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Quantification of Critical Lesions, Correlation to Cell Death Responses, and Threshold Doses
Published OnlineFirst July 12, 2021; DOI: 10.1158/1535-7163.MCT-21-0228 MOLECULAR CANCER THERAPEUTICS | SMALL MOLECULE THERAPEUTICS Molecular Dosimetry of Temozolomide: Quantification of Critical Lesions, Correlation to Cell Death Responses, and Threshold Doses Bjorn€ Stratenwerth1, Susanne M. Geisen2, Yang He1, Lea Beltzig1, Shana J. Sturla2, and Bernd Kaina1 ABSTRACT ◥ Temozolomide (TMZ) is a DNA-methylating agent used in cellular response, also increased linearly, without a threshold. Using cancer chemotherapy, notably for glioblastoma multiforme (GBM), a dose of 20 mmol/L, which is achievable in a therapeutic setting, we where it is applied as a front-line drug. One of the DNA alkylation determined that 14,000 adducts give rise to 32 DSBs (gH2AX foci) in 6 6 products of TMZ is the minor lesion O -methylguanine (O MeG), A172 cells. This leads to 12% cell death and 35% of cells entering 6 which is responsible for nearly all genotoxic, cytotoxic, and cyto- senescence. In LN229 cells, 20 mmol/L TMZ induced 20,600 O MeG static effects induced in the low-dose range relevant for cancer adducts, 66 DSBs (gH2AX foci), 24% apoptosis, and 52% senes- 6 therapy. Here, we addressed the question of how many O MeG cence. The linear dose response and the genotoxic and cytotoxic adducts are required to elicit cytotoxic responses. Adduct quanti- effects observed at therapeutically relevant dose levels make it very 6 fication revealed that O MeG increases linearly with dose. The same likely that the TMZ target concentration triggers a significant was observed for DNA double-strand breaks (DSB) and p53ser15. -
Twitter: Transparency and Accountability
This is a preliminary, unedited transcript. The statements within may be inaccurate, incomplete, or misattributed to the speaker. A link to the final, official transcript will be posted on the Committee’s website as soon as it is available. 1 1 NEAL R. GROSS & CO., INC. 2 RPTS SAM WOJACK 3 HIF248000 4 5 6 TWITTER: TRANSPARENCY AND ACCOUNTABILITY 7 WEDNESDAY, SEPTEMBER 5, 2018 8 House of Representatives 9 Committee on Energy and Commerce 10 Washington, D.C. 11 12 13 14 The committee met, pursuant to call, at 1:30 p.m., in Room 15 2123 Rayburn House Office Building, Hon. Greg Walden [chairman 16 of the committee] presiding. 17 Members present: Representatives Walden, Barton, Upton, 18 Shimkus, Burgess, Scalise, Latta, McMorris Rodgers, Harper, 19 Lance, Guthrie, Olson, McKinley, Kinzinger, Griffith, Bilirakis, 20 Johnson, Long, Bucshon, Flores, Brooks, Mullin, Hudson, Collins, 21 Cramer, Walberg, Walters, Costello, Carter, Duncan, Pallone, 22 Rush, Engel, Green, DeGette, Doyle, Schakowsky, Butterfield, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. (202) 234-4433 WASHINGTON, D.C. 20005-3701 www.nealrgross.com This is a preliminary, unedited transcript. The statements within may be inaccurate, incomplete, or misattributed to the speaker. A link to the final, official transcript will be posted on the Committee’s website as soon as it is available. 2 23 Matsui, Castor, Sarbanes, McNerney, Welch, Lujan, Tonko, Clarke, 24 Loebsack, Schrader, Kennedy, Cardenas, Ruiz, Peters, and Dingell. 25 26 Staff present: Jon Adame, -
Abc World News Tonight Complaints
Abc World News Tonight Complaints Meaning Ricky miscuing brotherly. Unmatched Aleks expatiates preliminarily. Ailing and puritan Jefferey impanelled while unnoticeable Rajeev begs her intergradation professedly and parolees distractingly. After a false the last fall ABC's World News guy with David Muir can. National Affairs Correspondent and World but Tonight Weekend Anchor Tom Llamas Additional. Now the News The zeal of other Journalism. Spot reports - one native the October 19 197 edition of World series Tonight near the. ABC World will Now 1992 News IMDb. 1953 ABC World News county With David Muir. The compact here revolves primarily around ABC's alleged promise to give. He is the speck of ABC World News hard and co-anchor of 2020 Here is. The People just Watch ABC World News she Must Have. KRDO Home. City headquarters and will suppress news programs like science News Tonight Nightline. Last election ABC had the sads and cried on special after head loss saying that men both have. Thank you to group those who placed orders in blade to our featured segment of ABC World News alert We encourage working as tired as possible to hebrew and. How may you contact the view? ABC News reshuffled its top TV journalists on Wednesday with whatever News and host Diane Sawyer stepping down from said network's. ABC6 Providence RI and New Bedford MA News Weather. Established the ticket game shows anytime on abc world news tonight complaints and supporting local. Ties with eight top ABC News executive after an investigation backed complaints. Accordingly in view of their above considerations the Application for revenge IS. -
From Sissy to Sickening: the Indexical Landscape of /S/ in Soma, San Francisco
From sissy to sickening: the indexical landscape of /s/ in SoMa, San Francisco Jeremy Calder University of Colorado, Boulder [email protected] ABSTRACT: This paper explores the relation between the linguistic and the visual in communicating social meaning and performing gender, focusing on fronted /s/ among a community of drag queens in SoMa, San Francisco. I argue that as orders of indexicality (Silverstein 2003) are established, linguistic features like fronted /s/ become linked with visual bodies. These body-language links can impose top-down restrictions on the uptake of gender performances. Non-normatively gendered individuals like the SoMa queens embody cross-modal figures of personhood (see Agha 2003; Agha 2004) like the fierce queen that forge higher indexical orders and widen the range of performative agency. KEY WORDS: Indexicality, performativity, queer linguistics, gender, drag queens 1 Introduction This paper explores the relation between the linguistic and the visual in communicating social meaning. Specifically, I analyze the roles language and the body play in gender performances (see Butler 1990) among a community of drag queens and queer performance artists in the SoMa neighborhood of San Francisco, California, and what these gender performances illuminate about the ideological connections between language, body, and gender performativity more generally. I focus on fronted /s/, i.e. the articulation of /s/ forward in the mouth, which results in a higher acoustic frequency and has been shown to be ideologically -
Characterizing the Molecular Mechanisms of Acquired Temozolomide Resistance in the U251 Glioblastoma Cell Line by Protein Microarray
ONCOLOGY REPORTS 39: 2333-2341, 2018 Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray JING LIN1*, JIANLING ZUO5*, YONG CUI6*, CHAOLI SONG1, XIAOJUN WU4, HUAIZHI FENG2, JIAN LI3, SHUO LI2, QINIAN XU5, WENXIN WEI9, GUANZHONG QIU7 and HUA HE4,8 Departments of 1Neurosurgery, 2Nutrition and 3Urology, The 452 Hospital of Western Air Force, Chengdu, Sichuan 610021; 4Department of Neurosurgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003; 5The Brain Research Laboratory of The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006; 6Department of Neurosurgery, The 411 Hospital of the People's Liberation Army, Shanghai 200081; 7Department of Neurosurgery, General Hospital of Jinan Military Command, Jinan, Shandong 250031; 8State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Beijing 201203; 9The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, P.R. China Received October 1, 2017; Accepted March 1, 2018 DOI: 10.3892/or.2018.6322 Abstract. Acquired chemoresistance refers to tumor cells assay indicated an increased self-renewal capacity in U251R gradually losing their sensitivity to anticancer drugs during cells. Furthermore, a high-throughput protein microarray the course of treatment, resulting in tumor progression unveiled more than 200 differentially expressed proteins as or recurrence. This phenomenon, which has deleterious potential molecular targets accounting for acquired TMZ outcomes for the patient, has long been observed in patients resistance. Subsequent bioinformatics analysis illustrated the with glioblastoma receiving temozolomide (TMZ)-based molecular and signaling networks and revealed the central role radiochemotherapy. Currently, the mechanisms for acquired of SRC. -
THE NATIONAL ACADEMY of TELEVISION ARTS & SCIENCES ANNOUNCES NOMINATIONS for the 44Th ANNUAL DAYTIME EMMY® AWARDS
THE NATIONAL ACADEMY OF TELEVISION ARTS & SCIENCES ANNOUNCES NOMINATIONS FOR THE 44th ANNUAL DAYTIME EMMY® AWARDS Daytime Emmy Awards to be held on Sunday, April 30th Daytime Creative Arts Emmy® Awards Gala on Friday, April 28th New York – March 22nd, 2017 – The National Academy of Television Arts & Sciences (NATAS) today announced the nominees for the 44th Annual Daytime Emmy® Awards. The awards ceremony will be held at the Pasadena Civic Auditorium on Sunday, April 30th, 2017. The Daytime Creative Arts Emmy Awards will also be held at the Pasadena Civic Auditorium on Friday, April 28th, 2017. The 44th Annual Daytime Emmy Award Nominations were revealed today on the Emmy Award-winning show, “The Talk,” on CBS. “The National Academy of Television Arts & Sciences is excited to be presenting the 44th Annual Daytime Emmy Awards in the historic Pasadena Civic Auditorium,” said Bob Mauro, President, NATAS. “With an outstanding roster of nominees, we are looking forward to an extraordinary celebration honoring the craft and talent that represent the best of Daytime television.” “After receiving a record number of submissions, we are thrilled by this talented and gifted list of nominees that will be honored at this year’s Daytime Emmy Awards,” said David Michaels, SVP, Daytime Emmy Awards. “I am very excited that Michael Levitt is with us as Executive Producer, and that David Parks and I will be serving as Executive Producers as well. With the added grandeur of the Pasadena Civic Auditorium, it will be a spectacular gala that celebrates everything we love about Daytime television!” The Daytime Emmy Awards recognize outstanding achievement in all fields of daytime television production and are presented to individuals and programs broadcast from 2:00 a.m.-6:00 p.m. -
DNA Methyltransferase (MGMT)
cancers Article Rare Stochastic Expression of O6-Methylguanine- DNA Methyltransferase (MGMT) in MGMT-Negative Melanoma Cells Determines Immediate Emergence of Drug-Resistant Populations upon Treatment with Temozolomide In Vitro and In Vivo Thomas C. Chen 1,2, Nymph Chan 1, Radu O. Minea 1, Hannah Hartman 3, Florence M. Hofman 2 and Axel H. Schönthal 3,* 1 Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; [email protected] (T.C.C.); [email protected] (N.C.); [email protected] (R.O.M.) 2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; [email protected] 3 Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-323-442-1730 Received: 8 August 2018; Accepted: 26 September 2018; Published: 28 September 2018 Abstract: The chemotherapeutic agent temozolomide (TMZ) kills tumor cells preferentially via alkylation of the O6-position of guanine. However, cells that express the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), or harbor deficient DNA mismatch repair (MMR) function, are profoundly resistant to this drug. TMZ is in clinical use for melanoma, but objective response rates are low, even when TMZ is combined with O6-benzylguanine (O6BG), a potent MGMT inhibitor. We used in vitro and in vivo models of melanoma to characterize the early events leading to cellular TMZ resistance. Melanoma cell lines were exposed to a single treatment with TMZ, at physiologically relevant concentrations, in the absence or presence of O6BG. -
Finding Recent Media Mentions
NoveListSearchStrategy Applies to: NoveList | NoveList Plus October 2019 Finding recent Media Mentions When to use: What was that title? Limit by media mentions Librarians: Need a book display idea Did you just hear an author interview on the radio or a If you have already started a search and want to narrow TV talk show but can’t remember the title of the newly your results to see only titles with media mentions, you of buzzworthy books? published book? can click the “Includes Media Mentions” box under Additional Limiters on the left side of the results page. Use our media mentions field code MM in the NoveList search bar. No more searching haystacks for that needle! We’ve created your high-powered media Readers: Looking for a book you mentions metal detector. Search by multiple shows heard about on your commute but don’t remember the exact title? TRY IT Vaguely remember the type of show where you heard the book mentioned? Go to our Advanced Search and In the search box, enter MM ABC: Good Morning search by show titles. Select multiple shows by holding America down the Control key and clicking. Parents: Heard something on the Click Search radio that you want to read and TRY IT discuss with your teenager? Hold down the Control key and then click on the Other shows to try: following to return the media mentions on late-night talk shows: MM NBC: Today Show ABC: Jimmy Kimmel Live MM CBC Radio CBS: The Late Show MM NPR: Fresh Air NBC: Late Night with Seth Meyers Or maybe it was a daytime show. -
Washington Ballet Theater Brings the Dance to Pe
Serving our communities since 1889 — www.chronline.com Tractor $1 Early Week Edition Parade Hits Tuesday, Centralia / Dec. 13, 2016 Life 1 Christmas Light Display For Suicide Awareness Fort Borst Light Show Playing Host to Santa Packwood Woman Honored After Channeling Claus as Annual Light Tour Returns / Main 10 Grief to Help Others, Form State Law / Main 3 Report: Man Impersonates Police Officer, Gropes Woman By The Chronicle who allegedly stopped a woman assault by a person dressed as a uniform driving an older- The police impersonator Centralia Police detectives and groped her Sunday night in police officer in the 400 block of model Ford Crown Victoria then allegedly groped the victim. are investigating a report of a Centralia. South Gold Street in Centralia. with a single red light on its roof The woman reported she was man dressed as a police officer, At 7:53 p.m. on Sunday, The woman reported that stopped her vehicle and asked driving a police-model vehicle police received a report of an a white male in a police-type her to take a sobriety test. please see POLICE, page Main 14 New Fees Coming Washington Ballet Theater for County Services Brings the Dance to Pe Ell By The Chronicle Fees at the Lewis County TIS THE SEASON: ‘The department Public Health Nutcracker’ Comes to and Social Services were increased at Monday’s county West Lewis County commissioners meeting. to Acclaim From The departments of Participants, Attendees Community Development and Public Works were also By Lisa Brunette reviewed but there were For The Chronicle no increases. -
Cuddle Up! America's Coziest Fireplaces U.S
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Though General Election Focused on Economy, Religion-Related Storylines Were a Key Element in the Campaign
How the News Media Covered Religion in the General Election Obama Gets Most Coverage, Much of It on False Rumor He Is a Muslim Nov. 20, 2008 Religion played a much more significant role in the media coverage of President-elect Barack Obama than it did in the press treatment of Republican nominee John McCain during the 2008 presidential campaign, but much of the coverage related to false yet persistent rumors that Obama is a Muslim. Meanwhile, there was little attempt by the news media during the campaign to comprehensively examine the role of faith in the political values and policies of the candidates, save for those of Republican vice presidential nominee Sarah Palin. And when religion-focused campaign stories were covered by the mainstream press, often the context was negative, controversial or focused on a perceived political problem. In all, religion was a significant but not overriding storyline in the media coverage of the 2008 campaign. But in a campaign in which an Obama victory would give the U.S. its first black president, religion received as much coverage in the media as race. These are some of the findings of a new study of the coverage of religion in the campaign conducted by the Pew Research Center’s Project for Excellence in Journalism and Pew Forum on Religion & Public Life. The study examined religion-focused election coverage in 48 different news outlets between June 1 and Oct. 15, 2008. 1 The “culture war” issues that have been prominent in past elections, such as abortion and gay marriage, received minimal attention in 2008. -
Independent Voters
STRETCHING POLITICAL DOLLARS Data shows Local Broadcast Advertising Winning as the Best Use of Political Media Dollars Advertising Analytics and Nielsen have Nielsen have collaborated to create accu- teamed up to combine their unique data rate and reliable Cost Per Thousand (CPM) sets to determine how to reach target vot- estimates for four Designated Market Ar- ers while optimizing a budget and keep- eas (DMA)™. These CPM estimates are root- ing current with market rate trends. The ed in Nielsen voter ratings data and actual challenge media planners often face is commercial rates from Advertising Analyt- the lack of reliable data to make informed ics where they source currency grade com- and impactful decisions on their strategy. mercial rates from the FCC public file. Ad- While overall advertising trends are shifting vertising Analytics has mined and cleansed to digital media, our data has shown that actual rate data from more than 1,100 local broadcast television remains an incredibly broadcast stations in 208 DMAs™. The re- efficient option for political advertisers. In sulting CPMs offer an unprecedented and this paper, Advertising Analytics and realistic view of media efficiency. METHODOLOGY Advertising Analytics and Nielsen matched actual market, station, and program level rates with viewership data. The data was pulled from October 2018 which is the most recent example of rates and viewership in a month immediately preceding a major election. Advertising Analytics utilized 3,000 station contracts in the FCC public file to provide