Gotowa bibliografia na temat „Julmuus”

Abstract Triple-negative breast cancer (TNBC) is a highly aggressive breast subtype of breast cancer that lacks targeted therapies. We have previously identified several novel stilbene compounds that effectively decreased viability of TNBC. Stilbenes are natural defense compounds produced by plants and have been popularized in recent years due to general observed health benefits. Resveratrol, the most widely studied stilbene, has been revealed to possess significant antioxidant and anti-cancer effects. Many stilbenes are classified as phytoestrogens, but unlike estrogens, stilbenes do not appear to negatively impact normal breast tissue or reproductive organ health. Thus, these compounds represent new alternatives for cancer therapeutic development. The focus of this research was to identify stilbene compounds with anti-migration and/or anti-invasive properties in TNBC cells and to determine the mechanism of these inhibitory effects. Two TNBC cell lines, MDA-MB-157 and BT-549, were treated with stilbene compounds at sub-lethal doses and assessed for effects on migration and invasion using transwell assays. Cell morphology changes were evaluated with results suggestive of reversal of epithelial-to-mesenchymal transition (EMT), a key contributor in the metastatic process and a common characteristic of many TNBC cells. Gene expression analysis confirmed stilbene-induced changes of EMT-related genes. These data indicate that stilbenes, like resveratrol and related analogues, reduce cell motility and invasion through regulation of EMT gene expression in TNBC cells. Development of synthetic analogs of natural compounds remains a viable drug development opportunity for new therapeutics. Citation Format: Lyndsay V. Rhodes, Kaelyn Julmeus. Novel stilbene compounds inhibit triple-negative breast cancer invasive potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 949.

Abstract Background: There has been a shift in the clinical trial landscape toward early-phase studies where data from well-designed and pivotal phase I/II trials is leading to accelerated drug approval. Our goal was to develop a standardized approach to the measurement and reporting of patient-reported outcomes (PROs) in early-phase trials to improve assessment of tolerability, address noted barriers to inclusion, and enhance patient-provider communication to inform treatment decisions and ultimately improve outcomes. Methods: The Office of Patient Centered Outcomes Research (OPCORe) was established in 2022 within the Center for Cancer Research at the National Cancer Institute (NCI) with the mission to advance understanding of the clinical benefit and tolerability of cancer therapies by integrating patient-centered approaches into CCR clinical trials by fostering education and collaboration with stakeholders. Implementation of regulatory/consortia guidelines related to use of core constructs, assessment frequency, and hypothesis-driven objectives and analysis plans through protocol template, development of data capture, email-based alerts and data visualization for clinical providers was developed and standardized templates for protocol language, research staff education, tools for workflow, and tracking implemented. Results: The OPCORe protocol template includes measurement of 3 constructs, including tolerability, clinical benefit and disease-specific impact, as well as anchors of meaningful change. Core symptomatic toxicities are measured to inform understanding across trials with agent/class-specific symptomatic toxicities added to assure relevance. Baseline and standardized weekly electronic capture of tolerability during early cycles with alerts to clinical research staff if moderate-severe toxicities reported helps facilitate patient check-ins. Repeat PROs assessments in later cycles are expanded to include disease-specific assessments and align with disease evaluation to further inform clinical impact. To date, we have collaborated with 7 research groups and developed approaches for first-in-human, phase I, and phase II studies with trial start-up and data collection in process. Conclusion: The value of including PROs in cancer trials is increasingly recognized by regulators, clinicians, patients, and advocates to advance understanding of the clinical benefit & tolerability of emerging therapies. Standardization and incorporation of PROs in earlier phase trials may enable PROs to be optimized, improve later phase trial design, and help inform health policy, support drug approval, and promote shared decision making between providers and patients to inform treatment decisions. Citation Format: Amanda L. King, Jason E. Levine, Elizabeth Vera, Yuti Gandhi, Elaine Novakovich, Theresa Yu, Sefanit Berhanu, Ciara Locke, Kaelyn Julmeus, Tito Mendoza, Terri S. Armstrong. Development and implementation of a systematic approach to measure patient-reported outcomes in early-phase cancer trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1302.

Vladislavs Nastavševs is one of the leading contemporary Latvian theatre directors. Nastavševs’ stage productions are constructed by combining elements of psychological theatre, performance art and postdramatic theatre, deliberately expanding the traditional boundaries between the stage and the audience, actors and spectators. Nastavševs’ performances usually contain visually impressive stage metaphors that generate both emotional and psychophysical influence on the spectators, thus exploring new types of performance perception and blurring the boundaries between life (reality) and theatre (fiction). Vladislav Nastavševs (1978) on üks tänapäeva läti teatri juhtivaid lavastajaid, kes alustas tegevust 21. sajandi teisel aastakümnel. Ta omandas teatrialase hariduse välismaal (Peterburis Vene Riiklikus Etenduskunstide Instituudis ja Londonis St. Martin’s College of Arts and Design, Drama Centre’is). Psühholoogilise teatri, performance’i ja postdramaatilise teatri elemente ühendades on ta välja töötanud väga erilise kunstnikukäekirja. Artikkel vaatleb piiride hägustumist lava ja vaatajate vahel Nastavševsi lavastustes ja uurib, kuidas elu (tegelikkuse) ja teatri (fiktsiooni) vahelise eraldusjoone kadumine väljendub tema lavastuste diskursuses. Nastavševsi lavastajategevust võib seostada tänapäeva teatri mitme tendentsiga. Esiteks, alates 1960. aastate lõpu performatiivsest pöördest on teater nihkunud aktiivsema vaatajatega suhtlemise poole, võttes teatrit osana „tegelikust elust“ ja muutes vahe teatri kui fiktsiooni ja elu kui tegelikkuse vahel segasemaks. Vladislavs Nastavševs vaidlustab oma lavastustes pidevalt piire tegeliku elu ja kunstimaailma vahel, püüdes uurida eri võimalusi ja aspekte teatri kui illusiooni (fiktsionaalse kunstimaailma) ja tegeliku elu vahelistes suhetes. Teiseks, nüüdisaegseid teatritendentse järgides sulatab Nastavševs oma lavastustes ühte eri kunstivorme (teater, tänapäeva tsirkus, visuaalne kunst, muusika, tants, performance, jne.), kaldudes seega interdistsiplinaarse esituskeele poole. Kolmandaks, nagu paljud tänapäeva Läti ja Euroopa teatritegelased, näiteks Alvis Hermanis (Läti), Ivo van Hove (Belgia), Frank Castorf, Thomas Ostermeier (Saksamaa), Katie Mitchell (Ühendkuningriik) ja teised, seob ka Vladislavs Nastavševs oma etendustes keeruka etendusesteetika loomiseks ühte tugevad visuaalsed, füüsilised ja auditiivsed teatrimärgid. Antonin Artaud’ „julmuse teatri“ idee mõjul kalduvad Nastavševsi lavastused tekitama vaatajas füüsilisi aistinguid – kasutatud lavametafoorid on niivõrd pingsad ja mõnikord naturalistlikud, et publik ei taju etendust mitte ainult emotsionaalselt või ratsionaalselt, vaid ka psühhofüüsiliselt (näiteks võib tekkida tugevaid reaktsioone nagu hirm või vastikustunne). Vaatajate tõeline elav reaktsioon muutub enamasti Nastavševi etenduste oluliseks osaks, luues lava ja publiku vahel sideme ja hägustades teatri ning elu vahelist piiri. Neljandaks, vastavalt postdramaatilise teatri ideele, mille tõi sisse saksa teatriteadlane Hans Thies-Lehmann, kasutab Nastavševs keeruliste lavametafooride ülesehitamiseks tihti näitleja keha, luues sellega füüsilisuse esteetikat. See tähendab, et toimub nihe dramaatilistelt (tekstipõhistelt) teatrivormidelt, kus tähendust (rolli) kannab näitleja postdramaatilise märgisüsteemi poole, kus näitleja keha pole lavale toodud etenduse iseseisva elemendina. Elu ja teatri, näitlejate ja lavastaja, lava ja publiku vaheliste piiride hägustumise teema on muutunud üheks Nastavševsi lavastuste juhtmotiiviks, mida on võimalik näidata kolmest peamisest aspektist. Esimene aspekt: oma lavastustes mängib Vladislavs Nastavševs ettekavatsetult ideega elust kui teatrist ja teatrist kui elust. Kõik tema uusimad lavastused põhinevad printsiibil „teater teatris“ ehk „metateater“, kus näitlejad mängivad tegelasi, kes käituvad ka oma elus nagu näitlejad. Valides lavastamiseks vene nn hõbedase ajajärgu modernistide teoseid (näiteks Mihhail Kuzmini romaan „Rändurid merel ja maal“ – esimene osa Riia Uues Teatris (2014), teine osa Daile Teatris (2016)), kujutab lavastaja seda vene kultuuri üht kunstirohkeimat perioodi tegevuspaigana, kus teatraalsus polnud ainult kunstniku loominguline väljendusvahend, vaid ka tema elulaad. Teine aspekt: oma lavastustes käsitleb Nastavševs teatristrateegiana enesepeegeldust ise oma lavastustes kohal olles. Suurema osa lavastuste puhul on ta totaalne autor (lavastaja, lava- ja kostüümikunstnik, helilooja, koreograaf, mõnikord ka näitleja) ning näiteks „Lootuse järve“ („Cerī bu ezers“ 2015, Riia Uus Teater) puhul ka lavastuse peategelane, luues sel viisil autobiograafilise lavateose. Kolmas aspekt: ühes oma kõige silmapaistvamas lavastuses, Federico Garcia Lorca „Verepulmas“ (2016, Läti Rahvusteater), uurib Nastavševs elu ja teatri vahelisi piire, muutes tavalist ruumilist tegevuspaika. Ta asetab vaatajad lavale, kust avaneb täisvaade kogu publikualale, ja kasutab kõiki nähtaval olevaid ruumipindu saalipõrandast kuni teise rõduni. Lavaline tegevus on üles ehitatud nii täpselt, et see mõjutab vaatajaid kõikvõimalikel tasanditel nii intellektuaalselt, emotsionaalselt kui psühhofüüsiliselt, võimaldades nii hägustada lava ja publiku vahelisi piire. Artiklis mainitud suundumused lubavad asetada Vladislavs Nastavševsi lavastajatöö nüüdisaegse Euroopa teatri raamistikku.

Research within translation characterises cultural references as being problematic for translators, meaning they must choose between different translation strategies as to how to transfer these references into the translated text. These strategies are often described in general terms according to how closely oriented they are to the target-culture or source-culture, known as domestication or foreignisation. Translation of literature into English is minimal in world terms and there is seemingly a lack of statistically comparable data concerning the translation of cultural references. This study investigates and compares translation strategies of words denoting cultural references in two translations of the 1998 Swedish Nordic Noir novel Sprängaren by Liza Marklund. The methodology in the study is based on descriptive translation studies, and a categorisation model for types of cultural references is used, as well as an adapted taxonomy model for evaluating translation strategies. Issues addressed are: what types of strategies are used; whether strategies change between translations; how the second translation stands in relation to the retranslation hypothesis and whether any general translation norms are apparent. Results show that a wide variety of translation strategies are used for different types of cultural references, with subtle differences in strategies used in each translation. However, both translations appear to be more domestication-oriented with little overall movement towards to the source culture, as the retranslation hypothesis suggests.