Abstract Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to its current standard-of-care regimen, which includes ...surgical resection followed by adjuvant ionizing radiation and temozolomide. Therapy resistance can be attributed to the abundance of genomic alterations in GBM tumors that evolve over time, which contribute to intra-and inter-tumoral heterogeneities that render targeted therapies as inadequate treatment options. Thus, there is an urgent unmet need for effective therapies targeting primary and recurrent GBM. Here, we investigated the impact of ionizing radiation on the transcriptome of patient derived GBM tumor spheres to identify key alterations and biological pathways involved in therapy resistance. Materials and methods: We acquired four independent human GBM tumor sphere cell lines, which were derived from patients and cultured in serum-free media. Tumor spheres were treated with either a sham radiation or a single dose of 10Gy. Using poly-A enrichment whole transcriptome sequencing, we evaluated transcriptional alterations occurring in GBM tumors spheres at 96h post-radiation. To do so, we performed differential expression analysis and gene set enrichment analysis (GSEA) to identify top differentially expressed genes and significant changes in biological phenomena. Additionally, we evaluated the cell viability response of these GBM tumor spheres to radiation. Results and discussion: PCA analysis of the four human GBM tumor sphere cell lines demonstrates that cell type has a substantial impact on variation among samples compared to non-irradiated and irradiated treatment conditions. Upon analysis of genes in common that are either upregulated or downregulated followed by GSEA, we identified enrichment of genes associated with inflammatory responses and ferroptosis repression (e.g., NUPR1, PTGS1, AOX1), and depletion of genes involved in fatty acid metabolism (e.g., INSIG1, PLA2G3, ACAT2). Furthermore, the GBM tumor sphere cell viability responses allowed us to stratify our models into radiosensitive and radioresistant subgroups. Conclusion: Radiosensitive human GBM tumor spheres exhibit transcriptional alterations in genes linked to inflammation and fatty acid metabolism to a greater extent compared to radioresistant tumor spheres. Our study characterizes the radiation response of patient derived GBM models, which is to be leveraged for combating therapeutic resistance. Citation Format: Arianna Richelle Izawa-Ishiguro, Subhiksha Nandakumar, Nicholas Carbone, Annalisa V. Ferrotta, Raashed Raziuddin, Kristen C. Vogt, Daniel A. Heller, Ingo K. Mellinghoff. Ionizing radiation induces lipid metabolism-associated vulnerabilities in glioblastoma multiforme 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 387.
This collection features essays, case studies, and pedagogical approaches that explore how educators managed the privacy, security, and safety concerns that rushed into our lives as we shifted into ...emergency remote learning in 2020. While the COVID-19 pandemic brought this concern into focus, privacy issues with online learning continue to exist alongside us and our students. This book provides readers insight into the current state of privacy issues, describes the challenges and rewards of developing more privacy-focused learning environments, and presents several resources and tools that readers can bring to their own teaching practices. Representing a variety of perspectives from K-12, higher education, and libraries, contributors describe the challenges they encountered and offer solutions to help ensure the safekeeping of students’ online lives. How do we navigate these online environments, who collects our data, and how can we protect our most vulnerable populations?
Genetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have ...prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric-antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Herein, we expanded the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with TCR-engineered T cells. We demonstrate that SEAKER cells localized specifically to tumors, and activated bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells were efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.
This study examined the feasibility of using Ecological Momentary Assessment (EMA) to examine important domains relevant to interregulatory health processes in overweight adolescent females in their ...natural environments. Participants were 20 overweight adolescent females engaged in a cognitive–behavioral and motivational interviewing intervention aimed at weight loss and improving mood (11–19 years old, 80% white, 15% African American, mean BMI = 39). During this EMA protocol, participants were asked to report their physical activity (PA), nutrition, mood, and sleep during 14 cellular phone calls over three extended weekends (Thursday to Monday). Simultaneously, participants wore an actigraph (armband and watch communicator) that provided instantaneous PA feedback (steps taken and kilocalories) and sleep parameters (duration and efficiency). EMA compliance rates for the armband and phone calls were 74.7 ± 0.3% and 64.2 ± 0.3%, respectively. Data from the armband and phone calls are presented to illustrate the depth of information acquired by utilizing this innovative methodology.
The National Study of Living-Learning Programs (NSLLP) survey instrument was designed to assess college environments and student learning and development outcomes associated with participation in ...living-learning programs. Data from the NSLLP show that students in living-learning programs demonstrate higher self-reported engagement and outcomes than students in traditional residence hall environments.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, ZRSKP
Framed guessability Cafaro, Francesco; Lyons, Leilah; Kang, Raymond ...
Proceedings of the 8th International Conference on Tangible, Embedded and Embodied Interaction,
02/2014
Conference Proceeding
Despite the wide availability of body-sensing technologies, the design of control gestures that feel natural and that can be intuitively "guessed" by the users is still an embodied interaction ...challenge. This is especially true for systems that require a set of complementary control gestures. Part of the problem lies in the separation between the locus of the interaction (the body) and the focus of the interaction (the screen). We extend Johnson's theory of Embodied Schemata with Embodied Allegories, in order to create a unifying context that spans across the locus and focus of interaction. We present results that demonstrate how this approach increases the chance that users select the same gesture or movement for producing an effect within the virtual context, and that the resultant gesture set is deemed more intuitive by users. We also present the accompanying methodology, "Framed Guessability," which can increase users' agreement when conducting Guessability Studies.
The purpose of this research study was to examine, for undergraduate women of various Asian American ethnic backgrounds, the influence of background contextual and college environment factors on ...their sense of academic self-efficacy and achievement in science, technology, engineering, and mathematics (STEM) majors. Social cognitive career theory and its critiques provided a theoretical foundation for relationships from past performance, socioeconomic status, acculturation, and college environment variables (compositional diversity, racial climate, gendered climate, academic peer support), to academic self-efficacy and achievement. Data were collected through an online survey. Instrumentation included the scales of Language, Identity, and Behavioral Acculturation; Gender Discrimination; Faculty and Classroom Behavior; Interactions with Peers; and Academic Milestones Self-efficacy. The participants were 228 Asian American undergraduate women in STEM at a large public, doctoral research extensive university on the east coast; the response rate was 51%. In three MANOVAs for nine social cognitive career variables, four ethnic groups (East, South, Southeast, and Multi-ethnic Asian American) significantly differed only on socioeconomic status. In path analysis, the initial model was not a good fit and was rejected. The model was respecified through statistical and theoretical evaluation, tested in exploratory analysis, and considered a good fit. The respecified model explained 36% of semester GPA (achievement) and 28% of academic self-efficacy. The academic achievement of Asian American women in STEM was related to past performance, background contextual factors, academic self-efficacy, academic peer support, and gendered climate. The strongest direct influence on achievement was academic self-efficacy followed by past performance. The total effect of Asian acculturation on achievement was negative and the total effect of American acculturation on achievement was not significant; academic self-efficacy mediated these complex relationships. The total effects of racial and gendered compositional diversity and racial climate on both academic self-efficacy and achievement were not significant. Students in majors with more female peers reported less academic peer support. In this study, when culturally specific variables embellished social cognitive career theory, the theory exhibited cultural validity for undergraduate Asian American women in STEM. The nature of the relationships among culturally specific variables and college environment variables, however, requires further study.
The National Study of Living-Learning Programs (NSLLP) survey instrument was designed to assess college environments and student learning and development outcomes associated with participation in ...living-learning programs. Data from the NSLLP show that students in living-learning programs demonstrate higher self-reported engagement and outcomes than students in traditional residence hall environments.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, ZRSKP
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