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Abstract Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.

Abstract The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer’s disease (sAD) into the brain of adult wild-type mice (Prnp +/+), Prnp 0/0 (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt 0/0 mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo.

Abstract Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed Aβ amyloid in Alzheimer’s disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Recombinant ASC specks accelerated SAA fibril formation and mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain (PYD). In a murine model of inflammatory AA amyloidosis, splenic amyloid load was conspicuously decreased in Pycard −/− mice which lack ASC. Treatment with anti-ASCPYD antibodies decreased amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (−logEC50 ≥ 2) in 19,334 hospital patients was

An often observed artifact in atomic force microscopy investigations of individual monolayer flakes of 2D materials is the inaccurate height derived from topography images, often attributed to capillary or electrostatic forces. Here, we show the existence of a Joule dissipative mechanism related to charge dynamics and supplementing the dissipation due to capillary forces. This particular mechanism arises from the surface conductivity and assumes significance specially in the context of 2D materials on insulating supports. In such scenarios, the oscillating tip induces in-plane charge currents that in many circumstances constitute the main dissipative contribution to amplitude reduction and, consequently, affect the measured height. To investigate this phenomenon, we conduct measurements on monolayer flakes of co-deposited graphene oxide and reduced graphene oxide. Subsequently, we introduce a general model that elucidates our observations. This approach offers valuable insights into the dynamics of surface charges and their intricate interaction with the tip.

Abstract Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits.

IntroductionDiabetic retinopathy (DR) is a microvascular complication of diabetes in which neurodegeneration has been recently identified as a driving force. In the last years, mesenchymal stromal cells (MSCs) and neurotrophins like Nerve Growth Factor (NGF), have garnered significant attention as innovative therapeutic approaches targeting DR-associated neurodegeneration. However, delivering neurotrophic factors directly in the eye remains a challenge. Hence, this study evaluated the effects of MSCs from human amniotic fluids (hAFSCs) and recombinant human NGF (rhNGF) delivered by human corneal lenticule (hCL) on a high glucose (HG) induced ex vivo model simulating the molecular mechanisms driving DR.MethodsPorcine neuroretinal explants exposed to HG (25 mM for four days) were used to mimic DR ex vivo. hCLs collected from donors undergoing refractive surgery were decellularized using 0.1% sodium dodecyl sulfate and then bioengineered with hAFSCs, microparticles loaded with rhNGF (rhNGF-PLGA-MPs), or both simultaneously. Immunofluorescence (IF) and scanning electron microscopy (SEM) analyses were performed to confirm the hCLs bioengineering process. To assess the effects of hAFSCs and rhNGF, bioengineered hCLs were co-cultured with HG-treated neuroretinal explants and following four days RT-PCR and cytokine array experiments for inflammatory, oxidative, apoptotic, angiogenic and retinal cells markers were performed.ResultsData revealed that HG-treated neuroretinal explants exhibit a characteristic DR-phenotype, including increased level of NF-kB, NOS2, NRF2 GFAP, VEGFA, Bax/Bcl2 ratio and decreased expression of TUBB3 and Rho. Then, the feasibility to bioengineer decellularized hCLs with hAFSCs and rhNGF was demonstrated. Interestingly, co-culturing hAFSCs- and rhNGF- bioengineered hCLs with HG-treated neuroretinal explants for four days significantly reduced the expression of inflammatory, oxidative, apoptotic, angiogenic and increased retinal markers.ConclusionOverall, we found for the first time that hAFSCs and rhNGF were able to modulate the molecular mechanisms involved in DR and that bioengineered hCLs represents a promising ocular drug delivery system of hAFSCs and rhNGF for eye diseases treatment. In addition, results demonstrated that porcine neuroretinal explants treated with HG is a useful model to reproduce ex vivo the DR pathophysiology.

Silicon photonics has found a profound place among emerging technologies in the past few decades due to several advantages. Due to a series of breakthroughs and increased funding from private and government sectors, the development of silicon photonics has accelerated especially starting from the two years 2004–2005 with a persisting and ever‐growing momentum. Among various components, the silicon photonic filters that selectively pass or block particular wavelengths with a finite bandwidth have found particular interest as they are useful in signal processing in different fields ranging from optical communication to microwave photonics and quantum photonics. Herein, a comprehensive review of silicon photonic filters focusing on the four most commonly used architectures, such as microring resonators, waveguide Bragg grating, Mach–Zehnder interferometers, and arrayed waveguide grating, encapsulating basics, and guidelines, in terms of simulating tools and topologies, of realizing reconfigurable and high‐performing filters for several applications, is provided. The novelty of this review relies on the fact that it summarizes these filter architectures covering a broad range of applications concisely and constructively and includes the basics, growth, and future trends, providing a clear understanding and importance of silicon photonic filters from research to commercialization perspective.

Abstract SARS-CoV-2 can re-structure chromatin organization and alter the epigenomic landscape of the host genome, but the mechanisms that produce such changes remain unclear. Here, we use polymer physics to investigate how the chromatin of the host genome is re-organized upon infection with SARS-CoV-2. We show that re-structuring of A/B compartments can be explained by a re-modulation of intra-compartment homo-typic affinities, which leads to the weakening of A-A interactions and the enhancement of A-B mixing. At the TAD level, re-arrangements are physically described by a reduction in the loop extrusion activity coupled with an alteration of chromatin phase-separation properties, resulting in more intermingling between different TADs and a spread in space of the TADs themselves. In addition, the architecture of loci relevant to the antiviral interferon response, such as DDX58 or IFIT, becomes more variable within the 3D single-molecule population of the infected model, suggesting that viral infection leads to a loss of chromatin structural specificity. Analysing the time trajectories of pairwise gene-enhancer and higher-order contacts reveals that this variability derives from increased fluctuations in the chromatin dynamics of infected cells. This suggests that SARS-CoV-2 alters gene regulation by impacting the stability of the contact network in time.

Abstract Background Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). Methods We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score 15 ml/min. Results 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p

Abstract Symbiotic fermented kinds of milk are products with probiotic microorganisms and a simultaneous prebiotic effect. The presence of fibers or oligosaccharides causes it. This work aimed to evaluate and model fermented milk beverage production with probiotic microorganisms and in situ Galactooligosaccharides (GOS) synthesis. GOS enzymatic production was maximized through the mathematical model, and finally, the mathematical prediction was experimentally validated. For this purpose, the enzymatic kinetics of GOS production from Aspergillus oryzae β-galactosidase enzyme was experimentally evaluated for different initial lactose concentrations (30%, 35%, and 40% w/v) and enzyme/lactose ratio (R: 0.2%, 0.4%, and 0.6%). In addition, the fermentative kinetics of lactic acid and biomass production were evaluated using the probiotic strain Lactobacillus acidophilus. The parameters correlation for both models was then performed. A unified model determined the process conditions that maximize GOS concentration in the fermented milk beverage. According to the model, the operating values that maximized the GOS production were 40% of initial lactose, R: 0.15%, 20 min of enzymatic reaction, and 17 h of fermentative reaction. The final fermented milk drink showed a GOS content of 2.9 g/portion of 200 g, guaranteeing the recommended daily values of the prebiotic with the consumption of two servings.

The investigation of the dynamics of Purkinje cell (PC) activity is crucial to unravel the role of the cerebellum in motor control, learning and cognitive processes. Within the cerebellar cortex (CC), these neurons receive all the incoming sensory and motor information, transform it and generate the entire cerebellar output. The relatively homogenous and repetitive structure of the CC, common to all vertebrate species, suggests a single computation mechanism shared across all PCs. While PC models have been developed since the 70′s, a comprehensive review of contemporary models is currently lacking. Here, we provide an overview of PC models, ranging from the ones focused on single cell intracellular PC dynamics, through complex models which include synaptic and extrasynaptic inputs. We review how PC models can reproduce physiological activity of the neuron, including firing patterns, current and multistable dynamics, plateau potentials, calcium signaling, intrinsic and synaptic plasticity and input/output computations. We consider models focusing both on somatic and on dendritic computations. Our review provides a critical performance analysis of PC models with respect to known physiological data. We expect our synthesis to be useful in guiding future development of computational models that capture real-life PC dynamics in the context of cerebellar computations.

The accurate detection of ID card Presentation Attacks (PA) is becoming increasingly important due to the rising number of online/remote services that require the presentation of digital photographs of ID cards for digital onboarding or authentication. Furthermore, cybercriminals are continuously searching for innovative ways to fool authentication systems to gain unauthorized access to these services. Although advances in neural network design and training have pushed image classification to the state of the art, one of the main challenges faced by the development of fraud detection systems is the curation of representative datasets for training and evaluation. The handcrafted creation of representative presentation attack samples often requires expertise and is very time-consuming, thus an automatic process of obtaining high-quality data is highly desirable. This work explores ID card Presentation Attack Instruments (PAI) in order to improve the generation of samples with four Generative Adversarial Networks (GANs) based image translation models and analyses the effectiveness of the generated data for training fraud detection systems. Using open-source data, we show that synthetic attack presentations are an adequate complement for additional real attack presentations, where we obtain an EER performance increase of 0.63 % points for print attacks and a loss of 0.29 % for screen capture attacks.

Research background. An innovative integrated bioprocess system for bioethanol production from raw sugar beet cossettes (SBC) and arabitol from remaining exhausted sugar beet cossettes (ESBC) was studied. This integrated three-stage bioprocess system is an example of the biorefinery concept to maximise the use of raw SBC for the production of high value-added products such as sugar alcohols and bioethanol. Experimental approach. The first stage of the integrated bioprocess system was simultaneous sugar extraction from SBC and its alcoholic fermentation to produce bioethanol in an integrated bioreactor system (vertical column bioreactor and stirred tank bioreactor) containing a high-density suspension of yeast Saccharomyces cerevisiae (30 g/L). The second stage was the pretreatment of ESBC with dilute sulfuric acid to release fermentable sugars. The resulting liquid hydrolysate of ESBC was used in the third stage as a nutrient medium for arabitol production by non-Saccharomyces yeasts (Spathaspora passalidarum CBS 10155 and Spathaspora arborariae CBS 11463). Results and conclusions. The obtained results show that the efficiency of bioethanol production increased with increasing temperature and prolonged residence time in the integrated bioreactor system. The maximum bioethanol production efficiency (87.22 %) was observed at a time of 60 min and a temperature of 36 °C. Further increase in residence time (above 60 min) did not result in the significant increase of bioethanol production efficiency. Weak acid hydrolysis was used for ESBC pretreatment and the highest sugar yield was reached at 200 °C and residence time of 1 min. The inhibitors of the weak acid pretreatment were produced below bioprocess inhibition threshold. The use of the obtained liqiud phase of ESBC hydrolysate for the production of arabitol in the stirred tank bioreactor under constant aeration clearly showed that S. passalidarum CBS 10155 with 8.48 g/L of arabitol (YP/S=0.603 g/g and bioprocess productivity of 0.176 g/(L.h)) is a better arabitol producer than Spathaspora arborariae CBS 10155. Novelty and scientific contribution. An innovative integrated bioprocess system for the production of bioethanol and arabitol was developed based on the biorefinery concept. This three-stage bioprocess system shows great potential for maximum use of SBC as a feedstock for bioethanol and arabitol production and it could be an example of a sustainable ‘zero waste’ production system.

Abstract Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.

Introdução: A participação da ciência no desenvolvimento do esporte de alto-rendimento é cada vez mais expressiva. Logo, a termografia infravermelha vem sendo utilizada no intuito de verificar a capacidade deste em determinar a magnitude da carga interna de partidas oficiais a qual os atletas estão sendo submetidos. Objetivo: Avaliar jogadores de futebol na pré-temporada através da termografia infravermelha. Materiais e Métodos: A amostra foi composta por 15 atletas de futebol (idade: 19,0 ± 0,9 anos; massa corporal: 70,3 ±8,0 kg; estatura: 176,2 ±0,1 cm; percentual de gordura: 5,7 ±1,8 %G). Foram realizadas a avaliação da composição corporal e posteriormente a termografia infravermelha. Resultados: A maior porcentagem dos pixels das coxas está relacionada com a zona de temperatura quente tanto no eixo anterior (49%, 35% a 54%) quanto no eixo posterior (46%, 42% a 53%). Já a maior porcentagem de pixels das pernas está relacionada com a zona de temperatura fria tanto no eixo anterior (39%, 33% a 46%) quanto no eixo posterior (45%, 29% a 55%). Quando verificado a assimetria entre MMII no eixo anterior e posterior não foi encontrado diferenças significativas entre as coxas (direita e esquerda) e as pernas (direita e esquerda) nas diferentes zonas de temperatura. Conclusão: O presente estudo contribuiu para a melhor compreensão do estado físico de atletas no período de pré-temporada. Os aumentos dos percentuais de pixels da temperatura de zona quente indicam o estresse fisiológico relacionado com o estado inflamatório dos atletas, sendo importante para a comissão técnica e departamento médico na tentativa de adequar e gerenciar a carga de treinamento e recuperação dentro de períodos de jogos.

Abstract A multistate platform model was developed to describe time‐to‐event (TTE) endpoints in an oncology trial through the following states: initial, tumor response (TR), progressive disease (PD), overall survival (OS) event (death), censor to the last evaluable tumor assessment (progression‐free survival [PFS] censor), and censor to study end (OS censor), using an ordinary differential equation framework. Two types of piecewise functions were used to describe the hazards for different events. Piecewise surge functions were used for events that require tumor assessments at the scheduled study visit times (TR, PD, and PFS censor). Piecewise constant functions were used to describe hazards for events that occur evenly throughout the study (OS event and OS censor). The multistate TTE model was applied to describe TTE endpoints from a published phase III study. The piecewise surge functions well‐described the observed surges of hazards/events for TR, PD, PFS, and OS occurring near scheduled tumor assessments and showed good agreement with all Kaplan‐Meier curves. With the flexibility of piecewise hazard functions, the model was able to evaluate covariate effects in a time‐variant fashion to better understand the temporal patterns of disease prognosis through different disease states. This model can be applied to advance the field of oncology trial design and optimization by: (1) enabling robust estimations of baseline hazards and covariate effects for multiple TTE endpoints, (2) providing a platform model for understanding the composition and correlations between different TTE endpoints, and (3) facilitating oncology trial design optimization through clinical trial simulations.

This study aimed to identify the relationship between body composition (fat-free mass and body fat percentage) and physical performance (countermovement jump, CMJ; throwing ball; maximal isometric handgrip strength, MIHS dominant and non-dominant hands; 10-m and 20-m sprints with and without ball) in Chilean professional basketball players. Its secondary aim was to analyze if there were differences in body composition and physical performance according to sex. This was a cross-sectional study that analyzed 23 professional basketball players with a mean age of 24.0 ± 4.92 years, distributed among male professional basketball players (male professional BPs, n = 12) and female professional basketball players (female professional BPs, n = 14). The main results indicate the correlation presented significant relationships between fat-free mass with CMJ (r = 0.760; p < 0.0001; ES = 1.43), MIHS dominant hand (r = 0.783; p < 0.0001; ES = 1.50) and MIHS non-dominant hand (r = 0.805; p < 0.0001; ES = 1.85), throwing ball (r = 0.586; p = 0.001; ES = 0.56), 10 m sprint with ball (r = −0.510; p = 0.007; ES = 0.35), and 20 m sprint with ball (r = −0.143; p = 0.046; ES = 0.16). As did body fat percentage with CMJ (r = −0.647; p = 0.000; ES = 0.56), throwing the ball (r = −0.657; p = 0.000; ES = 0.58), MIHS dominant hand (r = −0.745; p < 0.0001; ES = 1.17), and MIHS non-dominant hand (r = −0.820; p < 0.0001; ES = 1.50). In conclusion, body composition is related to physical performance in professional basketball players. Meanwhile, male professional BPs had better body composition and physical performance than female professional BPs.

Here, we employ polymer physics models of chromatin to investigate the 3D folding of a 2 Mb wide genomic region encompassing the human LTN1 gene, a crucial DNA locus involved in key cellular functions. Through extensive Molecular Dynamics simulations, we reconstruct in silico the ensemble of single-molecule LTN1 3D structures, which we benchmark against recent in situ Hi-C 2.0 data. The model-derived single molecules are then used to predict structural folding features at the single-cell level, providing testable predictions for super-resolution microscopy experiments.

Water kefir is a product obtained through the fermentation of sucrose solution, usually with some kind of dried fruit addition, by a combined culture of micro-organisms which are contained within kefir grains. Its popularity is rising because of the simplicity of its preparation and its anti-inflammatory, antioxidant, probiotic, and antibacterial effects. In this research, the water kefir production was studied in 250 mL jars, as well as in a horizontal rotating tubular bioreactor (HRTB). The first part of the research was conducted in smaller-scale (jars), wherein the optimal fruit and fruit portions were determined. These experiments included the addition of dried plums, apricots, raisins, dates, cranberries, papaya, and figs into 150 mL of initial sugar solution. Also, the optimal ratio between dried fruit and sucrose solution (0.2) at the beginning of the bioprocess was determined. The second part of this research was conducted using HRTB. The experiments in the HRTB were carried out by using different operational modes (constant or interval bioreactor rotation). A total of six different bioreactor setups were used, and in all experiments, figs were added at the beginning of the bioprocess (0.2 ratio between dried figs and sucrose solution). On the basis of the obtained results, the interval bioreactor rotation mode proved to be the better HRTB mode for the production of the water kefir, as the yield of the main fermentation products was higher, and their ratios were the most adequate for the quality of water kefir drink. The optimal results were obtained via HRTB setup 3/57 (3 min rotation, 57 min pause within 1 h) and rotation speed of 3 rpm. Furthermore, it is clear that HRTB has great potential for water kefir production due to the fact that HRTB experiments showed shorter fermentation times (at least five times) than water kefir production in jars.

Introduction: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be splited into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and postprandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or sleeve gastrectomy (SG) as the first step of SADI-S. Methods: Subjects submitted to SADI-S (n=7) or SG (n=7) at a tertiary referral public academic hospital, underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively. Results: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate (ISR) and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up. Conclusions: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. This data provides support for a surgeons’ choice of a two-step SADI-S without jeopardizing the weight loss outcomes.

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson’s disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE’s toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses.Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

A simple method for obtaining triplet-triplet absorption (TTA) spectra and triplet state (T1) lifetimes of long-lived triplets is presented and demonstrated with the polycyclic aromatic hydrocarbon coronene (both normal and perdeuterated forms) in a polymer matrix at room temperature. The TTA spectra obtained with a camera flash and a spectrophotometer are noisier but otherwise identical to those obtained with a state-of-the-art flash photolysis apparatus. The triplet lifetimes obtained from transient absorption are identical to the phosphorescence lifetimes of the same samples.

The purpose of this research is to develop a methodological approach to assessing the impact of the architecture effectiveness of the enterprise business model on the level of its competitiveness. The study methodology suggests the author’s approach to assessing the architecture effectiveness and the level of enterprise competitiveness. The scenario approach was used in order to the evaluate the connection between competitiveness, business model potential and enterprise architecture based on the economic-mathematical method of solving the nonlinear optimization problem through the use of hierarchical synthesis. The study was conducted according to the materials from 15 private clinics in Ukraine. The analysis of the obtained indices of architecture efficiency, competitiveness and potential level of the business model of the private clinics under study was carried out. It is determined that the level and growth rates of the enterprise architecture efficiency of private clinics have significant distinctions, which affect the level of their competitiveness. A group of leading companies in terms of the level of business model potential is singled out based on the definition of the correlation between the level of business model potential and the enterprise architecture efficiency. It is established that the level of business model potential of private clinics is substantially dependent on the level of enterprise architecture efficiency. It is proved that the efficiency of enterprise architecture has a significant influence on the potential and competitiveness of the business model. The novelty of the study consists in the methodological approach to assessing the impact of business model architecture on the level of its competitiveness, taking into consideration the identification of functional rather than strictly parametric correlation between variables. This research can be useful for professionals, scientists and researchers involved in developing and implementing effective business models and designing the enterprise architecture in order to achieve the company’s strategic intentions and to create and maintain competitive market positions.

Bioethanol, an alcohol produced by microbial fermentation, is traditionally produced from sugar-rich plants such as sugar cane, sugar beet and maize. However, there is growing interest in the use of lignocellulose, an abundant and inexpensive renewable energy source, as a potential substitute for the production of biofuels and biochemicals. Yeast Saccharomyces cerevisiae, which is commonly used for ethanol fermentation, cannot cope with lignocellulose due to a lack of lignocellulolytic enzymes and the inefficient functioning of the pentose phosphate pathway. The aim of this research was to isolate yeasts that can efficiently produce bioethanol and valuable byproducts from both glucose and xylose in a two-stage fermentation process using brewer’s spent grains. This approach should maximize sugar utilization and improve the economic viability of bioethanol production while contributing to waste valorization and sustainability. Kluyveromyces marxianus and Candida krusei were identified and tested with different initial concentrations of glucose and xylose. The results showed that both yeasts produced bioethanol from glucose but were inefficient with xylose, yielding valuable compounds, such as 2,3-butanediol and glycerol instead. A two-stage fermentation was then carried out with weak acidic hydrolysate from brewer’s spent grain. In the first stage, glucose was fermented by S. cerevisiae to produce bioethanol; in the second stage, xylose was fermented by K. marxianus and C. krusei to obtain other valuable products.

Plywood production relies on phenol–formaldehyde (PF), which is why bio-based wood adhesives (BBWAs) were developed as potential replacements, showing promising results in several tests performed. A control sample (PLY-C) with PF and two samples (PLY-1 and PLY-2) with BBWA were manufactured, on which physical and mechanical properties, adhesive bonding morphology, formaldehyde emissions, and accelerated UV aging were evaluated. The adhesive penetration results, into the wood cells, were according to the viscosity of each adhesive. About the mechanical properties, the sample PLY-2 presented the same MOE and tensile strength as the sample PLY-C and reached 87% of the sample PLY-C MOR in the parallel direction. On the other hand, the sample PLY-1 presented the same behavior in the Janka hardness test as the sample PLY-C. All the samples subjected to shear strength tests met the requirement, and the samples PLY-1 and PLY-2 reached 68% and 80% of the PLY-C sample, respectively. The samples manufactured with BBWA presented a decrease in formaldehyde emissions by 88% and they were less susceptible to color change than the control sample under UV aging. According to the results obtained, it is concluded that plywood manufactured with BBWA might be a considerable replacement for plywood manufactured with PF adhesives at a laboratory scale.

We are developing a phase-modulating micro mirror-array spatial light modulator to be used for real holography within the EU-funded project REALHOLO, featuring millions of pixels that can be individually positioned in a piston mode at a large frame rate. We found earlier that an electrostatic comb-drive array offers the best performance for the actuators: sufficient yoke forces for fast switching even at low voltages compatible with the CMOS addressing backplane. In our first design, the well-known electrostatic cross-talk issue had already been much smaller than would have been possible for parallel-plate actuators, but it was still larger than the precision requirements for high-image-quality holography. In this paper, we report on our analysis of the crucial regions for the electrostatic cross-talk and ways to reduce it while observing manufacturing constraints as well as avoiding excessively high field strengths that might lead to electrical breakdown. Finally, we present a solution that, in FEM simulations, reduces the remaining cross-talk to well below the required specification limit. This solution can be manufactured without any additional processing steps and suffers only a very small reduction of the yoke forces.

Taking the work conducted by the global navigation satellite system (GNSS) software-defined radio (SDR) working group during the last decade as a seed, this contribution summarizes, for the first time, the history of GNSS SDR development. This report highlights selected SDR implementations and achievements that are available to the public or that influenced the general development of SDR. Aspects related to the standardization process of intermediate-frequency sample data and metadata are discussed, and an update of the Institute of Navigation SDR Standard is proposed. This work focuses on GNSS SDR implementations in general-purpose processors and leaves aside developments conducted on field programmable gate array and application-specific integrated circuit platforms. Data collection systems (i.e., front-ends) have always been of paramount importance for GNSS SDRs and are thus partly covered in this work. This report represents the knowledge of the authors but is not meant as a complete description of SDR history.

Ochratoxin A (OTA) is one of the mycotoxins in the agriculture and livestock sectors. The poultry sector suffered from significant economic losses due to the adverse impacts of OTA on the growth rate, feed conversion ratio, and livability. Thus, the present investigation aimed to determine the impact of chamomile essential oil supplementation against OTA toxicity in growing quails. 360 one-week-old growing quails were distributed into six groups (n = 60) with four replicates of 15 birds. The groups were G1 (control negative), G2 (OTA 1 mg/kg diet, control positive), G3 (chamomile oil 0.5 g/kg diet), G4 (chamomile oil 1 g/kg diet), G5 (OTA 1 mg/kg diet + chamomile oil 0.5 g/kg diet), and G6 (OTA 1 mg/kg diet + chamomile oil 1 g/kg diet). Adding OTA significantly (P

ABSTRAK Ketergantungan peternak pada pakar atau dokter hewan karena terbatasnya pengetahuan dalam mengindentifikasi penyakit kerbau merupakan opsi yang sulit dan mahal. Dalam mengatasi hal tersebut, artikel ini menyajikan pengembangan sistem pakar diagnosis penyakit kerbau. Sistem ini diimplementasikan dalam bentuk web serta dirancang dengan mengumpulkan data tentang 17 jenis penyakit kerbau dan 49 gejala yang berkaitan. Proses diagnosis menggunakan kombinasi algoritma Forward Chaining dan Certainty Factor, yang memungkinkan sistem untuk mencocokkan gejala yang diamati dengan database penyakit kerbau menghasilkan diagnosis yang akurat. Hasil Pengujian sistem menunjukkan tingkat akurasi mencapai 100% dalam 15 kali pengujian berturut-turut. Hasil pengujian juga divalidasi oleh pakar spesialis kerbau. Kesimpulannya, sistem ini layak digunakan oleh peternak kerbau untuk mendiagnosis penyakit kerbau secara dini. Kata kunci: sistem pakar, penyakit pada kerbau, gejala, forward chaining, certainty factor  ABSTRACT Farmers' reliance on experts or veterinarians due to limited knowledge in identifying buffalo diseases is a difficult and expensive option. To address the problem, this paper presents the development of an expert system for buffalo disease diagnosis. The system is implemented on the web and designed by collecting data on 17 buffalo disease types and 49 associated symptoms. The diagnosis process uses a combination of Forward Chaining and Certainty Factor algorithms, which allows the system to match observed symptoms with the buffalo disease database resulting in an accurate diagnosis. System testing results showed an accuracy rate of 100% in 15 consecutive tests. Results were also validated by buffalo specialist experts. In conclusion, the system is feasible to be used by buffalo farmers to diagnose buffalo diseases early. Keywords: expert system, buffalo diseases, symptoms, forward chaining, certainty factor

La industrialización es el principal mecanismo de desarrollo económico en un país, que es medido a través del PIB. En el Ecuador, las actividades las actividades con mayor participación por ingresos son las actividades de producción y operaciones de metalmecánica como lo es la industria manufacturera. Por tal razón, el propósito de la investigación fue determinar el impacto del sector manufacturero dentro del PIB global, mediante el análisis de los ingresos del sector y la variación del PIB durante el periodo 2015-2022 con proyección hacia el año 2023. El método de análisis datos fue el modelado de regresión lineal. Los hallazgos revelaron que, los ingresos del sector crecieron en 0,10% con relación al año 2022. Es decir, el ingreso de la industria mantuvo un crecimiento constante en comparación al PIB del periodo analizado como resultado de las estrategias post-covid. Así pues, se determinó una relación directa entre las variables de estudio con una participación promedio de 26,66% en relación a otros sectores productivos tanto en bienes como servicios.

James Webb Space Telescope NIRCam images have revealed 154 reliable globular cluster (GC) candidates around the z = 0.0513 elliptical galaxy VV 191a after subtracting 34 likely interlopers from background galaxies inside our search area. NIRCam broadband observations are made at 0.9–4.5 μ m using the F090W, F150W, F356W, and F444W filters. Using point-spread-function-matched photometry, the data are analyzed to present color–magnitude diagrams and color distributions that suggest a relatively uniform population of GCs, except for small fractions of reddest (5%–8%) and bluest (2%–4%) outliers. GC models in the F090W versus (F090W–F150W) diagram fit the NIRCam data well and show that the majority of GCs detected have a mass of ∼10 ^6.5 M _⊙ , with metallicities [Fe/H] spanning the typical range expected for GCs (−2.5 ≲ [Fe/H]≲ 0.5). However, the models predict ∼0.3–0.4 mag bluer (F356W–F444W) colors than the NIRCam data for a reasonable range of GC ages, metallicities, and reddening. Although our data do not quite reach the luminosity function turnover, the measured luminosity function is consistent with previous measurements, suggesting an estimated peak at m _AB ∼ −9.4 ± 0.2 mag in the F090W filter.

A wealth of observations have long suggested that the vast majority of isolated classical dwarf galaxies ( M _* = 10 ^7 –10 ^9 M _⊙ ) are currently star forming. However, recent observations of the large abundance of “ultra-diffuse galaxies” beyond the reach of previous large spectroscopic surveys suggest that our understanding of the dwarf galaxy population may be incomplete. Here we report the serendipitous discovery of an isolated quiescent dwarf galaxy in the nearby Universe, which was imaged as part of the JWST PEARLS Guaranteed Time Observation program. Remarkably, individual red-giant branch stars are visible in this near-IR imaging, suggesting a distance of 30 ± 4 Mpc, and a wealth of archival photometry point to an sSFR of 2 × 10 ^−11 yr ^−1 and star formation rate of 4 × 10 ^−4 M _⊙ yr ^−1 . Spectra obtained with the Lowell Discovery Telescope find a recessional velocity consistent with the Hubble Flow and >1500 km s ^−1 separated from the nearest massive galaxy in Sloan Digital Sky Survey suggesting that this galaxy was either quenched from internal mechanisms or had a very high-velocity (≳1000 km s ^−1 ) interaction with a nearby massive galaxy in the past. This analysis highlights the possibility that many nearby quiescent dwarf galaxies are waiting to be discovered and that JWST has the potential to resolve them.

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history.

Extraosseous variants of odontogenic cysts are an infrequent clinical finding, although they have a relatively indolent biological behavior compared to their intraosseous counterparts; due to their nature and clinical appearance, these lesions can be confused with multiple entities that affect soft tissues, so their diagnosis can only be achieved through surgical removal and subsequent histopathological analysis. The extraosseous/peripheral variant of calcifying odontogenic cyst (E/PCOC) has a heterogeneous clinical presentation mainly in terms of size and involvement or not of adjacent anatomical structures such as bone and teeth; in addition, there are few cases reported to date; thus, there are still clinical features to be elucidated. This report presents a child affected by E/PCOC in an unusual location, as well as its therapeutic management, which at first time was suspected of endodontic nature, due to a history of dental trauma.

In the original publication [...]

Amoebiasis, a disease caused by the protozoan Entamoeba histolytica, represents a serious public health problem, mainly in developing countries. The first line of therapy for amoebiasis treatment is metronidazole (MTZ); however, clinical isolates of E. histolytica with resistance to MTZ and varying sensitivity to other antiamoebic drugs threaten the effectiveness of the prevention and treatment of this parasitic infection. Natural products stand out as a promising strategy to develop new, safe and more effective alternatives. In this study, we determined and compared the phytochemical profiles of Agave tequilana, Agave angustifolia, Agave rhodacantha, and Agave maximiliana and described their cytotoxic effect on E. histolytica trophozoites. The results show that the four Agaves kill E. histolytica in a species–time–dose-dependent manner. A morphologic analysis of the treated parasites showed evident morphological alterations suggestive of programmed cell death with nuclear alterations; it also highlighted the presence of rounded cells with protuberances/perforations in the membrane and cells that appeared to have exploded. The overall activity of Agave ethanolic extracts in E. histolytica can help provide new strategies to advance alternative treatments against amoebiasis.

New JWST/NIRCam wide-field slitless spectroscopy provides redshifts for four z > 8 galaxies located behind the lensing cluster MACS J0416.1−2403. Two of them, “Y1” and “JD,” have previously reported spectroscopic redshifts based on Atacama Large Millimeter/submillimeter Array measurements of [O iii ] 88 μ m and/or [C ii ] 157.7 μ m lines. Y1 is a merging system of three components, and the existing redshift z = 8.31 is confirmed. However, JD is at z = 8.34 instead of the previously claimed z = 9.28. JD’s close companion, “JD-N,” which was a previously discovered z > 8 candidate, is now identified at the same redshift as JD. JD and JD-N form an interacting pair. A new candidate at z > 8, “f090d_018,” is also confirmed and is at z = 8.49. These four objects are likely part of an overdensity that signposts a large structure extending ∼165 kpc in projected distance and ∼48.7 Mpc in radial distance. They are magnified by less than 1 mag and have an intrinsic M _UV ranging from −19.57 to −20.83 mag. Their spectral energy distributions show that the galaxies are all very young with ages ∼ 4–18 Myr and stellar masses of about 10 ^7–8 M _⊙ . These infant galaxies have very different star formation rates ranging from a few to over a hundred solar masses per year, but only two of them (JD and f090d_018) have blue rest-frame UV slopes β < −2.0 indicative of a high Lyman-continuum photon escape fraction that could contribute significantly to the cosmic hydrogen-reionizing background. Interestingly, these two galaxies are the least massive and least active ones among the four. The other two systems have much flatter UV slopes largely because of their high dust extinction ( A _V = 0.9–1.0 mag). Their much lower indicated escape fractions show that even very young, actively star-forming galaxies can have a negligible contribution to reionization when they quickly form dust throughout their bodies.