Shift In Focus Research Articles

Beyond Catalysts: Exploring Discharge Product Growth and Intrinsic Overpotential in Lithium-Oxygen Batteries.

The lithium-oxygen (Li-O2) battery, renowned for its exceptionally high theoretical energy density, is poised to revolutionize next-generation energy storage systems. However, its practical application depends on overcoming several challenges, particularly the high cathode overpotential, which significantly diminishes the battery's energy efficiency and durability. This study delves into the interactions at the cathode surface during oxygen reduction and evolution reactions (ORR/OER), extending the analysis beyond the initial reaction stages to encompass the extensive charge-discharge process. We introduce and define the concepts of intrinsic equilibrium potential and intrinsic overpotential, demonstrating that these critical parameters are predominantly influenced by the growth of discharge products, rather than the catalysts, thereby underscoring the inherent properties of the battery. This shift in focus from merely enhancing cathode catalysts to understanding and leveraging the intrinsic characteristics of the battery discharge process opens new avenues for optimizing and enhancing the performance of large-scale Li-O2 batteries. Furthermore, our findings indicate potential broader applications to other metal-oxygen systems, paving the way for the design of high-capacity, high-efficiency energy storage technologies.

Communities as Victims of Inter-Cattle Rustling Gangs in the Northern Regions of Kenya and Uganda

Cattle rustling remains a deeply rooted issue in the Northern regions of Kenya and Uganda and encompasses a complex and multi-faceted problem with far-reaching implications for victimized communities. This issue, originating from tribal tensions, territorial disputes, economic incentives, marginalization, and climate change, demands a comprehensive investigation. This study aims to shed light on the intricate dynamics of inter-cattle rustling attacks, delving into the temporal patterns, distinct attack characteristics, and their societal impact. In this context, the research objectives include determining patterns and trends of these attacks, assessing their impacts on affected communities, and proposing measures to enhance the protection and empowerment of these communities. The study employed a mixed methods research approach, which involved a target population of approximately 400,000 individuals from the Pokot and Sebei communities living along the Kenya-Uganda border. Data collection methods included semi-structured interviews with key informants, focus group discussions, and a review of existing reports and records. The study identified distinct temporal patterns of inter-cattle rustling attacks, with attacks occurring most frequently during specific timeframes, such as early morning, late morning, afternoon, and late evening. This temporal pattern offers insights into the strategic considerations of the attackers. In addition, the study revealed that attacks exhibit distinct characteristics depending on the time of day. In the morning, attacks are marked by swiftness, a "grab and run" mentality, and a readiness to eliminate opposition. Afternoons see a shift in focus, with caretakers becoming the primary targets. Evening raids are conducted with stealth and aim to drive stolen animals across the border. Further, the attackers, known as "Morans," were found to be well-prepared and armed, with a high level of coordination, particularly in morning and evening attacks. Their identity adds to the complexity of the confrontations. The impact of inter-cattle rustling attacks goes beyond economic losses, resulting in the loss of life, displacement of communities, closed schools, and the disruption of community centers. Entire sections of communities are forced to relocate, upending livelihoods and contributing to a sense of desolation. The attacks traumatize victim communities, with children, in particular, bearing a heavy psychological burden, especially in the brutal morning confrontations. This psychological impact further erodes the social fabric. Based on these findings, the study recommends implementing community-based resilience programs, establishing psychosocial support services, engaging in conflict resolution and mediation efforts, strengthening security measures, promoting sustainable resource management, providing economic opportunities, and facilitating cross-cultural dialogues. These recommendations are expected to contribute to the development of more effective policies and interventions. In summary, this study contributes valuable insights that can inform evidence-based policy development to address the multi-faceted challenge of cattle rustling and its diverse implications for the affected communities in the Northern regions of Kenya and Uganda.

Comparative evaluation of remineralizing efficacy of calcium sodium phosphosilicate, ginger, turmeric, and fluoride

ABSTRACT Background: White lesions, also known as white spots, are the earliest signs of tooth decay. At this stage, noninvasive preventive treatments, such as fluoride application, can help to slow down or even reverse the progression of white lesions. For decades, fluoride has held the spotlight as the go-to agent in oral preventive care, demonstrating significant remineralizing power. Recent scientific literature reveals a growing interest in alternative products as natural substances that demonstrate potential remineralizing effects on tooth enamel. This in vitro study aimed to evaluate the potential remineralizing effect of calcium sodium phosphosilicate (CSP), ginger, and turmeric. Materials and Methods: This in vitro study was designed to evaluate the remineralizing effects of various materials on the enamel of extracted human teeth. The aim was to compare the effectiveness of these different substances in promoting enamel remineralization. Enamel blocks were prepared and were divided into seven experimental groups: CSP, fluoride toothpaste, nonfluoride toothpaste, turmeric, ginger, fluoride varnish, and distilled water. In this study, sample mineralization is assessed through the quantitative photo-induced fluorescence test before demineralization, after demineralization, and after remineralization. Statistical analysis of the data was conducted using a one-factor analysis of variance test. The significance level was set at P < 0.05. Results: The best results were obtained by groups treated with turmeric (P < 0.0001), Enamelast fluoride varnish (P < 0.0001), and NovaMin (P < 0.01), as compared to other remineralizing treatments. Conclusion: While fluoride has undeniably revolutionized oral preventive care, the exploration of alternative products as natural substances and innovative compounds in recent scientific literature signals a shift in focus toward safer and potentially more diverse options.

New therapeutic target molecules for gastric and gastroesophageal junction cancer.

Molecularly targeted therapy for receptor tyrosine kinases (RTKs) has faced limitations in gastric and gastroesophageal junction (G/GEJ) cancer except for HER2-targeted agents, possibly due to inappropriate assay selection that has hindered identification of sensitive patients, in addition to coexisting genetic abnormalities as well as intratumoral heterogeneity. Immunohistochemistry of RTKs has, thus, proved largely unsuccessful for patient selection, and detection of RTK gene amplification as a true oncogenic driver is problematic given the small numbers of affected individuals. FGFR2 amplification is associated with poor prognosis in G/GEJ cancer, and immunohistochemistry of the FGFR2b protein isoform has proved effective for the detection of such FGFR2-dependent tumors. Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of ≥ 10%. Challenges to EGFR- and MET-targeted therapies are being tackled with antibody-drug conjugates (ADCs) and bispecific antibodies. CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials. Antibody-drug conjugates and ADCs that target CLDN18.2 are also being pursued for treatment of such patients. Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer.

Literature Review: Why do we need innovative design methods for future Mobility-as-a-Service (MaaS)?

Since its inception in 2014, Mobility-as-a-Service (MaaS) has been the subject of numerous trials and pilot studies globally, predominantly yielding favourable outcomes. However, specific issues that need to be clarified regarding its long-term development have been observed. This paper outlines the development stages of MaaS and the trials conducted across different nations. It highlights an ambiguity within user-centred design in the extant literature, specifically the inadequate exploration of user requirements. The discourse propounds the necessity for a paradigm shift in the research focus—advocating for a more profound inquiry into user needs instead of the prevailing emphasis on the advancement of enabling technologies and the operations of digital platforms. Given the increasing demand for personalisation within intricate transportation systems, comprehending users’ cognitive and psychological preferences emerges as paramount. Such an understanding is imperative to allow the service framework to adapt and identify principal offerings that resonate with user inclinations. Moreover, establishing an enduring dialogue between service providers and users is essential. The paper argues for design researchers to formulate and implement an innovative methodology that fosters the alignment of supply with demand, thereby enhancing the efficacy of Mobility as a Service.

Transition and management of patients with Duchenne Muscular Dystrophy: a narrative review based on Italian experts' opinion and real-world experience.

Duchenne Muscular Dystrophy (DMD) is a severe, progressive, X-linked disorder resulting in muscle wasting, progressive functional loss and cardiomyopathy. Therapeutic strategies feature glucocorticoid corticosteroids plus gene therapy/stop codon read-through, plus standards of care. Prolonged survival, delayed loss of ambulation (LoA), and innovative treatment prescriptions pose new clinical challenges, including identification of new outcome measures/targets and implementation of continuity of care. We report on the results of an Italian experts' meeting held in Rome, Italy on 20th April 2022. We aimed to: discuss challenges linked to transitioning from the ambulatory to the non-ambulatory phase, and from pediatric to adult care; collect experience on the importance of ongoing care and treatment in advanced disease stages and on the need to measure clinically relevant outcomes during disease progression after LoA. Following LoA the main management focus shifts to cardiac, respiratory, orthopaedics, nutrition and upper limbs function. More data on clinical needs, available treatments, standards of care, frequency of follow-up, and transition should be collected in order to facilitate management optimisation. Shared protocols should be developed, especially to improve patients' management in the acute setting. Transition from paediatric to adult services and from the ambulatory to the non-ambulatory phase require a multidisciplinary approach and the Identification of clinically meaningful outcome measures, which should be described in long-term longitudinal studies.

Genetically-encoded phase separation sensors for intracellular probing of biomolecular condensates.

Biomolecular condensates are dynamic membraneless compartments with enigmatic roles across intracellular phenomena. Intrinsically-disordered proteins (IDPs) often function as condensate scaffolds, fueled by their liquid-liquid phase separation (LLPS) dynamics. Intracellular probing of these condensates relies on live-cell imaging of IDP-scaffolds tagged with fluorescent proteins. Conformational heterogeneity in IDPs, however, renders them uniquely sensitive to molecular-level fusions, risking distortion of the native biophysical properties of IDP-scaffolds and their assemblies. Probing epidermal condensates in mouse skin, we recently introduced genetically encoded LLPS-sensors that circumvent the need for molecular-level tagging of skin IDPs. The concept of LLPS-sensors involves a shift in focus from subcellular tracking of IDP-scaffolds to higher-level observations that report on the assembly and liquid-dynamics of their condensates. Towards advancing the repertoire of intracellular LLPS-sensors, here we demonstrate biomolecular approaches for the evolution and tunability of epidermal LLPS-sensors and assess their impact in early and late stages of intracellular LLPS dynamics. Benchmarking against scaffold-bound fluorescent reporters, we found that tunable ultraweak scaffold-sensor interactions are key to the sensitive and innocuous probing of nascent and established biomolecular condensates. Our LLPS-sensitive tools pave the way for the high-fidelity intracellular probing of IDP-governed biomolecular condensates across biological systems.

Роль нарратива в новейшей русской драматургии

The research aims to answer the question: why is the role of storytelling increasing in the plays of young authors of the 2020s, rather than the showing that is appropriate for drama? The paper examines the genesis of drama narrativization in the 1990s-2010s (in the plays of Yevgeny Grishkovets, Nikolay Kolyada, Oleg Bogayev, etc.), traces the history of the issue in literary studies and criticism, and conducts a textual analysis of Polina Korotych’s play “Street” (2022) using the methods of modern narratology. The scientific novelty of the research lies in determining the specifics of narrativity in contemporary drama. The theoretical significance of the work is in applying the narratological analysis methodology to a modern dramatic text. As a result, it was found that contemporary drama often moves away from both showing-performativity and narrative as plot. The new narrativity of contemporary drama manifests itself in the fact that the play often turns into a narrative act from the perspective of the author or the characters. The events in the plays of Yevgeny Grishkovets, Dmitry Danilov, Polina Korotych, Olga Potapova, etc. become mental, not physical actions. The focus shifts to the verbalization of narration; the intrigue of the word becomes central in the reception of such plays. Similar phenomena are observed in other genres of contemporary literature, but drama is at the forefront of the modern literary process.

Blue Phase III from Bent-Core Liquid Crystals: Unveiling Thermal Stability & Unique Traits - A Comprehensive Review.

This review article mainly delves into the comprehensive development, thermal stabilization, characteristics, and applications of Blue Phase III (BPIII) derived from non-calamitic, mainly T-shaped and bent-core liquid crystals (BCLC). The discussion begins with discovering and characterizing various liquid crystal (LC) phases of BCLCs, emphasizing the significance of the nematic (N) phase in three and four-ring BCLCs. Following this, the focus shifts to the stabilization, properties, and potential applications of BPIII, particularly those derived from non-conventionalliquid crystals. The review highlights the exceptional electro-optical (E-O) properties of BPIII, including high Kerr constants and distinct phase transitions. Studies reveal the impact of chirality on thermal behavior, microscopic observations, and the influence of molecular structures on mesophase formation. Investigations into asymmetrical chiral liquid crystal diads and hydrogen-bonded complexes underscore the importance of molecular design in expanding BPIII ranges. Furthermore, achiral unsymmetrical BCLC designs reveal significant insights into the interplay between molecular structure, phase transitions, and E-O behavior.Additionally, the structural transformation and E-O properties of highly polar BCLCs are examined to stabilize BPIII at room temperature, achieving notable Kerr constants and low voltage requirements. These collective studies provide a thorough understanding of BPIII and its promising applications in materials science and technology.

Improving efficacy of repetitive transcranial magnetic stimulation for treatment of Parkinson disease gait disorders.

Parkinson disease (PD) is a neurodegenerative disorder that causes motor and cognitive deficits, presenting complex challenges for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a type of neuromodulation that can produce plastic changes in neural activity. rTMS has been trialed as a therapy to treat motor and non-motor symptoms in persons with Parkinson disease (PwP), particularly treatment-refractory postural instability and gait difficulties such as Freezing of Gait (FoG), but clinical outcomes have been variable. We suggest improving rTMS neuromodulation therapy for balance and gait abnormalities in PwP by targeting brain regions in cognitive-motor control networks. rTMS studies in PwP often targeted motor targets such as the primary motor cortex (M1) or supplementary motor area (SMA), overlooking network interactions involved in posture-gait control disorders. We propose a shift in focus toward alternative stimulation targets in basal ganglia-cortex-cerebellum networks involved in posture-gait control, emphasizing the dorsolateral prefrontal cortex (dlPFC), cerebellum (CB), and posterior parietal cortex (PPC) as potential targets. rTMS might also be more effective if administered during behavioral tasks designed to activate posture-gait control networks during stimulation. Optimizing stimulation parameters such as dosage and frequency as used clinically for the treatment of depression may also be useful. A network-level perspective suggests new directions for exploring optimal rTMS targets and parameters to maximize neural plasticity to treat postural instabilities and gait difficulties in PwP.

Enhancing 5G massive MIMO systems with EfficientNet‐B7‐powered deep learning‐driven beamforming

AbstractThe development of wireless communication systems is a challenging and constantly evolving field and the issue of gaining optimal performance is of utmost importance. This work intends to give a thorough and detailed description of massive MIMO technology and its properties, with a significant emphasis on digital beamforming (FDB) and hybrid beamforming (HBF) techniques and the potential of combining them with the most recent and exciting frontier of research: deep learning. On one hand, FDB provides accurate signal control but, on the other hand, it deals with substantial needs like high‐power consumption. This challenge makes the focus shift to HBF—the innovative technology successfully coupled with deep learning's powerful potential. The chosen research explores extensively the major areas of application and compatibility of this operating mode in a diverse range of operational situations in the interference environment as well as in different levels of noise conditions. Moreover, the study offers a comprehensive comparison, which is highly effective in exploring further methods that focus on improving spectral efficiency. Significantly, the “Proposed Method” is suggested to be at the leading position, which demonstrates superior performance. Showing outstanding generalization capability, versatile robustness, and efficiency of usage in the proposed framework rely on EfficientNet‐B7 as the major portion. This makes it adaptive to its dynamic surroundings and puts it as a powerful tool in the world of advanced connectivity and massive MIMO technology. Due to its core ability to respond to changes in conditions effectively and efficiently, the proposed framework is seen as one of the most powerful approaches that could be used to change wireless communication systems.

Age Bias & Female Leadership: Faulty Cheat Codes

This paper explores the intersection of age bias and gender bias in relation to female leadership. “Cheat codes” is a term originally applied to computer and video games to describe a code that, when used, allows the player to access features, level skips, or capabilities not otherwise available (Merriam-Webster, n.d.). As a metaphor, the term is meant to suggest a shortcut in decision-making toward a desired conclusion or outcome. In the context of this article, “faulty cheat codes” refer to society’s use of misinformed and unfair stereotypes as specious shortcuts to judge the abilities or qualifications of individuals based on their age, leading to incorrect conclusions or inappropriate actions. This piece highlights the detrimental effects of age bias on prominent female politicians, including Former Speaker Nancy Pelosi, and emphasizes the need for authentic conversations about cognitive abilities. The paper challenges the use of age as a flawed measure of competence and advocates for retiring negative stereotypes about aging. It also discusses the delayed entry of women into political office and the compounding effects of age and gender biases. By promoting positive narratives about aging and addressing ageism in our political discourse, society can create a more fair and inclusive political landscape that values the capabilities of individuals of all ages. The paper concludes by urging a shift in focus toward substantive political discussions and away from shallow indicators of competence based on age.

Multi-Criteria Decision Analysis for Sustainable Oil and Gas Infrastructure Decommissioning: A Systematic Review of Criteria Involved in the Process

The decommissioning of oil and gas (O&G, hereafter) facilities presents complex challenges when addressing the diverse needs of stakeholders. By synthesizing information from previous Multi-Criteria Decision Analysis (MCDA, hereafter) studies on decommissioning projects, this study aims to do the following: (a) formulate a structured set of criteria adaptable to MCDA for both offshore and onshore O&G decommissioning, (b) identify and analyze the evolving trends and regional disparities in MCDA for decommissioning, and (c) explore current O&G onshore decommissioning procedures and map specific criteria to these processes. Following a systematic literature review approach, this study analyzed 63 references across four stages from 2006 to 2024 and identified 158 criteria. These criteria were consolidated into a framework of 22 factors across dimensions comprising technical, environmental, societal, financial, health and safety considerations, and additional concerns from stakeholders. This study observed a significant focus shift from technical aspects to environmental considerations in decommissioning practices from 2011 onwards, reflecting growing awareness of sustainability. It also revealed regional differences, such as the technical emphasis in the North Sea and environmental concerns in Australia. Furthermore, this study refined O&G onshore decommissioning procedures and identified criteria gaps for further research, particularly in societal impact regarding public resource availability, recreational opportunities, and operating company reputation. The study provides a robust foundation for the development of future MCDA frameworks tailored to O&G infrastructure decommissioning projects, thus supporting long-term environmental and social sustainability.

Request Strategies of EFL University Learners at Jambi University

Making appropriate requests is a crucial aspect of pragmatic competence in language learning. This research aimed to investigate common request strategies used by EFL University Learners at Jambi University when making requests at the ages of 19, 20, and 21. This research design was an intrinsic case study to gain an in-depth knowledge of the phenomenon within its specific context. Data were collected through a written discourse completion test (DCT) from six participants, two from each age group. They were analyzed using discourse analysis, specifically focusing on the request strategies proposed by Blum-Kulka and Olshtain (1984), Blum-Kulka (1987), and Trosborg (1995). The findings reveal that most participants employed conventionally indirect (hearer-based) strategies in the form of ability, willingness, and permission (25 times, 83.3% frequency of semantic formulas) and conventionally indirect request (speaker-based) strategies in the form of desires/needs (3 times, 10% frequency of semantic formulas), followed by direct request strategies in the form of performatives (2 times, 6.6% frequency of semantic formulas). The research concluded that conventionally indirect request strategies (hearer-based) in the form of ability, willingness, and permission are mostly used in making requests among the studied age groups. It also found that age influenced how social power as a social variable maintained smooth social interactions in making requests. Those different age groups exhibited diversities in the use of directness level in making requests based on the age gap between the speaker and the hearer. Additionally, the research indicates how the focus shifts to the hearer's wants as the speaker casts requests in various direct forms. This suggests that people tend to make requests subtly, especially within academic settings. These findings have important implications for language teaching and pragmatics instruction, potentially influencing approaches to improving learner awareness of appropriate request strategies in academic and social contexts.

A novel and cost-effective model for cloud energy storage based on a dual storage setup in active distribution grid with resilience consideration

The rising occurrences of natural disasters, terrorist actions, and cyber-attacks that result in extensive, long-lasting, and expensive disruptions have necessitated a shift in focus towards the resilience of electrical grids for network operators. However, the task of designing a resilient network remains complex and costly. One potential solution to bolster resilience is the deployment of battery energy storage devices on the consumer side, known as distributed energy systems (DES). Despite its effectiveness, the high construction costs and lengthy payback period associated with investing in energy storage devices have led consumers to exhibit reluctance in adopting them. Cloud energy storage (CES) is an innovative and cost-effective solution to address those challenges. In the CES platform, investors install storage facilities in the network which can be rented by consumers to fulfill their needs and they become holders of the virtual batteries. By adopting this approach, consumers are relieved from the burden of maintenance, repair, and installation. While a single CES facility offers reduced costs and increased comfort for consumers, it compromises the resilience of the grid when compared to the Distributed Energy Storage (DES) mechanism. In order to bridge this gap, this paper proposes a dual CES model which serves as an intermediate solution between DES and single CES. The dual CES model strikes a balance between the resilience of the grid and cost-effectiveness. It provides a higher level of resilience compared to a single CES and a lower level compared to DES. Additionally, the costs associated with the dual CES model fall between that of a single CES and DES. This model not only increases the profit margin for investors but also enhances the overall comfort and well-being of consumers compared to the single CES. To validate the proposed model, a Mixed Integer Linear Programming (MILP) problem is formulated and simulated on the IEEE 33 bus network. Three cases are considered: DES, single CES, and dual CES. The results indicate that the dual CES reduces consumers' costs by 28 %, losses by 27 %, unsupplied load costs by 45 %, and return on investment by 33 %. Moreover, it increases the stability margin time by 2 intervals and improves robustness by 47 %.

Publications on COVID-19 and artificial intelligence: trends and lessons

Purpose: This study investigates shifts in scientific research focus, particularly the decline in COVID-19-related research and the rapid growth of artificial intelligence (AI) publications.Methods: We analyzed publication data from the Web of Science, comparing yearly publication counts for COVID-19 and AI research. The study also tracked changes in the impact factors of leading journals like <i>Science</i> and <i>Nature</i>, alongside those of top AI journals over the past decade. Additionally, we reviewed the top 10 most cited articles in 2021 from <i>Science</i> and <i>Nature</i> and the most influential AI publications from the past five years according to Google Scholar. The impact trends of the top 100 AI journals in computer science were also explored.Results: The analysis reveals a noticeable decline in COVID-19 related publications as the pandemic urgency diminishes, contrasted with the continued rapid growth of AI research. Impact factors for prestigious journals have shifted, with AI journals increasingly dominating the academic landscape. The review of top-cited articles further emphasizes these trends.Conclusion: Our findings indicate a significant shift in research priorities, with AI emerging as a dominant field poised to address future challenges, reflecting the evolving focus of the scientific community.

From expansion to efficiency: Machine learning-based forecasting of Japan's building material stocks under demographic declines

Japan's unique demographic trajectory, marked by population decline and aging, coupled with continued urbanization, presents distinct challenges for aligning built environment capacity with resource efficiency. This study aims to investigate the historical evolution and project future scenarios of building material stock (MS) and their spatial distribution across Japan's three major metropolitan areas. Through a comprehensive material flow and stock analysis, the historical accumulation of building materials from 2009 to 2020 was quantified, revealing a dominance of concrete and an increasing overall stock. The contributions of various driving factors to changes in construction areas were explored, identifying population dynamics as the predominant influence. Leveraging shared socioeconomic pathway scenarios (SSPs), this research forecasted building floor area and MS until 2050 under five distinct SSPs. The results indicated an overall reduction across all scenarios, yet with a continued concentration in high-density urban cores. The substantial gap between the highest and lowest projected MS scenarios highlighted opportunities for material conservation and emission reductions through sustainable practices. Sustainable urban development in densely populated regions necessitates a balance between infrastructure provision and environmental conservation, while in sparsely populated areas, the focus shifts to the efficient management and utilization of vacant properties and materials to cope with the impacts of significant population declines. By offering insights into the building floor area and MS implications of Japan's demographic changes, this study underscores the necessity of sustainable urban planning and resource management strategies to navigate the challenges posed by demographic shifts, ultimately contributing to sustainable development and environmental conservation goals.

HDAC6 inhibition disrupts HDAC6-P300 interaction reshaping the cancer chromatin landscape

BackgroundHistone deacetylases (HDACs) are crucial regulators of gene expression, DNA synthesis, and cellular processes, making them essential targets in cancer research. HDAC6, specifically, influences protein stability and chromatin dynamics. Despite HDAC6’s potential therapeutic value, its exact role in gene regulation and chromatin remodeling needs further clarification. This study examines how HDAC6 inactivation influences lysine acetyltransferase P300 stabilization and subsequent effects on chromatin structure and function in cancer cells.Methods and resultsWe employed the HDAC6 inhibitor ITF3756, siRNA, or CRISPR/Cas9 gene editing to inactivate HDAC6 in different epigenomic backgrounds. Constantly, this inactivation led to significant changes in chromatin accessibility, particularly increased acetylation of histone H3 lysines 9, 14, and 27 (ATAC-seq and H3K27Ac ChIP-seq analysis). Transcriptomics, proteomics, and gene ontology analysis revealed gene changes in cell proliferation, adhesion, migration, and apoptosis. Significantly, HDAC6 inactivation altered P300 ubiquitination, stabilizing P300 and leading to downregulating genes critical for cancer cell survival.ConclusionsOur study highlights the substantial impact of HDAC6 inactivation on the chromatin landscape of cancer cells and suggests a role for P300 in contributing to the anticancer effects. The stabilization of P300 with HDAC6 inhibition proposes a potential shift in therapeutic focus from HDAC6 itself to its interaction with P300. This finding opens new avenues for developing targeted cancer therapies, improving our understanding of epigenetic mechanisms in cancer cells.

Validation of the implementation of phased-array heating systems in Plan2Heat.

Hyperthermia treatment planning can be supportive to ensure treatment quality, provided reliable prediction of the heating characteristics (i.e., focus size and effects of phase-amplitude and frequency steering) of the device concerned is possible. This study validates the predictions made by the treatment planning system Plan2Heat for various clinically used phased-array systems. The evaluated heating systems were AMC-2, AMC-4/ALBA-4D (Med-Logix srl, Rome, Italy), BSD Sigma-30, and Sigma-60 (Pyrexar Medical, Salt Lake City, UT, USA). Plan2Heat was used for specific absorption rate (SAR) simulations in phantoms representing measurement set-ups reported in the literature. SAR profiles from published measurement data based on E‑field or temperature rise were used to compare the device-specific heating characteristics predicted by Plan2Heat. Plan2Heat is able to predict the correct location and size of the SAR focus, as determined by phase-amplitude settings and operating frequency. Measured effects of phase-amplitude steering on focus shifts (i.e., local SAR minima or maxima) were also correctly reflected in treatment planning predictions. Deviations between measurements and simulations were typically < 10-20%, which is within the range of experimental uncertainty for such phased-array measurements. Plan2Heat is capable of adequately predicting the heating characteristics of the AMC‑2, AMC-4/ALBA-4D, BSD Sigma-30, and Sigma-60 phased-array systems routinely used in clinical hyperthermia.

Chinese Fashion in China’s Fashion Magazines (2005-2015)

This paper explores the status of Chinese fashion media from 2005 to 2015 to understand the role of fashion discourse and information flows in mobilizing activity and meaning in the Chinese fashion industry. By examining ten-year issues of two fashion magazines, Vogue China and iLook, alongside interviews with two fashion media workers, this research reveals that during this period, the diffusion channels for Chinese fashion media are experiencing significant change, with a shift in focus to the presentation of more localized fashion content and the creation of a closer relationship between Chinese fashion media and the Chinese fashion industry. The rise of online fashion media has provided an unprecedented way of engaging Chinese consumers with Chinese fashion, supporting a two-way information flow and a new dimension of interaction. Despite this development, the continuing dominance of fashion retailing and consumption, much of this being comprised of global fashion brands, and the scarcity of fashion professionals in China continue to marginalize Chinese fashion discourse.