In ore regions impacted by mining and metal smelting emissions, distinguishing between geogenic anoma-lies and anthropogenic contamination poses a significant challenge. In a study from two areas with different mining histories in the Ore Mountains, Czech Republic, we demonstrate that targeted sampling of topsoils and subsoils respecting local geology and correct soil data treatment respecting soil textural variability effects are indispensable to correctly construct and interpret geochemical maps and identify anthropogenic contam-ination by As, Cu, Pb, and Zn. The list of analysed elements must include both potentially toxic and lithogenic elements, otherwise natural controls of soil composition cannot be deciphered. By using empirical cumulative distribution functions, we found that local backgrounds for As/Fe and Pb/Ti are significantly naturally ele-vated (5.7 to 9.8 times and 2.1 to 2.7 times higher, respectively) compared to the global averages. We con-structed geochemical maps with topsoil minus subsoil concentrations to show the main directions of spreading anthropogenic contamination. The anthropogenic diffuse contamination contribution was calcu-lated (1.12·10-4 and 1.42·10-4 for As/Fe and 16.5·10-4 and 16.2·10-4 for Pb/Ti, respectively), which corresponds to topsoil enrichment by ca. 15 and 14 mg kg-1 for As and ca. 35 and 42 mg kg-1 for Pb in the two study areas. Our study thus provided the first published quantitative estimates of geogenic and anthropogenic contribution to this well-known montane area. The obtained estimates were comparable to the results obtained previously from the local peat archives. The approach we used is efficient in deciphering natural and anthropogenic controls of PTEs in geochemically complicated areas.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

This paper presents an innovative testing framework, testFAILS, designed for the rigorous evaluation of AI Linguistic Systems, with a particular emphasis on various iterations of ChatGPT. Leveraging orthogonal array coverage, this framework provides a robust mechanism for assessing AI systems, addressing the critical question, "How should we evaluate AI?" While the Turing test has traditionally been the benchmark for AI evaluation, we argue that current publicly available chatbots, despite their rapid advancements, have yet to meet this standard. However, the pace of progress suggests that achieving Turing test-level performance may be imminent. In the interim, the need for effective AI evaluation and testing methodologies remains paramount. Our research, which is ongoing, has already validated several versions of ChatGPT, and we are currently conducting comprehensive testing on the latest models, including ChatGPT-4, Bard and Bing Bot, and the LLaMA model. The testFAILS framework is designed to be adaptable, ready to evaluate new bot versions as they are released. Additionally, we have tested available chatbot APIs and developed our own application, AIDoctor, utilizing the ChatGPT-4 model and Microsoft Azure AI technologies

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Artificial Intelligence (AI) experienced significant advancements in recent years, and its impact is already recognized across various industries. Yet, the rise of AI has led to a growing concern about its impact on meeting the Sustainable Development Goals (SDGs). The aim of this paper was to evaluate contributions and the potential impact of AI to sustainable development in the society domain. Furthermore, the study analyzed GPT-3 responses, as one of the largest language models developed by OpenAI, descriptively. We conducted a set of queries on the SDGs to gather infor-mation on GPT-3`s perceptions of AI impact on sustainable development. Analysis of GPT-3’s contribution potential towards the SDGs showcased its broad range of capabilities for contributing to the SDGs in areas such as education, health, and communication. The study findings provide valuable insights into the contributions of AI to sustainable development in the society domain and highlight the importance of proper regulations to promote the responsible use of AI for sustainable development. We plan subsequent research for effects on ecologic and economic domains of SDGs. We highlighted the potential for improvement in neural language processing skills of GPT-3 by avoiding imitating weak human writing styles with more mistakes in longer texts.

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

Forest degradation is known to be widespread in the tropics, but is currently very poorly mapped, in part because there is little quantitative data on which satellite sensor characteristics and analysis methods are best at detecting it. To improve this, we used data from the Tropical Forest Degradation Experiment (FODEX) plots in the southern Peruvian Amazon, where different numbers of trees had been removed from four 1 ha forest plots, carefully inventoried by hand and Terrestrial Laser Scanning before and after the logging to give a range of biomass change (ΔAGB) values. We conducted a comparative study of six multispectral optical satellite sensors (WorldView-3, SkySat, SPOT-7, PlanetScope, Sentinel-2 and Landsat 8) at 0.3 – 30 m spatial resolution, to find the best combination of sensor and remote sensing indicator for change detection. Spectral reflectance, the Normalized Difference Vegetation Index (NDVI) and texture parameters were extracted after radiometric calibration and image preprocessing. The strength of the relationships between the change in these values and field-measured ΔAGB (computed in % ha−1) was analysed. The results demonstrate that: (a) texture measures correlates more with ΔAGB than simple spectral parameters; (b) the strongest correlations are achieved for those sensors with spatial resolutions in the intermediate range (1.5 - 10 m), with finer or coarser resolutions producing worse results, and (c) when texture is computed using a moving square window ranging between 9 - 14 m in length. Maps predicting ΔAGB showed very promising results using a NIR-derived texture parameter for 3 m resolution PlanetScope (R2 = 0.97 and RMSE = 1.80 % ha−1), followed by 1.5 m SPOT-7 (R2 = 0.74 and RMSE = 5.25 % ha−1) and 10 m Sentinel-2 (R2 = 0.71 and RMSE = 5.55 % ha−1). Texture models derived from 0.3 m WorldView-3 improved with increasing window size, with highest R2 of 0.62 and RMSE = 6.35 % ha−1 for a window of 14 m in length. The degradation in our field plots is invisible to the 30 m resolution Landsat data. Our findings imply that, at least for lowland Peru, low-medium intensity disturbance can be detected best in optical wavelengths using a texture measure derived from 3 m PlanetScope data. That such data are being collected daily, and currently released free as monthly mosaics over tropical forests as part of the Norway’s International Climate and Forest Initiative (NICFI), is excellent news for monitoring such degradation.

Gene expression variations of plant leaf are investigated by irradiating seed and leaf with oxygen or air plasmas. Enhancement of leaf growth is induced by oxygen plasma irradiation on seeds, which is supported by increased gene expression for protein synthesis, oxidative-reduction reactions and decreased gene expression concerning DNA methylation and histone modification. Suppression of leaf growth is observed by the oxygen plasma, which would be owing to increased gene expression concerning heat shock protein and redox reaction, and decreased expression of photosynthesis and glycoprotein. Also, gene expression variation due to air plasma irradiation is almost same as that of oxygen plasma. Active oxygen species are major factors in both oxygen and air plasmas for the variation of gene expressions in plant.

Access to nasopharyngeal swabs for sampling remain a bottleneck in some regions for COVID-19 testing. This study develops a distributed manufacturing solution using only an open source manufacturing tool chain consisting of two types of open source 3-D printing and batch UV curing, and provides a parametric fully free design of a nasopharyngeal swab. The swab was designed using parametric OpenSCAD in two components (a head with engineered break point and various handles), which has several advantages: i) minimizing print time on relatively slow SLA printers, ii) enabling the use of smaller print volume open source SLA printers, iii) reducing the amount of relatively expensive UV resin, and iv) enabling production of handle on more accessible material extrusion 3-D printers. A modular open source UV LED box was designed, fabricated for $45 and tested for batch curing. Swabs can be fabricated for $0.06-$0.12/swab. The results of the mechanical validation tests showed that the swabs could withstand greater forces than would be expected in normal clinical use. The swabs were also able to absorb a significant amounts of synthetic mucus materials and passed abrasion and handling tests. The results show the open source swab are promising candidates for clinical trials.

This study provides designs for a low-cost, easily replicable open source lab-grade digital scale that can be used as a precision balance. The design is such that it can be manufactured for use in most labs throughout the world with open source RepRap-class material extrusion-based 3-D printers for the mechanical components and readily available open source electronics including the Arduino Nano. Several versions of the design were fabricated and tested for precision and accuracy for a range of load cells. The results showed the open source scale was found to be repeatable within 0.1g with multiple load cells, with even better precision (0.01g) depending on load cell range and style. The scale tracks linearly with proprietary lab-grade scales, meeting the performance specified in the load cell data sheets, indicating that it is accurate across the range of the load cell installed. The smallest loadcell tested(100g) offers precision on the order of a commercial digital mass balance. The scale can be produced at significant cost savings compared to scales of comparable range and precision when serial capability is present. The cost savings increase significantly as the range of the scale increases and are particularly well-suited for resource-constrained medical and scientific facilities.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

Porcine circovirus type 2 (PCV2) is a small non-enveloped DNA virus that causes swine immunosuppression by inducing apoptosis in lymphocytes. The ORF3 protein plays a major role in PCV2-induced apoptosis in porcine kidney cells, but there is little information regarding this protein in PCV2-infected lymphocytes. In this study, hybridoma screening and epitope mapping were determined by using an indirect ELISA. The mAb 7D3 against ORF3 peptide (residues 35–65) of PCV2 were generated in this study. In vivo situation, the mAb 7D3 recognized ORF3 protein existed in PCV2-infected apoptotic porcine PBMCs. It is noteworthy that thimerosal interfered with the binding of mAb 7D3 to epitope and it was diminished by adding cysteine. Additionally, thimerosal interacting with cysteine-containing peptide was demonstrated by the PTI assay. Furthermore, thimerosal specifically interacted with the antigen-binding sites of mAb 7D3. This study suggested that thimerosal blockade the occlusion of the antigen-binding sites of mAb 7D3 to bind ORF3 peptide (residues 35–65) via thimerosal interacting with cysteine residues which should be located within the antigen-binding sites of mAb 7D3. Overall, the mAb 7D3 has been characterized and it will be a valuables tool in future studies of ORF3 function and the wider mechanism of cell apoptosis caused by PCV2 infection. Similarly, these techniques will be useful for applications in detecting thimerosal too.

A preliminary study of a wind turbine design is carried out using a wind tunnel to obtain its aerodynamic characteristics. Utilization of data from the study to develop large-scale wind turbines requires further study. This paper aims to discuss the use of wind turbine data obtained from the wind tunnel measurements to estimate the characteristics of wind turbines that have field size. The torque of two small-scale turbines was measured inside the wind tunnel. The first small-scale turbine has a radius of 0.14 m and the second small turbine has a radius of 0.19 m. Torque measurement results from both turbines were analyzed using Buckingham π theorem to obtain a correlation between torsion and diameter variations. The obtained correlation equation is used to estimate the field measurement of turbine power with a radius of 1.2 m. The resulting correlation equation can be used to estimate the power generated by the turbine by the size of the field well in the operating area of the tip speed ratio of the turbine design.

(1) Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. (2) Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). (3) Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510 – 0.802) and Day 3 (AUC 0.698; 95% CI: 0.559 – 0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572 – 0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 g/L on Day 3, resulting in R2 of about 31% (p < 0.001). (4) Conclusion: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

This paper presents the development of a hardware-in-the-loop ground testbed featuring active gravity compensation via software-in-the-loop integration, specially designed to support research in autonomous robotic removal of space debris. The testbed is designed to replicate six degrees of freedom (6DOF) motion maneuvering to accurately simulate the dynamic behaviors of free-floating robotic manipulators and free-tumbling space debris under microgravity conditions. The testbed incorporates two industrial 6DOF robotic manipulators, a 3-finger robotic gripper, and a suite of sensors, including cameras, force/torque sensors, and tactile tensors. Such a setup provides a robust platform for testing and validating technologies related to autonomous tracking, capture, and post-capture stabilization within the context of active space debris removal missions. Preliminary experimental results have demonstrated advancements in motion control, computer vision, and sensor fusion. This facility is positioned to become an essential resource for the development and validation of robotic manipulators in space, offering substantial improvements in the effectiveness and reliability of autonomous capture operations in space missions.

(1) Background: Adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) have potential to impact long-term health outcomes. Understanding these interrelationships can inform the development of interventions to promote societal health (2) Methods: D/PMH was defined as a diagnosis of depression and/or more than 14 days of poor mental health in the previous month. Those reporting poor physical health for more than 14 days in the previous month or categorising their physical health as ‘fair’ or ‘poor’ were deemed to have PG/PPH. Seven categorical questions based on subscales in the Child and Youth Resilience Measure-28 were used to define PCEs.(3) Results: Increased ACEs exposure use significantly associated with increased odds of D/PHM (p&lt;0.001), increased odds of PG/PHH (p=0.010) and decreased odds of AR-SES (p&lt;0.001). Increased exposure to PCEs was significantly associated with decreased odds of D/PHM (p&lt;0.001), increased odds of PG/PHH (p&lt;0.001) and decreased odds of AR-SES (p&lt; 0.001). For all outcomes, exposure to PCEs reduced the strength of the association between ACEs and outcomes. (4) Conclusions: A positive dose response between the number of ACEs and adult D/PMH, PG/PPH and lower AR-SES exists within the Australian population. PCEs weaken this association, demonstrating their mitigating potential. PCEs promoted adult outcomes, irrespective of ACEs.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

The current work is dedicated to the search for new high-energy materials (HEMs) with improved characteristics which are gained through agglomeration with salts. The research was performed by Becke’s three-parameter hybrid functional approach with non-local correlation provided by Lee, Yang, and Parr and cc-pVTZ basis set. The geometry, total energy, and heat of formation of the most stable compounds forming due to 3-amino-5-[(2, 4, 6-trinitrophenyl) amino]-1H-1, 2, 4-triazole (APATO) within salts selected were obtained to foresee its influence on resistance to shock stimuli, detonation pressure, and velocity of the materials under study. Results obtained allow us to foresee that only agglomeration with precise salts could lead to significant improvement in the stability of the specific high-energy materials and the resistance to shock stimuli. We also show that the agglomeration leads to better energetic properties of the above compound, although the improvement could be insignificant in some cases.

Delivery systems of the biologically active substance such as proanthocyanidins (PCAN) produced through the electrospinning method were designed using a blend of poly(L-lactide-co-glycolide) and poly[(R,S)-3-hydroxybutyrate]. The research involved the structural and thermal characteristics of the developed electrospun three-dimensional fiber matrix, as well as hydrolytic degradation tests performed on them. Additionally, the release profile of PCAN from the electrospun nonwoven was determined using UV–VIS spectroscopy. Approximately 30% of PCAN was released from the tested electrospun nonwoven during the initial 15-20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern, and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide-co-glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fiber matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCAN for biomedical applications with promising antimicrobial activity.

This paper presents a) the novel hybrid learning method to train the type-1 non-singleton interval type-3 (IT3) fuzzy logic systems (IT3 NSFLS-1) and b) the novel method named enhanced Wagner-Hagras (EWH) IT3 NSFLS-1 fuzzy systems which includes the level alpha 0 output to calculate the output y alpha using the average of the outputs y alpha k instead of their weighted average. The development of the proposed methodology uses the orthogonal least square (OLS) method to train the consequent parameters and the back propagation (BP) method to train the antecedent parameters. This proposal dynamically changes the parameters of only the level alpha 0 minimizing some criterion function as new information becomes available to each level alpha k. The antecedent sets are type-2 fuzzy sets, the consequent sets are fuzzy centroids, the inputs are type-1 non-singleton fuzzy numbers with uncertain standard deviations, and the secondary membership functions are modeled as two Gaussians with uncertain standard deviation and the same mean. Based on the firing set of the level alpha 0, the proposed methodology calculates each firing set of each level alpha k to dynamically construct and update the EWH IT3 NSFLS-1 (OLS-BP) system. The algorithm was tested in a hot strip mill facility to predict the transfer bar surface temperature showing its superior capability to obtain the industrial pyrometer’s knowledge uncertainty for tuning and its better performance when compared with IT2 SFLS, IT2 NSFLS-1, GT2 SFLS, GT2 NSFLS-1, IT3 SFLS, and IT3 NSFLS-1 trained with the BP-BP algorithm.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

In the present study, linear novel polymer poly(1-(2-((3-amino-2-hydroxypropyl)amino)ethyl)-1'-ethyl-[4,4'-bipyridine]-1,1'-di-ium) (poly(AHAEBD)) and its complex with iron (ΙΙΙ) ([Fe(poly(AHAEBD)2].Na3) were synthesized and then their anticancer effects on A375 human malignant melanoma cells line were evaluated. The structure of the synthesized compounds was confirmed using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (1HNMR), field emission scanning electron microscopy (FE-SEM), X-ray energy diffraction analysis (EDS) and gel permeation chromatography (GPC). Also, the cytotoxicity of cisplatin as a reference, on A375 melanoma cell line was tested. The IC50 of polymer-complex [Fe(poly(AHAEBD)2].Na3 (0.71 µg/mL), cisplatin (4.58 µg/mL) and poly(AHAEBD) (1.73 µg/mL) were obtained. Our results revealed that the polymer-complex [Fe(poly(AHAEBD)2].Na3 exhibited better performance compared to cisplatin. Furthermore, the coordination with iron (III) enhanced the cytotoxicity levels of poly(AHAEBD). According to these findings, the synthesized polymer-complex demonstrates remarkable potential as an anti-cancer agent. This study could provide the basis for future research focused on employing this new polymer-complex for in vivo testing, highlighting its potential for therapeutic applications.

Animal-assisted pedagogy (AAP) is well known in classroom practice, but scientific evidence is still lacking. At the same time, the biggest challenge in education systems worldwide is the social in-tegration of students. In a pre-post design, 30 heterogeneous students (16f/14m) from four different school classes (grades 5-7) were interviewed (problem-centred interview) about their social inclu-sion and their social climate in class before and after being taught selected subjects with a school dog (of different breeds) for one school term. At the second measurement point, they were also asked about their perception of AAP. The data was analysed both qualitatively (Kuckartz) and in terms of the number of quotes on the main topics using MAXQDA analysis software. The presence of a dog in the classroom leads to an improved social climate and more social integration. In ad-dition, the perception of the other students and the teacher changes to a more positive and friendly image. Through AAP, a new social role is added to the classroom, where caring and bonding are prioritised. Social interaction and norms are influenced and sterotypical and individual roles can be changed. Therefore, AAP can be a key to promoting social inclusion in the school environment.

Forests, integral to human civilization, hold immense value and play a vital role in maintaining ecological harmony. Despite India's goal of extensive forest coverage, significant progress is still needed. Uncontrolled forest fires pose a severe threat, particularly in Uttarakhand's Pauri Garhwal district. To address this challenge, a comprehensive study examined surface and subsurface hydrological factors influencing the forest fire occurrences, such as elevation, aspect, slope, vegetation, proximity to human settlements, proximity to waterbodies, Active faults and lineament density. A total of 15 such factors were integrated with advanced techniques of remote sensing and GIS and coupled with historical fire data to create a precise forest fire risk map using the support vector machine algorithm. Forest fire risk map was classified into 5 distinct risk zones, Very High Risk (47.38 Km2), High Risk (275.98 km2, Moderate Risk (985.49 km2), Low Risk (1741.17 km2) and Very Low Risk (2374.11 km2) aiding in proactive fire management. By embracing this innovative tool, decision-makers can protect forests, preserve biodiversity, and ensure a sustainable future for generations to come.

To improve accessibility, this article describes a static, four-legged, walker that can be constructed from materials and fasteners commonly available from hardware stores coupled by open-source 3-D printed joints. The designs are described in detail, shared under an open-source license, and fabricated with a low-cost open-source desktop 3-D printer and hand tools. The resulting device is loaded to failure to determine the maximum load that the design can safely support in both vertical and horizontal failure modes. The experimental results showed the average vertical failure load capacity was 3680±694.3N, equivalent to 375.3±70.8kg of applied weight with the fractured location at the wood dowel handlebars. The average horizontal load capacity was 315.6±49.4N, equivalent to 32.2±5.1kg. The maximum weight capacity of a user of 187.1±29.3kg was obtained, which indicates the open-source walker design can withstand the weight requirements of all genders with a 95% confidence interval that includes a safety factor of 1.8 when considering the lowest deviation weight capacity. The design has a cost at the bottom of the range of commercial walkers and reduces the mass compared to a commercial walker by 0.5kg (19% reduction). It can be concluded that this open-source walker design can aid accessibility in low-resource settings.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.

Distinctive strains of Pantoea are used as soil inoculants for their ability to promote plant growth. Pantoea agglomerans strain C1, previously isolated from the phyllosphere of lettuce, can produce indole-3-acetic acid (IAA), solubilize phosphate, and inhibit plant pathogens, such as Erwinia amylovora. In this paper, the complete genome sequence of strain C1 is reported. In addition, experimental evidence is provided on how the strain tolerates arseniate up to 100 mM, and on how secreted metabolites like IAA and siderophores act as biostimulants in tomato cuttings. The strain has a circular chromosome and two prophages for a total genome of 4,846,925-bp, with a GC content of 55.2%. Genes related to plant growth promotion and biocontrol activity, such as those associated with IAA and spermidine synthesis, solubilization of inorganic phosphate, acquisition of ferrous iron, and production of volatile organic compounds, siderophores and GABA, were found in the genome of strain C1. Genome analysis also provided better understanding of the mechanisms underlying strain resistance to multiple toxic heavy metals and transmission of these genes by horizontal gene transfer. Findings suggested that strain C1 exhibits high biotechnological potential as plant growth-promoting bacterium in heavy metal polluted soils.

Direct Behavior Rating (DBR) as a behavioral progress monitoring tool can be designed as longitudinal assessment with only short intervals between measurement points. The reliability of these instruments has been evaluated mostly in observational studies with small samples based on generalizability theory. However, for standardized use in the pedagogical field, a larger and broader sample is required in order to assess measurement invariance between different participant groups and over time. Therefore, we constructed a DBR with multiple items to measure the occurrence of specific externalizing and internalizing student classroom behaviors on a Likert scale (1 = never to 7 = always). In a pilot study, two trained raters observed 16 primary school students and rated the student behavior over all items with a satisfactory reliability. In the main study, 108 regular primary school students, 97 regular secondary school students and 14 students in a clinical setting were rated daily over one week (five measurement points). IRT analyses confirmed the instrument’s technical adequacy, and latent growth models demonstrated the instrument’s stability over time. Further development of the instrument and study designs to implement DBRs are discussed.

Barriers to inventing electronic devices involve challenges of iterating electronic designs due to long lead times for professional circuit board milling or high-costs of commercial milling machines. To overcome these barriers this study provides open source (OS) designs for a low-cost circuit milling machine. First, design modifications for mechanical and electrical sub-systems of the OS D3D Robotics prototyping system are provided. Next, Copper Carve, an OS custom graphical user interface, is developed to enable circuit board milling by implementing backlash and substrate distortion compensation. The performance of the OS D3D circuit mill is then quantified and validated for: positional accuracy, cut quality, feature accuracy and distortion compensation. Finally, the return on investment is calculated for inventors using it. The results show by properly compensating for motion inaccuracies with Copper Carve, the machine achieves a motion resolution of 10 microns, which is more than adequate for most circuit designs. The mill is at least five times less expensive than all commercial alternatives and the material costs of the D3D mill are repaid from fabricating 20-43 boards. The results show that the OS circuit mill is of high-enough quality to enable rapid invention and distributed manufacturing of complex products containing custom electronics.

A useful and increasingly common additive manufacturing (AM) process is the selective laser melting (SLM) or direct metal laser sintering (DMLS) process. SLM/DMLS can produce full-density metal parts from difficult materials, but it tends to suffer from severe residual stresses introduced during processing. This limits the usefulness and applicability of the process, particularly in the fabrication of parts with delicate overhanging and protruding features. The purpose of this study was to examine the current insight and progress made toward understanding and eliminating the problem in overhanging and protruding structures. To accomplish this, a survey of literature was undertaken, focusing on process modeling (general, heat transfer, stress and distortion, and material models), direct process control (input and environmental control, hardware-in-the-loop monitoring, parameter optimization, and post-processing), experiment development (methods for evaluation, optical and mechanical process monitoring, imaging, and design-of-experiments), support structure optimization, and overhang feature design; approximately 140 published works were examined. The major findings of this study were that a small minority of the literature on SLM/DMLS deals explicitly with the overhanging stress problem, but some fundamental work has been done on the problem. Implications, needs, and potential future research directions are discussed in-depth in light of the present review.

The three dimensional conformable time fractional Kadomtsev-Petviashvili and the conformable time fractional modified Kawahara equations are solved by implementing the Kudryashov's procedure. The corresponding wave transformation reduces both equations to some ODEs. Balancing the nonlinear and the highest order derivative terms gives the structure of the solutions in the finite series form. The useful symbolic tools are used to solve the resultant algebraic systems. The solutions are expressed in explicit forms.

Anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids, homocysteine (Hcy)-thiolactone, and proteins modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of mechanisms by which low PON1 leads to disease and high PON1 is protective. Studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that disruption of these processes leads to disease.

In the present work, vertically aligned ultrathin 2D In2S3 nanosheets are grown with a chemical vapor deposition technique to enhance the photoresponse by increasing surface area, and optical absorption. The 2D vertically aligned In2S3 nanosheets have shown excellent PEC water-splitting in terms of excellent photocurrent density value of 4.5 mAcm-2, incident photon to current conversion efficiency is 53 % and hydrogen production of 90% has been achieved in the visible region with higher stability. Ultrathin vertically aligned In2S3 nanosheets also show high responsivity, high charge carrier density, lesser recombination rate, and a capacious space charge layer for excellent water-splitting performance. This straightforward method of creating ultrathin 2D nanosheets of In2S3 also has significant potential for other fields where effective absorption and charge separations are required, like photodetection, optical electronics, and gas sensing.

Klippel-Feil disease is a condition characterized by a defect in the spine, consisting in the fusion or non-separation of two or more vertebrae of the cervical tract. It usually affects 1 every 50.000 newborns, and the pathogenesis remains unknown to date, although the role of certain genes deputed in segmentation processes is being studied. A single case of gene Myosin Heavy Chain 3 (MYH3) mutation is described by researchers. Affected patients are often characterized by a relatively short neck and, therefore, poor mobility, a low hairline and obesity and may have other health problems of different nature. The frequent presence of comorbidities worsens the quality of life of these young patients. The following case describes the synergistic effect of Incobotulinum toxin type A and physiotherapy in a small patient with MYH3 mutation-related Klippel-Feil Syndrome (KFS) complicated by bilateral paraplegia, to improve the spasticity condition of the lower limbs. To assess improvements over time, the patient underwent rating scales to determine spasticity (Modified Ashworth Scale: MAS), the neck’s range of motion (ROM), and muscle tone by using MyotonProÒ. Specifically, measurements were taken on the day of the first medical examination (T0), the month after the injection and the startup of therapeutic exercise (T1), at three months (T2), and then once a month for a total of 6 months (T3, T4 and T5). This therapeutic approach led to entirely satisfactory results with the child’s well-being, prolonged until the sixth month and with a total absence of any side effects.

The monitoring of coastal waters using satellite data, from sensors including Sentinel-3 OLCI, has become a vital tool in the management of these water environments; especially when it comes to improving our understanding of the effects of climate change on these regions. In this study, Level-2 water products derived from different OLCI Sentinel-3 processors were validated against a comprehensive in situ dataset from the NW Baltic Sea proper region. The products validated were those of the regionally adapted Case-2 Regional Coast Colour (C2RCC) OLCI processor (v1.0 and v2.1), as well as the latest standard Level-2 OLCI case 2 (Neural Network) products from Sentinel-3’s processing baseline: Baseline Collection 003 (BC003), including “CHL_NN”, “TSM_NN”, and “ADG443_NN”. Furthermore, the effect of the current EUMETSAT system vicarious calibration (SVC) on the Level-2 water products was also validated. Results showed that the system vicarious calibration (SVC) reduces the reliability of the Level-2 OLCI products. For example, the application of these SVC gains to the OLCI data for the regionally adapted v2.1 C2RCC products resulted in RMSD increases of 36% for “conc_tsm”; 118% for “conc_chl”; 33% for “iop_agelb”; 50% for “iop_adg”; and 10% for “kd_z90max” using a ±3h validation window. The findings indicate that the current EUMETSAT SVC gains should be applied and interpreted with caution in the region of study at present. A key outcome of the paper recommends the development of a regionally specific SVC against AERONET-OC data for the region.

High-quality and large-size single crystals of lead-free Na0.5Bi0.5TiO3 were grown using the Czo-chralski technique. The crystals had pure perovskite structure with rhombohedral symmetry and were translucent in the visible and near infrared spectral ranges recorded in the interval 350-1050 nm. The energy gaps determined from the X-ray photoelectron spectroscopy (XPS) and optical measurements were approximately 2.92 eV. The current-voltage characteristics, depolarization current, dc (σdc) and ac (σac) electrical conductivity, and Seebeck coefficient of the crystals were investigated. The frequency/temperature-dependent electrical properties were also measured and analyzed through complex impedance spectroscopy. An overlapping reversible insulator-metal transition (resistive switching) on nanoscales, caused by the electric field, was detected. This was the first time that most of these investigations were performed for this material. The following conductivity mechanisms of NBT single crystals were identified: (i) quasi-free electron and hole conduction and hopping-charges mechanism at low temperatures, (ii) small polaron conductivity in the middle temperature range, and (iii) a significant contribution of the oxygen vacancies to conductivity in the high temperature range. The activation energy values determined from the conductivity data, the imaginary part of the electric impedance and the modulus indicate that the relaxation process in the high-temperature range is attributable to both single and double ionized oxygen vacancies, in combination with the hopping of electrons between Ti4+ and Ti3+. P-type electrical conductivity was also found. These discoveries create new possibilities of reducing the electrical conductivity of NBT and improving the process of effectively poling this material. The density of the electronic states was investigated using an ab initio method. The energy gap cal-culated for NBT (R3c) was 2.8 eV, and is well comparable to those determined from XPS and optical measurements. Our results indicate the possibility of tuning material properties by inten-tionally creating non-stoichiometry/structural defects (oxygen vacancies, cation excess and cation deficiency).

The combustion of PVC cables in fires results in the release of hydrogen chloride gas. In the European Union, Regulation (EU) No 305/2011, in force since 2017, requires the classification of cables permanently installed in buildings for reaction to fire, smoke, flaming droplets, and acidity. The additional classification for acidity is evaluated through EN 60754-2, involving pH and conductivity measurements. This study focuses on the essential research and development of low-smoke acidity PVC compounds for cables, mainly aiming to meet the stringent additional classifications for acidity, a1 or a2, which cannot be achieved with traditional PVC cables. Understanding the chemistry of thermal decomposition and combustion, especially in the presence of hydrogen chloride scavengers, is crucial for meeting the best acidity classification. The article reviews the current tube furnace tests used in the European Union for cable halogen and acidity assessments. It discusses the limitations of the existing method (EN 60754-2) and highlights the potential of emerging tests such as IEC EN 60754-3, which employs ion chromatography for improved sensitivity and specificity. In the experimental part of the article, various standard and low-smoke acidity cable compounds are tested using tube furnace experiments with different heating regimes. The concentrations of cations and anions in solution are measured through ion chromatography and inductively coupled plasma–optical emission spectrometry. This detailed analysis aims to identify the species influencing pH and conductivity, which is crucial for designing effective acid scavengers that do not impact conductivity. The conclusive results emphasize that HCl from PVC thermal decomposition is the primary driver of pH and conductivity, and the contribution from the decomposition of additives and byproducts from combustion is found to be negligible in most of the tested PVC compounds for cables. The findings underscore the importance of understanding the thermal decomposition of PVC compounds to design acid scavengers capable of trapping hydrogen chloride without adversely impacting conductivity.

The mechanisms underlying the de novo regeneration of adventitious roots are still poorly understood, particularly in trees. In this study, we developed a system for studying different modulators of adventitious rooting (AR) at physiological and molecular levels by using for the first time leaves excised from chestnut microshoots. The rooting response of leaves was ontogenetic-stage dependent, and similar to that of the original microshoots. Initiation of root primordia and root development were inhibited by application of N-1-naphthyl-phthalamic acid (NPA), although the effect of this inhibitor of auxin polar transport (PAT) depended on the timing of application. Expression of CsSCL1, an auxin-inducible gene in juvenile and mature shoots during AR, was upregulated by auxin only in rooting-competent leaves during the novo root organogenesis and the expression was reduced by the NPA treatment. This inhibitory effect on gene expression was detected during reprograming of rooting competent cells towards root initials in response to auxin, indicating that PAT-mediated upregulation of CsSCL1 is required in the initial steps of AR in chestnut leaves. The localized expression of CsSCL1 in the quiescent center (QC) also suggests a role for this gene in the maintenance of meristematic competence and root radial patterning.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

Artificial Intelligence (AI) has the power to generate scenarios and make predictions through the use of advanced algorithms and machine learning techniques. OpenAI’s GPT-3 AI is a state-of-the-art language model that has been trained on a large dataset of text, which allows it to generate hu-man-like text, and it can generate scenarios for different fields. However, GPT-3 was trained on data available up until June 2021, had no access to more recent data nor was connected to the internet. In this study, we investigated the capability of OpenAI’s GPT-3 AI to predict the Ukrainian war es-calation, which started in 2022 and had massive geopolitical effects. We used GPT-3´s capability to generate future scenarios, to check those scenarios for internal consistency, and to create a proba-bility estimate. The results showed that although GPT-3 described an open war as one of the low probability scenarios, its capability on predicting the future was limited. Furthermore, it became evident that checking internal consistency of the generated scenarios could be improved. We ap-preciated GPT-3 as very useful and powerful for generating future scenarios, but also concluded that its prediction capabilities of real-world events are limited, should be used with caution, and require further development.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico, ex vivo, and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) receptors are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. Acute pre-treatment with L-17 robustly increased c-Fos immunoreactivity in the amygdala (central nucleus), suggesting increased neuronal excitability in this brain area after L-17 administration. Acute L-17 also dose-dependently inhibited of 5-HT neurons of the dorsal raphe nucleus (DRN). This inhibition was partially reversed by subsequent administration of WAY100135, suggesting the involvement of extracellular 5-HT. Based on in silico predictions, c-Fos immunohistochemistry, and in vivo electrophysiology, we suggest that L-17 is a potent 5-HT reuptake inhibitor and/or partial 5-HT1A receptor antagonist. Thus, L-17 might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardio-protective properties, it can be useful in post-stroke and post-myocardial infarction (MI) depression. In general, combined in silico predictions and ex vivo neurochemical and in vivo electrophysiological assessment might be a useful strategy for early preclinical assessment of the affectivity and neural mechanism in action of the novel CNS drugs.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

Cationised hemp cellulose was prepared by etherification with two quaternary ammonium salts: 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTAC) and glycidyltrimethylammonium chloride (GTMAC) and examined for (i) the efficiency of Cr(VI) removal under acid mine-drainage (AMD) conditions, and (ii) antibacterial activity. Adsorbents were characterised by electron microscopy, Fourier transform infrared (FTIR), CP-MAS ¹³C nuclear magnetic resonance (NMR) spectroscopy, elemental composition and surface charge. FTIR and solid state ¹³C NMR confirmed the introduction of quaternary ammonium moieties on cellulose. ¹³C NMR also showed that cationisation decreased the degree of crystallisation and lateral dimensions of cellulose fibrils. Nevertheless, 47 % - 72% of Cr(VI) ions were removed from solutions at pH 4, by 0.1 g of CHPTAC and GTMAC-cationised cellulose, respectively. Adsorption kinetics followed the pseudo-second order model and isotherms were best described by the Freundlich and Dubinin-Radushkevich models. When GTMAC-modified cellulose was applied to AMD contaminated water (pH 2.7), however, Cr(VI) uptake removal decreased to 22% likely due to competition from Al and Fe ions. Nevertheless, cationised materials displayed considerable antibacterial effects, reducing the viability of Escherichia coli by up to 45 % after just 3 hours of exposure. Together, these results suggest that cationised cellulose can be applied in the treatment of Cr(VI)-contaminated mine water particularly if pre-treatments to reduce Fe and Al concentrations are applied.

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.

Two novel core-shell composites SiO2@PMDA-Si-Tb, SiO2@PMDA-Si-Tb-phen with SiO2 as the core and terbium organic complex as the shell, were successfully synthesized. The terbium ion was coordinated with organic ligand forming terbium organic complex in the shell layer. The bi-functional organosilane ((HOOC)2C6H2(CONH(CH2)3Si(OCH2CH3)3)2 (abbreviated as PMDA-Si) was used as the first ligand and phen as the second ligand. Furthermore, the silica-modified SiO2@PMDA-Si-Tb@SiO2, SiO2@PMDA-Si-Tb-phen@SiO2 core-shell-shell composites were also synthesized by sol–gel chemical route. An amorphous silica shell was coated around the SiO2@PMDA-Si-Tb and SiO2@PMDA-Si-Tb-phen core-shell composites. The core-shell and core-shell-shell composites both exhibited excellent luminescence in solid state. The luminescence of core-shell-shell composites was stronger than that of core-shell composites. Meanwhile, an improved luminescence stability property for the core-shell-shell composites was found in the aqueous solution. The core-shell-shell composites exhibited bright luminescence, high stability, long lifetime, and good solubility, which may present potential applications in the field of bio-medical.

Electricity demand forecasting has been a real challenge for power system scheduling in the different levels of the energy sectors. Various computational intelligence techniques and methodologies have been employed in the electricity market for load forecasting; although, scant evidence is available about the feasibility of each of these methods considering the type of data and other potential factors. This work introduces several scientific, technical rationale behind intelligent forecasting methods, based on the work of previous researchers in the field of energy. The fundamental benefits and main drawbacks of the aforementioned methods are discussed in order to depict the efficiency of each approach in various situations. In the end, a proposed hybrid strategy is represented.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Exact solutions to conformable time fractional (3+1)- dimensional equations are derived by using the modified form of the Kudryashov method. The compatible wave transformation reduces the equations to an ODE with integer orders. The predicted solution of the finite series of a rational exponential function is substituted into this ODE. The resultant polynomial equation is solved by using algebraic operations. The method works for the Jimbo-Miwa, the Zakharov-Kuznetsov and the modified Zakharov-Kuznetsov equations in conformable time fractional forms. All the solutions are expressed in explicit forms.

Abnormal platelet functions are associated with human morbidity and mortality. Maintaining physiological platelet function is critical to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer’s disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular injury sites. Platelets also release various pro-inflammatory, anti‐inflammatory, and angiogenic factors and shed microparticles in the circulation. The challenge for therapeutic intervention in these diseases will be identifying factors that preferentially block specific targets involved in platelets' complex contribution to inflammation or tumor progression while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors. Potent natural antiplatelet factors were investigated, including n-3 fats, polyphenols, and other bioactive compounds. This review describes the anti-platelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease.

The hetero Diels-Alder (HDA) reaction between the ambident heterodiene 3-methylene-2,4-chromandione (MCDO) and the non-symmetric methyl vinyl ether (MVE) is investigated within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) computational level. The aim of this study is to gain insight into the molecular mechanism and to elucidate the factors that control the selectivity found experimentally. DFT-based reactivity indices reveal that MCDO exhibits strong electrophilic character, while MVE displays a strong nucleophilic character. Meanwhile, Parr function explains the ortho regioselectivity of this HDA reaction. The highly polar nature of this HDA reaction, supported by the high global electron density transfer (GEDT) taking place at the transition state structures (TSs), accounts for the very low activation energy associated with the most favorable TS-4on. The ambident nature of MCDO allows the formation of two constitutional isomeric cycloadduct. In the case of MVE, the pseudocyclic selectivity is attained by a thermodynamic control. This polar HDA reaction displays an endo stereoselectivity and a complete ortho regioselectivity. A comparative Relative Interacting Atomic Energy (RIAE) analysis of the two diastereomeric TS-4on and TS-6on indicates a highly likeness between them, which explains the low pseudocyclic selectivity under kinetic control.

The demand for polymer composites with improved mechanical and electrical properties is crucial for advanced aerospace, electronics, and energy storage applications. Single-walled carbon nanotubes (SWCNTs) and iron oxide (Fe₃O₄) nanoparticles are key fillers that enhance these properties, yet challenges like orientation, uniform dispersion, and agglomeration must be addressed to realize their full potential. This study focuses on developing SWCNTs/Fe₃O₄ epoxy composites by keeping the SWCNT concentration constant at 0.03 Vol.% and varying Fe₃O₄ concentrations at 0.1, 0.5, and 1 Vol.% with two different configurations: randomly orientated (R-) and magnetic field-assisted horizontally aligned (A-) SWCNTs/Fe3O4 epoxy composites and investigates the effects of filler concentration, dispersion, and magnetic alignment on the mechanical and electrical properties. The research reveals that both composite configurations achieve an optimal mechanical performance at 0.5 Vol.% Fe₃O₄, while A- SWCNTs/Fe3O4 epoxy composites outperformed at all concentrations. However, at 1 Vol.% Fe₃O₄, mechanical properties decline due to nanoparticle agglomeration, which disrupts stress distribution. In contrast, electrical conductivity peaks at 1 Vol.% Fe₃O₄, indicating that the higher density of Fe₃O₄ nanoparticles enhances the conductive network despite the mechanical losses. This study highlights the need for precise control over filler content and alignment to optimize mechanical strength and electrical conductivity in SWCNTs/Fe₃O₄ epoxy nanocomposites.

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148bp fragment showing particularly strong expression in gill and intestine. It was sequenced and represented a piece of the AQP11 gene. However, as the fragment may have resulted from contaminating genomic DNA (in total RNA used to make cDNA), 5’ and 3’ RACE was performed to amplify the two ends of the putative cDNA. 5’ and 3’ RACE amplifications depend on the presence of a 5’ cap nucleotide and a poly A tail respectively on the putative AQP11 mRNA. Hence successful amplification was only possible from cDNA and not genomic DNA. Nested RACE amplifications were performed using gill and intestinal RACE cDNA but none of the DNA fragments were AQP11. Consequently, the spiny dogfish AQP11 gene may represent a pseudogene.

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.

Alzheimer's disease (AD) is characterized by abnormal amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-PET or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n=88) and some volunteers (n=66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Load shifting is one of the demand side management (DSM) strategies to support the efficiency in the electricity grid during the peak hours demand. Load shifting at the appliance level is interesting to review since the appliance usage is one of the main inputs in the load profile analysis. More review studies in load shifting at the appliance level are required as it is a specific issue of load profile research body, and still limited studies are available at this moment. It is also essential to focus on the appliance usage patterns to better understand the impacts and characteristics of the individual appliance. The existing studies in load shifting have applied common structured literature reviews, and our study addresses the transparency of each stage and sub-stage of the selection of the final list studies. The finding shows that efficiency has been achieved in the installed capacity reduction, cost including emission reductions, and peak consumption reduction. The most applied method in the load shifting at the appliance level is by developing the load shifting optimisation algorithms. This work contributes to provide a transparent process of applying a systematicity literature review, where it becomes a source of knowledge and grounded theory. It contributes to a limited and specific research of load shifting at the appliance level by highlighting and discussing the key findings for the readers. In specific, it contributes to improve energy efficiency by presenting the load shifting methods at the appliance level and identifying the controllable and uncontrollable appliances. This detail review study at the appliance level can make valuable contributions to support decision and policy-making by illuminating new dynamic system in load shifting area in specific, and demand side management in general for energy efficiency.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Consistent calibration and monitoring is a basic prerequisite for providing reliable time series of global and regional sea level variations from altimetry. The precision of sea level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) is assessed at eleven GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauges readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between gauge and altimetry which improves the agreement between the two data sets by 15-75%. The precision of the altimeters is depending on location and mission and is shown to be at least 1.8 to 3.7 cm based on an assumed precision of 2 cm for the gauges. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by WSV might complement the calibration and monitoring activities at dedicated CalVal stations.

In this paper I will address Dr. Sonne’s questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas and is more immature and more symptomatic while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions that Dr. Sonne presented and will discuss also my published theory on the physical nature of subjective experience and its relation to the brain and how that theory interacts with DBP, and how the 2 theories relate to subjective experience, will, behavior, psychopathology and its treatment.

The compound, C27H23N3 (1), crystallizes in the triclinic system of the P-1 space group. The unit cell comprises a dimer of 1, in which the monomers are linked by two complementary hydrogen bonds between N1 and H1-C1 of another molecule. The dimers form chains along the a-axis through intermolecular interactions between the N2 acceptor atoms and C17 donors from molecules in the nearest neighbouring dimer. These interactions form extended sheets of the dimers of 1, along the ab plane. The quinolinylmeth-2-yl groups of 1 lie in almost orthogonal planes and their N1/2(q) donor atoms being away from the apical amino N3 atom.

To assist firefighters and other first responders to use their existing equipment for respiration during the COVID-19 pandemic without using single-use, low-supply, masks, this study outlines an open source kit to convert a 3M-manufactured Scott Safety self-contained breathing apparatus (SCBA) into a powered air-purifying particulate respirator (PAPR). The open source PAPR can be fabricated with a low-cost 3-D printer and widely available components for less than $150, replacing commercial conversion kits saving 85% or full-fledged proprietary PAPRs saving over 90%. The parametric designs allow for adaptation to other core components and can be custom fit specifically to fire-fighter equipment, including their suspenders. The open source PAPR has controllable air flow and its design enables breathing even if the fan is disconnected or if the battery dies. The open source PAPR was tested for air flow as a function of battery life and was found to meet NIOSH air flow requirements for 4 hours, which is 300% over expected regular use.

Human milk fat is a concentrated source of energy and provides essential and long chain polyunsaturated fatty acids. According to previous experiments, human milk fat is partially lost during continuous enteral nutrition. However, these experiments were done over relatively short infusion times, and a complete profile of the lost fatty acids was never measured. Whether this lost happens considering longer infusion times or if some fatty acids are lost more than others remain unknown. Pooled breast milk was infused through a feeding tube by a peristaltic pump over a period of 30 minutes and 4, 12 and 24 hours at 2 ml/hour. Adsorbed fat was extracted from the tubes, and the fatty acid composition was analyzed by Gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss) after 24 hours was 0.6 ± 0.1%. Short-medium chain (0.7%, p=0.15), long chain (0.6%, p=0.56) saturated (0.7%, p=0.4), monounsaturated (0.5%, p=0.15), polyunsaturated fatty (0.7%, p=0.15), linoleic (0.7%, p=0.25), and docosahexaenoic acids (0.6%, p=0.56) were not selectively adsorbed to the tube. However, very long chain fatty (0.9%, p=0.04), alpha-linolenic (1.6%, p=0.02) and arachidonic acids (1%, p=0.02) were selectively adsorbed and therefore lost in a greater proportion than other fatty acids. In all cases, the magnitude of the loss was clinically low.

Given the high number of vehicle-crash victims, it has been established as a priority to reduce this figure in the transportation sector. For this reason, many of the recent researches are focused on including control systems in existing vehicles, to improve their stability, comfort and handling. These systems need to know in every moment the behavior of the vehicle (state variables), among others, when the different maneuvers are performed, to actuate by means of the systems in the vehicle (brakes, steering, suspension) and, in this way, to achieve a good behavior. The main problem arises from the lack of ability to directly capture several required dynamic vehicle variables, such as roll angle, from low-cost sensors. Previous studies demonstrate that low-cost sensors can provide data in real-time with the required precision and reliability. Even more, other research works indicate that neural networks are efficient mechanisms to estimate roll angle. Nevertheless, it is necessary to assess that the fusion of data coming from low-cost devices and estimations provided by neural networks can fulfill the reliability and appropriateness requirements for using these technologies to improve overall safety in production vehicles. Because of the increasing of computing power, the reduction of consumption and electric devices size, along with the high variety of communication technologies and networking protocols using Internet have yield to Internet of Things (IoT) development. In order to address this issue, this study has two main goals: 1) Determine the appropriateness and performance of neural networks embedded in low-cost sensors kits to estimate roll angle required to evaluate rollover risk situations. 2) Compare the low-cost control unit devices (Intel Edison and Raspberry Pi 3 Model B), to provide the roll angle estimation with this artificial neural network-based approach. To fulfil these objectives an experimental environment has been set up composed of a van with two set of low-cost kits, one including a Raspberry Pi 3 Model B, low cost Inertial Measurement Unit (BNO055 - 37€) and GPS (Mtk3339 - 53€) and the other having an Intel Edison System on Chip linked to a SparkFun 9 Degrees of Freedom module. This experimental environment will be tested in different maneuvers for comparison purposes. Neural networks embedded in low-cost sensor kits provide roll angle estimations very approximated to real values. Even more, Intel Edison and Raspberry Pi 3 Model B have enough computing capabilities to successfully run roll angle estimation based on neural networks to determine rollover risks situation fulfilling real-time operation restrictions stated for this problem.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Enhancing the acoustical quality in learning environments is mandatory, especially for Hearing Aids (HAs) users. When in-field evaluations cannot be performed, Virtual Reality (VR) can be adopted for the acoustical quality assessment of existing and new buildings, contributing to the acquisition of subjective impressions in lab settings. To ensure an accurate spatial reproduction of the sound field in VR also for HAs users, multispeaker-based systems can be employed to auralize a given environment. However, most systems are effortful due to costs, size and construction. This work deals with the validation of a VR-system based on a 16-speaker-array synced with a VR-headset, arranged to be easily replicated in small non-anechoic spaces and suitable for HAs users. Both objective and subjective validations are performed against a real university lecture room of 800 m3 and with 2.3 s of Reverberation Time at mid-frequencies. Comparisons of binaural and monoaural room acoustic parameters are performed between measurements in the real lecture room and its lab reproduction. To validate the AudioVisual experience, 32 normal-hearing subjects were administered the Igroup Presence Questionnaire (IPQ) on the overall sense of perceived presence. The outcomes confirm that the system is a promising and feasible tool to predict the perceived room acoustical quality.

1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. 2) Methods: Here, we report the effects of long-term treatment with a SPM, maresin like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. 3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in anti-inflammatory Iba1⁺Arg-1⁺-M2 microglia, inhibited phenotypic switching to pro-inflammatory N1 neutrophils, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and decreased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mitigates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegeneration. These findings provided the preclinical leads and mechanistic insights for the development of MarL1 into an effective modality to ameliorate AD pathogenesis.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs, n-3 PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), are essential polyunsatu-rated fats primarily obtained from fatty fish and plant-based sources. Compelling evidence from preclinical and epidemiological studies consistently suggests beneficial effects of ω-3 PUFAs on bone health and healthy aging processes. However, clinical trials have yielded mixed results, with some failing to replicate these benefits seen in preclinical models. This contraindication is mainly due to challenges such as low bioavailability, potential adverse effects with higher doses, and susceptibility to oxidation of ω-3 fatty acids, hindering their clinical effectiveness. This review provides an in-depth analysis of recent findings, focusing on clinical perspectives and encom-passing all relevant published studies to date, including preclinical and epidemiological research, with an emphasis on the role of omega-3 fatty acids in promoting bone health and supporting healthy aging. Additionally, it explores strategies to improve ω-3 PUFA efficacy, including na-noparticle encapsulation and incorporation of specialized pro-resolving mediators (SPM) derived from DHA and EPA, to mitigate oxidation and enhance solubility, thereby improving therapeutic potential. By consolidating evidence from various studies, this review underscores current in-sights and future directions in leveraging ω-3 PUFAs for therapeutic applications.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.

Covariant integral quantization with rotational symmetry SO(3) is established for the quantum motion on this group manifold, or, alternatively, for Gabor signal analysis on this group. We revisit the action of the related (non-unitary) Weyl-Gabor operator on the Hilbert space of square integrable functions on SO(3) and disclose a set of various properties. By selecting weight functions on the corresponding discrete-continuous phase space, one derives related coherent states and Wigner transform.

The seasonal variation in fatty acids and minerals concentrations was investigated through the analysis of Pecorino Romano cheese samples collected in January, April, and June. A fraction of samples contained missing values in their fatty acid profile. Probabilistic Principal component analysis coupled with Linear Discriminant Analysis was employed to classify cheese samples on a production season basis while accounting for missing data and quantifying the missing Fatty acids concentration for the sample in which they were absent. The levels of rumenic acid, vac-cenic acid and omega-3 compounds were positively correlated with the spring season, while the length of the saturated fatty acids increased throughout the production seasons. Concerning the classification performances, the optimal number of principal components (i.e., 5) achieved an ac-curacy in cross-validation equal to 98 %. Then, when the model was tasked to impute the lacking Fatty acid concentration values, the optimal number of principal components resulted in an R2 value in cross-validation of 99.53%

The theory of heterogeneous nucleation was initially developed as a part of condensed matter physics and later it was used as an important engineering tool to design metallurgical processes. The success leads to wide applications of the theory in metallurgical practice. For example, engineering heterogeneous nucleation in ductile iron has been used to reduce shrinkage defects, suppress cementite formation, and modify size and shape of micro-structural constituencies. This demonstrates how theoretical knowledge could benefit industry practice. This overview aims to summarize the authors’ published studies in co-authorship with colleagues and students, which covered different aspects of engineering heterogeneous nucleation in multiphase cast alloys. Several approaches for engineering heterogeneous nucleation using thermodynamic simulation and practical methods for improving efficiency of nucleation using co-precipitation technique and a local transient melt supersaturation were suggested. Automated Scanning Electron Microscopy Energy-Dispersive-X-ray (SEM/EDX) analysis and a high-resolution Transmission Electron Microscopy (TEM) were used to verify simulation predictions. Practical examples of controlling micro-porosity shrinkage in cast irons with spheroidal graphite are presented to illustrate the power of engineering heterogenous nucleation. The authors appreciate the great efforts that the co-authors have made on the original, overviewed articles here.

On April 17, 2019, a coach with tourists from Germany crashed in Madeira requiring repatriation by the German Air Force. The Advance Trauma Life Support (ATLS) concept was the central component of patient care. Data in Madeira were collected through a structured interview. The analysis of the Aeromedical Evacuation was based on intensive care transport records. In Germany all available were reviewed for data collection. Quality of life (HRQoL) was evaluated by the 12-item Short-Form Health Survey (SF-12). Twenty-eight prehospital patients were transported to the Level III Trauma Center in Funchal (Madeira). Five operative procedures were performed. Fifteen patients were eligible for Aeromedical Evacuation (AE). In the second hospital phase in Germany in total 82 radiological images and nine operations were performed. Hospital stay lasted 11 days (median, IQR 10–18). Median Follow-up (14 of 15 patients) was 16 months (IQR 16–21). 80% (8 out of 10) showed an increased risk for post-traumatic stress disorder (PTSD). Six key findings were identified in this study: divergent injury classification, impact of AE mission on health status, lack of communication, need of PTSD prophylaxis, patient identification, media coverage. Those findings may improve AE missions in the future e.g. required after armed conflicts.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.

Much evidence now indicates a direct crosstalk between thyroid hormones (THs) and the immune system. We previously showed that THs behave as anti-inflammatory agents in human leukemic THP-1 monocytes, but a potential neuroprotective effect of THs in microglia have been under-investigated. Microglia, the primary innate immune cells of the brain, play a pivotal role in the regulation of neuroinflammation and nongenomic integrin αvβ3-mediated action of THs appear to be involved. Integrin αvβ3 was highly expressed in activated BV-2 cells, while it was decreased by THs. In addition, THs facilitated wound healing in BV-2 murine microglia cells activated by lipopolysaccharide (LPS), through integrin αvβ3 and reactive oxygen species (ROS), with tetrac (a metabolite of TH) potentiated the inhibition of migration. Nitric oxide (NO) played a role with different mechanisms in the presence of either T3 or T4. Our data showed the capability of TH and analogues to modulate the M1-to-M2 microglial transition and suggest a new spectrum of actions in the central nervous system (CNS).

Lower respiratory infections (LRI), upper respiratory infections (URI), and nutritional deficiency (ND) in under-5 children from low-middle-income countries has been at a high level for decades, despite efforts that have been realized in some countries. The study used data extracted from the global burden of diseases (GBD) to analyze the trends behavior between 1990 and 2019, and evaluate their association with maternal factors. Between 1990 and 2019, the incidence of LRI decreased between 1.2 percent and 1.3 percent (1.2-1.3%) in different female age groups, and by nearly 1 to 1.3% in those of the male gender. The incidence of URI did not decrease (0.0%) in any of their age groups. ND incidence declined around 0.7 to 4.9% in the under-5 children. LRI declined mostly in the female age groups (1.2 to 1.3%), while ND decreased more in the male gender (0.9 to 4.9%). Maternal risk factors were strongly associated to the incidence of the three conditions with over 90 percent. Maternal prevalence of HIV/AIDS and tuberculosis positively impacted the incidence of LRI, URI, and ND in Chadian under-5 children. Although the incidence of LRI and ND declined, URI incidence remained steady between 1990 and 2019 in Chadian under-5 children. To improve the health and provide a healthy growth of under-5 children, the maternal prevalence of HIV/AIDS and tuberculosis infection should be strongly addressed for a prompt accomplishment of the sustainable development goals.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Footprints are powerful indicators for evaluating the impact of the bioeconomy of a country on environmental goods, domestically and abroad. In this study, we apply a hybrid approach combining a Multi-Regional Input-Output model and land use modelling to compute the agricultural land footprint (aLF). Furthermore, we added information on land-use change to the analysis and allocated land conversion to specific commodities. The German case study shows that the aLF abroad is larger by a factor of 2.5 to 3 than the aLF in Germany. In 2005 and 2010, conversion of natural and semi-natural land-cover types abroad allocated to Germany due to import increases was 2.5 times higher than the global average. Import increases to Germany slowed down in 2015 and 2020, reducing land conversion attributed to the German bioeconomy to the global average. The case study shows that the applied land footprint provides clear and meaningful information for policymakers and other stakeholders. The presented methodological approach can be applied to other countries and regions covered in the underlying database EXIOBASE. It can be adapted, also for an assessment of other ecosystem functions, such as water or soil fertility.

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

The carbonized elastomer-based composites (CECs) possess a number of attractive features in terms of thermomechanical and electromechanical performance, durability in aggressive media and facile net-shape formability, but their relatively low ductility and strength limit their suitability for structural engineering applications. Prospective applications such as structural elements of MEMS can be envisaged, since smaller principal dimensions reduce the susceptibility of components to residual stress accumulation during carbonization, and to brittle fracture in general. We report the results of operando in-SEM study of micro-deformation and fracture behavior of CECs based on NBR elastomeric matrices filled with carbon and silicon carbide. Nanostructured carbon composite materials were manufactured via compounding of elastomeric substance with carbon and SiC fillers using mixing rolling mill, vulcanization, and low-temperature carbonization. Double Edge Notched Tensile (DENT) specimens of vulcanized and carbonized elastomeric composites were subjected to in situ tensile testing in the chamber of the scanning electron microscope (SEM) Tescan Vega 3 using Deben Microtest 1 kN Tensile Stage. The series of acquired SEM images were analyzed by means of Digital Image Correlation (DIC) using Ncorr open source software to map the spatial distribution of strain. These maps were correlated with Finite Element Modelling (FEM) simulations to refine the values of elastic moduli. Besides, the elastic moduli were derived from unloading curve nanoindentation hardness measurements carried out using NanoScan-4D tester and interpreted using the Oliver-Pharr method. Carbonization causes significant increase of elastic moduli from 0.86 ± 0.07 to 14.12 ± 1.20 GPa for the composite with graphite and carbon black fillers. Nanoindentation measurements yield somewhat lower values, namely, 0.25 ± 0.02 GPa and 9.83 ± 1.10 GPa before and after carbonization respectively. The analysis of fractography images suggests that crack initiation, growth and propagation may occur both at the notch stress concentrator and relatively far from the notch. Possible causes of such response are discussed, namely, (1) residual stresses introduced by processing; (2) shape and size of fillers; and (3) the emanation and accumulation of gases in composites during carbonization.

Abstract: In order to accelerate deployment of distributed recycling by providing low-cost feed stocks of granulated post-consumer waste plastic, this study analyzes an open source waste plastic granulator system. It is designed, built and tested for its ability to convert post-consumer waste, 3-D printed products and waste into polymer feedstock for recyclebots of fused particle/granule printers. The technical specifications of the device are quantified in terms of power consumption (380 to 404W for PET and PLA, respectively) and particle size distribution. The open source device can be fabricated for less than USD$2000 in materials. The experimentally-measured power use is only a minor contribution to the overall embodied energy of distributed recycling of waste plastic. The resultant plastic particle size distributions were found to be appropriate for use in both recyclebots and direct material extrusion 3-D printers. Simple retrofits are shown to reduce sound levels during operation by 4dB-5dB for the vacuum. These results indicate that the open source waste plastic granulator is an appropriate technology for community, library, makespace, fab lab or small business-based distributed recycling.

In our previous published papers, considering 3 large atomic gravitational constants assumed to be associated with weak, strong and electromagnetic interactions, we have proposed the existence of a nuclear charge of magnitude, e_n=2.95e and developed a nuclear mass formula associated with strong and weak interactions having 4 simple terms and only one energy coefficient. Two important assumptions are, there exists a weak fermion of rest energy 585 GeV and strong coupling constant is the squared ratio of electromagnetic charge and nuclear charge. The aim of this paper is associated with understanding the mystery of quantum of magnetic flux, Planck’s quantum radiation constant and Reduced Planck’s constant. Proceeding further, quark charges, strong coupling constant, nuclear stability, nuclear binding energy, medium and heavy atomic X-ray levels and celestial magnetic moments can be understood in a unified approach. It may also be noted that, by considering integral nature of elementary particle masses, it seems possible to understand the discreteness of angular momentum. Considering our proposed e_n=2.95e=3e as a characteristic nuclear charge, it seems possible to understand the integral nature of quarks electromagnetic charge. With this idea, neutron, proton and pions decay can be understood very easily. In all the cases, up quark of charge (±2e) seems to play a crucial role with the internal transformation of down quark of charge (±e) and external observable elementary basic elementary particles. It needs further study at fundamental level.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.