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mrccis a versatile suite of quantum chemistry programs designed for accurate ab initioand density functional theory (DFT) calculations. This contribution outlines the general features and recent developments of the package. The most popular features include the open-ended coupled-cluster (CC) code, state-of-the-art CC singles and doubles with perturbative triples [CCSD(T)], second-order algebraic-diagrammatic construction, and combined wave function theory-DFT approaches. Cost-reduction techniques are implemented, such as natural orbital (NO), local NO (LNO), and natural auxiliary function approximations, which significantly decrease the computational demands of these methods. This paper also details the method developments made over the past five years, including efficient schemes to approach the complete basis set limit for CCSD(T) and the extension of our LNO-CCSD(T) method to open-shell systems. Additionally, we discuss the new approximations introduced to accelerate the self-consistent field procedure and the cost-reduction techniques elaborated for analytic gradient calculations at various levels. Furthermore, embedding techniques and novel range-separated double-hybrid functionals are presented for excited-state calculations, while the extension of the theories established to describe core excitations and ionized states is also discussed. For academic purposes, the program and its source code are available free of charge, and its commercial use is also facilitated. more...

High-density microelectrode arrays have opened new possibilities for systems neuroscience, but brain motion relative to the array poses challenges for downstream analyses. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from action potential data, DREDge enables automated, high-temporal-resolution motion tracking in local field potential data. In human intraoperative recordings, DREDge’s local field potential-based tracking reliably recovered evoked potentials and single-unit spike sorting. In recordings of deep probe insertions in nonhuman primates, DREDge tracked motion across centimeters of tissue and several brain regions while mapping single-unit electrophysiological features. DREDge reliably improved motion correction in acute mouse recordings, especially in those made with a recent ultrahigh-density probe. Applying DREDge to recordings from chronic implantations in mice yielded stable motion tracking despite changes in neural activity between experimental sessions. These advances enable automated, scalable registration of electrophysiological data across species, probes and drift types, providing a foundation for downstream analyses of these rich datasets. more...

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70–90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance. more...

A novel visible-light-induced hydrodesulfurization of a thioacetal was developed. The reaction operates under mild conditions using user-friendly tris(trimethylsilyl)silane as the reductant and a low catalyst loading of photoactive 4CzIPN. The expansion of the reaction scope was thwarted by the operationally hazardous nature of the process, occasionally producing fire. Careful examination of reaction mixtures allowed to identify silane (SiH4) as the likely culprit causing the pyrophoricity. more...

Perforation of the outer mitochondrial membrane triggered by BAX and facilitated by its main activator cBID is a fundamental process in cell apoptosis. Here, we employ a newly designed correlative approach based on a combination of a fluorescence cross correlation binding with a calcein permeabilization assay to understand the involvement of BAX in pore formation under oxidative stress conditions. To mimic the oxidative stress, we enriched liposomal membranes by phosphatidylcholines with truncated sn-2 acyl chains terminated by a carboxyl or aldehyde moiety. Our observations revealed that oxidative stress enhances proapoptotic conditions involving accelerated pore-opening kinetics. This enhancement is achieved through increased recruitment of BAX to the membrane and facilitation of BAX membrane insertion. Despite these effects, the fundamental mechanism of pore formation remained unchanged, suggesting an all-or-none mechanism. In line with this mechanism, we demonstrated that the minimal number of BAX molecules at the membrane necessary for pore formation remains constant regardless of BAX activation by cBID or the presence of oxidized lipids. Overall, our findings give a comprehensive picture of the molecular mechanisms underlying apoptotic pore formation and highlight the selective amplifying role of oxidized lipids in triggering formation of membrane pores. more...

The taxonomic status of the Neotropical bat genus Trachopsis reevaluated through an integrated study that incorporates morphological, morphometric, and molecular data across its extensive geographic range. Our research, which included previously unexamined geographical regions, revealed substantial insights into the diversity within Trachops. Genetic and morphological results support elevation of T. cirrhosus ehrhardti, distributed within the Atlantic Forest of Brazil, to species status due to differences in southeastern Brazil specimens. Conversely, our analysis found insufficient evidence to maintain the subspecific distinction of T. c. coffini, which lacks diagnosable morphological characters and is not genetically distinct from T. c. cirrhosusacross its distribution range. Additionally, our findings challenge a prior notion of latitudinal differentiation in body size in T. cirrhosus, because specimens from western South America and northeastern South America exhibit similar sizes to those from Central America. These results underscore the importance of revising the taxonomic framework for this bat genus—contributing to a more precise understanding of its evolutionary relationships—and further enhancing conservation efforts considering potential threats to the newly recognized species in the imperiled Atlantic Forest of Brazil.This study aims to clarify the taxonomic status and geographic distribution of Trachops cirrhosus, the Fringe-lipped Bat, through phylogenetic and morphological analyses. Our findings suggest changes to previous subspecific descriptions, and description of a new species. more...

SVA (SINE (short interspersed nuclear element)–VNTR (variable number of tandem repeats)–Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system. more...

Exenatide (Ex4), a GLP-1 incretin mimetic polypeptide, is an effective therapeutic agent against diabetes and obesity. We highlight the indirect role of Ex4’s structure-stabilizing Trp-cage (Tc) motif in governing GLP-1 receptor (GLP-1R) signal transduction. We use various Ex4 derivatives to explore how Tc compactness influences thermal stability, aggregation, enhancement of insulin secretion, and GLP-1R binding. We found that Ex4 variants decorated with fortified Tc motifs exhibit increased resistance to unfolding and aggregation but show an inverse relationship between the bioactivity and stability. Molecular dynamics simulations coupled with a rigid-body segmentation protocol to analyze dynamic interconnectedness revealed that the constrained Tc motifs remain intact within the receptor–ligand complexes but interfere with one of the major stabilizing contacts and recognition loci on the extracellular side of GLP-1R, dislodging the N-terminal activating region of the hormone mimetics, and restrict the free movement of TM6, the main signal transduction device of GLP-1R. more...

Endocrine disruptors are potential environmental contaminants that can cause toxicity in aquatic ecosystems, so the Water Framework Directive has established limits for these compounds. During our research, 41 bacterial strains were isolated and identified from sewage effluent and tested for their degradation capacities for bisphenol A, 17β-estradiol, and nonylphenol. All the isolated bacteria belonged to the Gammaproteobacteria class of Pseudomonadota phylum (members of Citrobacter, Enterobacter, Escherichia, Klebsiella, Kluyvera, Leclercia, Raoultella, Shigella. Acinetobacter, Aeromonas, and Pseudomonasgenera). During the experiments, only strains HF17, HF18 (Pseudomonas aeruginosa), and HF31 (Citrobacter freundii) were unable to grow on these compounds, all other bacterial strains could grow in the presence of the investigated endocrine disruptors. Based on the genomic analysis of the type strains, a set of genes involving aromatic compound degradation was detected, among the peripheral metabolic pathways, the quinate and benzoate degradation pathways proved to be widespread, among the central aromatic intermediates metabolism, the catechol branch of the beta-ketoadipate pathway was the most dominant. Pseudomonas fulvaHF16 strain could utilize the investigated endocrine disruptors: bisphenol A by 34%, 17β-estradiol by 52%, and nonylphenol by 54%. more...

The most important intermediate of methylene diphenyl diisocyanate (MDI), the most widely and quantitatively produced isocyanate in the world, is methylenedianiline (MDA). MDA is industrially produced from the reaction of aniline and formaldehyde catalysed by inorganic acids, most commonly HCl. The reaction parameters used during the synthesis of MDA have a fundamental impact on the quality parameters of the resulting MDA product mixture, and thus on the properties of the final MDI product mixture as well. Although MDA is an important industrial intermediate, currently its synthesis at the industrial level is based on empirical rules, knowledge and rule of thumbs, the effects of production parameters and their magnitude on product properties are not known and not published in the literature. In this study, the correlations between the independent operating parameters and dependent product quality parameters characterizing the MDA mixture were explored by developing different regression models with the use of experimental laboratory synthesis data in order to support the industrial synthesis process with easily deployable models with satisfactorily high accuracy. After investigating the laboratory experiment data from a total of 46 individual laboratory experiments, it was found that with machine learning models almost all of the independent parameters can be described with satisfactory accuracy. The models presented in this work demonstrate that it is possible to develop models that can be used to adjust the ring distribution, isomer ratios and selectivity of the reaction with minimising by-product quantities according to market demands or to different objective functions by fine-tuning the production parameters., thus achieving an optimal product portfolio and operating cost for the industrial process as well. more...

In this paper, novel position sensorless state estimators with improved robustness to permanent magnet (PM) flux linkage variations in permanent magnet synchronous machines (PMSMs) are presented. Unlike state estimators using conventional infinite inertia or electromechanical models, the estimators presented here can also estimate the PM flux linkage, so they are not sensitive to its uncertainty. For each models used for state estimation, a detailed observability study is presented. Due to the nonlinear models, extended and unscented Kalman filter algorithms are used for the implementation. To compare the sensitivity of conventional and proposed state estimators to uncertainty in electrical parameters, numerical simulations are carried out. In addition, the computational burden of the estimators is compared by real-time execution. more...

The escalation of code plagiarism in computer science education has necessitated the development of more sophisticated detection methods, particularly for binary files which pose a unique challenge. This study introduces a novel approach to plagiarism detection through binary decomposition, which decompiles binary files back into high-level code to reveal similarities that may be hidden at the binary level. The methodology is crucial for scenarios where students submit compiled programs, enabling the application of traditional code similarity analysis methods to detect instances of plagiarism. Statistical data on code similarity among student submissions in a C programming course are presented, highlighting the urgent need for robust detection strategies. This paper explores the ethical implications of plagiarism, the technical challenges of binary file analysis, and the potential for applying this technique across various programming languages and educational contexts. more...

We describe Phalacrocorax bakonyiensisn. sp. an extinct member of the cormorants (Phalacrocoracidae). The fossil was found in 2021 by geologist János Futó in the sediments of a small cave cavity on the side of Várhegy in Sümeg, a part of the Bakony Mountains of West Hungary, where Late Miocene (MN11–12) vertebrate fossils have been found in the past decades. The total number of bone fragments collected was 14, of which only three can be identified. Two of these belong to adults and one, due to its poor preservation and size, to a very young specimen. more...

Everything in the world is about risk, from individual decisions to global manipulations, which is of fundamental importance in a nuclear power plant environment. The question is whether, in a given situation, this risk is acceptable or no longer acceptable. In some respects, the risk analysis applied to construction projects differs from the risk analysis applied to nuclear installations. For nuclear installations, the risk as such is primarily nuclear risk. In view of this, for investments involving a nuclear installation, the risk analysis to be carried out must be carried out at two separate levels. The first level is the traditional construction risk analysis, and then as a second level, each risk item should be classified from a nuclear risk point of view. In this study, the nuclear exposure of construction risks will be presented. more...

Ammonia is a crucial component in the biogeochemical cycle of nitrogen, with various harmful environmental effects. The primary source of NH3is agriculture, particularly the application of fertilizers in crop cultivation. A significant portion of the nitrogen content from fertilizers, when applied without utilization, is released into the environment, becoming a source of loss and pollution. Emissions occur both from the soil and through stomata. However, if the compensation point concentration of the apoplast is lower than the nearby concentration of NH3, stomatal absorption occurs. Additionally, cuticular deposition processes and bidirectional exchange of droplets on foliage (rain, dew, guttation) contribute to the ammonia cycle within the canopy. Depending on the conditions, a considerable amount of the ammonia emitted by the soil can be recaptured by the canopy. This recapture helps reduce both nitrogen loss from fertilizers and environmental pollution. This article presents a general review of models simulating the bi-directional exchange of ammonia in the soil—plant—atmosphere system, focusing on determining ammonia loss and amounts recycled by the canopy. The review covers concepts and parameterization of various model inputs. more...

Domino Knoevenagel-cyclization reactions of N-arylcinnamylamines were carried out with active methylene reagents, which took place with five competing cyclization mechanisms: intramolecular hetero Diels–Alder reaction, stepwise polar [2 + 2] cycloaddition, styryl or aza-Diels–Alder reactions followed by rearomatization, and [1,5]-hydride shift-6-endo cyclization. In the stepwise aza-Diels–Alder reaction, the N-vinylpyridinium moiety acted as an azadiene, producing a condensed heterocycle with tetrahydroquinolizinium and tetrahydroquiniline subunits. Antiproliferative activity with low micromolar IC50values was identified for some of the novel scaffolds. more...

Currently, the antimicrobial activity of essential oils (EOs) is an outstanding research field due to antibiotic resistance of microorganisms. Thin-layer chromatography‒direct bioautography (TLC‒DB) is an effective, fast method to find components with antimicrobial activity in a mixture of plant compounds, e.g.,in EOs. The volatility and hydrophobic characters of EOs require special experimental conditions, and disc diffusion assay is not appropriate to explore the antimicrobial activity of them. The aim of this study was to use “R” mutants, which are more sensitive to synthetic antimicrobial drugs, in DB to increase the sensitivity of this method. Our hypothesis was that these mutants show sensitivity to some EOs (thyme, clove, and peppermint) as well. The chemical composition of our tested EOs was measured with gas chromatography‒mass spectrometry (GC‒MS). The main compounds (39.8% thymol, 78.8% eugenol, and 50.4% menthol) of EOs showed notable antibacterial activity in TLC‒DB. Based on our results, we suggest to use Salmonella minnesotaRe595 rough strain as test bacterium in bioautography, because it showed the highest sensitivity to the tested antibiotics (gentamicin and cephalexin) and EOs. Furthermore, this rough mutant could make TLC‒DB more faster, because only 4 h incubation time was enough to detect the inhibition zones of the active compounds used in this study. more...

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle. more...

In the present study, we investigated food resource niche parameters and the degree of specialization of two local Western Barn Owl (Tyto alba)populations in two different demographic phases as the crash (2015–2016) and outbreak (2019–2020) of the Common Vole (Microtus arvalis). The study was conducted in two parts of the Transdanubian region of Hungary, namely in Duna-Drava National Park (DDNP) in the southeastern part, and in Fertő-Hanság National Park (FHNP) in the north-western part. For the analysis, we used food consumption data of 20–20 randomly selected breeding pairs from the DDNP population, while 14 and 17 breeding pairs in FHNP population in the crash and outbreak periods, respectively. Since the small mammal consumption of owls represented 99.3% of the total number of individuals, only data of small mammals as main food resource were taken into account during the analysis. Based on a trait-based framework which taking into account the resemblance between resources, Rao’s quadratic entropy metrics was used to estimate the food resource niche breadth at local owl populations and the breeding pair level. The small mammal resource utilization of owls was dependent on populations. The niche breadth of DDNP population was significantly smaller than FHNP population. The estimated niche overlap at the individual level was significantly different between the two populations. The calculated value of specialization of barn owl populations was significantly higher in north-western than south-eastern population. The niche breadth of the owl population living in the DDNP was significantly higher during the crash period. In contrast, the estimated niche breadth of the population living in FHNP did not differ significantly between the two demographic phases. Based on our result, the applied trait-based framework of resource niche pattern analysis demonstrated that the differences of niche breadth were explored in more detail by this method between the local Barn Owl populations of different geographical region. more...

In recent years, Model‐Based Systems Engineering (MBSE) practices have been applied in various industries to design, simulate and verify complex systems. The verification and validation (V&V) of such systems engineering models are crucial to develop high‐quality systems. However, this is a challenging problem due to the complexity of the models and semantic differences in how different tools interpret the models, which can undermine the validity of the obtained results if they go undiscovered. To address these issues, we propose (i) a subset of the SysML language for which the practical semantic integrity of tools can be achieved and (ii) a cloud‐based V&V framework for this subset, lifting verification to an industrial scale. We demonstrate the feasibility of our approach on an industrial‐scale model from the aerospace domain and summarize the lessons learned during transitioning formal verification tools to an industrial context. more...

Potentially toxic elements (PTEs) in ecosystems and construction materials pose a significant environmental concern. Various qualitative and quantitative techniques are employed to analyse PTEs in a sample. This study explores an innovative approach that incorporates PTE (Cd, Zn, Cu, Pb) adsorbent ash, specifically adsorbed paper ash (APA) and adsorbed mulch ash (AMA), into mortar composites. This approach offers several advantages, including reduced reliance on waste landfills, energy recovery during the ashing process, and immobilisation of PTEs within a cement matrix. This study evaluated the elemental and microstructural characteristics of mortar composites incorporated with adsorbed ash by using a scanning electron microscope (SEM) equipped with energy-dispersive X-ray spectroscopy (EDS), followed by analysing the elemental maps with ImageJ software version 1.8.0. Parallel experiments were conducted to measure the leaching of mortar composites. The total elemental content of PTEs in the leachate solutions was quantified using an inductively coupled plasma-optical emission spectrometer (ICP-OES). The differences in adsorption capacity and leaching of PTEs observed between paper and mulch can be ascribed to their distinct affinities, which are influenced by the recorded pH levels. The examined elemental mapping revealed a consistent distribution across the APA and AMA mortar matrix structures, with greater intensity than the blank mortar sample. Furthermore, there is a reverse correlation between the order of percentage area coverage of the immobilised elements and the order of leaching, indicating that the PTEs were successfully immobilised. The percentage of PTE area coverage within AMA mortar composites followed the subsequent order: Pb > Cd > Zn > Cu, constituting 32.1 %, 28.6 %, 13.8 %, and 12.4 %, respectively. This order was also observed in the blank mortar composite, with percentages of 12.5 %, 8.6 %, 4.5 %, and 4.2 %, respectively. In the case of the APA mortar composite, the percentage of area coverage followed a different sequence: Cd > Pb > Zn > Cu, representing 27.7 %, 26.6 %, 14.5 %, and 14.1 %, respectively. The results also demonstrated notable improvements in the microstructure of the mortar when AMA and APA are incorporated, which is attributed to the ash additives’ micro-filling capacity. The findings contribute to advancing environmentally sound construction practices, with implications for sustainable waste management and pollution mitigation. more...

Current approaches to somatic symptom perception conceptualize somatic symptoms partly as somato-visceral or body illusions evoked by an interaction between bottom-up (sensory) and top-down (expectations, attention) processes. Similar processes of multisensory integration are assumed to contribute to the rubber hand illusion (RHI). Findings concerning the strength and direction of associations between these two phenomena, symptom perception and the RHI, are equivocal. Individuals of a non-clinical sample (N= 63; 56% females; Mage= 20.4; SD = 1.6) completed the Patient Health Questionnaire Somatic Symptom Scale (PHQ-15) and participated in an experiment that evoked the RHI. In repeated measures analyses of variance with the PHQ-15 score as covariate, no significant interaction effects between the PHQ-15 score and indicators of the RHI, i.e., proprioceptive drift (F(1,61) < 0.001 p= 0.993, partial η2< 0.001; BF10= 0.307), felt body ownership(F(1,59) = 0.043, p= 0.836, partial η2= 0,001; BF10= 0.501), and felt body disownership (F(1,59) = 0.148, p= 0.702, partial η2= 0.002; BF10= 1.972) were found. Overall, frequentist and Bayesian analysis indicated that the support for a possible association between the PHQ-15 and indicators of the RHI remains inconclusive, i.e., neither the null nor the alternative hypotheses were sufficiently supported. At least in this non-clinical sample, the association between somatic symptom distress and the strength of the RHI appears so weak (perhaps non-existing), that both phenomena (somatic symptom distress and the RHI) appear distinct and largely unrelated. more...

The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions. more...