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Abstract p53-mediated cell cycle arrest during DNA damage is dependent on the induction of p21 protein, encoded by the CDKN1A gene. p21 inhibits cyclin-dependent kinases required for cell cycle progression to guarantee accurate repair of DNA lesions. Hence, fine-tuning of p21 levels is crucial to preserve genomic stability. Currently, the multilayered regulation of p21 levels during DNA damage is not fully understood. Herein, we identify the human RNA binding motif protein 42 (RBM42) as a regulator of p21 levels during DNA damage. Genome-wide transcriptome and interactome analysis reveals that RBM42 alters the expression of p53-regulated genes during DNA damage. Specifically, we demonstrate that RBM42 facilitates CDKN1A splicing by counteracting the splicing inhibitory effect of RBM4 protein. Unexpectedly, we also show that RBM42, underpins translation of various splicing targets, including CDKN1A. Concordantly, transcriptome-wide mapping of RBM42-RNA interactions using eCLIP further substantiates the dual function of RBM42 in regulating splicing and translation of its target genes, including CDKN1A. Collectively, our data show that RBM42 couples splicing and translation machineries to fine-tune gene expression during DNA damage response.

Introduction: Vitiligo is a skin disease affecting melanocytes, characterised by the development of depigmented skin lesions. Methods: We used bibliometric analysis (BA) to identify high-quality research articles on vitiligo using criteria such as total citations, annual citations (AC) and journal impact factors. We extracted the 100 most-cited articles on vitiligo using the Web of Science database and analysed the results using Microsoft Excel 2019. Our search was limited to manuscript titles or abstracts containing the keyword ‘vitiligo’. The data extracted information such as title, author, year of publication, journal of publication, total citations and research area. We also calculated the AC rate to account for bias. Results: A total of 6,189 studies were retrieved. The 100 most-cited articles were published between 1976 and 2017. Of those, 75 were original articles, with the research foci being mainly pathogenesis (29%) and treatment (26%). The US was the most prolific publisher overall. We separately retrieved the highest cited data from 2018 to 2022 and tabled the top 10. Of those, 50% were original articles. Discussion: Our BA shows that developed countries published most of the vitiligo literature. Additionally, recent research has focused on targeted treatment approaches. We also highlight the increasing paediatric vitiligo research, specifically regarding therapies.

Plasmonic nanoparticles (NPs) have attracted significant attention due to their unique optical properties and broad optoelectronic and photonic applications. We investigate modifications of emission in hybrid structures formed by 60 nm silver NPs and GaN planar nanowires (NWs). Bare GaN NWs exhibit photoluminescence (PL) spectra dominated by broad bands peaking at ∼3.44 eV and ∼3.33 eV, attributed to basal plane stacking faults. In hybrids, two new narrow PL lines appear at 3.36 and 3.31 eV, resulting in PL enhancement at these energies. While the 3.36 eV line in hybrid structures can be explained using the Fröhlich resonance approximation based on the electric dipole concept, the appearance of two features at 3.36 and 3.31 eV indicates the splitting of resonance lines. This phenomenon is explained in framework of theoretical model based on the interaction of the dipole with its charge image, taking into account the quadrupole moment of the silver sphere and the quadrupole field of the charge image. A good agreement is obtained between the calculated Fröhlich resonance frequencies and the experimental PL lines in hybrid structures.

The combination of plasmonic nanoparticles and semiconductor substrates changes the properties of hybrid structures that can be used for various applications in optoelectronics, photonics, and sensing. Structures formed by colloidal Ag nanoparticles (NPs) with a size of 60 nm and planar GaN nanowires (NWs) have been studied by optical spectroscopy. GaN NWs have been grown using selective-area metalorganic vapor phase epitaxy. A modification of the emission spectra of hybrid structures has been observed. In the vicinity of the Ag NPs, a new emission line appears at 3.36 eV. To explain the experimental results, a model considering the Fröhlich resonance approximation is suggested. The effective medium approach is used to describe the enhancement of emission features near the GaN band gap.

Abstract Gallium oxide is a promising semiconductor with great potential for efficient power electronics due to its ultra-wide band gap and high breakdown electric field. Optimization of halide vapor phase epitaxy growth of heteroepitaxial $$\upbeta$$ β -Ga2O3 layers is demonstrated using a simulation model to predict the distribution of the ratio of gallium to oxygen precursors inside the reactor chamber. The best structural quality is obtained for layers grown at 825–850 °C and with a III/VI precursor ratio of 0.2. Although the structural and optical properties are similar, the surface morphology is more deteriorated for the $$\upbeta$$ β -Ga2O3 layers grown on 5 degree off-axis sapphire substrates compared to on-axis samples even for optimized process parameters. Cathodoluminescence with a peak at 3.3 eV is typical for unintentionally doped n-type $$\upbeta$$ β -Ga2O3 and shows the appearance of additional emissions in blue and green region at ~ 3.0, ~ 2.8, ~ 2.6 and ~ 2.4 eV, especially when the growth temperatures is lowered to 800–825 °C. Estimation of the band gap energy to ~ 4.65 eV from absorption indicates a high density of vacancy defects.

The field of perovskite light-emitting diodes witnesses rapid development in both device processing strategies and performances. Here Wang et al. develop high-quality perovskite-molecule composite thin films and achieve high quantum efficiency of 17.3% and half-lifetime of 100 h.

Developing growth techniques for the manufacture of wide band gap III-nitrides semiconductors is important for the further improvement of optoelectronic applications. A plasma-assisted halide phase vapor epitaxy (PA-HVPE) approach is demonstrated for the manufacture of undoped and In-doped GaN layers at ~600 °C. A dielectric barrier discharge (DBD) plasma source is utilized for the low-temperature activation of ammonia. The use of the plasma source at a growth temperature of ~600 °C increases the growth rate from ~1.2 to ~4–5 µm/h. Furthermore, the possibility for the growth of InGaN at ~600 °C has been studied. Precursors of GaCl and InCl/InCl3 are formed in situ in the reactor by flowing HCl gas over a melt of metallic Ga and In, respectively. The In concentration was low, in the order of a few percent, as the incorporation of In is reduced by plasma due to the activation of chlorine-containing species that etch the relatively poorly bonded In atoms. Nevertheless, the approach of using plasma for ammonia activation is a very promising approach to growing epitaxial III-nitrides at low temperatures.

The development of growth processes for the synthesis of high-quality epitaxial layers is one of the requirements for utilizing the ultrawide band gap semiconductor Ga2O3 for high-voltage, high-power electronics. A halide vapor phase epitaxy (HVPE) process used to grow β-Ga2O3 layer was optimized by modifying the gas inlet, resulting in improved growth uniformity. A conventional tube acting as an inlet for the Ga precursor GaCl gas was replaced with a shower head with four outlets at 45 degrees to the horizontal axis of the reactor. The modification was performed based on numerical calculations of the three-dimensional distribution of gases inside the growth chamber with different designs of the GaCl precursor inlet. It was shown that variation in the Ga/O ratio over the substrate holder was ~10% for a shower head compared with ~40% for a tube. In addition, growth with a tube leads to the film thickness varying by a factor of ~4 depending on the position on the holder, whereas when using a shower head, the thickness of the grown Ga2O3 layers became much more uniform with a total spread of just ~30% over the entire substrate holder.

The main focus of this article is the explanatory power that music has in Confucianism according to the Analects (Lunyu 論語) and The Classic of Rites (Liji 禮記), which is reaffirmed in the Song Dynasty by Zhou Dunyi in the chapters on music in Tongshu (通書, The Penetrating Book). The article suggests that Tongshu’s chapters on music demonstrate the non-linear and non-metaphysical musical nature of Confucianism. According to this suggestion, the chapters introduce a dynamic, living model for the Confucian Way, on its own terms. This musical model supports the early Confucian vision of a multifaceted person, progressing in a multi-dimensional Way within a multi-layered polysemic world. Progressing along the Way, self-cultivation appears as one’s task to develop the various musical potentialities inherent in her or himself. The article opens with the epistemological idea of “musical knowledge” acquired by attuned hearing that winds up in a creative, peacemaking heart. Next, it introduces the ontological idea of a government that models cosmic harmony, depicting the leader as having an orchestral conductor’s aptitude; last, it presents a pragmatic perspective on the idea of musical education through the rules of propriety, depicting the practitioner as a skillful music player.

Background: The study describes preschoolers' digital home environment, focusing on parent-child writing interactions using a smartphone and exploring its contribution to children's early literacy. Methods: Participants were 65 Israeli preschoolers (M = 62.37 months) from middle SES and one of their parents. Parents responded to questionnaires assessing the digital home environment (prevalence of digital devices, parental involvement in selecting digital content, children's independent digital activities and screen time). Parents were video recorded while assisting their children in writing a shopping list of three products using a smartphone (keyboard). We analysed how parents helped children segment words into their respective sounds (grapho-phonemic mediation) and type letters independently (printing mediation) and their reference to the orthography. Children's literacy skills (letter knowledge, phonological awareness and early writing) were assessed individually. Results: Findings showed that the homes are rich with technology and children are engaged daily with various digital devices. The level of parental involvement in selecting their children's digital content and the quality of their writing support positively related to children's early literacy skills. Children's independent digital activities were negatively related to their literacy skills. Hierarchical regression analyses showed that the nature of parental writing support predicted children's early literacy beyond parental involvement in selecting digital content and children's independent digital activities. Conclusions: The study reveals the benefits of parental involvement in their children's digital world and highlights the strength of parental writing support and the potential of parent-child digital activities in promoting children's early literacy.

The purpose of this work is to investigate the possibilities of climbing higher obstacles while maintaining the overall dimensions of a walking robot through design improvements and experiments. An original concept for the design of a walking robot with a minimum number of motors is presented. Geometric and force constraints for overcoming an obstacle and the conditions for maintaining static stability are determined. Experiments for overcoming a vertical obstacle are conducted with a 3D printed model. The 3D printed robot feet with different shapes and materials are used. The results of the experiments are presented graphically as a percentage of success against a baseline model. In this study, a dimensionless index to compare the height of the overcome obstacle and the dimensions of the robot is introduced. It allows to objectively compare the possibilities of overcoming obstacles between various types of mobile robots. Conclusions and guidelines for design improvements are made.

Abstract We have developed a method to fabricate GaN planar nanowires and cavities by combination of Focused Ion Beam (FIB) patterning of the substrate followed by Metal Organic Vapor Phase Epitaxy (MOVPE). The method includes depositing a silicon nitride mask on a sapphire substrate, etching of the trenches in the mask by FIB with a diameter of 40 nm with subsequent MOVPE growth of GaN within trenches. It was observed that the growth rate of GaN is substantially increased due to enhanced bulk diffusion of the growth precursor therefore the model for analysis of the growth rate was developed. The GaN strips fabricated by this method demonstrate effective luminescence properties. The structures demonstrate enhancement of spontaneous emission via formation of Fabry-Perot modes.

Tau is a microtubule-associated protein often found in neurofibrillary tangles (NFTs) in the brains of patients with Alzheimers disease. Beyond this context, mounting evidence suggests that tau localizes into the nucleus, where it may play a role in DNA protection and heterochromatin regulation. The molecular mechanisms behind these observations are currently unclear. Using in vitro biophysical experiments, here we demonstrate that tau can undergo liquid-liquid phase separation (LLPS) with DNA, mononucleosomes, and reconstituted nucleosome arrays under low salt conditions. Low concentrations of tau promote chromatin compaction and protect DNA from digestion. While the material state of samples at physiological salt is dominated by chromatin oligomerization, tau can still associate strongly and reversibly with nucleosome arrays. These properties are driven by taus strong interactions with linker and nucleosomal DNA. In addition, tau co-localizes into droplets formed by nucleosome arrays and phosphorylated HP1α, a key heterochromatin constituent thought to function through an LLPS mechanism. Importantly, LLPS and chromatin interactions are disrupted by aberrant tau hyperphosphorylation. These biophysical properties suggest that tau may directly impact DNA and chromatin accessibility and that loss of these interactions could contribute to the aberrant nuclear effects seen in tau pathology.

Abstract Novel hybrid organic-inorganic nanostructures fabricated to utilize non-radiative resonant energy transfer mechanism are considered to be extremely attractive for a variety of light emitters for down converting of ultaviolet light and for photovoltaic applications since they can be much more efficient compared to devices grown with common design. Organic-inorganic hybrid structures based on green polyfluorene (F8BT) and GaN (0001) nanorods grown by magnetron sputtering on Si (111) substrates are studied. In such nanorods, stacking faults can form periodic polymorphic quantum wells characterized by bright luminescence. In difference to GaN exciton emission, the recombination rate for the stacking fault related emission increases in the presence of polyfluorene film, which can be understood in terms of Förster interaction mechanism. From comparison of dynamic properties of the stacking fault related luminescence in the hybrid structures and in the bare GaN nanorods, the pumping efficiency of non-radiative resonant energy transfer in hybrids was estimated to be as high as 35% at low temperatures.

This article discusses Israeli Bible teachers' perceptions of the 'otherness' and their actions in a reality in which teachers are required to balance the tension between being experts in the field of knowledge, coping with a state curriculum that promotes a faith-religious worldview, and acting as educators in promoting discourse dealing with social issues of inclusion, respect, and tolerance for the 'other'. The research is qualitative-interpretive, based on interviews with 13 teachers. It focuses on describing and explaining Bible teachers' perceptions and interpreting their actions. Findings point to two main perceptions: (1) A perception that transcends the boundaries of biblical academic discourse and fosters a moral dialogue of integration, tolerance, openness, and awareness of the 'other' as part of the Bible teacher's role. (2) A perception focused only on biblical discourse and refrains from dealing with issues of 'otherness' in the lesson. This research offers new tools and courses of action to implement these perceptions. Its conclusions may encourage teachers to develop pedagogical flexibility and an ability to navigate through issues of 'otherness' while responding to social, value, and moral issues that arise spontaneously in the multicultural dialogue in Bible lessons.

Educational discourses have embraced therapeutic discourse, a psychology-based system of assumptions about the self, its boundaries, development and social relations. While scholars have debated the virtues of this therapeutic turn, there has been little empirical study of therapeutic discourse in teacher pedagogical discourse. This article, using theoretical frameworks of teacher learning and the sociology of therapeutic discourse and employing linguistic ethnographic methods, features close analysis of therapeutic discourse in teacher workplace conversations. The focal case, in which a teacher consults with her colleagues regarding a non-compliant student, features four episodes of therapeutic reasoning (ETRs) in which various therapeutic logics are employed. Analysis uncovered three central manifestations of therapeutic discourse especially pertinent to education: the role of emotions; perceptions of the self; and temporality. Attending to these manifestations in each ETR reveals conditions under which they may enhance or impede potential for teacher learning and pedagogic action. When therapeutic modes of reasoning are deployed by teachers to discuss their problems of practice, they are found to be multifaceted, elastic, and to bear potential for agentive teacher action under certain conditions. This article calls for a more nuanced, temporally-sensitive perspective on therapeutic discourse in education, and addresses implications for theory and practice.

In the nucleus, transcriptionally silent genes are sequestered into heterochromatin compartments comprising nucleosomes decorated with histone H3 Lys9 trimethylation and a protein called HP1α. This protein can form liquid-liquid droplets in vitro and potentially organize heterochromatin through a phase separation mechanism that is promoted by phosphorylation. Elucidating the molecular interactions that drive HP1α phase separation and its consequences on nucleosome structure and dynamics has been challenging due to the viscous and heterogeneous nature of such assemblies. Here, we tackle this problem by a combination of solution and solid-state NMR spectroscopy, which allows us to dissect the interactions of phosphorylated HP1α with nucleosomes in the context of phase separation. Our experiments indicate that phosphorylated human HP1α does not cause any major rearrangements to the nucleosome core, in contrast to the yeast homologue Swi6. Instead, HP1α interacts specifically with the methylated H3 tails and slows the dynamics of the H4 tails. Our results shed light on how phosphorylated HP1α proteins may regulate the heterochromatin landscape, while our approach provides an atomic resolution view of a heterogeneous and dynamic biological system regulated by a complex network of interactions and post-translational modifications.

BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (

Despite extensive investigations, some patients have no identifiable cause for their cholestatic liver enzyme abnormalities. The aim of this study was to document the clinical, laboratory, radiologic and histologic features of adult patients with idiopathic cholestasis (AIC). A computerised database of referred patients to a tertiary care hospital outpatient department for assessment of hepatobiliary disorders between 2005 and 2015 was employed to identify and describe features associated with AIC. Of 6,560 patient referrals, sufficient documentation to warrant a diagnosis of AIC was present in 17 (0.26%) cases. Of the 17, a disproportionate number were Canadian Inuit (7/60, 12% Inuit referrals vs. 10/6,500, 0.16% non-Inuit referrals, p

Composite nanostructures of coral reefs like p-type NiO/n-type ZnO were synthesized on fluorine-doped tin oxide glass substrates by hydrothermal growth. Structural characterization was performed by field emission scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray diffraction techniques. This investigation shows that the adopted synthesis leads to high crystalline quality nanostructures. The morphological study shows that the coral reefs like nanostructures are densely packed on the ZnO nanorods. Cathodoluminescence (CL) spectra for the synthesized composite nanostructures are dominated mainly by a broad interstitial defect related luminescence centered at ~630 nm. Spatially resolved CL images reveal that the luminescence of the decorated ZnO nanostructures is enhanced by the presence of the NiO.

Elucidating the structure and interactions of proteins in native environments is a fundamental goal of structural biology. Nuclear magnetic resonance (NMR) spectroscopy is well suited for this task but often suffers from low sensitivity, especially in complex biological settings. Here, we use a sensitivity-enhancement technique called dynamic nuclear polarization (DNP) to overcome this challenge. We apply DNP to capture the membrane interactions of the outer membrane protein Ail, a key component of the host invasion pathway of Yersinia pestis. We show that the DNP-enhanced NMR spectra of Ail in native bacterial cell envelopes are well resolved and enriched in correlations that are invisible in conventional solid-state NMR experiments. Furthermore, we demonstrate the ability of DNP to capture elusive interactions between the protein and the surrounding lipopolysaccharide layer. Our results support a model where the extracellular loop arginine residues remodel the membrane environment, a process that is crucial for host invasion and pathogenesis.