Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Abstract: The objective of Peter Chew Triangle Diagram is to clearly illustrate the topic solution of triangle and provide a complete design for the knowledge of AI age. Peter Chew's triangle diagram will suggest a better single rule that allows us to solve any problem of topic solution of triangle simple , directly and more accurately. There are two important rules for solving the topic solution of triangle today [1,2], namely the sine rule and the cosine rule. The sine rule is used to find a non-included angle when are given two sides and a non-included angle or the opposite side angle given when are given two angles and one side. The cosine rule normally is used to find the included angle when are given three sides or the third side when are given two sides and the included angle. Peter Chew Method[3] allow us to find the third side simple and directly when given two sides and a non-included angle. Peter Chew rule [4] allow us to find a non included angle simple, directly and more accurately when given 2 sides and an included angle. Aply Peter Chew Triangle Diagram to Education 4.0 Calculator , Peter Chew Triangle Diagram Calculator allows the Calculator to solve any problems in the topic solution of triangle simple, directly and more accurate. This can be effective in increasing students' interest in using technology while learning mathematics and will help in the learning of mathematics, especially when similar covid-19 issues arise in the future.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

In this paper is discussed sediment transport as a mechanical process that characterises a natural stream or channel flow regime. The objective of experimental work presented in this paper is to recall and to give another prospect of well-known Meyer-Peter and Müller approach for estimation of Shield’s number (θ_c,θ) in laboratory conditions, and calibration of dimensionless MPM number (A). For this purpose two different experiments are conducted, during the first experiment water amount flushed on the flume and bed slope was changed simultaneously until equilibrium state is achieved, meanwhile is estimated the critical Shield’s number (θ_c). While, during the second experiment, water amount was kept constant, only bed slope of flume was continuously tilted, meanwhile sediment, discharge and Shield’s number (θ) was determined for given hydraulic conditions. In addition calibration of dimensionless MPM number (A) was performed, where several iteration were considered until for (A=3.42), sediment discharge measured become almost equal with sediment discharge computed by using MPM formula. After these experiments, is concluded that MPM formula can be used also for other certain initial condition and similar procedure may be adopted to calibrate the dimensionless MPM number (A) .

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of a SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

The Australian dairy sheep industry is small and mostly based on a natural grass grazing system which can limit productivity. The current study tested different plant oil-infused and rumen protected polyunsaturated fats and their interactions with sire breeds to improve lactation traits and body condition score (BCS) of ewes grazing low quality pastures. It was hypothesised that supplementing lactating ewe diets plant-derived polyunsaturated oils will improve milk production and composition without compromising BCS. Sixty ewes (n=10/treatment) in mid-lactation, balanced by sire breed, parity, milk yield, body condition score, and liveweight were supplemented with: 1) control: wheat-based pellets without oil inclusion; wheat-based pellets including 2) canola oil (CO); 3) rice bran oil (RBO); 4) flaxseed oil (FSO), 5); safflower oil (SFO) and 6) rumen protected fat containing eicosapentaenoic acid and docosahexaenoic acid (RPO). Except for the control group, all supplementary diets included the same level of 50 ml/kg DM of oil and all diets were isocaloric and isonitrogenous. Experimental animals were grazed in the same paddock with ad libitum access to pasture, hay and water during the 10-week study. RPO was the most effective diet that enhanced milk, fat and protein yields by approximately 30, 13, and 31% respectively (P<0.0001). Significant increase in milk production was also observed in CO, RBO, and SFO (P<0.0001). Breed significantly influenced animal performance with higher milk yield recorded for crossbred Awassi x East Friesian (AW x EF) (578 g/day) vs purebred Awassi (452 g/day) (P<0.0001). This study provides empirical evidence for the use of rumen-protected and plant-derived oil-infused pellets as supplements under low quality pasture grazing conditions, to improve production performance of purebred Awassi and crossbred AW x EF ewes.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

The infrared (IR) satellite remote sensing of sea surface skin temperature (SSTskin) is challenging in the northern high latitude region, especially in the Arctic because of its extreme environmental conditions, and thus the accuracy of SSTskin retrievals is questionable. Several Saildrone uncrewed surface vehicles were deployed at the Pacific side of the Arctic in 2019, and two of them, SD-1036 and SD-1037, were equipped with a pair of IR pyrometers on the deck whose measurements have been shown to be useful in the derivation of SSTskin with sufficient accuracy for scientific applications, providing an opportunity to validate satellite SSTskin retrievals. This study aims to assess the accuracy of MODIS-retrieved SSTskin from both Aqua and Terra satellites by comparisons with collocated Saildrone-derived SSTskin data. The mean differences in SSTskin from the SD-1036 and SD-1037 measurements are different by ~0.4 K, largely resulting from differences in the atmospheric conditions experienced by the two Saildrones. The performance of MODIS on Aqua and Terra in retrieving SSTskin is comparable. Negative brightness temperature (BT) differences between 11 μm and 12 μm channels are identified as being physically based, but are removed from the analyses as they present anomalous conditions for which the atmospheric correction algorithm is not suited. Overall, the MODIS SSTskin retrievals show negative mean biases, -0.234 K for Aqua and -0.295 K for Terra. The variations in the retrieval inaccuracies show an association with diurnal warming events in the upper ocean from long periods of sunlight in the Arctic. Also contributing to inaccuracies in the retrieval is the surface emissivity effect in BT differences characterized by the Emissivity-introduced BT difference (EΔBT) index. This study demonstrates the characteristics of MODIS-retrieved SSTskin in the Arctic, at least at the Pacific side, and underscores that more in situ SSTskin data at high latitudes are needed for further error identification and algorithm development of IR SSTskin.

The objective of this paper was to verify the applicability of statistical learning (SL) compared to human reasoning with respect to the Universal Thermal Climate Index (UTCI), a complex tool for the assessment of outdoor thermal stress. UTCI is an equivalent temperature index based on the 48-dimensional output of an advanced model of human thermoregulation formed by 12 variables at four consecutive 30-minute intervals, which were calculated for 105642 thermal conditions from extreme cold to extreme heat. Comparing the performance of SL algorithms to the results accomplished by an international endeavor involving more than 40 experts from 23 countries, we found that random forests and k-nearest neighbors closely predicted UTCI values, but that clustering applied after dimension reduction algorithms (principal component analysis and t-distributed stochastic neighbor embedding) were inadequate for risk assessment in relation to the UTCI stress categories. This indicates a potential supportive role for SL, as it will not (yet) fully replace the bio-meteorological expert knowledge.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to 1) Characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; 2) Examine the diagnostic assays that have undergone development and validation for this group of viruses, and 3) Describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Due to significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to characterise the SGV detected and determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities.

Spray penetration into citrus canopies is critical for adequate coverage and deposition to ensure effective pest control. However, mismatch of air assistance to target canopy characteristics can lead to unintended spray loss through over penetration. To evaluate the effect of air assistance on on-target deposition, two sprayers (surrogates for airflow rates) were used to apply a fluorescent tracer dye solution @ target concentration of 300 ppm to 16 medium foliage density tree blocks in a commercial mandarin orchard. The complete factorial experiment in three replications comprised two ground speeds (1.6 and 4.8 km/h), two disc-core nozzles (TeeJet® D3-25 and D6-45), and either one or two nozzle rows to obtain a wide range of application rates (496 to 9,719 L/ha). Dye deposition significantly decreased with canopy depth (p=&lt;0.001) by nearly 7 times across the 3.4-m-wide canopies but was not significant over 1.2 to 2.2 m sampling height (p=0.867). Deposition obtained with the low airflow rate sprayer was significantly greater (p=&lt;0.001) than that obtained with the high airflow rate sprayer over the dose range likely due to too much air pushing out spray droplets. This study underscores the importance of matching the air assistance of orchard sprayers to the target canopy.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

In this article, we present solutions for one of the oldest mathematical problems, the Collatz Conjecture, and provide a proof for the Riemann Hypothesis, utilizing a new number theory based on newly discovered number properties, which will also be presented in this paper. This is made possible through the Sophy-Peter mathematical framework, built upon this new number theory. The Collatz Conjecture will be disproven, but as an alternative, the Oscillating Theorem will be introduced, with its correctness proven within this article. Furthermore, we present the general version of the Riemann zeta function, developed based on the new number theory. The correctness of this function is verified by comparing it with existing results of the zeta function. Using this approach and the Sophy-Peter framework, we have successfully proven the Riemann Hypothesis, long considered a millennium problem. Moreover, since the general zeta function is proven, this implies the correctness of the new number theory and the Sophy-Peter framework.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

The vertebrate basal ganglia are thought to play an important role in action selection—the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of tonic dopamine transmission. We show that when the tonic level of simulated dopamine in a robotic model of the basal ganglia is significantly reduced or increased, relative to an effective operating baseline, a variety of behavioral outcomes are observed that provide interesting comparisons with the results of human and animal studies. The main findings were that progressive reductions in the levels of simulated dopamine caused a slowing of the robot’s movements and eventually an inability to initiate movement. These states were partially relieved at increased salience levels (stronger sensory/motivational input). Conversely, increased levels of simulated dopamine could cause distortion of the robot’s motor acts through partially-expressed motor activity relating to losing actions; this could also lead to increased frequency of switching between behaviors. Levels of simulated dopamine that were either significantly lower or higher than baseline could cause changes to the timing of behavior switching that could cause a loss of behavioral integration, sometimes leaving the robot in a ‘behavioral trap’. That some analogous traits are observed in animals and humans affected by dopamine dysregulation suggests that embodied (robotic) models could prove useful in understanding the role of dopamine neurotransmission in basal ganglia function and dysfunction. That the effects of simulated dopamine on robot action selection were partially, but not fully, predictable from the selection properties of the non-embodied basal ganglia model, also points to the added value of using robotic models to explore the relationship between brain activity and behavior.

Gas chromatography-coupled mass spectrometry (GC-MS) has been used in biomedical research to analyze volatile, non-polar, and polar metabolites in a wide array of sample types. Despite advances in technology, missing values are still common in metabolomics datasets and must be properly handled. We evaluated the performance of ten commonly used missing value imputation methods with metabolites analyzed on an HR GC-MS instrument. By introducing missing values into the complete (i.e., data without any missing values) NIST plasma dataset we demonstrate that Random Forest (RF), Glmnet Ridge Regression (GRR), and Bayesian Principal Component Analysis (BPCA) shared the lowest Root Mean Squared Error (RMSE) in technical replicate data. Further examination of these three methods in data from baboon plasma and liver samples demonstrated they all maintained high accuracy. Overall, our analysis suggests that any of the three imputation methods can be applied effectively to untargeted metabolomics datasets with high accuracy. However, it is important to note that imputation will alter the correlation structure of the dataset, and bias downstream regression coefficients and p-values.

Molnupiravir, a prodrug known for its broad antiviral activity, demonstrated efficacy in animal models of Covid-19, prompting clinical trials where initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the rejection of molnupiravir for permanent market authorization in many countries. This report critically assessed 19 studies published in 17 reports that investigated the efficacy of molnupiravir in animal models of Covid-19 with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal Covid-19 models were disproportionately higher than the dose rec-ommended for human use. Specifically, when adjusted for body surface area, half of the doses of molnupiravir used in the animal studies were more than twice as high as the human dose. Addi-tionally, the drug was frequently given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that these design elements in the reported animal studies contributed to a bias favoring molnupiravir, and thus inflated expectations for its efficacy against Covid-19. Addressing these elements may offer avenues to enhance the clinical efficacy of mol-nupiravir for treatment of Covid-19 that include dose increment, early treatment, and admin-istration by inhalation along with use of molnupiravir in antiviral combination therapy.

The enhancement of health-beneficial omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart and kidney of prime lambs. Lambs grazing cocksfoot only had the highest 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100g and 55.2 mg/100 g, respectively). Supplementation of pellets with or without oil infusion to grazing lambs decreased the ALA and n-3 LC-PUFA contents and increased n-6/n-3 ratio in Longissimus dorsi muscle. The fatty acid content in internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA which may consequently enhance the omega-3 intake of Australian lamb consumers.

This study investigated live animal performance and carcass characteristics of Australian prime lambs fed oil based polyunsaturated fatty acid (PUFA) enriched pellets in a feedlot system. The tested hypothesis was that supplementation of lambs with a variety of dietary oil based PUFA enriched pellets would enhance growth and carcass characteristics compared with the control lambs on lucerne only. Seventy-two, 6 months old White Suffolk x Corriedale first-cross prime lambs with an average liveweight (LWT) of 35.7 ± 0.9 kg were allocated to six treatment groups in a completely randomised experimental design. The treatments were: (1) control: lucerne hay only; or lucerne hay plus wheat-based pellets infused with 50 ml/kg DM of oils from (2) rice bran (RBO); (3) canola (CO); (4) rumen protected (RPO); (5) flaxseed (FO) and (6) safflower (SO) dietary sources. All lambs had ad libitum access to lucerne hay and clean fresh water. Supplemented lambs were fed 1kg of pellet/head/day for 10 weeks. Feed intake, final LWT, average daily gain (ADG), body conformation and carcass characteristics of lambs in the supplemented groups were all greater than for the control group. SO lambs had the lowest ADG of 190.3 g/day. RBO and CO treatments had the lowest feed cost per unit gain of AU$ 3.0/kg. Supplemented lambs had similar over the hooks (OTH) incomes that were all higher than that of the control group. This empirical evidence-based data demonstrated that supplementation of lambs with RBO and CO had comparatively lower feed costs without compromising ADG, carcass characteristics and OTH income.

: In this study we evaluated, if single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1 and CYP27B1 are associated with Mandibular Retrognathism (MR). Samples from biologically-unrelated patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients having a retrognathic mandible (SNB<78º) were selected as cases and those with an orthognathic mandible (SNB=78º–82º) were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256 and rs307247), VDR (rs7975232), CYP24A1 (rs464653) and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p<0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 MR and 43 controls were included. In the genotype and allele distribution analysis, the SNPs rs694, rs307247 and rs464653 in were associated with MR (p<0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1 and CYP27B1 genes are associated with the presence of mandibular retrognathism.

Buruli ulcer is a chronic ulcerative disease of skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanised due to welfare concerns and poor prognosis, based on the presence of deep ulcerative lesions to paws, some of which exposed carpal or tarsal bones. These lesions were considered likely to cause partial or complete loss of limb function, which would severely affect the welfare and survival of these wild arboreal animals. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis, and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs and biological tissues collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. In addition to severe cutaneous lesions, infection extends to underlying bones and joints, and the systemic distribution of M. ulcerans throughout all major tissues and internal organs, as observed in these four cases, may further impact the health and fitness of infected possums. Further research is needed to investigate the epidemiology, pathogenesis and impacts of Buruli ulcer in possums, and to inform the design of interventions that may protect the health and welfare of possums and other affected animal species.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Exercising surds to represent figures is a common practice in scientific and Engineering fields, especially in scripts where calculators are banned or unapproachable. Peter Chew Theorem make result becomes simple when dealing with converting Quadratic Surds. The substance of the Peter Chew Theorem lies in enabling the forthcoming generation to simple break problems related to Quadratic Surds more effectively, easing a direct comparison with contemporary results. By employing the Peter Chew Theorem, one can streamline the tutoring and literacy of math, particularly concerning second- order direct equations with constant portions. This theorem's objective aligns with Albert Einstein's famed quotation Everything should be made as simple as possible, but not simpler.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

Let Vn(d) denote the least number such that every collection of nd-cubes with total volume 1 in d-dimensional (Euclidean) space can be packed parallelly into some d-box of volume Vn(d). We show that V3(d)=r1−dd if d≥11 and V3(d)=1r+1rd+1r−rd+1 if 2≤d≤10, where r is the only solution of the equation 2(d−1)kd+dkd−1=1 on 22,1 and (k+1)d(1−k)d−1dk2+d+k−1=kddkd+1+dkd+kd+1 on 22,1, respectively. The maximum volume is achieved by hypercubes with edges x, y, z such that x=2rd+1−1/d, y=z=rx if d≥11, and x=rd+(1r−r)d+1−1/d, y=rx, z=(1r−r)x if 2≤d≤10. We also proved that only for dimensions less than 11 there are two different maximum packings, and for all dimensions greater than 10 the maximum packing has the two smallest cubes the same.

Sustainable continuous cover forestry is defined and analyzed in several ways. The differential equation representing growth of the basal areas of individual trees, motivated by fundamental biological production theory by Lohmander (2017a), is analyzed and extended in different directions. From the solution of the differential equation, the basal area and the tree diameter are obtained as explicit functions of time. The diameter is a strictly increasing function of time. In the absence of competitors, the diameter increment is shown to be a strictly decreasing function of time. Hence, the diameter increment can also be interpreted as a strictly decreasing function of the diameter. Alternative forms of adjustment of the differential equation, with consideration of competition, are defined. If the competition is strong, with large trees in the vicinity of a particular tree, then the basal area increment, and the diameter increment, are reduced. The growth of a large tree is less sensitive than the growth of a small tree, to competition from other trees. Under strong competition, the basal area increment, and the diameter increment, are strictly concave functions of the size of the tree. The unique maximum of the diameter increment occurs at a higher diameter, if the competition increases. In dynamic equilibrium, the tree size frequency distribution is stationary. If natural tree mortality can be avoided via the harvest strategy, the tree size frequency distribution is a function of the size and competition dependent growth function, and the harvest strategy. Empirical tree size frequency data are used to simultaneously estimate parameters of a size and competition dependent growth function and the applied harvest strategy, via nonlinear optimization. The properties of the estimated growth function are consistent with the corresponding properties of the production theoretically motivated hypothetical function, and the properties of the estimated harvest strategy confirm the corresponding hypotheses. The R2 of the nonlinear regression exceeds 0.97. With access to an empirically estimated equilibrium tree size distribution, it is possible to: 1. Estimate size frequency relevant parameters of tree size and competition dependent growth functions for individual trees. 2. Estimate the applied harvest strategy. 3. Explain and reproduce the empirically estimated tree size equilibrium distribution.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

This paper discusses the tectonics of the St. Peter and St. Paul Archipelago (SPSPA) in the Equato-rial Atlantic Ocean, based on the joint-system geometry which show a North-South shorten-ing/transpressional uplift tectonism, is active leading to exhumation of the sub-oceanic mantle. These islets are the summits of a sigmoidal submarine ridge formed by mantle ultramafic rocks. The ridge is crossed by the principal transform deformation zone of the northern transform fault of the St. Paul Multifault System. The South flank ridge exposes serpentinized mantle perido-tites, while the North flank exposes strongly deformed/fractured ultramylonites, recording duc-tile and brittle deformation at lithospheric conditions. The SPSPA show multiple joint systems cutting mylonitic foliation of the exposed rocks, forming three main families: high-angle paral-lel joints of tectonic origin, serpentinization-related joints with random direction and load-release low-angle parallel joints. The tectonic joints show an average direction of N31°E and N28°W, forming a conjugate system with a N1ºW compression axes, coherent with a trans-pressive stress field. Accordingly, the earthquakes focal mechanism close to the islets also shows N-S compression. The previously reported active uplift with an average rate of 1.5 mm/year and the directions of the joint system here reported agreeing with a present-day active N-S compres-sive field at a high angle with the direction of the transform fault.

Immunological aging type definition requires establishing reference intervals from the distribution of immunosenescence biomarkers conditional on age. For 1,605 individuals (18–97 years), we determined the comprehensive IMMmune Age indeX IMMAX from flow cytometry-based blood cell sub-populations, and identified age-specific centiles by fitting generalized additive models for location, scale and shape. The centiles were uncorrelated with age, and facilitated the categorization of individuals as immunologically slow or fast aging types. Using its 50th percentile as reference, we rescaled IMMAX to equivalent years-of-life (EYOL), and computed the immunological age gap as difference between EYOL and chronological age. Applied to preliminary baseline and follow-up measurements from 53 participants of the Dortmund Vital Study (Clinical-Trials.gov Identifier: NCT05155397), the averaged changes in IMMAX and EYOL conformed to the 5-year follow-up period, whereas no significant changes occurred concerning IMMAX centiles and age gap. This suggested that the participants immunologically adapted to aging, and kept their relative positions within the cohort. Sex was non-significant. Methodical comparisons indicated that future confirmatory analyses with the completed follow-up examinations could rely on percentile curves estimated by simple linear quantile regression, while the selection of the immunosenescence biomarker will greatly influence the outcome, with IMMAX representing the preferable choice.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Here we review and describe a set of research priorities to meet present and future challenges posed to farmed animal production that build on progress, successes and resources from the Functional Annotation of ANimal Genomes (FAANG) project.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

The air in subterranean karst cavities is often depleted in methane (CH₄) relative to the atmosphere. Karst is considered a potential sink for the atmospheric greenhouse gas CH₄ because its subsurface drainage networks and solution-enlarged fractures facilitate atmospheric exchange. Karst landscapes cover about 14% of earth’s continental surface, but observations of CH₄ concentrations in cave air are limited to localized studies in Gibraltar, Spain, Indiana (USA), Vietnam, Australia, and by incomplete isotopic data. To test if karst is acting as a global CH₄ sink, we measured the CH₄ concentrations, δ¹³C_CH4, and δ²H_CH4 values of cave air from 33 caves in the USA and three caves in New Zealand. We also measured CO₂ concentrations, δ¹³C_CO2, and radon (Rn) concentrations to support CH₄ data interpretation by assessing cave air residence times and mixing processes. Among these caves, 35 exhibited subatmospheric CH₄ concentrations in at least one location compared to their local atmospheric backgrounds. CH₄ concentrations, δ¹³C_CH4, and δ²H_CH4 values suggest that microbial methanotrophy within caves is the primary CH₄ consumption mechanism. Only 5 locations from 3 caves showed elevated CH₄ concentrations compared to the atmospheric background and could be ascribed to local CH₄ sources from sewage and outgassing swamp water. Several associated δ¹³C_CH4 and δ²H_CH4 values point to carbonate reduction and acetate fermentation as biochemical pathways of limited methanogenesis in karst environments and suggest that these pathways occur in the environment over large spatial scales. Our data show that karst environments function as a global CH₄ sink.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

In the present work we revise and extend the Characteristic Crystallographic Element (CCE) norm, an algorithm used to simultaneously detect radial and orientational similarity of computer-generated structures with respect to specific reference crystals and local symmetries. Based on the identification of point group symmetry elements, the CCE descriptor is able to gauge local structure with high precision and finely distinguish between competing morphologies. As test cases we use computer-generated monomeric and polymer systems of spherical particles interacting with the hard-sphere and square-well attractive potentials. We demonstrate that the CCE norm is able to detect and differentiate, between others, among: hexagonal close packed (HCP), face centered cubic (FCC), hexagonal (HEX) and body centered cubic (BCC) crystals as well as non-crystallographic fivefold (FIV) local symmetry in bulk 3-D systems; triangular (TRI), square (SQU) and honeycomb (HON) crystals, as well as pentagonal (PEN) local symmetry in thin films of one-layer thickness (2-D systems). The descriptor is general and can be applied to identify the symmetry elements of any point group for arbitrary atomic or particulate system in two or three dimensions, in the bulk or under confinement.

Therapeutic measures aimed at optimising organ function prior to transplantation - whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal - have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a positive effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion in particular has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy, and therapeutic donor hypothermia in the intensive care unit after brain death confirmation have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to a favourable effect on graft survival in the long-term, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence on the basis of the large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Introduction Livestock abortigenic agents, which are microorganisms that lead to premature foetal death and expulsion before completion of the gestation period, are common in Africa and Asia. Abortion events cause economic losses by lowering reproduction (and hence herd/flock sizes) and effects on milk production. Despite the importance of livestock production for food security and livelihoods of millions of the world’s poorest communities, very little is known about the scale, magnitude or causes of livestock abortion in Africa. The aim of this review was to determine the current status of the burden of livestock abortion and surveillance measures adopted for livestock abortigenic pathogens in Africa and Asia, and to explore feasible surveillance technologies. Methodology A systematic literature search was conducted using Preferred Reporting of Systematic Reviews and Meta-analyses (PRISMA) guidelines in four databases for studies published between 1 Jan 1990 and 31 July 2021 that reported epidemiological surveys of livestock abortigenic pathogens in cattle, goats and sheep in Africa and Asia including; Brucella spp., Neospora caninum, Toxoplasma gondii, Rift valley fever virus, Coxiella burnetii, Chlamydia, Leptospira and Bovine viral Diarrhoea Virus. A meta-analysis was used to estimate the species-specific prevalence of the abortigenic diseases and the region where they were detected. Results In the systematic literature search, 48 full papers were included which in total included 50 species-specific surveillance reports from Africa and 19 from Asia. Adjusted median seroprevalence calculations estimated Brucella at 6.85% (range 1.2-11.6) of 9071 sheep, 3.35% (range 0.90-5.40) of 17,007 goats, 8.95% (range 0.50-63.60) of 171,733 cattle, Neospora at 6.80% (range 6.80 -6.80) of 555 sheep, 10.80 (range 10.80-10.80) of 185 goats, 12.65% (range 3.40- 25.60) of 3775 cattle, Toxoplasma at 27.50% (range 1.40 – 75.90) of 2284 sheep, 32.0% (range 20.00- 64.80) of 1226 goats, 7.50% (range 7.50 - 7.50) of 174 cattle, Coxiella at 9.20 (range 9.20 – 9.20) of 184 sheep, 24.20% (range 24.20-24.20) of 91 goats, 13.80% (range 13.80-13.80) of 217 cattle, Rift valley fever virus at 7.70 (2.40-40.00) of 874 sheep, 20.95 (range 2.50-40.00) of 547 goats, 7.45% (range 3.60-11.30) of 309 cattle, Bovine viral diarrhea virus at 78.90 (range 78.90 – 78.90) of 398 cattle, Leptospira at 70.50 (range 70.50 – 70.50) of 373 cattle and Chlamydia at 6.60 (6.60-6.60) of 803 sheep. We found that most studies, 45 (89%) used serological surveys, 1 (2%) used molecular and 1 (2%) reported to have used Mobile-phone based surveillance approach. Three studies (6.25%) of the 48 included were embedded in the national surveillance programs of the respective countries they were conducted, majority 89% were stand-alone cross-sectional studies. Conclusion In conclusion, livestock abortigenic pathogens are still a burden in many African and Asian countries.

The estuarine exchange flow increases longitudinal dispersion of passive tracers and traps sinking particles, potentially creating an estuarine turbidity maximum (ETM): a localized maximum of suspended particulate matter concentration in an estuary. The ETM can have many implications - dead zones due to increased turbidity or hypoxia from organic matter decomposition, naval navigation challenges, and other water quality problems. Using timescales, we investigate how the interaction between exchange flow and particle sinking leads to ETMs by modeling a sinking tracer in an idealized box model of the Total Exchange Flow (TEF) first developed by Parker MacCready. Results indicate that the balance of particle sinking and vertical mixing is critical to determining ETM size and location. We then focus on the role of ecology in ETM formation through the use of The Peter-Parker Model: a new biophysical model which combines the TEF box model with a Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) model, the likes of which were first developed by Peter J.S. Franks. Detritus sinking rates similarly influence detritus peak concentration and location (an ETM), but detritus ETMs occur in a different location than the sinking tracer due to the influence of the biological factors which create a time lag of about 1 day. Lastly, we characterize the flow of the models with a dimensionless parameter that compares timescales and summarizes the dynamics of the sinking tracer in ETM formation and can be used across systems.

Peatlands in Indonesia are one of the world's largest carbon sinks, helping to regulate greenhouse gas emissions and global climate change. Lophostemon suaveolens is a plant found in Papua's endemic peat ecosystem that grows well in wet areas with low fertility. It is geographically dispersed and has the potential for peatland re-habilitation. We present an efficient and reproducible protocol for in vitro multiplication of plantlets using nodal segments and shoot apices collected from plantlets. The Murashige and Skoog (MS) medium was sup-plemented with single and double kinds of PGRs (BAP and NAA). The concentration used in this study is based on the best findings of earlier preliminary research on single PGR treatment (0.5 ml/l BAP and 0.1 ml/l NAA) for the initiation stage. After 3 months of in vitro axillary shoot initiation, elongated shoots from plant-lets were separated from the clumps and multiplied. Until 6 months incubation, the potential multiplication of axillary shoots was determined by counting the number of nodule multiplication coefficients (NMC), shoot length, root length, and number of leaves (6 successive subculture). The highest average per plantlet of NMC (8.4 0.13) was observed in MS medium with a combination of 0.5 ml/l BAP and 0.1 ml/l NAA (double PGRs), with the longest shoots (5.91 0.17 cm), the longest root length (8.83 0.69 cm), and the most leaves (32 0.69). They were cultured in a pH 5 environment with a light photoperiod (40 mol/m2/s intensity) for 16 hours. When BAP and NAA were used together after acclimatization, seedling survival was highest. This is the first report of L. suaveolens in vitro multiplication, and the protocol could be used to propagate this peatland species on a large scale.

Background: Sexual dysfunction is the most common side effect encountered by cervical cancer patients during and after treatment, and rehabilitation strategies are needed to improve their quality of life. A variety of rehabilitation strategies have been reported in previous studies, varying by country, race and even continent. However, the common rehabilitation strategies used by cervical cancer survivors in Tanzania and their outcomes are unknown. The study aimed to unfold sexual rehabilitation strategies and outcome practiced by cervical cancer survivors who experienced sexual dysfunction during and after treatment in North-western Tanzania. Methods: Descriptive qualitative study were employed. Phenomenology study design used with a sample of 7 participants and data corrected via in-depth interview guided by 11 questions. Audiotaped and transcribed to get main themes and sub themes through deductive analysis. Results: Most participants reported inability to achieve an orgasm and low libido and dyspareunia after treatment. Most participants were eagerly to have their sexual activity recovered. However, they were not familiar with any rehabilitation strategy after the experience of sexual dysfunction. Even though, some of the participants attempted various interventions, but all were unsatisfactory leading to a significant decline in sexual interest and activity. Conclusion: Cervical cancer survivors are not familiar with any sexual rehabilitation strategies. Health education concerning various sexual rehabilitation strategies should be provided to survivors during and even after treatment.

This study develops a hybrid machine learning (ML) algorithm integrated with IoT technology to improve the accuracy and efficiency of soil monitoring and tomato crop disease prediction in Anakapalle, a south Indian station. An IoT device collected one-minute and critical soil parameters—humidity, temperature, pH values, nitrogen (N), phosphorus (P), and potassium (K)—essential for assessing soil health and optimizing crop growth. Kendall's correlations were computed to rank these parameters for utilization in hybrid ML techniques. Various ML algorithms including K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Decision Tree (DT), Random Forest (RF), and Logistic Regression (LR) were evaluated. A novel hybrid algorithm, 'Bayesian Optimization with KNN', was introduced to combine multiple ML techniques and enhance predictive performance. The hybrid algorithm demonstrated superior results with 95% accuracy, precision, and recall, and an F1 score of 94%, while individual ML algorithms achieved varying results: KNN (80% accuracy), SVM (82%), DT (77%), RF (80%), and LR (81%) with differing precision, recall, and F1 scores. This hybrid ML approach proved highly effective in predicting tomato crop diseases in natural environments, underscoring the synergistic benefits of IoT and advanced ML techniques in optimizing agricultural practices.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic VSL#3 at improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and VSL#3 treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n=64) was treated with rifaximin (seven days per month for three months) followed by VSL#3, and group B (n=60) was treated with a placebo. At the beginning of the study and after three months of treatment, all patients completed NIH-CPSI and IBS-SSS questionnaires to score the severity of their urogenital and gastrointestinal symptoms, and we measured seminal plasma levels of IL-6 and IL-10 using ELISA. We defined patients who improved following the treatment as those with a ≥6-point reduction in their NIH-CPSI score or ≥50-point reduction in their IBS-SSS score. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI and IBS-SSS scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs 4.4 pg/mL) relative to baseline, whereas levels of IL-6 and Il-10 did not change in the placebo group. The co-occurrence of two clinical phenotypes (IBS-D plus IIIa prostatitis) result in increased intestinal inflammation and altered immune activation, both of which can be balanced by treatment with rifaximin and VSL#3.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

The most recent National Research Council Nutrient Requirements for Sheep and Goats was published in 2007, one of the most consequential nutrient requirement recommendations for sheep and goats in the world. It is pertinent to continue the refinement and discussion of nutrient utilization and requirements for the purposes of enhancing the efficiency of production systems, maximizing resource economy, and minimizing the carbon footprint, among others. Progress has been made in the estimation of energy and protein requirements in sheep and goats, mainly utilizing empirical feeding experimentation, comparative slaughter technique and minimum endogenous loss method. In sheep, newer estimates of energy and protein requirements for maintenance and growth and partial efficiencies had been reported since 2007. There were suggestions that energy and protein requirements could have been affected by breed, wool growth, gender and size; with these reported values being similar or lower than the recommended values in international feeding systems such as NRC, ARC, INRA and AFRC. In goats, energy and protein requirements for growing goats were reported to be either higher or lower than the established recommendations, depending upon meat or dairy breeds. Effect of gender on energy requirement appeared to be related to the stage of growth or degree of maturity. Newer data also suggested that the guidelines of the major feeding systems for the entire growth phase may not be adequate for non-pregnant and non-lactating pubertal females. In multiparous pregnant goats, energy and protein requirements for maintenance did not appear to be affected by days of pregnancy, but efficiencies of metabolizable energy and metabolizable protein utilization for pregnancy were. There were suggestions that that metabolizable protein synthesis in the rumen can be predicted from energy intake using combined equations that encompass both sheep and goats, but more data on goats were called for to account for specific differences in nutrition. In addition to sulfur, there has been progress made on the estimation of maintenance and growth requirements of calcium, phosphorus, potassium and magnesium in goats, with suggestions on the consideration of gender and breed differences. Species, level of Intake, genotype, mature size, age, gender, body composition, use of tissue energy, activity, season, and acclimatization continue to be important considerations for the estimation of nutrient requirements in sheep and goats, with emerging factors such as climate change, heat stress, parasitism and secondary plant compounds. Model equations and partial efficiencies used by NRC to predict energy and protein requirements for maintenance, growth, lactation, and fiber have been highlighted and discussed for the purpose of a more focus discussion and refinement for the future. Potential and limitation of both traditional and emerging methodologies in determining the nutrient requirements in sheep and goats were discussed. To justify the research investment, emerging methodologies such as nutrigenomics will have to be linked more directly to the improvement of production efficiency via more precise prediction of nutrient requirement.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Free-living terrestrial mites (Acari) have persisted through numerous glacial cycles in Antarctica. Very little is known, however, of their genetic diversity and distribution, particularly within the Ross Sea region. To redress this gap, we sampled for mites throughout the Ross Sea region, East Antarctica, including Victoria Land and the Queen Maud Mountains (QMM), covering a latitudinal range of 72-85oS, as well as from Lauft Island near Mt Siple (73oS) in West Antarctica and Macquarie Island (54oS) in the sub-Antarctic. We assessed genetic diversity using mitochondrial cytochrome c oxidase subunit I gene sequences (COI-5P DNA barcode region), and also morphologically identified voucher specimens. We obtained 130 sequences representing four genera: Nanorchestes (n = 30 sequences), Stereotydeus (n = 46), Coccorhagidia (n = 18) and Eupodes (n = 36). Tree-based analyses (maximum likelihood) revealed 13 genetic clusters, representing as many as 23 putative species indicated by Barcode Index Numbers (BINs) from the Barcode of Life Datasystems (BOLD) database. We found evidence for geographically-isolated cryptic species, e.g. within Stereotydeus belli and S. punctatus, as well as unique genetic groups occurring in sympatry (e.g. Nanorchestes spp. in QMM). Collectively, these data confirm high genetic divergence as a consequence of geographic isolation over evolutionary timescales. From a conservation perspective, additional targeted sampling of understudied areas in the Ross Sea region should be prioritised, as further diversity is likely to be found for these short-range endemic mites.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Development of new techniques of multimodal treatment, diagnostics of various neoplasms and improvement of these techniques can significantly increase the life expectancy of patients with carcinomas of the colon and abdominal cavity organs, since prevention of various side effects of radiation therapy is one of the main problems of oncological care. Electron irradiation is one of the most promising types of radiation therapy. There are no data on proliferation and apoptosis of the colon epithelium after irradiation with electrons, especially in different modes (single and summary). Aim of the study: Morphological evaluation of apoptosis and proliferation of colonic epithelium after local irradiation with electrons at doses 2 Gy and 25 Gy. Materials and methods. Colon fragments from sexually mature Wistar rats (n=50, body weight 200 ± 10 g) were divided into three groups: I - control (n = 10); II - experimental group (n = 20; local single electron irradiation at a dose of 2 Gy), III - experimental group (n=30), local fractional irradiation with electrons at a total dose of 25 Gy. They were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and Cas3. Morphological disorders were accompanied by increased expression of pro-apoptotic molecules (caspase-3), and the period of regeneration by proliferative marker (Ki-67). Conclusions: Local fractional irradiation of the colon with electrons at a dose of 2 Gy and 25 Gy resulted in minor changes in the epithelium, a decrease in the number of goblet cells, but with preservation of regenerative potential, mild degenerative-dystrophic lesions. Intestinal crypts were damaged, leading to a decrease in Ki-67 and an increase in the number of caspase-3-positive epitheliocytes.

Relationships of the three bryophyte lineages (liverworts, mosses, and hornworts) to vascular plants is a pivotal question in the study of origin and evolution of land plants. In recent decades, this question has been subject to intense phylogenetic analyses using morphological characters, multigene DNA sequences, and genome structural characters. A tentative consensus reached ten years ago suggested that bryophytes are a paraphyletic group, with liverworts being sister to all other land plants and hornworts being sister to vascular plants. However, several more recent nuclear phylogenomic studies have concluded that bryophytes represent a monophyletic group that is sister to vascular plants. A discussion is presented here on strengths and weaknesses of different types of characters (morphological traits, nucleotide sequences, and genome structural arrangements), and their suitability for resolving deep phylogenetic relationships. Moreover, several criteria for credible phylogenetic reconstruction are proposed. Strong statistical support for reconstructed relationships should be derived from high quality, independent characters selected for suitability to the particular question being addressed. The relationships inferred in a study should be congruent with those from as many other lines of phylogenetic evidence as possible. Any incongruities should be explicable by well-understood biological mechanisms. It is concluded that the relationships of the three bryophyte lineages to vascular plants should currently be viewed as unresolved. This is a difficult phylogenetic problem; the land plants underwent a rapid radiation a long time ago. Yet, further exploration of analytical methods and careful choice of characters should lead to eventual elucidation of diversification patterns among early land plants.

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRM), able to recognise pathogen- or dan-ger-associated molecular patterns (PAMP, DAMP) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self-cells, and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at C-terminus). Pulmonary sur-factant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells, and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeo-stasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumourigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

In this study, the Bohler K 190 steel was used. The steel was manufactured by the powder metallurgy (PM) process. The boronizing process was carried out in the range of 1173 to 1323 K, for 1-10 h. The samples were boronized in solid medium, called the Durborid powder mixture. For the microstructural observations, the scanning electron microscopy was utilized for determining the morphology of interfaces and measuring the layers’ thicknesses. The phase composition of boride layers was also determined with X-ray diffraction analysis. To investigate the redistribution of chemical elements redistribution during the boronizing process, the EDS mapping and EDS point analysis were used. The boride layers were constituted by FeB and Fe2B phases except for 1173 K for 1 h. The values of Vickers microhardness of Fe2B, FeB and transition zone were estimated. Finally, to assess the boron activation energies in FeB and Fe2B, the so-called integral method was applied and the results in terms of activation energies were confronted with the literature data.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

This study focuses on the optimal deployment problem, and determines the optimal size of a military force to send to the battle field. The decision is optimized, based on an objective function, that considers the cost of deployment, the cost of the time it takes to win the battle, and the costs of killed and wounded soldiers with equipment. The cost of deployment is modeled as an explicit function of the number of deployed troops and the value of a victory with access to a free territory, is modeled as a function of the length of the time it takes to win the battle. The cost of lost troops and equipment, is a function of the size of the reduction of these lives and resources. An objective function, based on these values and costs, is optimized, under different parameter assumptions. The battle dynamics is modeled via the Lanchester differential equation system based on the principles of directed fire. First, the deterministic problem is solved analytically, via derivations and comparative statics analysis. General mathematical results are reported, including the directions of changes of the optimal deployment decisions, under the influence of alternative types of parameter changes. Then, the first order optimum condition from the analytical model, in combination with numerically specified parameter values, is used to determine optimal values of the levels of deployment in different situations. A concrete numerical case, based on documented facts from the Battle of Iwo Jima, during WW II, is analyzed, and the optimal US deployment decisions are determined under different assumptions. The known attrition coefficients of both armies, from USA and Japan, and the initial size of the Japanese force, are parameters. The analysis is also based on some parameters without empirical documentation, that are necessary to include to make optimization possible. These parameter values are motivated in the text. The optimal solutions are found via Newton- Raphson iteration. Finally, a stochastic version of the optimal deployment problem is defined. The attrition parameters are considered as stochastic, before the deployment decisions have been made. The attrition parameters of the two armies have the same expected values as in the deterministic analysis, are independent of each other, have correlation zero, and have relative standard deviations of 20%. All possible deployment decisions, with 5000 units intervals, from 0 to 150000 troops, are investigated, and the optimal decisions are selected. The analytical, and the two numerical, methods, all show that the optimal deployment level is a decreasing function of the marginal deployment cost, an increasing function of the marginal cost of the time to win the battle, an increasing function of the marginal cost of killed and wounded soldiers and lost equipment, an increasing function of the initial size of the opposing army, an increasing function of the efficiency of the soldiers in the opposing army and a decreasing function of the efficiency of the soldiers in the deployed army. With stochastic attrition parameters, the stochastic model also shows that the probability to win the battle is an increasing function of the size of the deployed army. When the optimal deployment level is selected, the probability of a victory is usually less than 100%, since it would be too expensive to guarantee a victory with 100% probability. Some of many results of relevance to the Battle of Iwo Jima, are the following: In the deterministic Case 0 analysis, the optimal US deployment level is 66200, the time to win the battle is 30 days and 14000 US soldiers are killed or wounded. If the marginal cost of the time it takes to win a victory doubles, the optimal deployment increases to 75400, the time to win a victory is reduced to 26 days, and less than 12000 soldiers are killed or wounded. In the stochastic Case 0 analysis, the optimal US deployment level is 65000, the expected time to win the battle is 46 days and almost 25000 US soldiers are expected to be killed or wounded. If the cost per killed or wounded soldier increases from 0 to 5 M $US, the optimal deployment level increases to 75000. Then, the victory is expected to appear after 35 days and 19900 US soldiers are expected to be killed or wounded.

A proxy war, between a coalition of countries, BLUE and a country, RED, is considered. RED wants to increase the size of the RED territory. BLUE wants to involve more regions in trade and other types of cooperation. GREEN is a small and independent nation that wants to become a member of BLUE. RED attacks GREEN and tries to invade. BLUE decides to give optimal arms support to GREEN. This support can help GREEN in the war against RED and simultaneously reduce the military power of RED, which is valuable to BLUE, also outside this proxy war, since RED may confront BLUE also in other regions. The optimal control problem of dynamic arms support, from the BLUE perspective, is defined in general form. The objective function is a weighted sum of the present value of the free GREEN territory and the present value to BLUE of the net loss of military resources in the RED army. The net loss of RED at a particular point in time is a function of the location of the front line and the size of the mobile GREEN forces behind the RED line. First, it is assumed that the expected net loss is proportional to the force ratio behind the red front line. It is proved that the net loss function is a strictly concave quadratic function of x, the location of the front line. It is also proved that the unique maximum of the net loss function occurs at the same front location, also if the net loss function is proportional to the strength ratio behind the RED lines, raised to any strictly positive exponent. From the BLUE perspective, there is an optimal position of the front. This position is a function of the weights in the objective function and all other parameters. Optimal control theory is used to determine the optimal dynamic BLUE strategy, conditional on a RED strategy, which is observed by BLUE military intelligence. The optimal arms support strategy for BLUE is to initially send a large volume of arms support to GREEN, to rapidly move the front to the optimal position. Then, the support should be almost constant during most of the war, keeping the war front location stationary. In the final part of the conflict, when RED will have almost no military resources left and tries to retire from the GREEN territory, BLUE should strongly increase the arms support and make sure that GREEN rapidly can regain the complete territory and end the war

Standardized gene nomenclature supports unambiguous communication and identification of the scientific literature associated with genes. To support the increasing number of annotated genomes that are now available for comparative studies, gene nomenclature authorities coordinate the assignment of approved gene names that can be readily propagated across species. Theofanopoulou et al. (Theofanopoulou et al. 2021) propose a new nomenclature for the genes encoding oxytocin and arginine vasopressin and their receptors. Rather than changing to a different nomenclature system, we propose minor updates to the current approved nomenclature of these vertebrate genes to better reflect their evolutionary history. We call on authors, journal editors and reviewers to help support communication and indexing of gene-related publications by working with existing gene nomenclature committees and ensuring that standardized gene nomenclature is routinely used.

In Escherichia coli, DNA replication termination is orchestrated by two clusters of Ter sites forming a DNA replication fork trap when bound by Tus proteins. The formation of a ‘locked’ Tus-Ter complex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at some Ter sites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermost Ter sites (TerA-E and G) were significantly bound by Tus. We also found that a single ectopic insertion of TerB in its non-permissive orientation could not be achieved, advocating against a need for ‘back-up’ Ter sites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture mostly found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow ancestral Tus-dependent DNA replication fork trap consisting of only two Ter sites.

The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the most ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, South America. Due to their natural characteristics as a hermaphroditic species with high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments to reactively control invasive mollusc populations and proactively prevent their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in open water systems was performed to evaluate molluscicides and identify toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize negative impact to water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners on invasive Asian clam management.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

In India, the divorce rate is rising year after year. Divorces are thought to have increased by more than a factor of two during the past two decades. India has great cultural diversity, and each of its states has something unique to offer. The divorce rate in India, which differs from state to state, is among the most frequently discussed subjects. More than 30% of marriages end in divorce in big cities like Delhi, Mumbai, Chennai, and Bangalore. Divorce applications have nearly tripled in the past few years in cities like Delhi, Bangalore, Mumbai, Kolkata, and Lucknow. In India, the divorce rate has increased, especially in small cities. Hence, the reasons behind divorce in India were explored in this article. In order to analyze the causes of divorce, the current study aimed to combine the critical components of TOPSIS and COPRAS methodologies in a fuzzy environment. Additionally, it is shown that a comparison study may pinpoint the characteristics that influence divorces the most.

How does the world around us work and what is real? This question has preoccupied humanity since its beginnings. From the 16th century onwards, it has been periodically necessary to revise the prevailing worldview. But things became very strange at the beginning of the 20th century with the advent of relativity theory and quantum physics. The current focus is on the role of information, there being a debate about whether this is ontological or epistemological. A theory has recently been formulated in which spacetime and gravity emerges from microscopic quantum information, more specifically from quantum entanglement via entanglement entropy. A latest theory describes the emergence of reality itself through first-person perspective experiences and algorithmic information theory. In quantum physics, perception and observation play a central role. Perception, interaction with the environment, requires an exchange of information. Via biochemical projection, information is given an interpretation that is necessary to make life and consciousness possible. The world around us is not at all what it seems.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

When discussing the concepts of risk, safety, and security, people have an intuitive understanding of what these concepts mean, and, to a certain level, this understanding is universal. However, when delving into the real meaning of these concepts, one is likely to fall into semantic debates and ontological discussions. In industrial parks, it is important that (risk) managers from dierent companies, belonging to one and the same park, have the same understanding of the concepts of risk, safety, and security. It is even important that all companies in all industrial parks share a common understanding regarding these issues. As such, this paper explores the similarities and dierences behind the perceptions of these concepts, to come to a fundamental understanding of risk, safety, and security, proposing a semantic and ontological ground for safety and security science, based on an etymological and etiological study of the concepts of risk and safety. The foundation has been induced by the semantics used in the ISO 31000 risk management guidance standard. Hence, this article proposes a coherent, standardized set of concepts and definitions with a focus on the notion “objectives” that can be used as an ontological foundation for safety and security science, linking “objectives” with the concepts of safety, security, risk, performance and also failure and success, theoretically allowing for an increasingly more precise understanding and measurement of (un)safety across the whole range of individuals, sectors and organizations, or even society as a whole.

This paper addresses the evolving landscape of electricity markets in Europe, with a focus on the integration of Renewable Energy Communities as introduced by the Renewable Energy Directive 2018/2001. Residents within a postal code area are highly incentivized to join a community, which enables them to exchange energy among themselves at lower procurement costs. Thereby, energy management systems optimize the operation of respective energy systems, with electrical load forecasting playing a key role. Given that prosumers may switch between communities on a daily basis, electricity demands within these groups will vary, leading to data that is non-stationary, discontinuous as well as non-identical and independently distributed. To encounter this issue, we propose a sophisticated forecasting model that applies federated learning, using informations from various distributed communities to learn domain-invariant features. To achieve this, we initially utilize synthetic electrical load time series at district level and aggregate them to profiles of Renewable Energy Communities with dynamic portfolios. Subsequently, we develop a forecasting model that accounts for the composition of residents of a Renewable Energy Community, adapt data pre-processing in accordance with the time series process, and detail a federated learning algorithm that incorporates weight averaging and data sharing. Following the training of various experimental setups, we ultimately evaluate their effectiveness. The findings suggest that our proposed framework is capable of effectively forecast non-stationary and discontinuous time series and that it can be applied to new, unseen data through the integration of knowledge from multiple sources.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

We propose two methods for obtaining estimations on the minimum distance and covering radius of orthogonal arrays. Both methods are based on knowledge about the (feasible) sets of distance distributions of orthogonal arrays with given length, cardinality, factors and strength. New bounds are presented either in analytic form and as products of an ongoing project for computation and investigation of the possible distance distributions of orthogonal arrays with parameters in doable ranges.

Wheeled mobile robot dynamics and suitable controller design are challenging but rewarding fields of study. By understanding the dynamics of wheeled mobile robots, it could be possible to design suitable hybrid control schemes for wheeled mobile robots. Since hybrid control schemes involve combining individual control methods to create a more effective overall control strategy. This can be done in a variety of ways, such as using fuzzy linear quadratic Gaussian control. We were therefore inspired to create dynamic models and their controller designs for the wheeled mobile robot by examining the dynamics of the wheeled mobile robot. The novelty of the current paper is to hybridize the different control schemes for wheeled mobile robots in order to get better performance. Entire systems models were simulated in a MATLAB/SIMULINK environment. The results obtained for the settling time response by FLQG were 87.1% over LQG; this study compared the effectiveness of current and previous FLQG controllers in external disturbances and found peak amplitude improvements of 71.25%. Therefore, the proposed controller is suitable for use with the wheeled mobile robot.

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

The Industrial Internet of things (IIoT) enabled smart system has entered into a golden era of rapid technology growth. IIoT is a concept to make every system interrelated such that they are able to collect and transfer data over a wireless network without human intervention. In this paper, we discuss the development of an IoT enabled system to monitor the vibration signature of equipment as part of prognosis and availability management system (P&AM) that serves to prevent unplanned operation downtime and catastrophic failure of a whole system. In order to simply the complexity of processing video content and performing inference, the Intel OpenVINO platform was selected because of it’s simplicity, portability across Intel AI processors, performance and comprehensiveness of it’s analytical and diagnostics capabilities that can be tested in Intel’s DevCloud. The IIoT system consists of a High Performance Computing (HPC) platform based on Intel’s Xeon processors and Movidius AI accelerator, Intel’s OpenVINO toolkit for AI, a Regul high performance programmable controller capturing vibration data through sensors and a low-latency network connection. Notifications of anomalies are sent to a smartphone. This paper reveals an approach for the features extraction and selection, known as feature engineering, of the equipment component we want to protect. Feature engineering is the first step for the P&AM of these components and extends to the whole system. The broader aim of this paper is to help technical leaders at the exploring or experimenting stages of their AI framework to learn the concepts of implementing algorithms using datasets that have real value to their companies. Datasets generated and referred to in this paper were generated by simulation under various material failure scenarios.

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modified putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 to 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

In atomic GdFe$_2$ films capped by 4$d$ and 5$d$ transition metals, we show that skyrmions with diameters smaller than 12 nm can emerge. The Dzyaloshinskii--Moriya interaction (DMI), exchange energy, and the magnetocrystalline anisotropy (MCA) energy were investigated based on density functional theory. Since DMI and MCA are caused by spin--orbit coupling (SOC), they are increased with 5$d$ capping layers which exhibit strong SOC strength. We discover a skyrmion phase by using atomistic spin dynamic simulations at small magnetic fields of $\sim$1 T. In addition, a ground state that a spin spiral phase is remained even at zero magnetic field for both films with 4$d$ and 5$d$ capping layers.

The power sectors in most African countries face an enduring problem of utility performance – electricity utilities have failed to deliver adequate, reliable and competitively priced electricity to support economic growth and improve the welfare of their populations. Despite more than two decades of power sector re-forms, outcomes have been varied and often disappointing. Using a case study de-sign, we explore the five key enduring power challenges. The research utilizes a more powerful analytical framework that combines power sector reform theory and principal-agent theoretical lens to explore the experience of power sector reforms in Kenya and provides a deeper understanding of drivers of utility performance and reform impacts. Empirical findings show that the structural, governance and regulatory reforms that previously created incentives for improved utility performance are increasingly threatened by political influence. Kenya Power’s financial viability has deteriorated in recent years and the regulator has been undermined. One of our major conclusions is that when the relationship between the principal (government) and agent (utility) is well understood and the agent is properly incentivized, performance improvements are possible. However, when the government undermines or muddies those incentives through conflicting political interventions, performance improvements can be reversed.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

This paper discusses two major applications of SU(3) theory, the first being the question of quantum brachistochrones and problems in time optimal control theory, the second being the use of spherical tensor decompositions of the special functions which are associated to SU(3) via the isotropic oscillator. We discuss the derivation of the quantum brachistochrone problem more generally from the perspective of von Neumann equations and matrix mechanics, arriving at an equivalent formulation to the Lagrangian method. Discussion is given to the application of such advanced methods in quantum computation, and some future directions that may be amenable to a similar sort of an