be possible. Finally, an outlook on the next steps is provided
Dos poemas:: Confirmación de los hechos; Arribos
No full textTwo fiction stories written by the author Ada Aurora Sanchez PeñaDos relatos de ficción escritos por la autora Ada Aurora Sánchez Peñ
Dos poemas:: Instante; Recuerdo, si
No full textTwo fiction stories written by the author Ada Aurora Sánchez PeñaDos relatos de ficción escritos por la autora Ada Aurora Sánchez Peñ
Survey and assessment of critical urban wetlands: City of Aurora
No full textReport prepared for: City of Aurora, U.S. Envronmental Protection Agency, Region 8.December 2020.Includes bibliographical references
Aurora
No full textThis paper is in support of my artist-based thesis research entitled Aurora. My practice is interdisciplinary with a focus on installation and sculpture, consistently engaged in questions surrounding culturally inherited power structures and resulting modes of representation. This thesis research critically investigates what is understood as “traditional” in North American domestic ornamentation through considerations of complicated and intertwined histories, commerce, personal memory and taste. This paper provides an art historical and contemporary art context for this line of artistic investigation. Focusing on contemporary artists, this paper seeks to highlight the current discourse around culturally inherited materials, in particular of those from hybridized cultural identities. Drawing from theorists engaged in Marxism, post- structuralism, post-modernism; a nuanced understanding of ornament as a commodity and social signifier is highlighted. An account for the breadth of my material research is outlined in this document, focusing on three major works that were exhibited in defense of this thesis, Aurora, Secret Garden and Like Countless Men on Horseback. A focus is emphasized around sets of gestural responses to materials; these are drawing, casting, tracing, folding, cutting, and staging. These gestures invite viewers to think through their own understanding of domestic ornamentation and inherited social structures, as they focus on perceptions of appropriation, nostalgia, monumentality and memory. This paper concludes with implications of this research. That networks of associations to the self, class and history resound through the maintenance of domestic ornamentation. These networks are not static and fluctuate through trend, social norms and ideas surrounding domesticity. Thus it is paramount that in the creation of works invested in this dialogue that ambiguity is facilitated to gain entry into layered, and possibly contradictory associations to the ornamentation of the home. The accumulation of my cultural identity, lived experience, influences and biases will continue to be investigated and articulated through my practice vis-à-vis symbolic socially constructed materials and beliefs
Bajza József és az Aurora pénze: (az Aurora-pör „hatalom-gazdasági” olvasata és a bajzai lélek)
No full textAfter the death of Károly Kisfaludy, the founder-editor of the ground-breaking literary almanac titled The Aurora. National Almanac, the so called Aurora Lawsuit broke out, which aimed to settle the control over the future fate of the publication. The literary consensus so far concluded that the polemics were won by József Bajza, who triumphed over his opponents, furthermore it was him who separated the hitherto confused definitions of author, editor and publisher, as well as the division of the rights of the publisher, author and editor, and he also managed to improve the recognition of the latter. The paper “reinterprets” the Aurora Lawsuit with a more critical view of József Bajza than before. Besides its purpose to prove that there was no superior triumph, it also aims to point out the basic motivation behind the situation, which was not discussed properly before, the aspect of power-financial gain.After the death of Károly Kisfaludy, the founder-editor of the ground-breaking literary almanac titled The Aurora. National Almanac, the so called Aurora Lawsuit broke out, which aimed to settle the control over the future fate of the publication. The literary consensus so far concluded that the polemics were won by József Bajza, who triumphed over his opponents, furthermore it was him who separated the hitherto confused definitions of author, editor and publisher, as well as the division of the rights of the publisher, author and editor, and he also managed to improve the recognition of the latter. The paper “reinterprets” the Aurora Lawsuit with a more critical view of József Bajza than before. Besides its purpose to prove that there was no superior triumph, it also aims to point out the basic motivation behind the situation, which was not discussed properly before, the aspect of power-financial gain
Depot, Aurora, Indiana
No full textThe town of Aurora overlooks a picturesque bend in the Ohio River. It was laid out in 1819 and was named for the Roman goddess of dawn by Judge Jesse Lynch Holman, author of fiction and poetry, and an early organizer of the Indiana Historical Society
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