At present European buildings typically consume two to five times more energy than predicted at the design stage. An important cause of this performance gap is the discrepancies between the design specification and the As-Built condition. Such discrepancies are mainly due to the gaps in knowhow between design, production and construction professionals. Design is more and more contained into a virtual environment and loses touch with the physical production and construction sites. As the construction sector enters the Industry 4.0 era, Building Information Modelling (BIM) based Mixed Reality can intertwine virtual and real worlds to bridge the knowhow gaps.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

The modification of land use is a crucial factor in the dysfunction of ecosystems. It considerably influences the hydrological cycle of basins. This study focuses on the Oueme basin, which represents almost half of the total area of Benin, and describes the current and future evolution of its land cover using the maps of the Land Use Land Cover Dynamics project (1975, 2000 and 2013). A temporal analysis of the surface states was performed with QGIS and the potential land cover in 2025, 2050 and 2085 was estimated using the Markov chain algorithm in the IDRISI software. The results show that the Oueme basin is predominantly savanna (77.70% in 1975, 66.29% in 2000 and 57.10% in 2013). Forest areas, which represented the second class in 1975 with a total proportion of 13.34%, have gradually decreased to 8.66% and 6.89% respectively in 2000 and 2013. Conversely, cultivated areas more than tripled in 2000 and quadrupled in 2013. Residential areas are increasing very strongly in the southern part of the basin with an amplification in the recent period (6% between 2000-2013 against 2% between 1975-2000). The recent period is more exposed to changes in surface condition and these changes are likely to be amplified in the future (probable total disappearance of forested areas in 2085). We recommend clarifying the impacts that each land use category generates/will generate on the hydrological cycle of this basin.

The phylogeny of Neoaves, the largest clade of extant birds, has remained unclear despite intense study. The difficulty associated with resolving the early branches in Neoaves is likely driven by the rapid radiation of this group. However, conflicts among studies may be exacerbated by the hypothesis that relationships are sensitive to the data type analyzed. For example, analyses of coding exons typically yield trees that place Strisores (nightjars and allies) sister to the remaining Neoaves, while analyses of non-coding data typically yield trees where Mirandornites (flamingos and grebes) is the sister of the remaining Neoaves. Our understanding of data type effects is hampered by the fact that previous analyses have used different taxa, loci, and types of non-coding data. Herein, we provide strong corroboration of the data type effects hypothesis for Neoaves by comparing trees based on coding and non-coding data derived from the same taxa and gene regions. A simple analytical method known to minimize biases due to base composition (coding nucleotides as purines and pyrimidines) resulted in coding exon data with increased congruence to the non-coding topology using concatenated analyses. These results improve our understanding of the resolution of neoavian phylogeny and point to a challenge - data type effects - that is likely to be an important factor in phylogenetic analyses of birds (and many other taxonomic groups). Using our results, we provide a summary phylogeny that identifies well-corroborated relationships and highlights specific nodes where future efforts should focus.

Both the use of plastic and its decomposition products lead to the distribution of plastic all over the earth and finally to the uptake by all kind of living beings including humans. Still, it is widely unknown what risks harbor the widespread uptake of plastics for human health, espe-cially regarding contributing factors like size, shape and surface composition. We assessed the uptake of polymethylmethacrylate (PMMA)-nano- and microbeads for HEK293-, A549- and MRC5 cells. Via confocal microscopy, we localized multiple PMMA-beads inside the cytosol of cells. Uptake of PMMA-beads did not alter cell growth and cell division, implying no short-term toxicity towards human cells. Further, we used a cAMP response element binding protein (CREB)-mediated reporter assay to assess whether internalized PMMA-nanobeads alter cell-signaling pathways. In contrast to the in vitro transcription, where the addition of PMMA-nanobeads abolished the transcription, no changes regarding CREB-mediated cell sig-naling are given in HEK293-cells. Our data led to the assumption that PMMA-nano-and mi-crobeads are internalized via endocytosis and end up as lysosomes within the cells cytosol. Therefore, we concluded differences regarding the surface composition of the PMMA-nanobeads mainly affect its potential to alter cell signaling. These findings emphasize the key role the sur-face composition plays regarding microplastic and its risks for human health.

Despite the long history of using protein sequences to infer the tree of life the potential for different parts of protein structures to retain historical signal remains unclear. We propose that it might be possible to improve analyses of phylogenomic datasets by incorporating information about protein structure; we test this idea using the position of the root of Metazoa (animals) as a model system. We examined the distribution of “strongly decisive” sites (alignment positions that support a specific tree topology) in a dataset comprising >1,500 proteins and almost 100 taxa. The proportion of each class of strongly decisive sites in different structural environments was very sensitive to the model used to analyze the data when a limited number of taxa were used but they were stable when taxa were added. As long as enough taxa were analyzed, sites in all structural environments supported the same topology (ctenophores sister to other animals) regardless of whether standard tree searches or decisive sites were used to select the optimal tree. However, the use of decisive sites revealed a difference between the support for minority topologies for sites in different structural environments; buried sites and sites in sheet and coil environments exhibited equal support for the minority topologies whereas solvent exposed and helix sites had unequal numbers of sites supporting the minority topologies. Given the plausible trees equal support for minority topologies is consistent with discordance among gene trees, making it possible the relatively slowly evolving buried (and sheet and coil) sites are giving an accurate picture of the true species tree as well as the amount of conflict among gene trees. Alternatively, the apparent support could reflect currently uncharacterized processes of molecular evolution. Regardless, it is clear that analyses of the deepest branches in the animal tree of life using sites in different structural environments are associated with a subtle data type effect that results in distinct phylogenetic signals.

Leukemia cutis (LC) is defined as leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and in T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis and treatment of leukemic skin involvement in different types of leukemia

The usage of biotechnological molecules and processes is an indispensable part of the resource technology research. The development of novel biomolecules therefore needs to be adapted to the existing applicational conditions and biological processes are to be examined. Novel biosorbents may not only contribute to future applications but can be of further used, e.g. to better understand the interaction of known metal- and metalloid-interacting biological molecules and materials. This review highlights biotechnological approaches published so far for bioremediation as well as metal recovery with a special spotlight on cobalt, nickel and arsenic.

Phylogenomics, the use of large datasets to examine phylogeny, has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life; this could reflect, at least in part, the poor-fit of the models used to analyze heterogeneous datasets. Some of the heterogeneity may reflect the different patterns of selection on proteins based on their structures. To test that hypothesis, we developed a pipeline to divide phylogenomic protein datasets into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had distinct signals for the topology of the deepest branches in the metazoan tree. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of exposed sites (on the surface of proteins) yielded a tree that placed ctenophores sister to all other animals whereas sites buried inside proteins yielded a tree with a sponge-ctenophore clade. These differences in phylogenetic signal were not ameliorated when we repeated our analyses using the CAT model, a mixture model that is often used for analyses of protein datasets. In fact, the heterogeneous CAT model resulted in several rearrangements that are unlikely to represent evolutionary history. However, analyses conducted after recoding amino acids to limit the impact of deviations from compositional stationarity increased the congruence in the estimates of phylogeny for exposed and buried sites; after recoding amino acids both trees supported placement of ctenophores sister to all other animals. These results provide striking evidence that it is necessary to achieve a better understanding of the constraints due to protein structure to improve phylogenetic estimation.

The degradation and detachment of the polyamide (PA) layer in thin-film composite (TFC) membranes due to chlorine based chemical cleaning and material difference of PA layer and substrate are two major bottlenecks of forward osmosis (FO) technology. In this study, a new type of FO membranes were prepared by controlling self-polymerization of dopamine (DA) in the aqueous phase and the reaction with trimesoyl chloride (TMC) during interfacial polymerization (IP) process. These membranes were characterized by attenuated total reflection Fourier transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FESEM) and water contact angle measurements. The influence of synthesis parameters such as pH of the aqueous phase, reaction time, temperature, and monomer concentrations were systematically investigated. The optimized membrane showed enhanced structure stability in ethanol (7.1 times higher) and chlorine resistance (72.3 times higher) than the conventional Piperazine(PIP)/TMC membrane due to（poly-dopamine）PDA bio-adhesion and polyester groups in the membrane structure. In general, DA/TMC membranes could be an effective strategy to fabricate high-performance FO membranes with excellent structural stability and chlorine resistance.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.

The factors that determine the relative rates of amino acid substitution during protein evolution are complex and they are known to vary among taxa. We estimated relative exchangeabilities for pairs of amino acids from clades spread across the tree of life and assessed the historical signal in the distances among these clade-specific models. We trained these models separately on collections of arbitrarily selected protein alignments and on ribosomal protein alignments. In both cases we found a clear separation between the models trained using multiple sequence alignments from bacterial clades and the models trained on archaeal and eukaryotic data. We assessed the predictive power of our novel clade-specific models of sequence evolution by asking whether fit to the models could be used to identify the source of multiple sequence alignments. Model fit was generally able to classify protein alignments correctly at the level of domain (bacterial versus archaeal), but the accuracy of classification at finer scales was much lower. The only exceptions to this were the relatively high classification accuracy for two archaeal lineages: Halobacteriaceae and Thermoprotei. Genomic GC content had a modest impact on relative exchangeabilities despite having a large impact on amino acid frequencies. Relative exchangeabilities involving aromatic residues exhibited the largest differences among models. There were a small number of exchangeabilities that exhibited large differences in comparisons among major clades and between generalized models and ribosomal protein models. Taken as a whole, these results reveal that a small number of relative exchangeabilities are responsible for much of the structure of the “model space” for protein sequence evolution. If we look beyond the information that these clade-specific models reveal about protein evolution the models themselves are likely to be useful tools for phylogenomic inference across the tree of life.

Avian sex chromosomes evolved after the divergence birds and crocodilians from their common ancestor, so they are much younger than the better-studied chromosomes of mammals. It has long been recognized that there may have been several stages to the evolution of avian sex chromosomes. For example, the CHD1 undergoes recombination in paleognaths but not neognaths. Genome assemblies have suggested there may be variation in the timing of barriers to recombination among Neognathae, but there remains little understanding of the extent of this variability. Here, we look at partial sequences of ATP5F1A, which is on the avian Z and W chromosomes. It is known that recombination of this gene has independently ceased in Galliformes, Anseriformes, and at least five neoavian orders, but whether there are other independent cessations of recombination among Neoaves is not understood. We used a combination of data extracted from published chromosomal-level genomes with data collected using PCR and cloning to identify Z and W copies in 22 orders. Our results suggest there may be at least 19 independent cessations of recombination within Neognathae, and 3 clades that may still be undergoing recombination (or have only recently ceased recombination). Analyses of ATP5F1A protein sequences revealed an increased amino acid substitution rate for W chromosome gametologs, suggesting relaxed purifying selection on the W chromosome. Supporting this hypothesis, we found that the increased substitution rate was particularly pronounced for buried residues, which are expected to be more strongly constrained by purifying selection. This highlights the dynamic nature of avian sex chromosomes, and that this level of variation among clades means they should be a good system to understand sex chromosome evolution.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

COVID-19 may not be a ‘youth disease’ but nevertheless impacts the life of young people dramatically, loneliness and negative mood being an unexpected additional pandemic. Many young people rely on social media for their feeling of connectedness with others. However, social media are suggested to have many negative effects on people’s anxiety. Instead of self-disclosing to others, design may develop alternatives to employ social robots for self-disclosure. In a follow-up on Duan et al. (2021), we report on a lab experiment of self-disclosing negative emotions to a social-media group as compared to writing a conventional diary journal or to talk to an AI-driven social robot after negative mood induction (i.e. viewing shocking earthquake footage). Participants benefitted the most from talking to a robot rather than from writing a journal page or sharing their feelings on social media. Self-disclosure on social media or writing a journal page did not differ significantly. In the design of interventions for mental well-being, human helpers thus far took center stage. Based on our results, we propose design alternatives for an empathic smart-home, featuring social robots and chatbots for alleviating stress and anxiety: a social-media interference chatbot, smart watch plus speaker, and a mirror for self-reflection.

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pretransplant serum concentrations of Cav-1 and the occurrence of rejection during follow up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute rejection episodes. Moreover, Cav-1 could be therapeutically useful for attenuating graft rejection.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

A Gem-quality rubies and sapphires are often commercially heat treated at about 800°C or higher temperatures to enhance their colour and clarity, and hence quality. For this study, selected corundum samples containing diaspore- and goethite inclusions were heated step-by-step to a maximum of 1000 °C with the aim to monitor the dehydration and phase transformation of these oxyhydroxides to corundum and hematite during heating. Based on our experiments and in agreement with literature, the dehydration of diaspore in corundum occurs between 525 to 550 °C, whereas goethite transforms to hematite already between 300 and 325 °C. As both, diaspore and goethite are common inclusions in rubies, sapphires, and other corundum varieties, these dehydration reactions and phase transformations can be considered important criteria to separate unheated stones from heated ones, specifically in cases in which other methods (e.g. microscopy, FTIR) are unsuccessful.

The formation and propagation of cracks occurs through irreversible dislocation movements at notches, material defects and grain boundaries. Since this process is partly thermally controlled, the resistance to dislocation movements at low temperatures increases. This slows both fatigue initiation and fatigue crack propagation. From recent experimental data, it can be seen that fatigue crack growth is accelerated below the fatigue transition temperature (FTT) that correlates with the ductile-brittle transition temperature (DBTT) found by well-known fracture mechanics tests, i.e., Charpy impact, fracture toughness, and CTOD. Hence, this study investigates the relation between FTT and DBTT in S500 high-strength steel base material and welded joints at low temperatures using fatigue crack growth, fracture toughness tests as well as scanning electron microscopy. From the tests, an almost constant decrease in fatigue crack propagation rate is determined with decreasing test temperature even below the DBTT.

Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy. This treatment is profoundly underutilized in the palliative care of these patients. The objective of this review is to discuss the pharmacology, pharmacokinetics, side effects, available evidence of effectiveness of pancreatic enzyme use for patients with pancreatic cancer, and challenges along with proposed solutions regarding its use. Pancrelipase is an expensive drug, and it is inactive if not taken correctly. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use of pancreatic enzyme replacement therapy. Pancreatic enzyme replacement therapy (PERT) is a key strategy in managing symptoms of EPI and can improve quality of life, which is a central focus in palliative care.

Detailed sonographic assessment of the fetal neuroanatomy plays a crucial role in prenatal diagnosis, providing valuable insights into timely well-coordinated fetal brain development and detecting even subtle anomalies that may impact neurodevelopmental outcomes. With recent advancements in artificial intelligence (AI) in general and medical imaging in particular, there has been growing interest in leveraging AI techniques to enhance the accuracy, efficiency, and clinical utility of fetal neurosonography. The paramount objective of this scoping review is to discuss the latest developments in AI applications in this field, focusing on image analysis, automation of measurements, prediction models for neurodevelopmental outcomes, visualization techniques, and integration into clinical routine.

Prescriptions for fuels management are universally applied across forest types in British Columbia, Canada, to reduce fire behaviour potential in the wildland-urban interface. Fuel thinning treatments are assumed to reduce the potential for sustained ignition and crown fire initiation by reducing surface fuel loading. We hypothesized that these prescriptions are not appropriate for the coastal wet forests in the Whistler region of the province. Our study measured the efficacy of fuel thinning treatments in four stands located in the Whistler community forest. We examined several in-stand microclimate variables during snow melt in the spring and at the height of fire danger in late summer, at thinned and unthinned locations paired using GIS- analysis. We found that thinning increased the wildfire risk based on the differences between unthinned and thinned areas in the same forest stand.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

It remains poorly understood how the life history strategies and transmission ecologies of viruses of plants, arthropods, and vertebrates are interrelated. The present analysis hinges on the virus transmission success. Virus transmission reflects where in the host-body viruses are retained or replicating. Plants, arthropods, and vertebrates share a protective outer-layer, a circulatory system, and reproductive organs. The latter enables vertical virus transmission and associates with virus-host mutualism. Two broadly opposing virus life history strategies are considered. Acute viruses tend to be replicative and are swiftly transmitted to the next host. Instead, persistent viruses keep virus replicating costs and host damage to a minimum. The intertwined life histories and transmission ecologies are accordingly pieced together, based on the virus mono- or instead dual-host tropism, the location of virus retention or replication on or in the host-body, the presence of cyclical or mechanical transmission by arthropods, and of horizontal and vertical host-to-host transmission modes. It is shown that in the arthropod and in the vertebrate animal host, virus circulation in the hemocoel or blood circulation goes hand-in-hand with vertical transmission. Instead, plant phloem viruses do not transmit via seed. The latter is the rule for the plant-only viruses. The risk management implications are discussed in brief.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e. partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked ’Braeburn’ apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5 % SSC over all study years. SSC modelling with longitudinal linear mixed-effect (LME) models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Small and medium-sized family farms are the place of life and source of income for about half of the population. The aim of the analysis was to determine the relationship between Eco-Efficiency, Human Capital Efficiency in small and medium-sized family farms. The analyses were carried out using an economic measure (value of agricultural production per work hour calculated per 1 ha) and synthetic measures: human capital and environmental measures. The synthetic measures were determined using the CRITIC-TOPSIS method by defining weights for variables used in the synthetic measures. The analyses covered five countries, namely: Lithuania (960 farms), Moldova (532 farms), Poland (696 farms), Romania (872 farms), and Serbia (524 farms). All the countries qualified for analysis are characterised by a high fragmentation of agricultural holdings. The analyses carried out allowed us to formulate the following conclusions: the Eco-Efficiency and Human Capital Efficiency indexes increase with area for small and medium-sized family agricultural farms. An increase in the Eco-Efficiency index with an increase in farm area leads to a suspicion that the smaller the farm area is, the more extensive the agricultural production being carried out. In addition, an increase in human capital efficiency with an increase in the area of a farm indicates that there is inefficiency in the utilisation of human capital resources in the agricultural farms studied.

Many academics are critical of the current publishing system, but it is difficult to create a better alternative. This review relates to the Sciences and Social Sciences, and discusses the primary purpose of academic journals as providing a seal of approval for perceived quality, impact, significance, and importance. The key issues considered include the role of anonymous refereeing, continuous rather than discrete frequency of publications, avoidance of time wasting, and seeking adventure. Here we give recommendations about the organization of journal articles, the roles of associate editors and referees, measuring the time frame for refereeing submitted articles in days and weeks rather than months and years, encouraging open access internet publishing, emphasizing the continuity of publishing online, academic publishing as a continuous dynamic process, and how to improve research after publication. Citations and functions thereof, such as the journal impact factor and h-index, are the benchmark for evaluating the importance and impact of academic journals and published articles. Even in the very top journals, a high proportion of published articles are never cited, not even by the authors themselves. Top journal publications do not guarantee that published articles will make significant contributions, or that they will ever be highly cited. The COVID-19 world should encourage academics worldwide not only to rethink academic teaching, but also to re-evaluate key issues associated with academic journal publishing in the future.

This review article deals with the pathways of cellular and global molybdate distribution in plants, especially with a full overview for the model plant Arabidopsis thaliana. In its oxidized state as bioavailable molybdate, molybdenum can be absorbed from the environment. Especially in higher plants, molybdenum is indispensable as part of the molybdenum cofactor (Moco), which is responsible for functionality as a prosthetic group in a variety of essential enzymes like nitrate reductase and sulfite oxidase. Therefore, plants need mechanisms for molybdate import and transport within the organism, which is accomplished via high-affinity molybdate transporter (MOT) localized in different cells and membranes. Two different MOT-families were identified. Especially legumes like Glycine max or Medicago truncatula have an increased numbers of MOT1-family members for supplying their symbionts with molybdate for nitrogenase activity. In Arabidopsis thaliana especially, the complete way of molybdate through the plant is traceable. Not only the uptake from soil by MOT1.1 and its distribution to leaves, flowers and seeds by MOT2-family members was identified, but also inside the cell the transport trough the cytoplasm and the vacuolar storage mechanisms depending on glutathione were described. Finally, supplying the Moco biosynthesis complex by MOT1.2 and MOT2.1 was demonstrated.

H-adaptivity is an effective tool to introduce local mesh refinement in FEM-based numerical simulation of crack propagation. The implementation of h-adaptivity could benefit the numerical simulation of fatigue or accidental load scenarios involving large structures such as ship hulls. In engineering applications, the element deletion method is frequently used to represent cracks. However, the element deletion method has some drawbacks such as strong mesh dependency and loss of mass or energy. In order to mitigate this problem, the element splitting method could be applied. In this study, a numerical method called ‘h-adaptive element splitting’ (h-AES) is introduced. The h-AES method is applied in FEM programs by combining h-adaptivity with the element splitting method. Two examples using the h-AES method to simulate cracks in large structures under linear-elastic fracture mechanics scenario are presented. The numerical results are verified against analytical solutions. Based on the examples, the h-AES method is proven to be able to introduce mesh refinement in large-scale numerical models that consist of structured coarse meshes. By employing the mesh refinement introduced in this paper, very small cracks are well represented in large structures.

The maximal prime gaps upper bound problem is one of the major mathematical problems to date. The objective of the current research is to develop a standard which will aid in the understanding of the distribution of prime numbers. This paper presents theoretical results which originated with a researchin the subject of the maximal prime gaps. the document presents the sharpest upper bound for the maximal prime gaps ever developed. The result becomes the Supremum bound on the maximal prime gaps and subsequently culminates with the conclusive proof of the Firoozbakht's Hypothesis No 30. Firoozbakht's Hypothesis implies quite a bold conjecture concerning the maximal prime gaps. In fact it imposes one of the strongest maximal prime gaps bounds ever conjectured. Its truth implies the truth of a greater number of known prime gaps conjectures, simultaneously, the Firoozbakht's Hypothesis disproves a known heuristic argument of Granville and Maier. This paper is dedicated to a fellow mathematician, the late Farideh Firoozbakht.

Africa spans the hemispheres from temperate region to temperate region, has a long history of hominin evolution and yet has a relatively poorly understood Quaternary climate history. Speleothems, as archives of terrestrial hydroclimate variability, can help reveal this history, and here we review the progress made to date, with a focus on the first version of the Speleothem Isotopes Synthesis & Analysis (SISAL) database. The geology of Africa has limited development of large karst regions to four areas - the northern and eastern coasts bordering the Mediterranean and the Indian Ocean, west Africa and southern Africa. Exploitation of the speleothem palaeoclimate archives in these regions is uneven, with long histories of research in South Africa and Morocco but no investigations elsewhere e.g. West Africa. Consequently, the evidence of past climate change reviewed here is irregularly sampled in both time and space. Nevertheless, we show evidence of migration of the monsoon belt, with enhanced rainfall during interglacials observed in northeast Africa, southern Arabia and the northern part of southern Africa. Evidence from East Africa also indicates significant centennial scale rainfall variability. In northwestern and southern Africa precession and eccentricity influence speleothem growth, largely through changing synoptic storm activity.

The experiments were designed to know the function of ascorbic acid against salinity on germination, different biochemical and micronutrients concentrations of Solanum melongena. Ascorbic acid was applied as foliar spray on leaves and given in roots through irrigation at 100 and 200 ppm to the plants growed in non saline, 60mM and 100mM salt stress conditions. Different biochemical parameters i.e. chlorophyll, carotenoids, carbohydratrates, protein and micro nutrients concentrations of Solanum melongena were observed under different salt stress concentrations from control (non-saline), 60mM NaCl and 100mM NaCl solutions. The rates of different biochemical parameters and micro nutrients concentrations exhibited decrease in saline media in comparison with their respective control while ascorbic acid used as a foliar spray and through irrigation in roots at the concentration of 100 ppm and 200 ppm resulted promotion in non saline control as compared with salt concentrations media. It was determined that chlorophyll concentration was decreased considerably under salt stress. Amongst micro nutrients ionic composition of Na, K and Na/K ratio resulted that plants treated with different NaCl concentrations at 60mM NaCl and 100mM salt concentrations showed increase in Na and K ions and ascorbic acid were used as a foliar spray and in roots showed decrease in Na and K ions. Overall from the outcomes of the study it was observed that salinity stress significantly decrease vegetative and reproductive parameters that could be improved with the using of ascorbic acid. Best concentration found were 200 ppm ascorbic acid contributed towards an increase in growth irrespective of non-saline and saline conditions. Based on these findings, ascorbic acid treatment helps in alleviating the negative effects of salinity.

Stalk rot caused by Fusarium fungi is one of the most widespread and devastating diseases of maize, and the introduction of resistant genotypes is one of the most effective strategies for controlling the disease. Breeding genotypes with genetically determined resistance will also allow less use of crop protection products. The aim of the research was to identify molecular markers and associated candidate genes determining maize plant resistance to Fusarium stalk rot. The plant material for the study consisted of 122 maize hybrids, which were sown in plots of 10 m2, in a complete randomized block design, in three repetitions, at two locations (Smolice: 51 42’ 58.904’’ N, 17 13’ 29.13’’ E and Kobierzyce: 50 58’ 19.411’’ N, 16 55’ 47.323’’ E). The analyzed genotypes were simultaneously subjected to next-generation sequencing using the Illumina platform. The results of the observation of the degree of infection and sequencing were used for association mapping, which ultimately resulted in the selection of 10 molecular markers important at both places. Among the identified markers, two SNP markers that are located inside candidate genes play an important role. Marker 4772836 is located inside the serine/threonine-protein kinase bsk3 gene, while marker 4765764 is located inside the histidine kinase 1 gene. Both genes can be associated with plant resistance to Fusarium stalk rot, and these genes can also be used in breeding programs to select resistant varieties.

Impressively increasing availability of the mechanical circulatory/cardiac support systems (MCS) worldwide, together with the deepening of the knowledge of critical care medical practitioners, have inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction of LV end-diastolic pressure, reduction of pressure in the left atrium and decrease of the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and better oxygen delivery/demand ratio are achieved. The combination of VA ECMO and Impella device, also called ECPELLA seems to be a promising strategy which may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed potential benefits of this strategy. However, the ongoing research has brought a series of new questions, as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way? Benefits and potential risks of LV unloading and its timing are being discussed in current review.

A disaster wrecks those affected. It spares many in the affected areas, yet those spared may be indirectly impacted. Specific risks are often inherent within a social system or physical location, but they can also be created due to unavoidable natural or technological hazards. The consequences, however, can be similar in that they wreak havoc in communities and destroy economic systems. The analytical framework of deterrence and coping has ascertained beneficial in many circumstances, but a cost benefit calculation is a must to infer the feasibility of planning strategy and resource allocation. This study points to the Cost-Benefit Analysis (CBA) of flood management by District Disaster Management Kulgam. The assessment is established on secondary pooled data collected from administration offices, NGOs, published Journals, and local and national newspapers. It also characterised the strategy, the technique adopted, and the sources of flood damage cost information. The totalled benefits report for 78686.18 lakh of rupees, and that of total costs account for 2218.75lakh of rupees. The Benefit-Cost ratio greater than one (>1) indicates that Flood Management in District Kulgam was economically feasible and successfully governed. The State of Jammu and Kashmir put up with necessary prevention and administration measures to break the spell of devastation due to floods to significant status.

The local reactive power control in distribution grids with a high penetration of distributed energy resources (DERs) is essential in future power system operation. Appropriate control characteristic curves for DERs support stable and efficient distribution grid operation. However, the current practice is to configure local controllers collectively with constant characteristic curves that may not be efficient for volatile grid conditions or the desired targets of grid operators. To address this issue, this paper proposes a time series optimization-based method to calculate control parameters, which enables each DER to be independently controlled by an exclusive characteristic curve for optimizing its reactive power provision. To realize time series optimizations, the open-source tools pandapower and PowerModels are interconnected functionally. Based on the optimization results, Q(V)- and Q(P)-characteristic curves can be individually calculated using the linear decision tree regression to support voltage stability and provide reactive power flexibility and potentially reduce grid losses and component loadings. In this paper, the newly calculated characteristic curves are applied in two representative case studies, and the results demonstrate that the proposed method outperforms the reference ones suggested by grid codes.

The increasing complexity of the design and operation evaluation process of multi-energy grids (MEGs) requires tools for the coupled simulation of power, gas and district heating grids. Most tools analyzed in this paper either do not allow coupling of infrastructures, simplify the grid model or are not publicly available. We introduce the open source piping grid simulation tool pandapipes that – in interaction with pandapower - fulfills three crucial criteria: clear data structure, adaptable MEG model setup and performance. In an introduction to pandapipes we illustrate how it fulfills these criteria through its internal structure and demonstrate how it performs in comparison to STANET®. Then we show two case studies that have been performed with pandapipes already. The first case study demonstrates a peak shaving strategy as interaction of a local electricity and district heating grid in a small settlement. The second case study analyzes the potential of a power-to-gas device to serve as flexibility in a power grid under consideration of gas grid constraints. They both show the importance of a clear database, a simple simulation setup and good performance to set up different large and complex studies on grid infrastructure design and operation.

In December 2012, DOAJ’s parent company, IS4OA, announced they would introduce new criteria for inclusion in DOAJ [1] and that DOAJ would collect vastly more information from journals as part of the accreditation process – and that journals already included, would need to reapply in order to be kept in the registry. My hypothesis was that the journals removed from DOAJ on May 9th 2016 would chiefly be journals from small publishers (mostly single journal publishers) and that DOAJ journal metadata information would reveal that they were journals with a lower level of publishing competence than those that would remain in the DOAJ. Among indicators of publishing competence could be the use of APCs, permanent article identifiers, journal licenses, article level metadata deposited with DOAJ, archiving policy/solutions and/or having a policy in SHERPA/RoMEO. The analysis shows my concerns to be correct.

Biofilm formation in unicellular eukaryotes, such as Candida albicans and Saccharomyces cerevisiae, represents a significant challenge in various sectors, including healthcare, agriculture, and industry. These biofilms are resistant to conventional antimicrobial treatments due to their protective extracellular matrix and complex regulatory mechanisms, such as quorum sensing (QS) and cyclic AMP (cAMP) signaling. Recent advances in the understanding of biofilm formation pathways have led to the identification of novel compounds that target these regulatory mechanisms. This review highlights breakthroughs from 2024 research, focusing on the inhibition of quorum sensing, disruption of extracellular matrix synthesis, and transcriptional/post-transcriptional regulation of biofilm-related genes. The application of these discoveries in Vietnam is particularly promising, given the country's challenges with biofilm-related infections in healthcare and productivity losses in agriculture and aquaculture. Natural product-based approaches, especially those derived from Vietnam's marine biodiversity, offer environmentally sustainable solutions for biofilm control. However, translating these laboratory findings into scalable, cost-effective applications faces challenges such as resistance development, environmental sustainability, and regulatory constraints. This review provides a comprehensive overview of compounds targeting biofilm regulatory mechanisms, evaluates their potential applications in Vietnam, and discusses future research directions, emphasizing the need for interdisciplinary collaboration to address the complexities of biofilm control.

The rise of fintech in the financial sector presents a transformative shift towards digitalization and sustainability, leveraging technologies like AI to minimize environmental footprint. Neobanks not only challenge traditional banking models but also offer innovative solutions that align with sustainable objectives. The purpose of this paper is to analyze the impact of neobanks on global sustainability, from economic, environmental, and social point of view. A comprehensive literature review of existing literature and current sustainable practices of neobanks was conducted. We have found that neobanks significantly positively contribute towards environmental sustainability with reduced paper use and logistics requirements of banking services. By offering more accessible and affordable banking services they importantly contribute towards higher financial inclusion, and with innovative products towards more competitive and innovative financial markets. AI-based tools they employ are increasing financial literacy and social inclusion. We also highlight concerns regarding electronic waste management, potential high energy consumption, required digital literacy and cybersecurity risks. We conclude that despite the mentioned risks, neobanks importantly contribute to global sustainability in many ways, and will even more in the future. Our findings can help neobanks shape sustainable practices and guide policymaking, as well as spread awareness of sustainable impact of banking services.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is the desmoplastic reaction of the tumor stroma, the formation of which is orchestrated by transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that the TGF-β pathway is controlled by transcriptionally active p73 (TAp73) through secretion of biglycan (Bgn) via intermittent expression of the TGF-β signaling intermediates, Smad3 and Smad4. Genetic knockout of TP73, and, as a consequence, deficient induction of Smad3/Dpc4 and secretion of Bgn led to activation of TGF-β signaling through a (Smad-independent) ERK pathway, favoring epithelial-mesenchymal transition (EMT) and cell motility. Except for BGN, these functions of TAp73 have recently been shown to also operate in human PDAC cells and are reminiscent of what we previously observed for the small GTPase, RAC1b. This prompted us to hypothesize that TAp73 and RAC1b are part of the same tumor-suppressive pathway in human PDAC cells. The two objectives of this study, therefore, were to reveal i) if the regulatory interactions between TAp73 and Bgn previously discovered in murine PDAC-derived cells also operate in their human counterparts, and ii) if RAC1b collaborates with TAp73 in these tumor-suppressive activities in human PDAC cells. Using a variety of experimental approaches, including mutual rescue experiments, we were able to show that the previously proposed tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b is as an upstream activator of this pathway. Our findings highlight the complex role of TGF-β in pancreatic tumorigenesis and might have implications for therapeutic approaches targeting this growth factor for inhibition.

Vitamin D is crucial for athletes' health and performance. Although the exact vitamin D requirements for athletes have not been established, maintaining 25(OH)D levels of at least 40 ng/ml is considered beneficial. This study aimed to determine whether an individual loading dose formula for vitamin D supplementation is suitable to meet a target value of 40 ng/ml and is more effective than standardized supplementation. In a 10-week supplementation study during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D<30ng/ml) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. Total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40ng/ml, and after the 10-week period. Additionally, a vitamin D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/ml were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1+-10.9 ng/ml vs. 32.5+-6.4 ng/ml, p<0.001). This study demonstrated that the examined formula is suitable for athletes to achieve a 25(OH)D concentration of 40 ng/ml. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

The most important plastic resins used for wire coating are Polyvinyl Chloride (PVC), Nylon, Polysulfone and Low-high density polyethylene (LDPE / HDPE). In this article,the coating process is performed using elastic-viscous fluid as a coating material for wire coating in a pressure type coating die. The elastic-viscous fluid is electrically conducted in the presence of an applied magnetic field. The governing non-linear equations are modeled and then solved analytically by utilizing an Adomian decomposition method (ADM). The convergence of the series solution is established. The results are also verified by Optimal Homotopy Asymptotic Method (OHAM). The effect of different emerging parameters such as non-Newtonian parameters α and β, magnetic parameter M and the Brinkman number Br on solutions (velocity and temperature profiles) are discussed through several graphs. Additionally, the current result also compares with the published work already available in the literature.

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood. The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments. HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dl), triglycerides (45.45 ± 0.39 mg/dl), LDL-c (66.12 ± 0.10 mg/dl), VLDL-c (19.34 ± 0.16 mg/dl), and a decrease in HDL-c (10.34 ± 0.18 mg/dl). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dl), triglycerides (32.33 ± 0.16 mg/dl), LDL-c (50.34 ± 0.15 mg/dl) and VLDL-c (13.15 ± 0.45 mg/dl) respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dl). 15-oxo ursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol). It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats which might lead to new medication with significant hypolipidemic potential.

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Indoor farming systems enable plant production in precisely controlled environments, managing factors such as lighting, photoperiod, and nutrient supply, to enhance crop yield and quality. However, the implementation of stable growth conditions and the absence of stress stimulants can weaken plants' defense responses and limit the accumulation of bioactive, health beneficial phytochemicals. A potential solution is the controlled application of stressors, such as supplemental ultraviolet (UV) light, which stimulates secondary metabolites (SM) synthesis and increase overall antioxidant potential. To this end, we analyzed the efficiency of short-term pre-harvest supplementation of red-green-blue (RGB, LED) spectrum with ultraviolet B (UV-B, 311 nm) or C (UV-C, 254 nm) light to boost phytochemicals synthesis. Additionally, given the biological harm of UV radiation due to high-energy photons, we monitored plants’ photosynthetic activity during treatment. Our analyses showed that UV-B radiation, applied with a cumulative dose of 15.622 kJ m–2, did not negatively impact photosynthetic activity while significantly increasing the overall antioxidant potential of lettuce through enhanced levels of polyphenolic SM (total phenolics, flavonoids, anthocyanins) and ascorbic acid. Conversely, UV-C radiation, applied with a lower cumulative dose of 6.008 kJ m–2, induced anthocyanin accumulation in the green leaf cultivar but significantly harmed the photosynthetic apparatus and limited plant growth. These results are crucial for understanding the potential of UV light supplementation in producing functional plants.

Abstract The aim of the present review is to discuss the roles of vitamin K and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. Adequate vitamin K status is required for carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanism, such as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through dietary adequacy of vitamin K (phylloquinone or menaquinone). Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3 we find that an adequate supply of vitamin K on top of an optimal vitamin D status seems to add to the benefit for maintaining bone health. More research related to synergism and possible mechanisms of vitamins D3 and K interaction in bone health is needed.

Artificial intelligence (AI) systems are poised to become deeply integrated into society. If developed responsibly, AI has potential to benefit humanity immensely. However, it also poses a range of risks, including risks of catastrophic accidents. It is crucial that we develop oversight mechanisms that prevent harm. This article outlines a framework for evaluating and auditing AI to provide assurance of responsible development and deployment, focusing on catastrophic risks. We argue that responsible AI development requires comprehensive auditing that is proportional to AI systems’ capabilities and available affordances. This framework offers recommendations toward that goal and may be useful in the design of AI auditing and governance regimes.

Climate change is likely to have a complex effect on the growth of plants, their phenology, plant-pollinator interactions, and reproductive success. Therefore, we tested the impact of three key factors (temperature, water, and nitrogen supply) on traits, pollination, and seed production in Sinapis alba (Brassicaceae). We grew the plants in different combinations of temperature, water, and nitrogen supplementation, measured multiple vegetative and floral traits, and assessed the response of pollinators in the field. We also evaluated the effect of growing conditions on seed set in plants exposed to pollinators and hand-pollinated plants. Our results show that water stress impaired vegetative growth, decreased flower production, reduced visitation by pollinators and seed set, while nitrogen availability played an important role in nectar production. Temperature modulated the effect of water and nitrogen availability on vegetative and floral traits and strongly affected flowering phenology and flower production. We demonstrated that changes in temperature, water, and nitrogen availability induce changes in plant vegetative and floral traits which impact flower visitation and consequently plant reproduction. Climate change, particularly increasing temperature combined with reduced precipitation, thus may impact plant-pollinator interactions with negative consequences for the reproduction of wild plants and insect-pollinated crops.

As it turns out, both isotope scaling and density limits are phenomena closely linked to fluid closure. The necessity to include ion viscosity arises for both phenomena. Thus, we have added ion viscosity to our model. The experimental isotope scaling has been successfully recovered in our fluid model through parameter scans. Although ion viscosity typically exerts a small effect, the density limit is manifested by increasing the density by approximately tenfold from the typical experimental density. In our case, this increase originates from the density in the Cyclone base case. Notably, these phenomena would not manifest with a gyro-Landau fluid closure. The isotope scaling is nullified by the addition of a gyro-Landau term, while the density limit results from permitting ion viscosity to become comparable to the gyro-Landau term. The mechanism of zonal flows, demonstrated analytically for the Dimits upshift, yields insights into the isotope scaling observed in experiments. In our approach, ion viscosity is introduced in place of the Landau fluid resonances found in some fluid models. This implies that the mechanism of isotope scaling operates at the level of fluid closure in connection with the generation of zonal flows. The strength of zonal flows in our model has been verified, particularly in connection with the successful simulation of the nonlinear Dimits shift. Consequently, a role is played by our approach in the temperature perturbation part of the Reynolds stress.

The e-commerce sector is in a constant state of growth and evolution, particularly within its subdomain of online food delivery. As such, ensuring customer satisfaction is critical for companies working in this field. One way to achieve this is by providing accurate delivery time estimation. While companies can track couriers via GPS, they often lack real-time data on traffic and road conditions, complicating delivery time predictions. To address this, a range of statistical and machine learning techniques are being employed, including neural networks and specialized expert systems, with different degree of success. One issue with neural networks and machine learning models is their heavy dependence on vast, high quality data. To mitigate this issue we propose two Bayesian generalized linear models to predict time of the delivery. Utilizing a linear combination of predictor variables, we generate practical range of outputs with Hamiltonian Monte Carlo sampling method. These models offer a balance of generality and adaptability, allowing for tuning with expert knowledge. They were compared with PSIS-LOO and WAIC criteria. Results show that both models accurately estimated delivery times from the dataset, while maintaining numerical stability. Model with more predictor variables proved to be more accurate.

Simple Summary: This review explores the origin of Leukemic Stem-Like Cells (LSLCs) from (Very) Small Leukemic Stem-Like Cells ((V)SLSLCs) and Cancer Stem Cells (CSCs) from trans-formed Very Small Embryonic-Like Stem Cells (VSELSCs). Understanding this relation is a step toward uncovering the mechanisms behind cancer and leukemia initiation and development. We explore how these very small precursor cell stages might contribute to the initiation and progres-sion of cancer as well as leukemia with a focus on Acute Myeloid Leukemia (AML) as a model. Abstract: Recent experimental findings indicate that CSCs originate from transformed VSELSCs, which are early precursor stages of healthy stem cells. This discovery marks a crucial step in understanding the mechanisms that drive cancer development and initiation. Our team's follow-up studies on leukemia, lung cancer, and healthy embryonic kidney cells have, for the first time, identified stag-es resembling very small precursor stem cells in continuously growing cell lines. These findings suggest the existence of (Very) Small Cancer Stem Cells ((V)SCSCs) or (V)SLSCs within respective subpopulations of CSCs and LSCs in vivo. In this review, we explore theoretical examples of how leukemia progresses through various stages, highlighting the role of these very small precursor cells as fundament primitive stages. We also discuss the potential implications of further research into these unique cellular stages for advancing cancer and leukemia treatment and prevention strategies.

Residual stresses in fiber metal laminates (FML) inevitably develop during the manufacturing process. The main contributor to these stresses is the difference in the coefficients of thermal expansion (CTE) between fibers and metal in combination with high process temperatures. To quantify these stresses, the use of specimens with an asymmetric layup is an easily adaptable method. The curvature that develops after the manufacturing of flat laminates with an asymmetrical layer stack is a measure of the level of residual stresses evolving during cure. However, the accuracy of the curvature evaluation is highly dependent on specimen design and other influencing parameters. In this work a large set of FML specimens is investigated to identify relevant influencing parameters and derive conclusions about specimen design and evaluation techniques. For certain layups and process parameters, there is a good correlation between the curvature and the stress-free temperature, which is further covered by analytical solutions for bimetals. This correlation is the basis to transfer curvature into a stress-free temperature that can consequently be used for the quantification of residual stress levels in more complex FMLs. The transfer is validated by in-situ strain measurements during cure using a strain gage technique. Based on the results, the application of asymmetric specimens for residual stress characterization in more complex laminates is presented in the form of a workflow.

The success of deep learning (DL) in offline brain-computer interfaces (BCIs) has not yet translated into efficient online applications. This is due to three primary challenges. First, most DL solutions are designed for offline decoding, making the transition to online decoding complex and unclear. Second, the use of sliding windows in online decoding increases the computational complexity of DL training. Third, DL models typically require large amounts of training data, which are often scarce in BCI applications. To address these issues and enable real-time decoding, even across different subjects without calibration data, we first introduce a novel approach called real-time adaptive pooling (RAP). RAP modifies the pooling layers of existing offline DL models towards the online decoding requirements. Additionally, it significantly reduces the computational demand during training by jointly decoding consecutive windows. To reduce the amount of training data required, our approach leverages different levels of domain adaptation. We show how different settings enable different adaptation solutions. The results demonstrate that our approach is both powerful and can be calibration-free, providing a robust and practical solution for real-time BCI applications. These findings pave the way for the development of co-adaptive and highly efficient DL-based online BCI systems.

We apply a well known technique of theoretical physics, known as Geometric Algebra or Clifford algebra, to linear electrical circuits with non-sinusoidal voltages and currents. We rederive from the first principles the Geometric Algebra approach to the apparent power decomposition. The important new point consists in a choice of a natural convenient basis in the Clifford vector space which simplifies considerably the presentation. Thus we are able to derive a number of general results which are missing in the former papers. In particular, a natural correspondence with the Current Physical Components approach is shown.

The suspended test masses of gravitational-wave (GW) detectors require precise alignment to be able to operate the detector stably and with high sensitivity. This includes the continuous counter-acting of seismic disturbances, which, below a few Hertz, are not sufficiently reduced by the seismic isolation system. The residual angular motion of suspended test masses is further suppressed by the Angular Sensing and Control (ASC) system. However, in doing so, the angular motion can be enhanced by the ASC at higher frequencies where the seismic isolation system is very effective. This has led to sensitivity limitations between about 10 Hz and 25 Hz of the LIGO detectors in past observation runs. The observed ASC noise was larger than simple models predict, which means that more accurate detector models and new simulation tools are required. We present Lightsaber, a new time-domain simulator of the ASC in LIGO. The simulation is a nonlinear simulation of the optomechanical system consisting of the high-power cavity laser beam and the last two stages of suspension in LIGO including the ASC. The main noise inputs are power fluctuations of the laser beam at the input of the arm cavities, read-out noise of sensors used for the ASC, displacement noise from the suspension platforms, and noise introduced by the suspension damping loops. While the plant simulation uses local degrees of freedom of individual suspension systems, the control is applied on a global angular basis, which requires a conversion between the local and global bases for sensing and actuation. Some of the studies that can be done with this simulation concern mis-centering of the beam-spot (BS) position on the test masses, the role of laser power fluctuations for angular dynamics, and the role of the various nonlinear dynamics.

This article introduces a new way of using a Fibre Bragg Grating (FBG) sensor for detecting the presence and number of occupants in the monitored space in a Smart Home (SH). CO₂ sensors are used to determine the CO₂ concentration of the monitored rooms in an SH. CO₂ sensors can also be used for occupancy recognition of the monitored spaces in SH. To determine the presence of occupants in the monitored rooms of the SH, the newly devised method of CO₂ prediction, by means of an Artificial Neural Network (ANN) with a Scaled Conjugate Gradient (SCG) algorithm using measurements of typical operational technical quantities (indoor temperature, relative humidity indoor and CO₂ concentration in the SH) is used. The goal of the experiments is to verify the possibility of using the FBG sensor in order to unambiguously detect the number of occupants in the selected room (R104) and, at the same time, to harness the newly proposed method of CO₂ prediction with ANN SCG for recognition of the SH occupancy status and the SH spatial location (rooms R104, R203, and R204) of an occupant. The designed experiments will verify the possibility of using a minimum number of sensors for measuring the non-electric quantities of indoor temperature and indoor relative humidity and the possibility of monitoring the presence of occupants in the SH using CO₂ prediction by means of the ANN SCG method with ANN learning for the data obtained from only one room (R203). The prediction accuracy exceeded 90% in certain experiments. The uniqueness and innovativeness of the described solution lie in the integrated multidisciplinary application of technological procedures (the BACnet technology control SH, FBG sensors) and mathematical methods (ANN prediction with SCG algorithm, the Adaptive Filtration with of LMS algorithm) employed for the recognition of number persons and occupancy recognition of selected monitored rooms of SH.

This article describes the use of the PI ProcessBook software tool for visualization and indirect monitoring of occupancy of SHC rooms from the measured operational and technical quantities for monitoring of daily living activities for support of independent life of elderly persons. The proposed method for data processing (predicting the CO₂ course using neural networks from the measured temperature indoor T_i (°C), temperature outdoor T_o (°C) and the relative humidity indoor rHi (%)) was implemented, verified and compared in MATLAB SW tool and IBM SPSS SW tool with IoT platform connectivity. Within the proposed method, the Stationary Wavelet Transform de noising algorithm was used to remove the noise of the resulting predicted course. In order to verify the method, two long-term experiments were performed, (specifically from February 8 to February 15, 2015, from June 8 to June 15, 2015) and two short-term experiments (from February 8, 2015 and from June 8, 2015). For the best results of the trained ANN BRM within the prediction of CO₂, the correlation coefficient R for the proposed method was up to 90%. The verification of the proposed method confirmed the possibility to use the presence of persons of the monitored SHC premises for rooms ADL monitoring.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) the strength of the evidence for a wastewater-human AMR association, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordance correlation coefficient (CCC) to quantify agreement between AMR prevalence in wastewater and human compartments, and logistic regression to identify study features (e.g. sampling methods) associated with high-agreement (defined as wastewater-human AMR prevalences within ±10%). Of 8,867 records and 232 full-text methods reviewed, 29 studies were included. AMR prevalence data was extractable from 20 studies conducting phenotypic-only (n=11), genotypic-only (n=1) or combined (n=8) AMR detection. Overall wastewater-human AMR concordance was reasonably high for both phenotypic (CCC=0.81 [95% CI 0.74-0.87]) and genotypic comparisons (CCC=0.88 (95% CI 0.85-0.91)) despite diverse species-phenotypes/genotypes and study design. Logistic regression was limited by inconsistent reporting of study features, and limited sample size; no significant relationships between study features and high wastewater-human AMR agreement were identified. Based on descriptive synthesis, composite/flow-proportional sampling of wastewater influent, longitudinal sampling >12 months, and time/location-matched comparisons generally had higher-agreement. Further research and clear and consistent reporting of study methods is required to confirm optimal practice.

In two previous papers, we calculated the dielectrophoresis (DEP) force and corresponding trajectories of high- and low-conductance 200-µm 2D spheres in a square 1x1mm chamber with plane-versus-pointed, plane-versus-plane and pointed-versus-pointed electrode configurations by applying the law of maximum entropy production (LMEP) to the system. Here, we complete these considerations for configurations with four-pointed electrodes centered on the chamber edges. The four electrodes were operated in either object-shift mode (two adjacent electrodes opposite the other two adjacent electrodes), DEP mode (one electrode versus the other three electrodes), or field-cage mode (two electrodes on opposite edges versus the two electrodes on the other two opposite edges). As in previous work, we have assumed DC properties for the object and the external media for simplicity. Nevertheless, every possible polarization ratio of the two media can be modeled this way. The trajectories of the spherical centers and the corresponding DEP forces were calculated from the gradients of the system’s total energy dissipation, described by numerically-derived conductance fields. In each of the three drive modes, very high attractive and repulsive forces were found in front of pointed electrodes for the high and low-conductance spheres, respectively. The conductance fields predict bifurcation points, watersheds, and trajectories with multiple endpoints. The high and low-conductance spheres usually follow similar trajectories, albeit with reversed orientations. In DEP drive mode, the four-point electrode chamber provides a similar area for DEP measurements as the classical plane-versus-pointed electrode chamber.

Background: Self-harm (SH) refers to self-injury or intentional self-poisoning with varying degrees of suicidal intent and is a major public health issue for children and adolescents (C&A) worldwide. Given significant gaps exist in our understanding of the associated psychopathology in C&A, this paper outlines the protocol for a prospective clinical study examining risk factors of SH and additional candidate parameters (not routinely assessed) during an acute SH episode. Methods: The EXPAAND (EXploring Psychiatric and Attentional risk-factors in Adolescents Needing intervention for Deliberate self-harm) is a randomised control trial to assess additional novel candidate risk factors for SH in C&A and to evaluate the effectiveness of SH-targeted brief psychological intervention (Therapeutic Assessment (TA)), within a real-world acute clinical setting, as we include neurodiversity and gender diversity in this study. EXPAAND is conducted in 4 phases: (i) recruitment & randomisation; (ii) extended assessment; (iii) randomised intervention; and (iv) follow-up observational period to ascertain clinical outcomes for comparison. Expected Results: We envisage that by diagnosing and treating attentional disorders when detected will mitigate potential confounding effects of these conditions. We also expect that SH-focused TA will be effective in reducing subsequent SH and in improving engagement in follow-up and subsequent treatments.

Dystonia is a neurological disorder that results in atypical uncontrolled motions or postures caused by either continuous or intermittent contractions of the muscles. Subtypes of dystonia vary in their symptoms and severity; they can affect people of all ages and cause significant disability and poor quality of life. Identifying genes responsible for single or mixed dystonia variants has improved our understanding of its pathogenesis. The mechanisms underlying several of the most prevalent genetic dystonias, including idiopathic dystonia, TOR1A, THAP1, and KMT2B mutations, involve anomalies in transcriptional regulation, striatal dopaminergic signaling, synaptic plasticity, and a loss of inhibition at neuronal circuits. Dystonia is mostly diagnosed based on clinical indicators, and the diagnosis and etiology of this illness remain a problem. In this review, we tried to summarize novel updates about genetic causes and treatment of focal dystonia.

The main purpose of the work was to determine the powder composition and properties of iron-based sinters used as a matrix in metallic diamond tools. The FeCuSnNi sinters obtained from a mixture of commercial powders were used for research. The material was subjected to milling in a ball mill and sinter have been performed with the hot-pressing technique in a graphite mold. The physical and mechanical properties of the sinters were tested. The investigations of obtained sinters concerned density, porosity, hardness, oxygen content, static tensile test and analysis of microstructure. The static tensile test was carried out with the use of a universal testing machine UTS-100. The study of the microstructure of sinters was performed using the JSM-7100F scanning electron microscope. The sinters are characterized by a high coefficient of thermal expansion and good mechanical properties. The FeCuSnNi sinter revealed a complex phase structure. Spot chemical analysis revealed the presence of Fe solution, Cu solution and the presence of iron oxides oxides. Nickel atoms were present throughout the sinter volume. The obtained results indicate that the presented material can be used as a matrix of a diamond-metal composite in diamond tools for the processing of natural stones and building materials.

The aim of this work is research dedicated to the search for new bactericidal systems for use in cosmetic formulations, dermocosmetics, or the production of wound dressings. Over the last two decades chitosan due to its special biological activity, has become a highly indispensable biopolymer with very wide application possibilities. Literature reports on the antibacterial effects of chitosan are very diverse, but our research has shown that they can be successfully improved through chemical modification. Therefore, in this study, results on the synthesis of new Schiff bases chitosan – dCsSB-SFD and dCsSB-PCA obtained using two aldehydes: sodium 4-formylbenzene-1,3-disulfonate (SFD) and 2-pyridine carboxaldehyde (PCA) respectively. Chitosan derivatives synthesized in this way demonstrate stronger antimicrobial activity. Carrying out the procedure of grafting chitosan with a caproyl chain allowed obtaining compatible blends of chitosan derivatives with κ-carrageenan, which are stable hydrogels with a high swelling coefficient. Furthermore, covalently bounded PCL improved the solubility of obtained polymers in organic solvents. With this respect, the Schiff base-containing polymers obtained in this study, with special hydrogel and antimicrobial properties are very promising materials for the potential use as a controlled-release formulation of both, hydrophilic and hydrophobic drugs in cosmetic products for skin health.

This study examines the impact of decentralisation on corruption levels in water utilities across central India, challenging the widely held assumption that decentralisation reduces corruption. Using experience-based measures and a natural experiment approach, the research compares corruption levels between centralised and decentralised water supply agencies Madhya Pradesh and Chhattisgarh. The study employs a longitudinal survey conducted from over five years, focusing on bribery in various aspects of water service provision. Results indicate that decentralised agencies exhibit significantly higher levels of corruption compared to centralised ones, particularly in the initial stages of decentralisation. While a gradual reduction in corruption is observed over time, the difference between decentralised and centralised utilities remains significant in the medium term. These findings contradict the simplistic view of decentralisation as a cure-all for governance issues and highlight the need for a more nuanced understanding of its effects on public service provision. The study contributes to the ongoing debate on decentralisation policies and their implications for corruption in developing countries, offering valuable insights for managers

The Ramanujan primes are the least positive integers Rn having the property that if m ≥ Rn, then π_m − π_(m/2) ≥ n. This document develops several bounds related to the Ramanujan primes, sharpening the currently known results. The theory presented is by no means exhaustive, however it provides insights for future research work. Alternatively, we may say that it is a road map which may be followed to make further discoveries.

In this research paper, we implement the theory of the primorial function, to develop the Supremum and Infimum bounds for the sum of (log(p))². There are, however, considerable computational difficulties related to these bounds. Therefore, from a pragmatic point of view, a set of Upper and Lower bounds had been developed to bypass this issue. Despite the increased estimation error, the Upper and Lower bounds are still considered sufficiently accurate, while facilitating an easy and fast computation of the estimate of the sum.

This research paper aims to explicate the complex issue of the Riemann's Hypothesis and ultimately presents its elementary proof. The method implements one of the binomial coefficients, to demonstrate the maximal prime gaps bound. Maximal prime gaps bound constitutes a comprehensive improvement over the Bertrand's result, and becomes one of the key elements of the theory. Subsequently, implementing the theory of the primorial function and its error bounds, an improved version of the Gauss' offset logarithmic integral is developed. This integral serves as a Supremum bound of the prime counting function Pi(n). Due to its very high precision, it permits to verify the relationship between the prime counting function Pi(n) and the offset logarithmic integral of Carl Gauss. The collective mathematical theory, via the Niels F. Helge von Koch equation, enables to prove the RIemann's Hypothesis conclusively.

This work deals with aerofoil aerodynamic features optimization, not only to improve flight features, but also to improve economy, ecology and safety of parameters of flight technique. In cruise mission, occupying the most flight time, the most important parameter is aerodynamic drag, which directly influences the aeroplane operational economy of transportation. Drag reduction is adequately reflected in the fuel consumption reduction. Consumption reduction is also adequately reflected in the flight ecology. In take-off and landing mission, the safety is priority and directly influences the aerofoil geometry. For cruise mission the new modified evolutionary algorithms (EA) are used to parameters incoming to Bezier-PARSEC 3434 parametrization. Such aerofoil is processed and evaluated by the Xfoil program. The change of model parameters results to optimal aerofoil shape. The DCAG (Direct Control Aerofoil Geometry) is unique developed mechanical device, makes possible the change of curvature of aerofoil, and also aerofoil geometry. DCAG is based on the rotary principle, which makes it possible to define the curvature of aerofoil for every roll as well as defining the geometry in the variable parts of aerofoil. For take-off and landing mission the best combination of slots and flaps is choosed. To improve of laminarity and reduce turbulent flow the DCAG is used. The work results to optimization, which is 50 times faster in comparison to ordinary optimization, with minimum of input parameters (flight speed, chord length, range of angles of attack and fitness function). The optimized aerofoil can achieve savings in fuel consumption up to 44% in comparison with unoptimized aerofoil, the aerodynamic drag reduction up to 44%. The output was checked by ANSYS Fluent simulation.

AbstractThis work deals with aerofoil aerodynamic features optimization, not only to improve flight features, but also to improve economy, ecology and safety of parameters of flight technique.In cruise mission, occupying the most flight time, the most important parameter is aerodynamic drag, which directly influences the aeroplane operational economy of transportation. Drag reduction is adequately reflected in the fuel consumption reduction. Consumption reduction is also adequately reflected in the flight ecology. In take-off and landing mission, the safety is priority and directly influences the aerofoil geometry.For cruise mission the new modified evolutionary algorithms (EA) are used to parameters incoming to Bezier-PARSEC 3434 parametrization. Such aerofoil is processed and evaluated by the Xfoil program. The change of model parameters results to optimal aerofoil shape.The DCAG (Direct Control Aerofoil Geometry) is unique developed mechanical device, makes possible the change of curvature of aerofoil, and also aerofoil geometry. DCAG is based on the rotary principle, which makes it possible to define the curvature of aerofoil for every roll as well as defining the geometry in the variable parts of aerofoil.For take-off and landing mission the best combination of slots and flaps is choosed. To improve of laminarity and reduce turbulent flow the DCAG is used.The work results to optimization, which is 50 times faster in comparison to ordinary optimization, with minimum of input parameters (flight speed, chord length, range of angles of attack and fitness function).The optimized aerofoil can achieve savings in fuel consumption up to 44% in comparison with unoptimized aerofoil, the aerodynamic drag reduction up to 44%.The output was checked by ANSYS Fluent simulation.

Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I₂/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H₂O₂ dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,’-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted towards a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.

Interaction between multiple phases especially liquid-gas is one of the most common phenomena in industrial systems. Computer Vision enables modern systems to derive an automated and robust image-processing technique to address this issue. However, diverse experimental conditions still make it a challenging task to overcome. In Deep Learning, instance segmentation has created a niche in various computer vision applications as it aims to provide different instance IDs to objects belonging to the same class. In this paper, we propose a novel approach employing the YOLO (You Look Only Once) an end-to-end deep learning architecture for the detection and segmentation of bubbles in fluid flows. YOLOv5 offers significant improvements in both speed and accuracy compared to its predecessors like YOLOv3. Therefore, we train the YOLOv5 network on a dataset consisting of annotated images representing instances of bubbles across varied fluid flow environments. This paper provides both qualitative and quantitative evaluation of three YOLOv5 networks (small, medium, and extra-large) in detecting and segmenting bubbles with high accuracy and efficiency. Based on the metrics all three YOLOv5 models achieved high precision above 0.98 for bounding box detection and 0.97 for segmentation mask, and high recall value greater than 0.97 for box and 0.96 for mask quality was achieved. The achieved results indicate that the models accurately localize bubbles within the image frame, and distinguish bubble pixels from the background. Also, mean average precision (mAP50-95) consistently exceeds 0.84 across all models for the bounding box and 0.73 for the segmentation mask. The ascertained results emphasize the potential of YOLOv5 architecture as a powerful tool for automated bubble analysis in real-world applications. Our research contributes to advancing the field of deep neural networks in fluid systems and provides a fresh approach for future developments in automated bubble analysis.

Marine renewable energy technologies have a great potential in supplying clean electricity to millions of people across the globe, if technical and economic conditions are in right. So far, ocean energy projects are commonly started by SMEs or educational institutions with limited budgets. Therefore, any effort to reduce expenses is of great value. One of the areas involving substantial expenses are the inevitable seabed inspection prior to deployment of marine renewable energy device. Detailed seabed inspections can also reduce the risk of associated with deployment of structures on uneven seabed, especially marine renewable energy devices with gravity foundations. By reducing the costs and risks of such surveys prior and during the installation phases, the feasibility of marine renewable energy projects can be more favoured and competitive. In this perspective, this study proposes a cost and time effective technique for seabed surveys. The proposed technique involves the use of high precision and inexpensive sonar systems and underwater optical cameras integrated into a versatile and compact subsea monitoring platform. It also involves simple and practical data acquisition and processing protocols that do not requires hi expertise for operation. The results obtained showed that high resolution bathymetric maps and detailed seabed inspections imagery can be acquired. This study concludes that a simple and inexpensive subsea monitoring platform comprising a multibeam, dual beam and video cameras can be effective for high resolution seabed inspection and bathymetric measurements for marine energy applications.

There has been observational evidence about spin axes of quasars in large quasar groups correlated over hundreds of Mpc. This is seen in the radio spectrum as well as in the optical range. There is not yet a satisfactory explanation of this "spooky" alignment. This alignment cannot be explained by mutual interaction at the time that quasars manifest themselves optically. A cosmological explanation could be possible in the formation of superconducting vortices (cosmic strings) in the early universe, just after the symmetry-breaking phase of the universe. We gathered from the NASA/IPAC and SIMBAD extragalactic databases the right ascension, declination, inclination, position angle and eccentricity of the host galaxies of 3 large quasar groups to obtain the azimuthal and polar angle of the spin vectors. The alignment of the azimuthal angle of the spin vectors of quasars in their host galaxy is confirmed in the large quasar group U1.27 and compared with two other groups in the vicinity, i.e., U1.11 and U1.28. It is well possible that the azimuthal angle alignment fits the predicted azimuthal angle dependency in the theoretical model of the formation of general relativistic superconducting vortices, where the initial axially symmetry is broken just after the symmetry breaking of the scalar-gauge field.} \keyword{quasar groups; alignment spin vectors; host galaxy; cosmic strings; symmetry breaking; scalar-gauge field.

We show that the Einstein field equations for a five-dimensional warped spacetime, where only gravity can propagate into the bulk, determine the dynamical evolution of the warp factor of the four-dimensional brane spacetime. This can be explained as a holographic manifestation. The warped 5D model can be reformulated by considering the warp factor as a dilaton field ($\omega$) conformally coupled to gravity and embedded in a smooth $M_4 \otimes R$ manifold. On the brane, where the U(1) scalar-gauge fields live, the dilaton field manifests itself classically as a warp factor and enters the evolution equations for the metric components and matter fields. We write the Lagrangian for the Einstein-scalar-gauge fields in a conformal invariant setting. However, as expected, the conformal invariance is broken (trace-anomaly) by the appearance of a mass term and a quadratic term in the energy-momentum tensor of the scalar-gauge field, arising from the extrinsic curvature terms of the projected Einstein tensor. These terms can be interpreted as a constraint in order to maintain conformal invariance. By considering the dilaton field and Higgs field on equal footing on small scales, there will be no singular behavior, when $\omega\rightarrow 0$ and one can deduce constraints to maintain regularity of the action. Our conjecture is that $\omega$, alias warp factor, has a dual meaning. At very early times, when $\omega \rightarrow 0$, it describes the small-distance limit, while at later times it is a warp (or scale) factor that determines the dynamical evolution of the universe. We also present a numerical solution of the model and calculate the (time-dependent) trace-anomaly. The solution depends on the mass ratio of the scalar and gauge fields, the parameters of the model and the vortex charge $n$.

The DEP force is usually calculated from the object’s point of view using the interaction of the object’s induced dipole moment with the inducing field. Recently, we described the DEP behavior of high- and low-conductive 200-µm 2D spheres in a square 1x1mm chamber with a plane-versus-plane electrode configuration from the system’s point of view. Here we extend our previous considerations to the plane-versus-plane and pointed-versus-pointed electrode configurations. The trajectories of the sphere center and the corresponding DEP forces were calculated from the gradient of the system’s overall energy dissipation for given starting points. The dissipation’s dependence on the sphere’s position in the chamber is described by the numerical “conductance field”, which is the DC equivalent of the capacitive charge-work field. While the plane-versus-plane electrode configuration is field-gradient free without an object, the presence of the highly or low-conductive spheres generates structures in the conductance fields, which result in very similar DEP trajectories. For both electrode configurations, the model describes trajectories with multiple endpoints, watersheds, and saddle points, very high attractive and repulsive forces in front of pointed electrodes, and the effect of mirror charges. Because the model accounts for inhomogeneous polarization within the objects, the approach allows the modeling of the complicated interplay of attractive and repulsive forces near electrode surfaces and chamber edges. Non-reversible DEP forces or asymmetric magnitudes for the highly and low-conductive spheres in large areas of the chamber indicate the presence of higher-order moments, mirror charges, etc.

In the Czech Republic, the Universal Soil Loss Equation provides the basis for defining the soil protection strategy. Field rainfall simulators were used to define the actual cover-management factor values of the most extensively seeded crops in the Czech Republic. More than 380 simulations between 2016 and 2021 provided data. The methodology focused on multi-seasonal measurements to cover the most important phenological phases. A comparison with the original USDA values for maize showed that it is desirable to redefine the C-factor. 71 fallow plot experiments showed that the rainfall-runoff relation is much easier to replicate than the actual sediment transport. For 30-minute intensive rainfall, the runoff ratio reached 62%, and the coefficient of variation was 25%. On saturated soil, the runoff ratio reached 81% and the coefficient of variation dropped to 12%. Soil protection techniques have a significant effect on runoff reduction. Maize seeded after cover crops and combined with reduced tillage or direct seeding can reduce the runoff ratio to 10-20% for ‘dry’ conditions and to 12-40% for ‘saturated’ conditions. Concerning soil loss, the variations are greater, with the coefficient of variation reaching 42% during fallow plot experiments. The reader should consider associated uncertainties.

The first attempt to control and mitigate an epidemic outbreak caused by a previously unknown virus occurs primarily via non-pharmaceutical interventions (NPIs). In case of the SARS-CoV-2 virus, which since the early days of 2020 caused the COVID-19 pandemic, NPIs aimed at reducing transmission enabling contacts between individuals. The effectiveness of contact reduction measures directly correlates with the number of individuals adhering to such measures. Here, we illustrate by means of a very simple compartmental model how partial noncompliance with NPIs can prevent these from stopping the spread of an epidemic.

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

The paper presents a new type of hydraulic clutch operating with magnetorheological (MR) fluids and the results achieved from both theoretical analysis and experimental measurement. The hy-draulic clutch system of its own design with MR working fluid and a rotating magnetic field lo-cated is designed. The principle of this clutch is to use a rotating magnetic field created by an al-ternating current electromagnet to set the MR fluid in motion. In the tests of the hydraulic clutch with a rotating magnetic field, MR fluid produced on their own, consisting of solid iron particles of various diameters mixed with a silicone oil, are used as working fluids. The rheological properties of MR fluids are assessed on the basis of tests carried out with a Brookfield DV2T rheometer equipped with a magnetic device for generating the magnetic field of its own design. The char-acteristics of the hydraulic clutch with MR working fluid and the rotating magnetic field are tested on a specially built test stand. As a result of the research, it has been found that the torque transmitted by the clutch is the greater, the higher the rotational speed of the magnetic field and the lower the rotational speed of the beaker in which the working fluid is placed, and that the greatest torque occurs for the working fluid with the highest iron content. Based on the analysis of the structure and characteristics of the clutch in which the magnetic field is used, it has been shown that the design of the developed clutch is similar to that of an induction clutch, and its characteristics correspond to the characteristics of the eddy current clutch. Therefore, the proposed new clutch working with MR fluid and the rotating magnetic field can be applied to stationary power transmission system similarly to an eddy current clutch.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

The sustainable use of precious water resources requires effective water management. In the European Union, water management is mainly regulated by the Water Framework Directive (2000/60/EC), introducing an integrated river basin management approach. As EU directive, the legislation needs to be implemented in the Member States, entailing not only legal transposition, but also application and enforcement in Member States. One major instrument introduced by the Water Framework Directive is the environmental goal achievement obligation of art. 4 WFD, containing also a deterioration ban with several exemptions. This study compares transposition, application and enforcement of the exemption of permanent deterioration (art. 4 (7) WFD) in the context of the environmental goal achievement obligation regime in Lower Saxony (Germany) and the Netherlands. The study rests on a legal analysis of literature, policy documents and jurisprudence. Although based on the same EU directive wording and case law of the European Court of Justice, the deterioration ban and the exemption of permanent deterioration are implemented rather differently: While the deterioration ban is predominantly understood as planning obligation in the Netherlands, it became an important permit requirement in Lower Saxony since the Weser-ruling of the European Court of Justice.

The objective of this study was to evaluate the efficacy of fungal treatment (Pleurotus ostreatus) of urea-treated rice stubble on growth performance in slow-growing goats. Eighteen crossbred Thai native x Anglo-Nubian male goats (average body weight: 20.4 ± 2.0 kg) were randomly assigned to three experimental total mixed rations containing 35% rice stubble (RS) that was either untreated (URS), urea treated (UTRS) or treated with urea and fungi (UFTRS). URS and UTRS were cultivated and harvested from aseptically fungal spawn, incubated at 25-30 °C for 25 days. Indicators of growth performance were monitored and faeces were collected quantitatively to assess nutrient digestibility, during a 12-week feeding trial. All goats remained healthy throughout experiment. The goats fed UFTRS had a lower feed conversion ratio (kg feed/kg growth) compared to goats fed URS or UTRS. Compared to URS, dietary UFTRS increased nutrient digestibility of slow-growing goats, such as OM (+8.5%), CP (+5.5%), NDF (+39.2%), and ADF (+27.4%). Likewise, dietary UFTRS tended to increase rumen ammonia concentrations but rumen pH and volatile fatty acids were not affected by UFTRS. In conclusion, the present study indicates that the fungal treatment of RS is an effective tool to improve the growth performance of slow-growing goats.

The genus Aphanommata in the Old World is reviewed. Aphanommata kuscheli sp. nov. from São Nicolau and A. strakai sp. nov. from Fogo (both Cape Verde islands) are described. Aphanommata euphorbiarum (Wollaston, 1867) from Santo Antão in the Cape Verde islands is redescribed and its lectotype is designated. All three Aphanommata species from the Cape Verde islands as well as A. filum (Mulsant & Rey, 1859) from Old World are diagnosed, illustrated, and keyed. Mature larva of A. kuscheli sp. nov. is described, larval morphology is discussed and the current state of knowledge about immature stages of Cossoninae is summarized. Vertical and inter-insular distributional pattern of Cape Verde Aphanommata and Pselactus is reviewed and discussed.

Background: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoid malignancy. The majority of patients are asymptomatic and HCL is usually diagnosed incidentally during a routine blood cell counts. In symptomatic patients, typical symptoms are related to pancytope-nia and splenomegaly. In this review we present, rare clinical symptoms in patients with HCL. Methods: A literature search was conducted of PubMed, Web of Science, and Google Scholar for articles concerning hairy cell leukemia, leukemia cutis, bone lesions, neurological manifesta-tions, pulmonary symptoms, ocular manifestations, cardiac manifestation, rare symptoms. Publications from January 1980 to August 2024 were scrutinized. Additional relevant publica-ions were obtained by reviewing the references from the chosen articles. Results: Extra medul-lary and extra nodal manifestations of classic HCL are rare. However, leukemic involvement in the skin, bone, central nervous system, gastrointestinal tract, heart, kidney, liver, lung, ocular and other organs have been reported.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered, but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider effects of ice loading and its stochastic nature on fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

Implementation of novel blood-based biomarkers is desired to reduce diagnostic delay and burden for myositis patients. In this retrospective study, the potential of C-X-C motif chemokine ligand 10 (CXCL10) and growth differentiation factor 15 (GDF15) was explored in an established patient cohort diagnosed with immune-mediated necrotizing myopathy (IMNM; n=21), sporadic inclusion body myositis (IBM; n=18), polymyositis (PM; n=3), dermatomyositis (DM; n=2), and anti-synthetase syndrome (ASS; n=1), comparing with healthy controls (n=10) and patients with a hereditary neuromuscular disorder (n=14). CXCL10 and GDF15 were quantified in sera with enzyme-linked immunosorbent assays and immunolocalized in skeletal muscle tissue. In myositis patients, serum CXCL10 levels were significantly increased 9.6--fold compared to healthy and 4.2-fold compared to disease controls. Mean levels in IBM (929±658 pg/ml) were significantly higher than in IMNM (425±324 pg/ml). With the threshold set to 180pg/ml of CXCL10, myositis patients could be differentiated from healthy and disease controls with a sensitivity of 0.80 and a specificity of 0.71. Incorporating a threshold of 300 pg/ml for GDF15 reduced false negatives to two IMNM patients only. Subsets of muscle-infiltrating immune cells expressed CXCL10, and serum levels correlated with muscle inflammation grade. We propose adding circulating CXCL10 and GDF15 to the blood-based diagnostic toolkit for myositis as a valuable patient-friendly approach.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

In mesoscale eddies, chemical properties and biological composition are different from those in surrounding water, due to their unique physical processes. It is unclear how physical-biological coupling occurs in warm-core eddies, particularly since no study has examined the relationship between bacteria and viruses. The purpose of the present study was to examine the influence of anticyclonic warm eddy on the relationship between bacterial and viral abundances as well as viral activity (viral production) in different depths. In the core of warm eddy, bacterial abundance (0.48 to 2.82 ×105 cells mL−1) fluctuated less than that of the outside eddy (1.12 to 7.03×105 cells mL−1). In particular, there was four-folds higher of viral-bacterial abundance ratio (VBR) estimated within the eddy below DCM than the outside eddy. We suggest that prevailing physical forces with downwelling at the center of the anticyclonic warm eddy, viruses can also be transmitted into the deep ocean directly through adsorption on particulate organic matter during sinking. Overall, our findings provide valuable insights into the interaction between bacterial and viral communities and their ecological mechanism within the warm eddy.

Background: The Covid-19 pandemic was in reality a syndemic there the balance between a multitude of biological (Nature-made) and socio-political (men-made) factors determined individually the outcome of every single infection, on a scale of nothing-to-fatal. Blaming the virus for everything bad that happened to us after January 2020 is incorrect. Now, in ~ 2 years distance from the syndemic, it may be timely and possible to uncover the human contribution to this historical event and learn of it. Objective: To identify and use some qualitative approach to estimate the objective, statistical / epidemiological ‘value’ of the virus-selected individuals (in age-normalized groups) for the rest of the society. This non-political, non-religious approach may be the only way to understand the benefit / cost ratio of actions and emergency orders we had to survive in addition to the virus itself. Methods: Statistical data were obtained from publicly available official databases, including the relevant actuarial tables and evaluated by widely used statistical methods. The estimation of statistical/epidemiological ‘value of life’ was based, strictly and exclusively, on the real age and the statistically calculated Residual Life Expectancy (RLE, i.e. remaining years alive at a given age). The American healthcare expenses were compared to the corresponding healthcare costs/capita in other similarly well-developed west-European countries. This was the only available method to get some ideas about the magnitude of the well-established (rational) healthcare spending and compare it to the American standards. Results 1) Life expectancy uninterruptedly increased in USA since 1933, due to continuous reduction of Mortality Rate of the youngest and oldest citizens. COVID didn’t stop the population growth (+8.2 M /2020-2023). 2) The total count of Excess COVID associated Deaths (XCD) is ~ 2-times as much as the official statistic was able to explain by virus infection. It is speculated that these Complementary Covid Deaths (CCD) are probably the unexpected side-effects of the pandemic related emergency orders. 3) The worldwide ‘longevity’ trend exponentially increased the healthcare expenses, especially the care of elderly. However the USA is unique in this aspect and the healthcare costs are irrationally much higher than in any other country. 4) We can see a large economic incentive in the development of excesses under COVID syndemic. Conclusions The harm of the COVID virus - as well as the benefits of the mandatory, emergency actions during the pandemic - were grossly over-estimated. Professional, unbiased (non-religious, non-political) and independent reviews are strongly recommended.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3–4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008-2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3–4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children’s reciprocal social and repetitive behaviors and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no association between plasma PCB concentrations and autistic behavior, However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest quartile of plasma PCB concentrations compared with the lowest quartile; for instance, an average increase of 1.1 [95%PCI: −0.5, 2.6] in the mean SRS (exposure contrast 4^th versus 1^st quartile) for PCB138 translated to an odds ratio of 1.6 [95%PCI: 1.0, 2.5]. Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Agricultural intensification is considered essential for meeting growing demand for food and biomass for energy and material purposes. Intensifying grasslands is a so-far under-represented although promising option, given their large land area and relatively low management levels. This study quantifies the bioenergy potential from intensifying temporary grasslands in Europe and the integral greenhouse gas emission effects in 2030. We first conduct a literature review of intensification options for European grasslands and then apply the environmental impact assessment model MITERRA-Europe to implement the key intensification option of using multi-species grass mixtures. The results show that 853 kha (or 8%) of temporary grassland could be made sustainably available for additional biomass production. This can be translated into a bioethanol potential of 23 PJ/yr and an emission mitigation potential of 5.8 Mt CO2-eq/yr (if conventional grass mixture from surplus temporary grassland is used for energy) or 72 PJ/yr and 4.0 Mt CO2-eq/yr (if surplus temporary grassland is used for grassy energy crops). Although the bioenergy potential is limited, the intensification measure’s key advantage is that it results in a better environmental performance of temporary grasslands. This makes it a key option for sustainably producing bioenergy in areas with high shares of temporary grasslands.