73 research outputs found
Redox generation of nitric oxide to radiosensitize hypoxic cells
No full textPurpose: Previous studies have shown that nitric oxide (NO) delivered from NO donor agents sensitizes hypoxic cells to ionizing radiation. In the present study, nitroxyl (NO?), a potential precursor to endogenous NO production, was evaluated for hypoxic cell radiosensitization, either alone or in combination with electron acceptor agents.Methods and Materials: Radiation survival curves of Chinese hamster V79 lung fibroblasts under aerobic and hypoxic conditions were assessed by clonogenic assay. Hypoxia induction was achieved by metabolism-mediated oxygen depletion in dense cell suspensions. Cells were treated with NO? produced from the nitroxyl donor Angeli’s salt (AS, Na2N2O3, sodium trioxodinitrate), in the absence or presence of electron acceptor agents, ferricyanide, or tempol. NO concentrations resulting from the combination of AS and ferricyanide or tempol were measured under hypoxic conditions using an NO-sensitive electrode.Results: Treatment of V79 cells under hypoxic conditions with AS alone did not result in radiosensitization; however, the combination of AS with ferricyanide or tempol resulted in significant hypoxic radiosensitization with SERs of 2.5 and 2.1, respectively. Neither AS alone nor AS in combination with ferricyanide or tempol influenced aerobic radiosensitivity. The presence of NO generated under hypoxic conditions from the combination of AS with ferricyanide or tempol was confirmed using an NO-sensitive electrode.Conclusion: Combining NO? generated from AS with electron acceptors results in NO generation and substantial hypoxic cell radiosensitization. NO? derived from donor agents or endogenously produced in tumors, combined with electron acceptors, may provide an important strategy for radiosensitizing hypoxic cells and warrants in vivo evaluation
Silence, death, and the invisible enemy: AIDS activism and social movement ‘newness
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PEMBERITAAN BUY-BACK INDOSAT (Study Analis Framing Model Gamson dan Modigliani Pada Pemberitaan Media OnlineViva.co.id dan DetikNews.com)
No full textCampaign activities are one of the strategic that are often used by presidential candidate to win the election. In campaign activities, presidential candidate try to gain popularity and electability the voters. Usually to realize this, the success teams occupied themselves with the casuistic questions that were in each candidate pair. So the role of the media is very important. In this case the function of the media is nothing but to overthrow political opponents in addition to seeing their political friends. This article as a whole discusses how the media focus on reporting on some of the upcoming casuistic candidates, namely backing Indosat. The author will use online media detiknews.com and viva.co.id, which are the ideologies of the two media, both of which support the number one candidate pair. but the news produced from the two media is slightly different. Through the analysis of framing William A. Gamson and Modigliani the author will look at how the differences in packaging of the two media are in constructing Indosat buy-back news
The cytotoxicity of nitroxyl: possible implications for the pathophysiological role of NO
No full textIn addition to the broad repertoire of regulatory functions nitric oxide (NO) serves in mammalian physiology, the L-arginine:NO pathway is also involved in numerous pathophysiological mechanisms. While NO itself may actually protect cells from the toxicity of reactive oxygen radicals in some cases, it has been suggested that reactive nitrogen oxide species formed from nitric oxide synthase (NOS) can be cytotoxic. In addition to NO, the one electron reduction product NO- has been proposed to be formed from NOS. We investigated the potential cytotoxic role of nitroxyl (NO-), using the nitroxyl donor Angelis's salt, (AS; sodium trioxodinitrate, Na2N2O3) as the source of NO-. As was found to be cytotoxic to Chinese hamster V79 lung fibroblast cells over a concentration range of 2-4 mM. The presence of equimolar ferricyanide (Fe(III)-(CN6)3-), which converts NO- to NO, afforded dramatic protection against AS-mediated cytotoxicity. Treatment of V79 cells with L-buthionine sulfoximine to reduce intracellular glutathione markedly enhanced AS cytotoxicity, which suggests that GSH is critical for cellular protection against the toxicity of NO-. Further experiments showed that low molecular weight transition metal complexes associated with the formation of reactive oxygen species are not involved in AS-mediated cytotoxicity since metal chelators had no effect. However, under aerobic conditions, AS was more toxic than under hypoxic conditions, suggesting that oxygen dramatically enhanced AS-mediated cytotoxicity. At a molecular level, AS exposure resulted in DNA double strand breaks in whole cells, and this effect was completely prevented by coincubation of cells with ferricyanide or Tempol. The data in this study suggest that nitroxyl may contribute to the cytotoxicity associated with an enhanced expression of the L-arginine:NO pathway under different biological conditions
Decolonizing transness in sport media: the frames and depictions of transgender athletes in Sports Illustrated
No full text2016 Fall.Includes bibliographical references.This discourse analysis examines depictions of trans athletes in Sports Illustrated and sport culture through the lens of queer theory and the interpretive-packages model proposed by Gamson & Modiglani (1989). Four interpretive packages emerged from the print content: (1) Marginalization, (2) Labeling, (3) Fighting and Fairness and (4) Pride and Affirmation. The results illustrate that discourse has generally become more sensitive to trans issues. The author presents these results with cautious optimism. Blindingly affirming and romancing the transgender can be equally as superficial as marginalization, and representations of trans athletes secured by one person are problematic. Researchers and sport organizations should dismantle antiquated, coercive sex segregation in traditional sport and decolonize how it contributes to gender-based oppression. The author recommends that media outlets focus on presenting fair, accurate and inclusive representations of transness that combat oppressive positions
Abstract 5861: Enhanced radiosenistivity of EGFR-TKI sensitive and resistant NSCLC cells by abemaciclib is mediated by altered DNA repair and metabolic pathways
No full textAbstract
Dysregulation of the p16(INK4a)-CyclinD-CDK4/6-Rb pathways in patients with NSCLC (Non-Small Cell Lung Cancer) is a rational therapeutic target. The current study investigated the radiosensitizing potential of a novel CDK4/6 inhibitor, LY2835219 (LY, Abemaciclib) in NSCLC cell lines with varied genomic context to identify genomic and metabolic biomarkers that are predictive of a response over conventional EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. NSCLC cell lines were exposed to LY (0-10uM) for 24 hr immediately after 0-10 Gy radiation. Cell survival was assessed by clonogenic assay and cell cycle distribution was quantified by flow cytometry. Dose modifying factors (DMF) were calculated at 10% survival from radiation survival curves. Altered DNA repair pathways and metabolic profiling of cells post LY treatment was assessed by immunoblot and LC/MS mass spectrometry analysis. LY treatment enhanced radiosensitivity of EGFR-TKI sensitive (HCC827, PC9) and EGFR-TKI resistant (H820 and H1975) cell lines with DMF of 1.3 (±0.06), 1.4 (±0.30), 1.5 (±0.51) and 1.3 (±0.02), respectively. Values in the parenthesis indicates standard deviation. Wild type EGFR expressing cells (A549 and H460) also showed enhanced radiosensitivity by LY with DMF of 1.6 (±0.09) and 1.75(±0.15), respectively. Interestingly, no radiation enhancement by LY was observed for cells deficient in functional PTEN (H1650), Rb (H82) and p53 (H460 DNp53 and H1299) protein. Radiosensitization was also observed for cells made resistant to third generation EGFR-TKI, AZD9291. Flow cytometry analysis of majority of cell types exposed to LY exhibited 55% to 94% G1 arrest (depending on cell type). Mechanistically, the combinatorial treatment in radiosensitive cells showed elevated phosphorylated-γH2Ax. Combination treatment also reduced expression of ATR, ATM, DNA-PK, Rad51 and Chk-2 suggestive of reduced DNA repair compared to radiation alone. LY treatment brought major changes in the glycolysis/TCA/ total amino acids. LY increased significantly Acetyl-CoA, fumarate and malate, indicating enhanced oxidative phosphorylation. LY significantly elevated Uric acid levels suggestive of oxidative stress and elevated nucleotide degradation. Finally, administration of 100mg/kg LY2835219 for five days in combination with fractionated dose of radiation (3 Gy) significantly delayed tumor regrowth in H460 xenograft (p< 0.014). Collectively, our pre-clinical data indicates altered Rb, p53 and PTEN status are distinct predictive biomarkers of response for LY mediated radiosensitivity and provides an alternative therapeutic option in overcoming EGFR-TKI resistance in NSCLC.
Note: This abstract was not presented at the meeting.
Citation Format: Sarwat Naz, William DeGraff, Anastasia Sowers, Rajani Choudhuri, Maria Wissler, Janet Gamson, John Cook, James B. Mitchell. Enhanced radiosenistivity of EGFR-TKI sensitive and resistant NSCLC cells by abemaciclib is mediated by altered DNA repair and metabolic pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5861. doi:10.1158/1538-7445.AM2017-5861</jats:p
Normal Sins: Sex Scandal Narratives as Institutional Morality Tales
No full textSex scandals are widely assumed to be tales of individual transgression, serving as reminders of the normative sexual order. This paper, a qualitative multiple-case comparison of three contemporary media-conveyed sex scandals narratives, suggests otherwise. Drawing on extensive news documents, the study considers three stories, each revolving around the same sexual behavior, but each playing out in a different institutional environment: televangelist Jimmy Swaggart\u27s encounter with prostitute Debra Murphree in 1988, actor Hugh Grant\u27s encounter with prostitute Divine Brown in 1995, and presidential advisor Dick Morris\u27 encounter with prostitute Sherry Rowlands in 1996. On the one hand, within the same overarching narrative, different themes become dominant. In one case, the relationship with a prostitute gives rise to a story primarily focused on hypocrisy; in another, to a story focused mainly on recklessness; in the last, to a story focused mainly on amorality and disloyalty. On the other hand, the stories share a common dynamic and common themes: the discussions of sexual misbehavior, which kick each story into gear, are rapidly edged out by themes of inauthenticity, and by suggestions that hypocrisy, risk, or disloyalty are facilitated by the man\u27s particular institutional environment. Sex scandal stories, rather than remaining stories of individual sexual transgression, are transformed into institutional morality tales. Such a pattern, the author argues, results from pronounced needs on the part of mainstream media organizations to both mimic and distinguish themselves from tabloid media, and from journalists\u27 interest in transforming soft into hard news stories. While they draw on and buttress familiar cultural givens about masculine sexuality, these scandal stories offer an even more theoretically challenging twist: an unexpected cultural reversal, in which sexual sins as narrated by American news media, reveal not individual, but institutional pathologies; not a normative order, but institutional decay
A set of nine principles for distributed-design information storing
No full textThe issues of distributed working are many, with problems relating to information access and information acquisition the most common (Crabtree et al., 1997). Keeping track of project and team information is becoming more complex as design is increasingly being carried out collaboratively by geographically dispersed design teams across different time zones. The literature notes that little prescription or guidance exists on information management for designers (Culley et al., 1999) and Hicks (2007) highlights a relative lack of overall principles for improving information management. Additionally, evidence from earlier studies by the author into ‘How information is stored in distributed design project work’ reinforces the need for guidance, particularly in a distributed context (Grierson, 2008). Distributed information collections were found to be unorganised, contained unclear information and lacked context. Storing and sharing of distributed information was often time consuming and the tools awkward to use. This can lead to poor project progress and can impact directly on the quality and success of project outcomes (Grierson et al., 2004, 2006). This paper seeks to address these issues by presenting the development, implementation and evaluation of a set of Principles and a Framework to support distributed design information storing in the context of a Global Design class. Through both quantitative and qualitative evaluation methods the Principles were found to help in a number of ways – with the easy access of information; the structuring and organising of information; the creation of an information strategy; the making of information clear and concise; the supporting of documentation during project work; and the strengthening of team work; all helping teams to work towards project outcomes
Socio-Historical Studies of the National Woman\u27s Party and the National Women\u27s Trade Union League
No full textIn every society there are individuals or groups of people who have the power to control, or at least direct, various resources. Resources, an ambiguous term, can mean anything from monetary supplies to legislative sanctions to different objects or opportunities.. Just as there will be individuals controlling these assets, there will also be groups perceiving and expressing discontent. For example, these people may be dissatisfied with the power groups\u27 methods of leadership; they may perceive their needs to be neglected and/or they may want to seize control of these assets and channel resources into their own hands for the betterment of their group. One might even understand this inevitable aspect of conflict in society as part of a continuing reinforcement of the status quo which functions to enhance what the particular society has designated as \u27natural\u27. As a society allows people to voice their protests and malcontent, a power structure is in a position to display its strength by repressing their actions and words and then punishing, them by ignoring them or by coopting members of the group or the group\u27s demands into the authority structure. The issue of conflict is essential for an understanding of social organization, for as William Gamson notes, a system cannot function effectively if it must devote too much of its resources to problems of integration and conflict management. Conflict is built into a system which can only handle a certain number of demands; some people will always be dissatisfied. The point then is that there are two vantage points- the perspective from the challenge group which seeks to exert influence and the authority perspective which seeks to contain conflict and maintain a stable society
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