Search Results (630)

The Long Interspersed Element-1 (L1) retrotransposon is an ancient genetic parasite that comprises a significant part of the human genome. ORF2p is a multifunctional enzyme with endonuclease (EN) and reverse transcriptase (RT) activities that mediate target-primed reverse transcription of RNA into DNA. Structural studies of LINE-1 ORF2p consistently show a single Mg²⁺ cation in the reverse transcriptase active site, conflicting with the common DNA polymerase mechanism which involves two divalent cations. We explored a reaction pathway of the DNA elongation based on the recent high-resolution ternary complex structure of the ORF2p. The combined quantum and molecular mechanics approach at the QM (PBE0-D3/6-31G**)/MM (CHARMM) level is employed for biased umbrella sampling molecular dynamics simulations followed by umbrella integration utilized to obtain the free energy profile. The nucleotidyl transfer reaction proceeds in a single step with a free energy barrier of 15.1 ± 0.8 kcal/mol, and 7.8 ± 1.2 kcal/mol product stabilization relative to reagents. Concerted nucleophilic attack by DNA O3′ and proton transfer to Asp703 occur without a second catalytic metal ion. Estimated rate constant ∼60 s⁻¹ aligns with RT kinetics, while analysis of the Laplacian of the electron density along the cleaving P-O bond identifies a dissociative mechanism. Full article

The intensified exposure to high temperature in urban areas, resulting from the combination of heat waves and the urban heat island (UHI) effect, necessitates a deeper understanding of the climate–health relationship. This knowledge directly influences the strategies employed by policy makers and urban planners in their efforts to regenerate cities and protect their population. Nature-based solutions and the widely accepted 15 min city model, characterized by a polycentric structure, should drive the implementation of effective adaptation policies, especially given the persistent delay in mitigation efforts. However, it is less clear whether current or future policies are adequately structured to broadly address the complex forms of social vulnerability. A prime example of this complexity is the demographic shift observed since the mid-20th century, characterized by a relative increase in the elderly population, and a shrinking youth demographic. While extensive literature addresses the physiological impacts of heat wave on human health, evidence regarding the neuro-psychological and cognitive implications for elderly individuals, who frequently suffer from chronic diseases, remains less comprehensive and more fragmented. The purpose of this concise review is to emphasize that crucial findings on the climate–health relationship, particularly concerning the elderly, have often been developed within disciplinary silos. The lack of comprehensive interdisciplinary integration coupled with an incomplete understanding of the full spectrum of vulnerabilities (encompassing both physiological and cognitive) may lead to urban policies that are egalitarian in principle but fail to achieve true equity in practice. This review aims to bridge this gap by highlighting the need for a more integrated approach to urban policy and regeneration. Full article

Introduction: The number of older adults living with frailty undergoing gastrointestinal cancer surgery is increasing. To address the unique needs of the population, a whole pathway perioperative geriatrics strategy—PRIME—was developed to integrate geriatric principles into surgical care. The objective of this study was to evaluate the implementation of PRIME using validated structural, process, and outcome quality indicators. Materials and Methods: This retrospective cohort study included 106 consecutive patients aged 70 years and older who underwent gastrointestinal surgery for cancer or pre-cancerous lesions at a single institution between 1 July 2020 and 5 October 2023. The whole pathway perioperative geriatrics strategy, PRIME, includes preoperative comprehensive geriatric assessment (CGA), collaborative care between surgery, geriatrics, and anesthesia, and post-operative co-management. Implementation was evaluated using validated structural, process, and outcome quality indicators. Results: Most structural indicators (five of eight) were implemented. In terms of process indicators, 96.2% (n = 102) received CGA prior to or within 24 h of admission. Adherence to screening was high: 97.2% for dementia, 96.2% for functional status, and 95.3% for frailty. The median number interventions resulting from CGA was 17 (IQR 14–20). Serious complication, delirium, and functional decline occurred in 19.8%, 27.1%, and 19.8%, respectively. Conclusions: Implementation of a perioperative geriatrics strategy for older adults undergoing gastrointestinal cancer/pre-cancer lesion surgery is feasible, with high adherence to structural and process quality indicators. Full article

Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that γδ T cells contribute to EILV/CHIKV-induced host protection against WT CHIKV infection. TCRδ^−/− mice, which are deficient of γδ T cells, had impaired CHIKV-specific CD8⁺ T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8⁺ T cells of EILV/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, γδ T cells expanded quickly in response to EILV/CHIKV vaccination. TCRδ^−/− mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, γδ T cells contribute to EILV/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV/CHIKV vaccination. Full article

The Directed Energy Deposition (DED) process has demonstrated high efficiency in manufacturing steel parts with complex geometries and superior capabilities. Understanding the complex interplays of alloy compositions, cooling rates, grain sizes, thermal histories, and mechanical properties remains a significant challenge during DED processing. Interpretable and data-driven modeling has proven effective in tackling this challenge, as machine learning (ML) algorithms continue to advance in capturing complex property structural relationships. However, accurately predicting the prime mechanical properties, including ultimate tensile strength (UTS), yield strength (YS), and hardness value (HV), remains a challenging task due to the complex and non-linear relationships among process parameters, material constituents, grain size, cooling rates, and thermal history. This study introduces an ML model capable of accurately predicting the UTS, YS, and HV of a material dataset comprising 4900 simulation analyses generated using the “JMatPro” software, with input parameters including material compositions, grain size, cooling rates, and temperature, all of which are relevant to DED-processed low-alloy steels. Subsequently, an ML model is developed using the generated dataset. The proposed framework incorporates a physics-based DED-specific feature that leverages “JMatPro” simulations to extract key input parameters such as material composition, grain size, cooling rate, and thermal properties relevant to mechanical behavior. This approach integrates a suite of flexible ML algorithms along with customized evaluation metrics to form a robust foundation to predict mechanical properties. In parallel, explicit data-driven models are constructed using Multivariable Linear Regression (MVLR), Polynomial Regression (PR), Multi-Layer Perceptron Regressor (MLPR), XGBoost, and classification models to provide transparent and analytical insight into the mechanical property predictions of DED-processed low-alloy steels. Full article

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

Canvases and preparation layers consist of diverse materials that respond differently to mechanical stress. In a canvas painting, elongations and shrinkages can cause deformations—either recoverable or permanent—as well as shear stresses and potential cracks, which may weaken the overall structure. This study aims to better understand the interaction between the canvas and preparatory strata in terms of mechanical behavior. To achieve this, a set of canvases and the same types of canvases with preparation layers were selected. Two types of linen and two types of polycotton were chosen to represent contemporary materials currently available in fine-art stores. Additionally, an accelerated aging process was applied to the samples to compare their mechanical response before and after aging. By examining the mechanical behavior of both primed and unprimed canvases through dynamometric tests, a method to evaluate the mechanical degradation attributable to the ground layer has been developed and explained in detail. This method is applicable to cases with similar characteristics. Analysis of the force/elongation graphs for the ground layer allows for the calculation of how this layer evolves with increasing elongation and how the mechanical degradation worsens. The results highlight the differing mechanical behaviors among the analyzed canvas types in both the warp and weft directions, as well as the degradation values resulting from both the aging process and the dynamometric testing of the canvases and ground layers. Full article

The soft-reset process, or a sequence of charge emissions from a floating storage node through a transistor biased in a subthreshold bias condition, is modeled by a master (Kolmogorov–Bateman) equation. The Coulomb interaction energy after each one-charge emission leads to a stepwise potential increase, giving correlated emission rates represented by Boltzmann factors. The governing probability distribution function is a hypoexponential type, and its cumulants describe characteristics of the single-charge Coulomb interaction at room temperature on a mesoscopic scale. The cumulants are further extended into a complex domain. Starting from three fundamental assumptions, i.e., the generation of non-degenerated states due to single-charge Coulomb energy, the Markovian property of each emission event, and the independence of each state, a moment function is identified as a product of mutually prime elements (algebraically termed as prime ideals) comprising the eigenvalues or the lifetimes of the emission states. Then, the algebraic structure of the moment function is found to be highly analogous to that of an integer uniquely factored into prime numbers. Treating the lifetimes as analogs of the prime numbers, two types of zeta functions are constructed. Standard analyses of the zeta functions analogous to the prime number problem or the Riemann Hypothesis are performed. For the zeta functions, the analyticity and poles are specified, and the functional equations are derived. Also, the zeta functions are found to be equivalent to the analytic extension of the cumulants. Finally, between the number of emitted charges and the lifetime, a logarithmic relation analogous to the prime number theorem is derived. Full article

Let $\mathfrak{R}$ be a commutative ring with identity $1\ne 0$. The weakly zero-divisor graph of $\mathfrak{R}$, denoted $W_{\Gamma }(\mathfrak{R})$, is the simple undirected graph whose vertex set consists of the nonzero zero-divisors of $\mathfrak{R}$, where two distinct vertices $\mathfrak{a}$ and $\mathfrak{b}$ are adjacent if and only if there exist $r\in \mathrm{ann}(\mathfrak{a})$ and $s\in \mathrm{ann}(\mathfrak{b})$ such that $rs=0$. In this paper, we study the signless Laplacian spectrum of $W_{\Gamma }({\mathbb{Z}}_n)$ for several composite forms of n, including $n=p^2{q}^2$, $n=p^{2}qr$, $n=p^m{q}^m$ and $n=p^{m}qr$, where $p, q, r$ are distinct primes and $m\ge 2$. By using generalized join decomposition and quotient matrix methods, we obtain explicit eigenvalue formulas for each case, along with structural bounds, spectral integrality conditions and Nordhaus–Gaddum-type inequalities. Illustrative examples with computed spectra are provided to validate the theoretical results, demonstrating the interplay between the algebraic structure of ${\mathbb{Z}}_n$ and the spectral properties of its weakly zero-divisor graph. Full article

Natural killer (NK) cells are promising candidates for adoptive immunotherapy, but their clinical application requires standardized expansion protocols that yield functional cells in sufficient numbers. This study examined how initial seeding density and donor-intrinsic variability affect NK cell proliferation and receptor phenotype during in vitro expansion in a G-Rex^® 24-well plate under IL-2 stimulation. NK cells from healthy donors were analyzed longitudinally by flow cytometry, and targeted SNP sequencing of selected receptor genes (IL2RA, IL2RB, FCGR3A, NCR1, KLRK1, and ICAM-1) was performed to assess potential genetic contributions. A seeding density of 2.0 × 10⁶ cells/cm² promoted high expansion rates and favorable expression of activating receptors including CD16a, NKp46, and NKG2D. Nonetheless, marked inter-donor differences were observed. Some donors exhibited impaired proliferation and aberrant receptor expression, possibly associated with high-priority SNPs and distinct haplotype structures. Others showed robust proliferation despite the absence of identifiable genetic drivers, suggesting the involvement of variants in other genes or non-genetic mechanisms such as epigenetic priming or adaptive NK-cell differentiation. These results highlight the influence of both culture conditions and donor-intrinsic factors on NK-cell expansion outcomes. Integrating phenotypic and genetic analyses may improve the reproducibility and personalization of NK-cell-based manufacturing protocols for therapeutic use. Full article

Sustainability in the construction and building sector with the use of greener and more eco-friendly building materials can minimize carbon footprint, which is one of the prime goals of the twenty-first century. The use of natural fibers in ancient and traditional buildings and structures is not new, but in the last fifty years, only man-made fibers have predominantly occupied the market for structural retrofitting or upgrading. This research investigated the potential of utilizing natural fibers, particularly jute fiber products, to enhance masonry’s thermal and structural characteristics. The study meticulously investigated the utilization of materials such as jute net (with a mesh size of 2.5 cm × 1.25 cm), jute fiber diatons, and jute fiber composite mortar (with 1% jute fiber with respect to the dry mortar mass) in the context of masonry upgrading. The research evaluated the structural and thermal performance of these upgraded walls. Notably, the implementation of natural fiber textile-reinforced mortar (NFTRM) resulted in an astounding increase of over 500% in the load-bearing capacity of the walls, while simultaneously enhancing insulation by more than 36%. Furthermore, the study involved a meticulous analysis of crack patterns during in-plane cyclic testing utilizing the advanced Digital Image Correlation (DIC) tool. The upgraded/retrofitted wall exhibited a maximum crack width of approximately 7.84 mm, primarily along the diagonal region. Full article

Laser powder bed fusion (L-PBF) is a unique technology that enables manufacturing geometrically complex metal alloys, including Ti-6Al-4V parts. The microstructure of Ti-6Al-4V is determined by its localized thermal history, which is affected by not only the L-PBF process but also the geometry of the part. Understanding the microstructure at specific locations in complex geometries is of great importance in predicting the mechanical performance of Ti-6Al-4V parts. This work investigates the effects of geometric features on the local microstructure. Three geometries, namely, holes, overhangs, and penholders, were designed and used for this study. Three different laser powers, namely 150 W, 250 W, and 350 W, were set to print those geometries. The use of a lower laser power results in improved print quality. While the martensite phase dominates the bulk of the L-PBF Ti-6Al-4V parts, a fine α+β lamellar structure can form at down-skin regions of printed horizontal holes and overhangs. Moreover, the direction of the columnar prime β grain can shift due to directional heat dissipation. The local microstructural evolution after heat treatment is investigated as well. Full article

There has been much interest in the mathematical investigation of critical sets and unavoidable sets in Latin Squares, Sudoku, and their applications to practical problems in areas such as agriculture and cryptology. This paper considers the associated structures of Strictly Concentric Magic Squares (SCMSs) and Prime Strictly Concentric Magic Squares (PSCMSs). A framework of formal definitions is given that leads to the definitions of critical sets and unavoidable sets. Minimal critical sets are of interest in Latin Squares, and in this article, the cardinality of minimal critical sets of SCMS is given for all n, n odd. Two families of unavoidable sets are established for SCMS, leading to a complete classification of unavoidable sets of minimum PSCMS of order 5. Full article

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

This paper introduces a novel method for selecting parameters of finite fields formed by 2 × 2 matrices over a finite field of integers modulo a prime p. The method aims to simultaneously determine both the field parameters and primitive elements, thereby optimizing the construction of cryptographic algorithms. The proposed approach leverages the properties of quadratic residues and non-residues, simplifying the process of finding matrix field parameters while maintaining computational efficiency. The method is particularly effective when the prime number p is either a Mersenne prime or (p + 1)/2 is also a prime. This study demonstrates that the resulting matrix fields can be practically computed, offering a high degree of flexibility for cryptographic protocols such as key agreement and secure data transmission. Compared to previous methods, the new method reduces the parameter search space and provides a structured way to identify primitive elements without the need for a separate search procedure. The findings have significant implications for the development of efficient cryptographic systems using matrix-based finite fields. Full article