Transforming Activity Research Articles

Abstract 7072: MYC acetylated lysine residues drive oncogenic cell transformation and regulate select genetic programs for cell adhesion-independent growth and survival

Abstract The MYC oncogenic transcription factor is acetylated by the p300 and GCN5 histone acetyltransferases. The significance of MYC acetylation and functions of specific acetylated lysine (K) residues have remained unclear. Here, we show that the major p300-acetylated K148(149) and K157(158) sites in human (or mouse) MYC and the main GCN5-acetylated K323 residue are reversibly acetylated in various malignant and non-malignant cells. Oncogenic overexpression of MYC enhances its acetylation and alters regulation of site-specific acetylation by proteasome and deacetylase inhibitors. Acetylation of MYC at different K residues differentially affects its stability in a cell type- dependent manner. Lysine-to-arginine substitutions indicate that although none of the acetylated K (AcK) residues is required for MYC stimulation of adherent cell proliferation, individual AcK sites have gene-specific functions controlling select MYC-regulated processes in cell adhesion, contact inhibition, apoptosis, and/or metabolism, and are required for the malignant cell transformation activity of MYC. Each AcK site is required for anchorage-independent growth of MYC-overexpressing cells in vitro, and both the AcK148(149) and AcK157(158) residues are also important for the tumorigenic activity of MYC-transformed cells in vivo. These AcK residues may also preferentially activate transcription via facilitating MYC binding to several cancer-associated target gene promoters and via enhancing RNAP II recruitment. With the knowledge that MYC lysine residues can be acetylated by HATs GCN5 and P300, some HATs and HAT associated cofactors (i.e. YEATS2 and PIN1) are important for MYC recruitment to DNA binding. By identifying MYC acetylation-dependent coregulators and their oncogenic function, we proposed to understand whether and how MYC acetylation residues cooperate with its cofactors and influence malignant transformation in breast cancer cells.Overall, this study will uncover the functions and mechanisms of MYC acetylation in regulation of malignant transformation and the impact on breast cancer initiation and progression. By analyzing deregulated target genes and MYC-relevant coactivators, the MYC AcK site-specific signaling pathways identified may offer new avenues for selective therapeutic targeting of MYC oncogenic activities. Citation Format: Jeffrey J. Pino, Matthew Hurd, Yifan Zhao, Kay Jang, Michael Allevato, Marina Vorontchikhina, Wataru Ichikawa, Ryan Gates, Emily Villalpando, Michael Hamilton, Francesco Failo, Songqin Pan, Yue Qi, Yu-wen Hung, Thomas Girke, David Ann, Victoria Seewaldt, Ernest Martinez. MYC acetylated lysine residues drive oncogenic cell transformation and regulate select genetic programs for cell adhesion-independent growth and survival [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 7072.

Conceptualising praxis, agency and learning: A postabyssal exploration to strengthen the struggle over alternative futures

Educational researchers are increasingly striving on the edge of possibility to re-imagine and realise the future. Activist scholarship requires appropriate philosophical and theoretical bases, what Stetsenko refers to as ‘dangerous’ – useful in the struggle for a better world. How might praxis, agency and learning be charged with transgressive spirit? This paper considers the Theory of Practice Architectures and Transformative Activist Stance, established frameworks that dangerously address praxis, agency and learning. Adopting a postabyssal approach, contributions from the Global South and East are drawn on to develop an epistemologically plural basis for thinking differently about praxis, agency and learning. Recent Latin American scholarship reinvigorates Freirean ideas through connections with Fals Borda and contemporary feminist pedagogues, centred on a notion of feeling-thinking. Luitel’s interpretations of Vedic philosophy provide radically different ideas of negative dialectics, chaos, responsibility and liberation. An open-minded, open-hearted, open-ended approach is crucial to making these ideas more useful in the struggle over alternative, more equitable and just futures.

The Influence of Transformational Leadership on Work Motivation Has an Impact on Teacher Performance in Senior High Schools in Southwest Sumba Regency

The quality of learning is influenced by many aspects, the most important of which is the teacher's ability. This research to analyze and explain the impact of transformational leadership and work motivation on teacher performance. Quantitative research was carried out on high school teachers in the West Sumba district. The number of teachers was 726 people. Determining the number of illustrations using a random sampling method, Morgan's recipe was corrected with Warwich's and Lininge's recipes. The results obtained were 300 respondents. The collection uses a closed-type questionnaire with 5 options. The analysis uses the multivariate Structural Equation Modeling (PLS-SEM) method. The research results are: (1) transformational leadership has an important positive direct influence on the encouragement of activity, experimental facts, T-Statistics is 2.517, P-Values is 0.012 (2) leadership has an important positive direct effect on teacher ability T-Statistics experimental fact is 2,795 P-Values is 0.008( 3) encouragement of activities has a direct positive influence on the teacher's ability T-Statistics experimental fact is 14.448 P-Values is 0.000(4) leadership Transformational leadership indirectly influences teacher ability through activity encouragement as proven by experiments. T-Statistics is 2.461. P-Values are 0.014. Research findings show that transformational leadership and activity encouragement have an important influence and are predictors of increasing teacher ability.

Hacker education and transformative agency: an empirical study in hacker communities and in the school case of Conexão Escola-Mundo

ABSTRACT This paper investigates how particular aspects of hacker education are perceived as drivers of transformative agency in hacker communities and a brazilian school by applying a qualitative study of a broader mixed-method research. The analysis revealed a multidimensional understanding of hacker education, pointing to elements of a transformative activist stance based pedagogy in digitalized societies. Six dimensions emerged: inquietude, action-fun, collective, society-community, sharing and the humanistic-technological dimension. The findings indicate that in both contexts, the co-creative process, in addition to strengthening the sense of community, is what drives participants to act as transformative agents through the artifacts they can create.

The biotic effects of lignite on humic acid components conversion during chicken manure composting

Targeted regulation of composting to convert organic matter into humic acid (HA) holds significant importance in compost quality. Owing to its low carbon content, chicken manure compost often requires carbon supplements to promote the humification progress. The addition of lignite can increase HA content through biotic pathways, however, its structure was not explored. The Parallel factor analysis revealed that lignite can significantly increase the complexity of highly humified components. The lignite addition improved phenol oxidase activity, particularly laccase, during the thermophilic and cooling phases. The abundance and transformation functions of core bacteria also indicated that lignite addition can influence the activity of microbial transformation of HA components. The structural equation model further confirmed that lignite addition had a direct and indirect impact on enhancing the complexity of HA components through core bacteria and phenol oxidase. Therefore, lignite addition can improve HA structure complexity during composting through biotic pathways.

Recognizing Stereotypes and Their Impact on Health: A Transformative Learning Activity for Undergraduate Health Science Students

Stereotypes are simplified generalizations that act as mental shortcuts which help us understand the world. However, these oversimplifications fail to capture the diversity within groups and communities. This is particularly adverse in healthcare settings as stereotypes are cognitive frameworks from which implicit biases emerge—affecting how individuals and groups are perceived, evaluated, and treated. Specifically, stereotypes linked to race, ethnicity, gender, and sexuality exert profound and detrimental influence on healthcare access, quality, and decision-making for marginalized populations. Thus, recognizing and understanding stereotypes are crucial for combatting health disparities prevalent in our society. Accordingly, it is essential that students receive instruction and training that allows them to understand the impact of stereotypes, acknowledge implicit biases, and advocate for equitable and unbiased healthcare for all. Health science instructors can facilitate this growth through the implementation of transformative education and learning. Transformative education is an approach to learning that aims to create profound personal and societal changes by fostering critical thinking, self-awareness, and social responsibility. The transformative learning activity presented in this manuscript seeks to enhance students’ understanding of stereotypes’ role in perpetuating health disparities and their impact on marginalized communities. By fostering critical reflection, open dialog, and collaborative problem-solving, the activity equips students to comprehend the multifaceted dimensions of stereotypes in healthcare and prepares them to address the challenges of an increasingly diverse and socially complex world. Through transformative education, students are nurtured to become competent healthcare professionals who champion equitable and unbiased care and bridge understanding and empathy across communities.

Direct observations of dynamic and reverse transformation of Ti-6Al-4V alloy and pure titanium

This paper focused on the characterization and mechanism of the dynamic transformation from the alpha to beta phase during the hot deformation of Ti-6Al-4V alloy and pure titanium. The investigation employed in-situ neutron diffraction and atomistic simulations for a comprehensive understanding of the process. Dynamic transformations were observed during deformation of the Ti-6Al-4V alloy and pure titanium below the beta-transus temperatures (temperatures at which (alpha + beta) / alpha → beta). In the dynamic transformation of Ti-6Al-4V, the lattice parameters of the beta phase continuously increased during deformation in the tensile and transverse directions, a trend inconsistent with the behavior of flow stress. The anomalous variations in lattice parameters were attributed to element diffusion (i.e. a decrease in vanadium content in beta phase). During isothermal holding after unloading, the in-situ neutron diffraction results for Ti-6Al-4V and pure titanium indicated a sluggish reverse transformation from the beta to alpha phase. The mechanism of dynamic transformation was explored through in-situ neutron diffraction and atomistic simulations, which revealed twofold effects of deformation on dynamic transformation. Firstly, deformation led to a significant rise in the Gibbs energy of the alpha phase relative to the beta phase, expanding the beta phase region and diminishing the alpha phase region. Secondly, deformation lowered the energy barriers associated with dynamic transformation, facilitating the activation of dynamic transformation more readily than in the equilibrium state before deformation.

Whole blood thiamine, intravenous thiamine supplementation and delirium occurrence in the intensive care unit: retrospective cohort analyses.

Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.

Digital Transformation and ESG Performance: A Quasinatural Experiment Based on China’s Environmental Protection Law

The bioeconomy model provides an alternative view of global economic systems by putting sustainable practices combined with digital approaches at the forefront to tackle issues such as climate change. To address this new business trends, financial institutions began to set up the environmental, social, and governance (ESG) business units to evaluate their business strategies. This paper is aimed at examining the nonfinancial effect created by the digital transformation (DT) activities, highlighting the role of enterprise heterogeneity after the implementation of Environmental Protection Law (EPL) in China. We employ the panel data of A-share listed companies from 2010 to 2020, selecting DT and ESG indicators as the important representations of “Industry 5.0.” Our empirical results demonstrate a positive impact of EPL on the ESG performance in sight of resource enterprises (REs), environmental enterprises (EEs), and polluting enterprises (PEs), but a negative impact of EPL on the DT indicators among those environmental related industries. Additional causal relationship regression reveals that enterprise DT has an intrinsic promoting effect on the ESG performance, emphasizing on the high risk of digitization process being the shock transmitters to enterprise nonfinancial indices. Notably, the connectedness of environmental policy illustrates dynamic patterns by parallel trend test and propensity score matching (PSM) DID regression. This paper is prone to benefit lawmakers, regulators, and firm executives responsible for analyzing and assessing enterprise digitization behavior by exploring the influence of macrolevel environmental policy.

DIGITAL TRANSFORMATION CYCLE IN BUSINESS LANDSCAPE: THE MANAGERIAL PERSPECTIVE

Research on digital transformation activities on top managers of businesses has revealed that a most executives believes that they can buy digital technology, apply it across the business, and see the benefits within a few months. In similar studies, it was determined that the rate of cases where digital transformation failed in such businesses reached up to 70%. Therefore, considering the depth and scope of change required for companies to be successful in the digital transformation process, these thoughts and expectations of company executives are unrealistic. In addition, it expresses another misconception that it would be sufficient for the digital transformation process to be carried out only by the information technology managers (CIO) and simply the IT team. In this study, the application challenges and opportunities that arise in the digital transformation process will be explained within the framework of changing company business models, and the factors that determine success and failure will be emphasized based on managerial perspective.

INTERLEUKIN-11 AND CARDIOVASCULAR PATHOLOGY

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. An important task in cardiology is the search and study of new biomarkers. Scientific interest is actively focused on the study of interleukin-11 (IL-11). The purpose of the literature review was to analyze experimental and clinical studies devoted to the study of IL-11 as a diagnostic and prognostic marker in CVD. Material and methods. The article provides an overview of current publications. An analysis of literature sources was carried out, including all relevant publications in the databases PubMed, RSCI, MedLine, Google Scholar, Science Direct. Results. In endothelial cells, IL-11 primarily promotes angiogenesis, thereby exerting a beneficial effect on coronary heart disease. IL-11 also promotes vascular remodeling by inducing smooth muscle cell transformation and fibroblast activation. IL-11 may be involved in the onset and progression of pulmonary hypertension through the JAK/STAT3 pathway and aortic dissection processes through the non-classical ERK pathway. Conclusion. The presented literature review indicates the potentially important diagnostic and prognostic value of IL-11 assessment. Regulating the concentration and expression of IL-11 may be a promising strategy for the treatment of CVD.

Students’ Algebraic Thinking Skills Through Creative Problem Solving Learning Models

This research aims to describe algebraic thinking skills in two-variable linear equation systems material through the steps of the Creative Problem Solving learning (CPS) learning model using worksheets. The research subjects were students of SMP Negeri 02 Sembawa class VIII-7 in the 2023/2024 academic year. The type of research is descriptive qualitative. The data collection techniques are written tests and interviews. Indicators of algebraic thinking skills include indicators at generational, transformational and meta-global level activities. After implementing CPS in learning, the test results showed that the percentage of students' algebraic thinking skills for generational activities in question number one was 48% and number two was 89%. For transformational activities, the percentage of students who were able to achieve them was 38% for number one and 38% for number two. Meanwhile, for meta-global level activities, the percentage of students who were able to achieve them was 45% for number one and 82% for number two. It can be concluded that the indicators of algebraic thinking skills that appear most frequently are in generational activities.

Spatial analysis of CSR and societal transformation: A global scenario

The societal transformation is a crucial phenomenon and it depict the strength of the nation and corporate sectors responsibility towards society. Corporates Social Responsibility (CSR) is the mainstream for the societal transformation. The CSR activities probably differs as per the policies and rules of the nation. But, the prime motto of the CSR is fulfil the Economic, Environment and social needs of the nation. Hence, the present study has analyzed the contribution of the top ten countries contribution towards CSR activities for societal transformation. The data were collected from secondary sources analyzed by using Correlation and ANOVA.

Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug’s binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.

Atomic/molecular layer deposition strategies for enhanced CO2 capture, utilisation and storage materials.

Elevated levels of carbon dioxide (CO2) in the atmosphere and the diminishing reserves of fossil fuels have raised profound concerns regarding the resulting consequences of global climate change and the future supply of energy. Hence, the reduction and transformation of CO2 not only mitigates environmental pollution but also generates value-added chemicals, providing a dual remedy to address both energy and environmental challenges. Despite notable advancements, the low conversion efficiency of CO2 remains a major obstacle, largely attributed to its inert chemical nature. It is imperative to engineer catalysts/materials that exhibit high conversion efficiency, selectivity, and stability for CO2 transformation. With unparalleled precision at the atomic level, atomic layer deposition (ALD) and molecular layer deposition (MLD) methods utilize various strategies, including ultrathin modification, overcoating, interlayer coating, area-selective deposition, template-assisted deposition, and sacrificial-layer-assisted deposition, to synthesize numerous novel metal-based materials with diverse structures. These materials, functioning as active materials, passive materials or modifiers, have contributed to the enhancement of catalytic activity, selectivity, and stability, effectively addressing the challenges linked to CO2 transformation. Herein, this review focuses on ALD and MLD's role in fabricating materials for electro-, photo-, photoelectro-, and thermal catalytic CO2 reduction, CO2 capture and separation, and electrochemical CO2 sensing. Significant emphasis is dedicated to the ALD and MLD designed materials, their crucial role in enhancing performance, and exploring the relationship between their structures and catalytic activities for CO2 transformation. Finally, this comprehensive review presents the summary, challenges and prospects for ALD and MLD-designed materials for CO2 transformation.

Ruthenium catalyzed transformation of levulinic acid to γ-valerolactone in water

Efficient transformation of biomass derived LA to GVL is achieved over a Ru-pyridylamine based molecular catalyst in water at 80 °C using HCOOH, where the role of the ligand was found to be crucial in achieving high catalytic activity (yield 95%).

«Хвала труду» Ивана Ильина как манифест российской модерности

The article presents the results of a study of alternative versions of modernization. Along with the widespread identification of the modernization process with the Westernization of non-Western societies, the concept of multiple modernization by Shmuel Eisenstadt is analyzed. Russian religious philosophy, being in opposition to the processes that constitute the essence of the Western type of modernization, in particular the transformation of technology from a means of human existence into the goal of his existence, contains examples of a positive reaction to the transformative labor activity of people. Ivan Ilyin in his work “Praise to Labor” demonstrates a special way of demonstrating the value of everyday work as the realization of “God's idea”.

Cation and anion co-partial substitution induced centrosymmetric to noncentrosymmetric structural transformation to construct nonlinear-optical rare-earth oxythiogermanates

MxEu18−xGe9O5S31 (R3) were obtained by cationic and anionic co-partial substitution of β-Eu2GeS4 (P21/m), which induced centrosymmetric to noncentrosymmetric structural transformation and balanced second-order nonlinear optical activity.

Zachowania pracowników muzeów w okresie COVID-19 w perspektywie ekonomii behawioralnej na przykładzie Muzeum Okręgowego w Rzeszowie

Purpose – The pandemic has hampered the functioning of all cultural institutions, including museums. The only way to reduce the transmission of the virus in the population was to change behavior. NPI (nonpharmaceutical interventions) are tools that tried to control the course of the pandemic. The aim of the article was to identify behavioral errors in the work of professional employees of the District Museum in Rzeszów during the COVID‑19 pandemic. Research method – The method of critical literature analysis was used. In the form of a case study, the work of the District Museum in Rzeszów was analyzed, using information from participant observation and structured interviews. Results – The pandemic crisis has led to increased digital transformation activities and highlighted problems related to the financing aspect. The identified errors in the behavior of museum employees were errors resulting from information overload, uncertainty of the future, concerns about the use of interventions, and wishful thinking. Originality / value / implications / recommendations – The originality of the study results from the diagnosis of the research gap relating to museum employees in terms of their response to non‑medical interventions in the workplace during the COVID pandemic. There are no known analyzes of behavioral errors at the workplace in relation to non‑medical interventions. Therefore, this is an innovative approach to the topic and important from the point of view of implementing regulatory solutions during the crisis.

Algebraic thinking ability of grade VIII students using a Problem-Based Learning (PBL)

Students still have limited algebraic reasoning skills, so a learning model called Problem-Based Learning (PBL) is utilized as a teaching strategy to help student develop their algebraic thinking abilities. This study uses the learning model Problem-Based Learning (PBL) to the algebraic thinking skills of class VIII students. The method of research is descriptive qualitative research. The students in class VIII students of SMPN 1 Lahat participated in this study. Problem-Based Learning (PBL) worksheet in accordance with three algebraic thinking abilities: generational activities, transformational activities, and global, meta-level, and mathematical activities. Data for the study came from observations, interviews and written exams. Data from the results of observation sheets are used to see the emergence of indicators of students' algebraic thinking during learning with a total of 2 sessions; data from the results of written tests are used to categorize students' algebraic thinking abilities after learning, taking 2 students from each category, and interviews to clarify the results of students' answers. The findings of this study show that students possess a range of low, medium, and high levels of algebraic thinking ability. The result of the implementation learning model showed that 14 students were in the medium category and 17 students were in the low category.