Search Results (706)

This study proposes an optimized approach to address the high computational demands and significant GPU memory consumption commonly associated with Transformer-based models. Building upon the HAT framework, a shallow feature extraction module is enhanced to improve local feature representation, thereby achieving a better balance between computational efficiency and model performance. Furthermore, inspired by self-supervised learning (SSL) techniques and incorporating shift operations, the proposed method effectively reduces both the number of parameters and the overall computational load. The resulting ISR-SHA model is trained and evaluated on the DF2K dataset, achieving approximately a 30% reduction in FLOPs and parameter count compared to the original HAT model, with only marginal declines in PSNR (0.02) and SSIM (0.0006). Experimental results confirm that ISR-SHA outperforms most existing super-resolution models in terms of performance while significantly enhancing computational efficiency without compromising output quality. Full article

The radical-mediated intramolecular translocation of cyano groups has been recognized as a useful tool for the site-selective functionalization of organic molecules. The process is believed to proceed through the addition of an in situ-generated carbon-centered radical to the nitrile triple bond, followed by the β-scission of the resulting cyclic iminyl radical intermediate to relocate the cyano group and produce a more stable carbon radical for further elaboration. Beginning in the early 1960s and continuing for the next forty years, the research in this particular area has seen a surge of growth during the past two decades with advancements in radical chemistry and photocatalysis. The present article attempts to conduct a comprehensive review of existing studies on this topic by covering the literature from 1961 to 2025. The procedures developed for the purpose are grouped and discussed in four sections according to the strategies used to generate the initial carbon radicals, which include (i) hydrogen-atom transfer (HAT), (ii) radical addition to the π system, (iii) halogen-atom transfer (XAT), and (iv) the homolytic fission of a C-C single bond. In each section, a specific emphasis will be placed on reaction conditions, substrate scopes, and mechanisms. Full article

The acute rise in temperature due to marine heatwaves has a strong impact on marine phytoplankton. To determine whether these effects depend on ambient temperature and cell size, we acclimated two diatom species, smaller Thalassiosira pseudonana (Hasle and Heimdal, 1970) and larger Thalassiosira rotula (Meunier, 1910), at low (LAT), medium (MAT) and high ambient temperatures (HAT) and examined their physiochemical and transcriptional responses to temperature rise (AT + 6 °C). The specific growth rate (µ) of smaller cells was increased by 32% due to temperature rise at LAT, but decreased by 13% at HAT, with the stimulatory and inhibitory extent being ~50% less than that of larger cells. At LAT, chlorophyll a (Chl a), carotenoid (Car) and carbon (POC) contents were increased in smaller cells due to temperature rise, but were decreased in larger cells; at HAT, Chl a and Car were increased in both smaller and larger cells and POC was increased in only smaller cells. At LAT, temperature rise led to a disproportionate increase in photosynthesis and dark respiration, resulting in an increase in carbon utilization efficiency (CUE) in smaller cells and a decrease in CUE in larger cells; at HAT, there was a decrease in CUE in both the smaller and larger cells, but to a lesser extent in the former than in the latter. Our results also show that smaller cells cope with the acute temperature rise mainly by strengthening their enzyme activity (e.g., the antioxidant system) and conservatively regulating their metabolism, while larger cells mainly regulate their photosynthetic and central carbon metabolism. Moreover, larger cells can outperform their smaller counterparts when the temperature rise occurs at lower ambient temperature. Full article

Shaking off the forgetfulness towards the methodological power of inosine-mediated error-prone PCR (epPCR), this study reintroduces an often-underappreciated method as a considerably powerful approach for generating aptamer libraries from a single decameric ATCG-repeat-oligonucleotide. The aim was to demonstrate that this simple way of creating sequence diversity was suitable for delivering functional starting libraries for a set of ten whole-cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) processes. This epPCR method uses inosine to introduce targeted mutations, avoiding the need for commercial oligo pools or large-scale synthesis. We applied this method to a “universal aptamer” and subjected the three resulting libraries to two rounds of selection against ten diverse targets including probiotic and pathogenic bacteria (Gram-negative and -positive) as well as human cell lines. The enriched aptamers exhibited new binding specificities, demonstrating that the approach supports functional selection. Much like dusting off an old tool and finding it perfectly suited for a modern task, this work shows that revisiting established techniques can address current challenges in aptamer development. Our main finding is that epPCR provides a robust, cost-effective strategy for generating starting libraries and lowers the barrier for initiating successful SELEX campaigns. Full article

Cowpea (Vigna unguiculata L.) pods are an underexploited by-product of legume production with significant antioxidant potential. Their recovery and characterization support sustainable waste valorization in agri-food systems. This study aimed to optimize the extraction of phenolic compounds (PCs) with antioxidant capacity (AOC) from cowpea pods and identify key bioactives through experimental and theoretical approaches. First, high-intensity ultrasound extraction was optimized using response surface methodology with ethanol–water mixtures. Under optimal conditions (20% amplitude, 15 min, 50% ethanol), the ethanolic extract (Eo) showed higher total phenolic content (TPC) and AOC than the aqueous extract (Wo). Subsequently, fractionation by Sephadex LH-20 chromatography yielded fractions E2 and W2 with enhanced TPC and AOC. Phytochemical profiling showed that E2 was enriched in caftaric acid, p-coumaric acid, and morin, while W2 had higher levels of caftaric, p-coumaric, and caffeic acids. Finally, density functional theory was used to assess thermodynamic parameters linked to antioxidant mechanisms (HAT, SET-PT, SPLET), revealing morin as the most effective radical scavenger, followed by caffeic and caftaric acids. These findings show that AOC depends not only on phenolic concentration but also on molecular structure and solvent interactions. Thus, cowpea pod extracts and fractions hold promise for antioxidant-rich formulations in food, nutraceutical, or cosmetic applications. Full article

Nucleobase and nucleoside analogs are critical components of antimetabolite chemotherapy treatments used to disrupt DNA replication and induce apoptosis in rapidly proliferating cancer cells. However, the development of resistance to these agents remains a major clinical challenge. This review explores the epigenetic mechanisms that contribute to acquired chemoresistance, focusing on DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These epigenetic alterations regulate key processes such as DNA repair, drug metabolism, cell transport, and autophagy, enabling cancer cells to survive and resist therapeutic pressure. We highlight how dysregulation of DNA methyltransferases (DNMTs) and histone acetyltransferases (HATs) modulates expression of transporters (e.g., hENT1, ABCB1), DNA repair enzymes (e.g., Polβ, BRCA1/2), and autophagy-related genes (e.g., CSNK2A1, BNIP3). Furthermore, emerging roles for long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in regulating nucleoside export and DNA damage response pathways underscore their relevance as therapeutic targets. The interplay of these epigenetic modifications drives resistance to agents such as gemcitabine and 5-fluorouracil across multiple tumor types. We also discuss recent progress in therapeutic interventions, including DNMT and HDAC inhibitors, RNA-based therapeutics, and CRISPR-based epigenome editing. Full article

When Wittgenstein (2009, § 116) writes that “[w]hat we do is to bring words back from their metaphysical to their everyday use”, many will presumably read this is an anti-religious statement. According to the everyday use of the word “metaphysical”, religion is metaphysical, one would then argue. However, the target of Wittgensteinian investigations is language “on holiday” (2009, § 38), that is, when language does not do any job. This explains why Wittgenstein can claim that philosophy “leaves everything as it is” (2009, § 124): removing “a wheel that can be turned though nothing else moves with it” means removing something that is “not part of the mechanism” and therefore does not change the mechanism (2009, § 271). In other words, “metaphysics” does here not stand for a specific subject matter, such as religion. But what does it mean that something is “not part of the mechanism”? How does one show that something is not? Is it possible that religion is an instance of language on holiday? These questions are far more complex than they may seem at first, and the answer to the last question is not a general one—ultimately, it has to be answered in the first person. How do these difficulties manifest themselves? After a methodological discussion of the above points (sec. 1), two sections (2–3) discuss two examples of contexts in which these difficulties come into view. The discussions of these two examples thus aim to clarify what the distinction between the metaphysical and the non-metaphysical amounts to in two specific cases. In particular, the difference between a relation to a belief and to a person is highlighted. Paying attention to this difference is one way of getting out of the difficult constellation of religious belief and metaphysics. Full article

Inverse lithography technology (ILT) based on the gradient descent (GD) algorithm, which is a classical local optimal method, can effectively improve the lithographic imaging fidelity. However, due to the low-pass filtering effect of the lithography imaging system, GD, although able to converge quickly, is prone to fall into the local optimum for the information in the corner region of complex patterns. Considering the high-frequency information of the corner region during the optimization process, this paper proposes a resolution layering method to improve the efficiency of GD-based ILT algorithms. A corner-rounding-inspired target retargeting strategy is used to compensate for the over-optimization defect of GD for inversely optimizing the complex pattern layout. Furthermore, for ensuring the manufacturability of masks, differentiable top-hat and bottom-hat operations are employed to improve the optimization efficiency of the proposed method. To confirm the superiority of the proposed method, multiple optimization methods of ILT were compared. Numerical experiments show that the proposed method has higher optimization efficiency and effectively avoids the over-optimization. Full article

Background/Objectives: Hepatic artery thrombosis (HAT) is a serious vascular complication in patients undergoing orthotopic liver transplantation (OLT). It is associated with a high risk of graft loss, re-transplantation (re-OLT), and mortality. This study aimed to evaluate the incidence and management of HAT, analyzing potential risk factors. The secondary objectives included quantifying 90-day postoperative morbidity and mortality rates. Methods: In this retrospective, observational, single-center study, data from liver transplant donors and recipients who underwent OLT between 2004 and 2024 were analyzed. HAT was classified as early (e-HAT, ≤30 days) or late (l-HAT, >30 days). Univariate statistical analysis was performed to identify the risk factors associated with HAT occurrence. Multivariate analysis was not performed due to the small number of HAT events, which would increase the risk of model overfitting. Results: In the 20 year study period, a total of 532 OLTs were performed, including 37 re-OLTs. The rates of major morbidity, reoperation, and mortality within 90 days were 44.5%, 22.3%, and 7.1%, respectively. HAT occurred in 2.4% of cases (e-HAT: 1.6%; l-HAT: 0.7%). Among e-HAT cases, 66.6% were asymptomatic and identified through routine postoperative Doppler ultrasound. All e-HAT cases were surgically treated, with a re-OLT rate of 33.3%. Three l-HAT cases required re-OLT. Overall, the HAT-related mortality and re-OLT rates were 7.6% and 46.1%, respectively. At a follow-up of 86 months, the rate of graft loss was 9.2%, and the rate of post-OLT survival was 77%. Patients who developed HAT had a higher donor-to-recipient body weight ratio and longer warm ischemia times (WITs). Additionally, patients undergoing re-OLT had a higher risk of developing HAT. Conclusions: Although the incidence of HAT is low, its clinical consequences are severe. Early Doppler ultrasound surveillance is crucial for detecting e-HAT and preventing graft loss. A high donor-to-recipient body weight ratio, a prolonged warm ischemia time, and re-OLT seem to be associated with a high risk of HAT. Full article

Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. Full article

Rapid and accurate detection of primary waves (P-waves) using high-rate Global Navigation Satellite System (GNSS) data is essential for earthquake monitoring and tsunami early warning systems, where traditional seismic methods are less effective in noisy environments. We applied a wavelet-based method using a Mexican hat wavelet and dynamic threshold to thoroughly analyze the three-component displacement waveforms of the 2009 Padang, 2012 Simeulue, and 2018 Palu Indonesian earthquakes. Data from the Sumatran GPS Array and Indonesian Continuously Operating Reference Stations were analyzed to determine accurate displacements and P-waves. Validation with Indonesian geophysical agency seismic records indicated reliable detection of the horizontal component, with a time delay of less than 90 s, whereas the vertical component detection was inconsistent, owing to noise. Spectrogram analysis revealed P-wave energy in the pseudo-frequency range of 0.02–0.5 Hz and confirmed the method’s sensitivity to low-frequency signals. This approach illustrates the utility of GNSS data as a complement to seismic networks for the rapid characterization of earthquakes in complex tectonic regions. Improving the vertical component noise suppression might further help secure their utility in real-time early warning systems. Full article

In utero exposure to per- and polyfluoroalkyl substances (PFAS) presents significant health concerns, primarily through their role in inducing epigenetic modifications that have lasting consequences. This review aims to elucidate the impact of prenatal PFAS exposure on epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation, focusing on developmental and long-term health outcomes. The review synthesizes findings from various studies that link PFAS exposure to alterations in DNA methylation in fetal tissues, such as changes in the methylation of genes like IGF2 and MEST, which are linked to disruptions in growth, neurodevelopment, immune function, and metabolic regulation, potentially increasing the risk of diseases such as diabetes and obesity. We also highlight the compound-specific effects of different PFAS, such as PFOS and PFOA, each showing unique impacts on epigenetic profiles, suggesting varied health risks. Special attention is given to hormonal disruption, oxidative stress, and changes in histone-modifying enzymes such as histone acetyltransferases (HATs) and deacetylases (HDACs), which are pathways through which PFAS influence fetal development. Additionally, we discuss PFAS-induced epigenetic changes in placental tissues, which can alter fetal nutrient supply and hormone regulation. Despite accumulating evidence, significant knowledge gaps remain, particularly regarding the persistence of these changes across the lifespan and potential sex-specific susceptibilities. We explore how advancements in epigenome-wide association studies could bridge these gaps, providing a robust framework for linking prenatal environmental exposures to lifetime health outcomes. Future research directions and regulatory strategies are also discussed, emphasizing the need for intervention to protect vulnerable populations from these environmental pollutants. Full article

Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders. Full article

Thin steel plates with stiffeners are widely used in shipbuilding, aeronautics, and civil construction due to their lightness and structural strength. This study presents a numerical model developed using ANSYS Mechanical APDL with SHELL281 finite elements to evaluate the deflection of thin steel plates with trapezoidal-shaped box-beam stiffeners, known as hat-stiffened plates. The structure is analyzed under a uniformly distributed load perpendicular to the plate, with simply supported boundary conditions. The constructal design method combined with the exhaustive search technique is employed to optimize the geometry. A volume fraction of 30% is used, transferring material from the reference plate (without stiffeners) to the stiffeners, defining parameters such as number, height, and thickness—considered degrees of freedom. The stiffener angle is fixed at 120°. The results show that increasing stiffener height and reducing thickness generally improve structural performance by reducing deflections. The best configuration with transverse stiffeners reduced deflection by 97.15% compared to the reference plate, and by 79.27% compared to the best longitudinal configuration from previous studies. Therefore, transverse stiffeners were more effective than longitudinal ones. This study highlights the importance of stiffener orientation and geometry in the structural optimization of thin steel plates. Full article

Hydrogen atom transfer (HAT), a concerted charge transfer involving two elementary particles, a proton and an electron, plays a key role in many areas of chemistry and biochemistry. A molecular dynamics study based on density functional theory was performed to investigate the reaction mechanism of hydrogen atom transfer from quercetin anions to the hydroxyl radical in a neutral aqueous media. Intrinsic bond orbital (IBO) analysis of a series of structures obtained from trajectories was performed in simulations in which the reaction occurred, and the electron flow along the reaction coordinate was determined and applied to investigate the reaction mechanism. The reaction in the simulations proceeded rapidly as proton-coupled electron transfer (PCET) or electron transfer–proton transfer (ET-PT) depending on the initial position and solvation of the reactants. Full article