Browsing by Subject "Resistance"

Now showing 1 - 10 of 10

Open Access
Detection of phosphorylation signatures specific to cancer-related PI3-Kinase isoforms p110α and p110β
(2023-01) Sulaiman, Mahnoor
The PI3K signaling pathway is required for many physiological activities, but it is commonly disrupted during cancer formation. The PI3K p110α and βisoforms, encoded by the PIK3CA and PIK3CB genes, are lipid kinases that phosphorylate PIP2 to PIP3 to activate the PI3K pathway. However, the distinct molecular targets of these isoforms have yet to be discovered, making targeted treatment problematic. According to cancer genomics research, the PIK3CA gene is commonly altered in cancers, but the PIK3CB gene is frequently amplified. The clinical usage of Pan-PI3K inhibitors has resulted in significant side effects, prompting the development of isoform-specific inhibitors. However, it has been shown that these drugs trigger alternate signaling systems downstream, leading in resistance to single-agent treatment. Our research intends to uncover distinctive protein-protein interactions of PI3K isoforms, as well as the consequent different phospho-proteomic signatures, which might be crucial determinants of specific cellular activities. This will be accomplished by using isogenic MEF cells that are only dependent on the p110α or p110β isoforms, isoform-specific pharmacological inhibitors BYL-719 and KIN 193, and a high-resolution mass spectrometry-based method to determine the phosphorylation levels of these protein samples. The predictive biomarkers discovered in this study can be utilized to identify patients who will benefit from PI3K-targeted drugs and to better understand the resistance mechanisms that may arise in response to pathway inhibition.
Open Access
An emotional economy of mundane objects
(Routledge, 2015) Kuruoğlu, A. P.; Ger, G.
This article illuminates the affective potentialities of objects. We examine the circulation of Kurdish music cassettes in Turkey during the restrictive and strife-laden period of the 1970s, 1980s, and 1990s. We find that the practices comprising circulation - recording, hiding, playing, and exchanging cassettes - constituted tactical resistance and generated communal imaginaries. We illuminate the "emotional economy" that is animated by a mundane object: the cassette, through its circulation, becomes saturated with emotions, establishes shared emotional repertoires, and habituates individuals and collectives into common emotional dispositions. Cassettes thus play a part in shaping and reinforcing an emotional habitus that accompanies the emergence of a sense of "us," the delineation of the "other," and the relationship between the two. We thus demonstrate the entwinement of materiality and emotions, and examine how this entwinement generates emotional structures that shape and perpetuate the imagining of community as well as the enactment of resistance.
Open Access
Empowerment and resistance strategies of working women in Turkey: the case of 1960–70 graduates of the girls’ institutes
(Sage Publications Ltd., 2002) Cindoglu, D.; Toktaş, Ş.
This article deals with the empowerment and resistance strategies used by working women in Turkey. In order to explore the ways in which gender ideologies are produced and resisted, a very specific group of women were studied using life history and focus group interviews. The interviews were conducted with women who had graduated between 1960 and 1970 from Girls' Institutes. The Girls' Institutes were all-female high schools and the curriculum of these institutes was particularly geared towards modern domestic, or homemaking skills. However, despite the notion of producing modern women for the domestic sphere, most of the graduates have chosen to work outside their homes. Of these working women some have remained single, some have not had children. These outcomes present a paradox. The article focuses on the resolution of these paradoxes, the power and resistance manoeuvres that women employ and their relationship to the processes of modernization and westernization in Turkey.
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Fiskobirlik direnişi
(Bilkent University, 2020) Gürçay, Ece; Erdağ, Erdem Deniz; Akçakoca, Mustafa Emre; Ateş, Yiğit; Balcıoğlu, Selçuk
Türkiye'nin en köklü birliklerinden biri olan Fiskobirlik fabrikasında 1992 ile 1993 yılları arasında işveren ve işçiler arasında toplu sözleşme ile başlayan bir anlaşmazlık vardı. Bu anlaşmazlık daha sonrasında işçilerin greve gitmesi ile devam etti. İş verenler kadro hakkını iptal etmek, işçilerde kazanılmış kadro hakkını geri vermek istemiyordu. Fiskobirlik'te yapılan grev oylamasına işçiler %72 ile greve evet dediler ve Ankara'ya doğru olan yolculukları başladı. Yıllarını Fiskobirlik'e vermiş çalışanlarının neredeyse tamamının işten atılması söz konusu olmuş Öz Gıda-İş sendikası ve Fiskobirlik çalışanları bu haksızlığı reddederek hak arayışına girmiştir. Ezici bir çoğunluğu kadın olan işçiler Öz Gıda-İş sendikasının yadsınamaz yardımı ile 55 günü grevde 8 ay süren mücadeleyi kazandılar ve bu mücadele sonrasında işçilerin ortalama net ücretleri eski para ile 1 milyon 200 bin liradan 2 milyon 857 bin liraya yükseldi, 1253 işçiye kadro alındı ve bunun gibi işçinin lehine olan birçok hak kazandılar.
Open Access
Going local: an agency-based approach to collapse, resistance, and resilience in Hittite Anatolia
(Walter de Gruyter GmbH, 2024-05-24) Gerçek, Nebahat İlgi
Crisis and collapse have long been prominent themes in Hittite studies (much more so than the related topics of resistance and resilience) and most of the extant body of scholarship on these themes have concentrated on the disintegration of the Hittite Empire around 1200 BCE. Though the events, conditions and processes that culminated in the disintegration of the Hittite Empire elude historical reconstruction, recent studies have unanimously rejected monocausal explanations of collapse in favor of the view that it was brought about by a combination of factors - internal, external, acute or chronic. In Hittite scholarship, the study of collapse and its aftermath have typically operated within a markedly state-centered and progressivist framework, focusing primarily on figuring out "what went wrong." Meanwhile, especially in text-based studies, the agency and resilience of local, small(er)-scale, peripheral, and non-state individuals and communities, as well as their role in the construction, maintenance, and collapse of the Hittite empire, remain largely overlooked. The aim of the present paper is to shift the focus and scale of analysis away from the state, and to draw out from the textual record, the long-term agency, resistance, and resilience of local, small-scale, and often non-state individuals, communities, or socio-political institutions, which have typically been left out of text-based modern narratives. This paper will reassess the prominent view of the Hittite king (and state) as the absolute political, military, judicial, and religious authority, and argue that certain local and non-state communities and socio-political institutions exercised diverse kinds of agency, were remarkably resilient in the long term, and survived the final collapse of the Hittite state. In order to situate the inquiry in its broader scholarly and intellectual context, it will begin with an overview of where things stand in the study of the Hittite collapse. The next step will be to identify individual or collective local actors in the textual record. It will lastly focus on the interactions of diverse local agents with the Hittite state.
Open Access
Gülten Akın şiirinde işkence ve ahlak
(Bursa Uludağ Üniversitesi, 2009) Akgül, Alphan Yusuf
Gülten Akın şiiri işkence gibi sosyal sorunlarla yakından ilişkilidir. Onun Oğlunu Soran Kadının Şiiri ve Şifahi adlı şiirleri, şiirin işkenceye karşı nasıl bir direnme stratejisi olarak kullanılabileceğini gösteren işlevsel örneklerdir. Öte yandan, bu şiirler yalnızca birer ağıt değil, aynı zamanda işkence eyleminin çıkmazlarını gösteren birer ahlaki manifestodur. Dolayısıyla, bu şiirler J.M. Coetzee’nin Barbarları Beklerken adlı romanında işkence üzerine yaptığı spekülasyonlarla ilişkilendirilebilir: Bir kurbanın işkenceden ruhunu kurtarabilmesi mümkün müdür? İşkencecinin ellerini yıkayarak işkence suçundan aklanması mümkün müdür? Akın’ın yanıtı, işkence üzerine Stoacı argümanlarla örtüşür. İnsanoğlu bir aklî ruha sahiptir, dolayısıyla o, aklî ruhunu kullanarak bedensel hazları ve acıları göz ardı edebilir. İşkence mağdurunun direnme stratejisi de bu aklî ruha dayanır. Çünkü mağdur bedensel acıyı göz ardı edebildiği sürece, işkencecinin işlevi anlamını yitirecektir. Böylece, mağdur ruhunu işkenceden kurtarabilecek, oysa, işkenceci ellerini yıkayabildiği hâlde, asla suçundan arınamayacaktır. Çünkü mağdurun bedeni, işkencecinin ise ruhu kirlenmiştir. Başka deyişle, bedensel temizlik, işkenceci için daima simgesel bir arınma olarak kalacaktır.
Open Access
Internet censorship in Turkey
(Alexander von Humboldt Institute for Internet and Society, 2015) Akgül, M.; Kırlıdoğ, M.
This study aims to explore Turkish citizen-consumers' understanding of and reactions to censorship of websites in Turkey by using in-depth interviews and online ethnography. In an environment where sites such as YouTube and others are increasingly being banned, the citizen-consumers' macro-level understanding is that such censorship is part of a wider ideological plan and their micro-level understanding is that their relationship with the wider global network is reduced, in the sense that they have trouble accessing full information on products, services and experiences. The study revealed that citizen-consumers engage in two types of resistance strategies against such domination by the state: using irony as passive resistance, and using the very same technology used by the state to resist its domination. © The Author(s) 2013.
Open Access
Targeting TACC3 induces immunogenic cell death and enhances T-DM1 Response in HER2-positive breast cancer
(American Association for Cancer Research, 2024-05-02) Gedik, Mustafa Emre; Saatçi, Özge; Oberholtzer, Nathaniel; Üner, Meral; Akbulut Çalışkan, Özge; Çetin, Metin; Aras, Mertkaya; İbiş, Kübra; Çalışkan, Burcu; Banoğlu, Erden; Wiemann, Stefan; Üner, Ayşegül; Aksoy, Sercan; Mehrotra, Shikhar; Şahin, Özgür
Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2 alpha phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance. Accordingly, ICD-related gene signatures in pretreatment samples correlated with clinical response to T-DM1-containing therapy, and increased infiltration of antitumor CD8(+) T cells in posttreatment samples was correlated with better T-DM1 response. Transforming acidic coiled-coil containing 3 (TACC3) was overexpressed in T-DM1-resistant cells, and T-DM1 responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacologic inhibition of TACC3 restored T-DM1-induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition in vivo elicited ICD in a vaccination assay and potentiated the antitumor efficacy of T-DM1 by inducing dendritic cell maturation and enhancing intratumoral infiltration of cytotoxic T cells. Together, these results illustrate that ICD is a key mechanism of action of T-DM1 that is lost in resistance and that targeting TACC3 can restore T-DM1-mediated ICD and overcome resistance.
Open Access
Understanding images of environmental resistance : village women from ‘Gokova’ to ‘Yesil Yol’
(2016-09) İrhan, Mehmet Can
In 1984, a group of women occupied the road of Gökova to block the experts of electric institution who came to Gökova for technical measure works for the thermal power plant construction. The newspapers wrote the event as “Women say ‘no’ to the plant!” In the following years, while the projects of power plants and appeared, the reactions of locals and environmentalists increasingly continued. And in almost all reactions the village women appeared as the faces of movements. This study began through a desire to understand the village women images of grassroots environmental movements. It attempts to figure out how these images are represented by the media. To this aim, we look at news reports of ten different grassroots environmental movements, which were published in the Turkish newspapers. By looking at visual and textual discourse of the news reports, we explore the images according to three main approaches; composition of images, the signs of social subjects and differences, and the relationship with the context.
Open Access
XPS measurements for probing dynamics of charging
(Elsevier, 2010) Süzer, Şefik; Sezen, H.; Ertas, G.; Dâna, A.
The technique of recording X-ray photoemission data while the sample rod is subjected to ±10.0 V (dc) or square-wave pulses (ac) with varying frequencies in the range of 10-3 to 103 Hz for probing charging/discharging dynamics of dielectric materials, is reviewed. Application of this technique introduces charging shifts as well as broadening of the peaks, which depend non-linearly on the polarity, as well as on the frequency of the pulses applied. These changes have been measured on: (i) an artificially created dielectric sample consisting of a Au metal strip connected externally to a series resistor of 1 MΩ and a parallel capacitor of 56 nF, and two real dielectric films; (ii) a 20 nm organic polystyrene film spin-coated on a silicon substrate; (iii) a 10 nm SiO2 inorganic layer thermally grown on silicon. A simple circuit model is introduced to simulate the charging shifts and the peak broadenings. Although this simple model faithfully reproduces the charging shifts in all three cases, and also some of the broadenings for the artificial dielectric and the polystyrene film, the additional broadening in the negatively charged peaks of the SiO2 dielectric film cannot be accounted for. It is also claimed that these experimental findings can be used for extracting material-specific dielectric properties.