Nearest-neighbour clustering is a simple yet powerful machine learning algorithm that finds natural application in the decoding of signals in classical optical-fibre communication systems. Quantum k-means clustering promises a speed-up over the classical k-means algorithm; however, it has been shown to currently not provide this speed-up for decoding optical-fibre signals due to the embedding of classical data, which introduces inaccuracies and slowdowns. Although still not achieving an exponential speed-up for NISQ implementations, this work proposes the generalised inverse stereographic projection as an improved embedding into the Bloch sphere for quantum distance estimation in k-nearest-neighbour clustering, which allows us to get closer to the classical performance. We also use the generalised inverse stereographic projection to develop an analogous classical clustering algorithm and benchmark its accuracy, runtime and convergence for decoding real-world experimental optical-fibre communication data. This proposed `quantum-inspired' algorithm provides an improvement in both the accuracy and convergence rate with respect to the k-means algorithm. Hence, this work presents two main contributions. Firstly, we propose the general inverse stereographic projection into the Bloch sphere as a better embedding for quantum machine learning algorithms; here, we use the problem of clustering quadrature amplitude modulated optical-fibre signals as an example. Secondly, as a purely classical contribution inspired by the first contribution, we propose and benchmark the use of the general inverse stereographic projection and spherical centroid for clustering optical-fibre signals, showing that optimizing the radius yields a consistent improvement in accuracy and convergence rate.

Background and objective K. pneumoniae appeared to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and methods All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia from 1 January to 31 October 2023 were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, mcr-5) were investigated. Results There was a total of 379 MDR-K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of them, there were 9 (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1,-2,-3,-4,-5 genes. Conclusions The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A were coproducers of NDM-1 and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

This article investigates on the radial and non-radial geodesic structures of the generalized K-essence Vaidya spacetime. Within the framework of K-essence geometry, it is important to note that the metric does not possess conformal equivalence to the conventional gravitational metric. This study employs a non-canonical action of the Dirac-Born-Infeld kind. In this work, we categorize the generalized K-essence Vaidya mass function into two distinct forms. Both the forms of the mass functions have been extensively utilized to analyze the radial and non-radial time-like or null geodesics in great details inside the comoving plane. Indications of the existence of wormhole can be noted during the extreme phases of spacetime, particularly in relation to black holes and white holes, which resemble the Einstein-Rosen bridge. In addition, we have also detected the distinctive indication of the quantum tunneling phenomenon around the central singularity.

HIV-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in PBMCs of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.

A better understanding of background tropospheric ozone delivers multiple benefits. Robust estimates of regional background ozone assist policy makers to understand the limits to reducing ozone by controlling anthropogenic emissions alone and assist in characterising changes in the atmospheric environment and its composition. Long time series of background ozone measurements can also help quantify the influence of human activity on the global and regional atmosphere. Background tropospheric ozone measurements representative of continental air masses are however scarce in Australia, limiting our knowledge of background atmospheric composition. Here we use k-means clustering to identify a cluster of measurements from the long-term monitoring station at Oakdale, NSW which are likely to be representative of background air. The cluster is associated with NOx-limited air masses of continental origin. From this analysis we estimate background ozone representative of Eastern Australia. We find recent (2017-2022) mean ozone mixing ratios of 28.5 ppb and identify a statistically significant (α=0.05) trend in the mean of +1.8 (1.0 – 2.8) ppb/decade. Our methods demonstrate that some long-term monitoring stations within or near urban areas can provide suitable conditions and datasets for regional Global Atmosphere Watch monitoring.

UV induced photoluminescence of organosilica films with ethylene and benzene bridging groups in their matrix and terminal methyl groups on the pore wall surface is studied to reveal optically active defects and understand their origin and nature. Careful selection of the film’s precursors and conditions of deposition and curing, analysis of chemical and structural properties led to the conclusion that luminescence sources are not associated with the presence of oxygen-deficient centers, as in the case in pure SiO2. It is shown that the sources of luminescence are the carbon-containing components that are part of the low-k-matrix, as well as the carbon residues formed upon removal of the template and UV induced destruction of organosilica samples. A good correlation between the energy of the photoluminescence peaks and the chemical composition is observed. This correlation is confirmed by the results obtained by the Density Functional theory. The photoluminescence intensity increases with porosity and internal surface area. The spectra become more complicated after annealing at 400 °C, although Fourier transform infrared spectroscopy does not show these changes. The appearance of additional bands is associated with compaction of low-k matrix and segregation of template residues on the surface of the pore wall.

The prevalence of obesity in Korean adults was 56.1% in 2019. This study aimed to find obesity phenotypes from the KNHANES(2015–2019) and determine the risk factors associated with each type. In 15,179 participants, three obesity phenotypes, high BMI (short heavy obesity, n=1,685), high waist circumference (WC) (tall abdominal obesity, n=549), and BMI/WC combination (heavy abdominal obesity, n=3,538), were compared to non-OB (n=9,425). Marital status, lower income and education levels were highly associated with abdominal obesity. Insufficient exercise or skipping breakfast were associated with the WC or BMI/WC obesity type. The BMI/WC risk was 3.25 times higher in males with high TG and 4.6–4.8 times higher in females with high FAS or TG, and the risk increased to 7-8 times higher in three combinations (HYP+HDLc+FBS) compared to the control. The K-Score to test balanced diets was lower in BMI/WC than in others. Low intakes of FI-4(fruits) in men and FI-2(meat), FI-3 (vegetables), and FI-5 (milk/milk products) in women with BMI/WC and WC types, but BMI type was not associated with diets. Compared to BMI, the BMI/WC or WC obesity type was an indicator of metabolically unhealthy obesity associated with obesogenic environments including food/diets pattern and unhealthy behaviors.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Difference in two quantum states defined for a point in space time is represented by space time curvature and the superposition of these quantum states will affect the momentum of mass existed at that point. Analogy of the same with Einstein’s General relativity field equation and Einstein’s gravitational constant , indicated an equation containing ‘Hubble’s constant H , Einstein’s gravitational constant ‘H’ and Siva’s constant ‘K’. Its output is a quadratic equation. Solution to this quadratic equation predicted a fundamental force particle. This solution gives the diameter of that particle. From the fundamental principles, the diameter of this force particle gives the coupling constant of that fundamental force. Prediction and review of this particle may provide us new insights in to quantum physics and standard model of particle physics. From the first principles, it is discussed that this particle can be claimed as a force carrying particle of a fundamental force related to dark matter. This work has provided simple explanation to reconcile quantum nature of space time with smooth space time of General Relativity. This has demanded the necessity to introduce a new postulate in quantum mechanics which is beyond Hilbert space and Dirac notation. A new perspective of uncertainty principle in quantum mechanics has been elaborated.

Hyper-spectral images contain a wide range of bands or wavelength due to which they are rich in information. These images are taken by specialized sensors and then investigated through various supervised or unsupervised learning algorithms. Data that is acquired by hyperspectral image contain plenty of information hence it can be used in applications where materials can be analyzed keenly, even the smallest difference can be detected on the basis of spectral signature i.e. remote sensing applications. In order to retrieve information about the concerned area, the image has to be grouped in different segments and can be analyzed conveniently. In this way, only concerned portions of the image can be studied that have relevant information and the rest that do not have any information can be discarded. Image segmentation can be done to assort all pixels in groups. Many methods can be used for this purpose but in this paper, we discussed k means clustering to assort data in AVIRIS cuprite, AVIRIS Muffet and Rosis Pavia in order to calculate the number of regions in each image and retrieved information of 1st, 10th and100th band. Clustering has been done easily and efficiently as k means algorithm is the easiest approach to retrieve information.

Animal behavior analysis is a crucial tasks for the industrial farming. In an indoor farm setting, extracting Key joints of animal is essential for tracking the animal for longer period of time. In this paper, we proposed a deep network that exploit transfer learning to trained the network for the pig skeleton extraction in an end to end fashion. The backbone of the architecture is based on hourglass stacked dense-net. In order to train the network, key frames are selected from the test data using K-mean sampler. In total, 9 Keypoints are annotated that gives a brief detailed behavior analysis in the farm setting. Extensive experiments are conducted and the quantitative results show that the network has the potential of increasing the tracking performance by a substantial margin.

Data mining plays a critical role in the sustainable decision making. The k-prototypes algorithm is one of the best-known algorithm for clustering both numeric and categorical data. Despite this, however, clustering a large number of spatial object with mixed numeric and categorical attributes is still inefficient due to its high time complexity. In this paper, we propose an efficient grid-based k-prototypes algorithms, GK-prototypes, which achieves high performance for clustering spatial objects. The first proposed algorithm utilizes both maximum and minimum distance between cluster centers and a cell, which can remove unnecessary distance calculation. The second proposed algorithm as extensions of the first proposed algorithm utilizes spatial dependence that spatial data tend to be more similar as objects are closer. Each cell has a bitmap index which stores categorical values of all objects in the same cell for each attribute. This bitmap index can improve the performance in case that a categorical data is skewed. Our evaluation experiments showed that proposed algorithms can achieve better performance than the existing pruning technique in the k-prototypes algorithm.

Recently, representation formulae and monotonicity properties of generalized k-Bessel functions, Wk v,c., were established and studied by SR Mondal [24]. In this paper, we pursue and investigate some of their image formulae. We then extract solutions for fractional kinetic equations, involving Wk v,c, by means of their Sumudu transforms. In the process, Important special cases are then revealed, and analyzed.

Predicting the outcome of a future game between two National Basketball Association (NBA) teams poses a challenging problem of interest to statistical scientists as well as the general public. In this article, we formalize the problem of predicting the game results as a classification problem and apply the principle of maximum entropy to construct NBA maximum entropy (NBAME) model that fits to discrete statistics for NBA games, and then predict the outcomes of NBA playoffs by the NBAME model. The best NBAME model is able to correctly predict the winning team 74.4 percent of the time as compared to some other machine learning algorithms which is correct 69.3 percent of the time.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

There is currently much interest in avoiding precious metals in Catalysis. The devel-opment of nickel catalysts to replace palladium in the Mizoroki-Heck reaction is a relevant case in this line of research since both elements share many chemical features. This contri-bution focuses on -Phenyl elimination in alkylnickel complexes. This is the microscopic reverse of olefin insertion (or carbometallation), a fundamental step of the Heck cycle that is usually considered irreversible and selectivity-determining. However, the potential reversibil-ity of carbometallation is generally concealed by the facile beta-hydrogen elimination that follows. Where -hydrogen elimination is hindered, beta-aryl elimination may ensue. We have previously shown that cationic 2-methyl-2-phenylpropyl (neophyl) palladium com-plexes supported by bidentate ligands experience -Ph elimination, which can be seen as an example of olefin de-insertion. In this contribution, we report that -phenyl elimination can also occur in their nickel analogs, in which case fast hydrolyses of the resulting phenyl product can follow the reaction. We investigated the mechanism of these processes and compared their feasibility for nickel and palladium catalysts using DFT calculations. These results are relevant information for the design of nickel-based catalysts for the Heck reac-tion.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

Cissus populnea Guill. & Perr. (Vitaceae) is used in traditional medicine to treat microbial infec-tions, venereal diseases, and infertility, among others. The aim of the research is to isolate and characterize the antimicrobial constituent(s) from the stem of C. populnea. The n-butanol fraction of C. populnea being most active was subjected to silica gel column chromatography which led to the isolation of a white solid and white crystalline substances coded compounds C1 and C4C5, respectively. Spectral analysis (1D & 2D-NMR) of the isolated compounds and comparison with literature data indicated C1 to be Bis-(2-ethyloctyl)-phthalate and C4C5 to be a mixture of stig-masterol and β-sitosterol; C4C5 exhibited zone of inhibition ranging from 24 – 29 mm against the test organisms with Candida albicans being the most sensitive organism while Trichophyton rubrum was the least sensitive organism. The standard drugs, Ciprofloxacin had 27 – 37 mm while Flu-conazole and Fulcin exhibited zone of inhibition ranging from 34 mm and 29 – 32 mm, respec-tively. The MIC and MBC/MFC values for C4C5 ranges from 12.5 – 25.0 µg/cm3 and 25.0 – 50.0 µg/cm3 against MRSA, S. aureus, E. coli, C. albicans, T. rubrum, and T. mentagrophyte, respectively. In conclusion, three bioactive compounds were identified for the first time from the stem of C. populnea

Abstract: The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ and Hippo signaling is also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicated increased nuclear localization of Yes associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in absence or presence of by exogenously added TGFβ2. To confirm the molecular mechanisms of verteporfin induced inhibition of TGFβ2-dependent extra-cellular matrix (ECM) reorganization we performed gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirmed that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell be-havior and ECM remodeling is mediated by YAP1. Thus, TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease.

In this work, we present a study of ordinary muon capture (OMC) on 136Ba, the daughter nucleus of the 136Xe double beta decay (DBD). OMC rates to low-lying nuclear states (below 1 MeV of excitation energy) in 136Cs are assessed by using both the interacting shell model (ISM) and the proton-neutron quasiparticle random-phase approximation (pnQRPA). We also add the chiral two-body (2BC) meson-exchange currents and use an exact Dirac wave function for the captured s-orbital muon. OMC can be viewed as a complementary probe of the wave functions in 136Cs, the intermediate nucleus of the 136Xe DBD. At the same time OMC can be considered as a powerful probe of the effective values of the weak axial-type couplings in a 100-MeV momentum-exchange region relevant for the neutrinoless DBD. The present work represents the first attempt to compare the ISM and pnQRPA results for the OMC on a heavy nucleus by including also the exact muon wave function and the 2BC. Sensitivity estimates of the present and future neutrinoless DBD experiments will clearly benefit from the future OMC measurements through the OMC calculations similar to the present one.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Mitochondrial dysfunctions remained a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria which is also known as the power-generating set of the cell, have a dominant role in several processes associated with the genomic integrity and cellular equilibrium maintenance. They are involved in maintaining optimal cells functioning and guidance from possible DNA damage which could lead to mutations and onset of diseases. Conversely, system perturbations which could be due to environmental factors or senescence induce changes in the physiological balance and result in the mitochondrial functions impairment. The focal point of this review focuses on mitochondrial dysfunction as a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria which are common amongst the most recurring neurodegenerative diseases including Alzheimers and Parkinsons disease. Do mitochondrial dysfunctions represent an early event in causing a shift towards neuropathological processes?

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

Pancreatic beta cells secrete insulin in response to stimulation with glucose and other nutrients, and impaired insulin secretion plays a central role in development of diabetes mellitus. Pharmacological management of diabetes includes various antidiabetic drugs, including incretins. The incretin hormones, glucagon-like peptide-1 and gastric inhibitory polypeptide, potentiate glucose-stimulated insulin secretion by binding to G protein-coupled receptors, resulting in stimulation of adenylate cyclase and production of the secondary messenger cAMP, which exerts its intracellular effects through activation of protein kinase A or the guanine nucleotide exchange protein 2A. The mo-lecular mechanisms behind these two downstream signaling arms are still not fully elucidated and involve many steps in the stimulus-secretion coupling cascade, ranging from the proximal regula-tion of ion channel activity, to the central Ca2+ signal, and the most distal exocytosis. In addition to modifying intracellular coupling, the effect of cAMP on insulin secretion could also be at least partly explained by the impact on intercellular coupling. In this review, we systematically describe the possible roles of cAMP at these intra- and inter-cellular signaling nodes, keeping in mind the rele-vance for the whole organism and translation to humans.

Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 has been associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using a single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike Adrenergic receptor β2 (ADRβ2), agonist induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties and there was no significant impact of the substitution of Tryptophan with Arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

In humans, finely tuned gamma synchronization (60-90 Hz) rapidly appears at movement onset in a motor control network involving primary motor cortex, the basals ganglia and motor thalamus. Yet the functional consequences of brief movement-related synchronization are still unclear. Distinct synchronization phenomena have also been linked to different forms of motor inhibition, including relaxing antagonist muscles, rapid movement interruption and stabilizing network dynamics for sustained contractions. Here I will introduce detailed hypotheses about how intra- and inter-site synchronization could interact with firing rate changes in different parts of the network to enable flexible action control. The here proposed cause-and-effect relationships shine a spotlight on potential key mechanisms of cortico-basal ganglia-thalamo-cortical communication. Confirming or revising these hypotheses will be critical in understanding the neuronal basis of flexible movement initiation, invigoration and inhibition. Ultimately, the study of more complex cognitive phenomena will also become more tractable once we understand the neuronal mechanisms underlying behavioural readouts.

Accruing evidence on the influence of β-carotene regarding the prevention of several chronic diseases - in addition to its well-acknowledged role in vision has been a strong driver for developing alternative delivery systems. Though oral delivery is accepted as the most fitting, mild and safe path for delivering bioactive agents, β-carotene delivery via food items poses challenges due to its lipophilic nature, poor water-solubility, high chemical/photochemical instability and poor oral bioavailability. Nanotechnology has opened new windows for delivering bioactive agents. Their physiochemical characteristics, i.e. small size, high surface area, unique composition, biocompatibility and biodegradability make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in target tissues, but also lessens its sensitivity against environmental factors during processing. Regardless of these benefits, nanocarriers inherit some limitations, such as variations in sensory quality, modification of the food matrix, increasing costs, as well as limited consumer acceptance and regulatory challenges. This research area has been rapidly evolved, with a plethora of innovative nano-engineered materials, including micelles, nano/microemulsion, liposomes, niosomes, solid-lipid nanoparticles and nanostructured lipid carriers. These nano-delivery systems make conventional delivery systems appear archaic and promise better solubilization, protection during processing, improved shelf-life, higher bioavailability as well as controlled and targeted release. This review provides information on the state of knowledge on β-carotene nano-delivery systems adopted for developing functional foods: depicting their classification, composition, preparation methods, challenges, release-and absorption of β-carotene in the GIT and possible risks and future prospects.

Background: The antimalarial drug chloroquine and antimicrobial drug azithromycin have received significant attention during the current COVID-19 pandemic. Both drugs can alter cardiac electrophysiology and have been associated with drug-induced arrhythmias. Meanwhile, sympathetic activation is commonly observed during systemic inflammation and oxidative stress (e.g., in SARS-CoV-2 infection), and may influence the electrophysiological effects of chloroquine and azithromycin. Here, we investigated the effect of beta-adrenergic stimulation on proarrhythmic properties of chloroquine and azithromycin using a detailed in silico model of ventricular electrophysiology. Methods: Concentration-dependent chloroquine and azithromycin-induced alterations in ion-channel function were incorporated into the Heijman canine ventricular cardiomyocyte model. Single and combined drug effects on action-potential (AP) properties were analyzed using a population of 592 models accommodating inter-individual variability. Sympathetic stimulation was simulated by an increase in pacing rate and experimentally validated isoproterenol-induced changes in ion-channel function. Results: At 1 Hz pacing, therapeutic doses of chloroquine and azithromycin (5 and 20 µM, respectively) individually prolonged AP duration (APD) by 33% and 13%. Their combination produced synergistic APD prolongation (+161%) with incidence of proarrhythmic early afterdepolarizations in 53.5% of models. Increasing the pacing frequency to 2 Hz shortened APD and together with 1 µM isoproterenol corrected the drug-induced APD prolongation. No afterdepolarizations occurred following increased rate and simulated application of 0.1-1 µM isoproterenol. Conclusion: Sympathetic stimulation limits chloroquine- and azithromycin-induced proarrhythmia by reducing their APD-prolonging effect, suggesting the importance of heart rate and autonomic status monitoring in particular conditions (e.g., COVID-19).

The significance of Kashmir conflict as one of the world’s longest running conflicts has frequently drawn the attention of both communication and international relations’ scholars which makes it an important issue from the perspective of interdisciplinary approach. The researchers have attempted to assemble a brief history of the Indian held Jammu and Kashmir Conflict from the time of partition in 1947 to the developments which took place till 2019 in the light of the available literature. The paper provides substantial historical context of the important events like instrument of accession, UN resolutions on Kashmir conflict, Simla Accord, Gawkadal Massacre , Lahore Declaration, Kargil War, killing of Burhan Wani, Uri attack and Article 370’s abrogation .

High concentrations of sodium (Na+), chloride (Cl-), calcium (Ca2+), and sulphate (SO42-) are fre-quently found in saline soils. Crop plants cannot successfully develop and produce because salt stress impairs the uptake of calcium, potassium, and water into plant cells. Different intracellular and extracellular ionic concentration changes by salinity, including those of calcium, potassium, and protons. These cations serve as stress signaling molecules in addition to being essential for ionic homeostasis and nutrition. Maintaining an appropriate K+: Na+ ratio is one crucial plant mechanism for salt tolerance, which is a complicated trait. Another important mechanism is the ability for fast extrusion of Na+ from the cytosol. Calcium is established as a ubiquitous secondary messenger, which transmits various stress signals into metabolic alterations that cause adaptive responses. When plants are under stress, the cytosolic-free Ca2+ concentration can rise to 10 times or more from its resting level of 50-100 nanomolar. Reactive oxygen species (ROS) are linked to the calcium alterations, and are produced by stress. Depending on the type, frequency and intensity of the stress, the cytosolic calcium signals oscillate, are transient, or persist for a longer period and exhibit specific "signatures". Both the input and efflux of Ca2+ from the cytosol affect the length and amplitude of the signal. According to several reports, under stress calcium alterations can occur not only in the cytoplasm of the cell but also in the cell walls, nucleus and other cell organelles and the calcium waves propagate through the whole plant. Here, we will focus on how wheat and other important crops absorb Na+, K+ and Cl- when plants are under salt stress, as well as how calcium, potassium, and pH cause intracellular signaling and homeostasis. Similar mechanisms in the model plant Arabidopsis will also be considered.

To verify the concept of the metasurfaced reverberation chamber (MRC) which was proposed. This paper reports on measurements in the reverberation chamber (RC) performance by using a 1-bit random coding metasurfaced stirrer. The measurement results are validated and compared with that from two mechanical stirrers (horizontal stirrer and vertical stirrer). Figures of merit such as quality factor (Q factor), number of samples, standard deviation, angle autocorrelation, average K-factor, total scattering cross section (TSCS) and the enhanced back scattering coefficient (eb) are presented. Results indicate the feasibility of the MRC technique in the operation frequency of the RC. And it is possible to enlarge the test volume of the RC by using the 1-bit random coding metasurface stirrer.

Spatiotemporal climate variability is a leading environmental constraint to the rain-fed agricultural productivity and food security of communities in the Abbay basin and elsewhere in Ethiopia. The previous one-size-fits-all approach to soil and water management technology targeting did not effectively address climate-induced risks to rain-fed agriculture. This study, therefore, delineates homogenous climatic regions and identifies climate-induced risks to rain-fed agriculture that are important to guide decisions and selection of site-specific technologies for green water management in the Abbay basin. The k-means spatial clustering method was employed to identify homogenous climatic regions in the study area, while the Elbow method was used to determine an optimum number of the climate clusters. The k-mean clustering used the Enhancing National Climate Services (ENACTS) daily rainfall, minimum and maximum temperatures, and other derived climate variables that include daily rainfall amount, length of growing period (LGP), rainfall onset and cessation dates, and rainfall intensity, temperature, potential evapotranspiration (PET), soil moisture and AsterDEM to define climate regions. Accordingly, 12 climate clusters or regions were identified and mapped for the basin. Clustering a given geographic region into homogenous climate classes is useful to accurately identify and target locally relevant green water management technologies to effectively address local-scale climate-induced risks. The study has also provides a methodological framework that can be used in the other river basins of Ethiopia and indeed elsewhere.

The utilization of tempered blast furnace (BF) slag through the direct fiber forming process to create high-value thermal insulation materials offers a dual benefit: it efficiently harnesses the latent heat within unused slag and substantially enhances the value of blast-furnace slag utilization. However, gauging the melting properties of iron slag under high temperatures is a challenge. In this study, we explore the melting behavior of SiO2 within a high-temperature molten pool. We employ dynamic visual data (video stream) captured via a non-contact charge coupled device (CCD) video recording system to extract SiO2 contours through image processing. The change in image centroid characteristics is used to establish a convolution function relationship, and MATLAB's traversal search algorithm determines SiO2's centroid position. Given that SiO2 is proportionate to crucible pixels, the area of SiO2 is calculated through pixel statistics within these contours. Subsequently, we propose a new indirect method to process image information, yielding SiO2 volume and mass at different time points. An exponential fitting yields the melting rate function of SiO2. Finally, we compare this indirect method with shape from shading (SFS), quantitative characterization, and dimensional analysis techniques. We also discuss the strengths and limitations of each method. Our findings reveal that the indirect solution method presented here boasts straightforward calculation steps and imposes minimal image format requirements. This research provides theoretical and technical support for blast-furnace slag's direct fiber forming process.

Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach in cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support a role of ERVs in tumor development and encourage further search for antiretroviral agents to treat malignancies in which endogenous retroviruses are active.

The impact of nutrients on the environment, particularly on water bodies, has led to extensive studies for nutrient control. Within this context, studies have been focused on source separation of human urine from domestic wastewater to recover nutrients. Potassium is one of the most important components of human urine. However, data on potassium removal or recovery are quite limited except for some indirect information through use of zeolites for mostly ammonia removal. Potassium struvite or K-struvite (MgKPO₄·6H₂O) is a sparingly soluble salt belonging to struvite and has the potential of being used as a means of potassium and phosphate recovery from segregated human urine. This study aimed to assess the potential of K-struvite precipitation for control and recovery of nutrients. Within this context, K-struvite precipitation experiments were performed on both synthetically prepared samples and synthetic human urine solution to determine effect of operation parameters i.e. pH, stoichiometry, and temperature on potassium recovery performance. Results indicated that process performance as well as type of solid phases co-precipitated with K-struvite were closely related to initial potassium concentration, pH and reaction stoichiometry. At pH 10, the potassium recovery efficiency was maximized up to 87% by application of 100% excess dose of Mg and P for both synthetic samples and synthetic human urine solution. On the other hand, application of excess dose of K did not provide any improvement in K recovery efficiency. The effect of temperature on solubility of K-struvite was insignificant at the temperature of 24-90°C. Solid phase analyses confirmed that K-struvite was co-precipitated with either Mg₃(PO₄)₂, MgNaPO₄·7H₂O, or MgHPO₄·7H₂O depending on pH and stoichiometry instead of a pure compound.

The contamination on the insulators may increase its surface conductivity and, as a consequence, electrical discharges occur more frequently, which can lead to interruptions in the power supply. To maintain reliability in the electrical distribution power system, components that have lost their insulating properties must be replaced. Identifying the components that need maintenance, is a difficult task as there are several levels of contamination that are hardly noticed during inspections. To improve the quality of inspections, this paper proposes to use the k-nearest neighbours (k-NN) to classify the levels of insulator contamination, based on the image of insulators at various levels of contamination simulated in the laboratory. Using computer vision features such as mean, variance, asymmetry, kurtosis, energy, and entropy are used for training the k-NN. To assess the robustness of the proposed approach, statistical analysis and a comparative assessment with well-consolidated algorithms such as decision tree, ensemble subspace, and support vector machine models are presented. The k-NN showed results of up to 85.17 % accuracy using the k-fold cross-validation method, with an average accuracy higher than 82 % for multi-classification of the contamination of the insulators, being superior to the compared models.

Osteoporosis is a bone condition where bones become weaker, leading to fractures, especially in older adults and postmenopausal women. Bioceramics for bone regeneration have indeed emerged as a promising solution for conditions like osteoporosis. Choosing the right bioceramic depends on how quickly it dissolves, how strong it is, and whether the body will react to it. Studies show that bioceramics can help bones grow back by activating (bone morphogenetic protein) BMP, (mitogen-activated protein kinase) MAPK, and Wingless/integrated (Wnt)/β-catenin pathways in the body when combined with stem cells, drugs, and supports. However, bioceramics have some problems like not being flexible enough and being prone to breaking, as well as difficulties in growing stem cells and finding the right supports for different bone types. While there has been progress in improving bioceramics for bone healing, we need to keep looking for new ideas from other areas of medicine to keep improving them. This review aims to add to the expanding field of scientific research by offering a detailed look at how bioceramics and growth factors contribute to bone regeneration. Ultimately, this knowledge will help in creating new types of bioceramics that can improve bone regrowth, providing new treatment options for people with bone diseases.

Adamantinomatous Craniopharyngioma (ACP) is a rare epithelial tumor located in the craniopharyngeal duct, often associated with high morbidity and a high long-term recurrence rate. ACP is predominantly diagnosed in children below the age of 15 and accounts for a majority of Craniopharyngioma cases in the United States. It is most commonly caused by a mutation in exon 3 of the CTNNB1 gene, which promotes overaccumulation of β-Catenin in the WNT pathway. As β-Catenin accumulates, it over-activates the transcription factor, causing an over-transcription of WNT proteins and uncontrolled cell growth. Current methods of treatment for ACP are centered around surgical intervention and radiotherapy, including gross-total resection (GTR), subtotal resection (STR), and a combination of subtotal resection and adjuvant radiotherapy (STR+XTR). These methods of treatment are associated with high risk due to the proximity of ACP to critical structures near the craniopharyngeal duct. High recurrence rates and morbidity are closely associated with current methods of treatment and other methods have yet to be attempted in craniopharyngioma. This review will explore two possible methods of non-surgical and non-radiological therapeutic interventions. The use of RNAi therapy and CRISPR may provide insight and be a potential way to treat ACP with increased quality of life and decreased recurrence rates.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

The study evaluated the impact of supplementing ZH in combination with D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper x Katahdin cross lambs (37.3±5.72 kg) were utilized in a 29 d experiment in a complete randomized block design with a 2x2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg /kg PV-1) and two levels of D3 for 7 d (0 and 1.5x106 IU/d-1). ZH improved (P≤0.05) average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p≤0.03). However, ZH increased (p<0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (P≤0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus muscle (LM) by 1.7% (p=0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve meat tenderness produced by ZH supplementation.

We developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. Near-infrared laser irradiation stimulated the generation of reactive oxygen species, causing short-term reactive molecular species and spatial-temporal restricted photodamage to the biological targets. The reactive molecular species and spatial-temporal restricted photodamage enhanced the release and uptake of chemotherapy drugs and increased the sensitivity to chemotherapy drugs in ovarian cancer cells. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. SN38/IR820-Lipo@FSH exhibited good drug-loading properties and the in vitro release was slow. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited good tumor-targeting ability and anti-ovarian cancer activity in vivo. The SN38/IR820-Lipo@FSH exhibited specific targeting to A2780 ovarian cancer cells. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Modelling diameter distribution is an integral part of forest management. It requires the use of a suitable probability density function or cumulative distribution function with the appropriate fitting method. In this study, we compared the suitability of eight probability density functions fitted by derivative and optimization methods used for diameter distribution estimation of forest stands. The derivation and optimization were used on A Charlier, beta, generalized beta, gamma, Gumbel, Johnson’s SB, and Weibull (2 and 3-parameter). We used data from 167 permanent sample plots from Atlantic forest (Quercus robur) and 59 temporary sample plots from tropical forests (Tectona grandis). The quality of the fits was evaluated with different indices such as Kolmogorov–Smirnov, Cramer-von Mises, mean absolute error, bias and mean squared error. The results showed Johnson’s SB function was more suitable for describing the diameter distribution of the stands. Johnson’s SB, 3-parameter Weibull and generalized beta had consistent performance regardless of the fitting methods. The quality of fits produced by gamma, Gumbel and 2-parameter Weibull was poor.

Ischemic heart disease is the leading cause of mortality worldwide. There is evidence of the participation of Aβ in thrombosis and clinical manifestations of acute coronary syndromes. In this study, we investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in acute coronary syndrome. This is a single-center, cross-sectional, observational, and correlation study that included 65 patients within the first 12 hours after symptom onset (chest pain, shoulder pain, or chest discomfort) with ST-elevation and non-ST elevation myocardial infarction who were admitted in the Coronary Care Unit, biochemical parameters of Aβ peptides levels were evaluated. Our results show that NSTEMI patients had a higher prevalence of hypertension, diabetes, smoking, and prior myocardial infarction when compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI, but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) in both groups. In this analysis, NSTEMI patients had higher prevalence of cardiovascular risk factors. Considering the toxic properties of Aβ-42 in coronary endothelial cells and cardiomyocytes, this peptide may be useful in risk stratification scores in patients with NSTEMI.

Background: Inhalation exposure to carcinogenic metals like cadmium (Cd) is a significant global health concern linked to various cancers. However, understanding their precise carcinogenic mechanism remains elusive. Methods: Using the colon cancer (CC) rat model and implanted intestinal stent, exposed them to atomized oxygen and nitrogen (O2/N2) gas containing Cd. Results: Atmospheric Cd intensified inflammation in CC cells, heightening nicotinamide adenine dinucleotide phosphate 1 (NOX1) activity, generating increased reactive oxygen species (ROS). This escalated ROS production triggered abnormal Wnt protein secretion, activating the Wnt/β-catenin pathway, stimulating CC cell proliferation. No discernible body weight effect was seen in CC mice, possibly due to later-stage tumor weight gain, masking rat changes. Cd facilitated colon tumor restructuring and cell migration later. Intestinal stents inhibited superoxide dismutase 1 (SOD1) in CC mice's tumors, with no clear effects on NOX1, SOD2, and catalase (CAT) enzymes. Elevated ROS levels didn't substantially impact Wnt/β-catenin and might slow its imbalance. Stent implantation eased inflammation, reducing CC cell proliferation but induced discomfort in rats, reducing food intake and weight. Conclusion: Cd might partially foster CC tumorigenesis via the ROS-mediated Wnt/β-catenin pathway. The effect of Cd on the invasive effect of intestinal stents in cancerous colon was not significant.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

In this paper we introduce the concept of Nano Beta Closure, Nano Beta Interior and study the relationship between them also study some of their properties. Based on these notions we introduced the topological Approach to Decision Making and Its Application in the Medical Field" which describes the use of topological methods in decision-making, specifically through the utilization of nano beta closure and nano beta interior. These mathematical tools are applied in the medical field to improve diagnostic accuracy and aid in treatment planning. The authors demonstrate the effectiveness of this approach through a case study on the diagnosis of Chronic Kidney. The results show that the topological approach using nano beta closure and nano beta interior provides a reliable and accurate method for medical decision-making. Finally, we introduce a medical application for disease groups patients of with chronic kidney. To identify the main causative agent of kidney disease. where using this approach, the medical team can identify the specific areas of the kidney that are affected by the infection, as well as the extent of damage and any potential complications. This information is used to create an individualized treatment strategy that is customized to meet the specific requirements of the patient. and medical history. We write an algorithm that can be a helpful tool for doctors to utilize in diagnosing infection disease Chronic Kidney infections. By utilizing this approach, clinicians can provide accurate diagnoses, develop effective treatment plans, and ultimately improve patient outcomes. finally, we show that fractals hold significant importance in future nano topological generation of the human factor. Their unique properties and self-similar patterns offer insights into the complex organization of biological systems and provide a foundation for designing advanced Nanosystems.

Three-dimensional matrices are a new strategy used to tackle type I diabetes; a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), component that has been used to support cell growth. However, pure collagen possesses some difficulties including low stiffness and strength, and high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta-pancreatic cells. We analyzed the physicochemical characteristic of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced viability, proliferation, respiratory capacity and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Grazing exclusion has been proved to be one of the main measures for rehabilitating degraded arid steppes. However, the effect of this management practice on plant species diversity and composition is ambiguous, specially under prolonged droughts. Concurrently considering the responses of individual plant species, diversity of functional groups, α-diversity, and β-diversity (and its components) may be crucial to the holistic understanding of grazing exclusion effects on plant communities under drought conditions. Here, we investigated the response of these diversity measures to short-term sheep exclusion under severe drought episode in arid steppes of Alfa-grass (Stipa tenacissima) with a long evolutionary history of livestock grazing. Individual species responses were tested based on species occurrence and abundance in either grazed or grazing-excluded steppes, in addition, we used indicator species analysis to assess the strength of the association between plant species and management type. Likewise, α-diversity, abundance- and incidence-based β-diversity, as well as the functional groups’ diversities were quantified using Hill Numbers and compared between the two management types. Sheep grazing exclusion enabled the recovery of various Alfa-steppe indicator species and improved the size of regional species pool, overall α-diversity, and the diversity of therophytes. This management practice decreased the abundance-based β-diversity and the nestedness-resultant fraction of the incidence-based β-diversity at the local scale, while at the landscape scale increased the abundance-based β-diversity and its balanced variation fraction and reduced the incidence-based β-diversity and its turnover component. Furthermore, protection from grazing altered β-diversities scaling patterns by maintaining higher balanced variation in species abundance at large spatial scale and greater abundance-gradient in species composition at the fine-scale. Our results suggest that the implementation of short-term grazing exclusion in degraded arid steppes would be the appropriate management practice for vegetation restoration and plant diversity conservation during prolonged drought periods.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

Predictions of mean values of statistical variables of large scale turbulent flow by the widely used basic k-ϵ model and a new fundamentally based model are verified against published results of Direct Numerical Simulations DNS of the Navier-Stokes equations. The verification concerns turbulent channel flow at shear Reynolds numbers of 950, 2000 and 104. The basic k-ϵ model is largely based on empirical formulations accompanied by calibration constants. This contrasts with the new model where descriptions of leading statistical quantities are based on the general principles of statistical turbulence at large Reynolds number. Predicted values of major output variables such as turbulent viscosity, diffusivity of passive admixture, temperature, and fluid velocities compare well with DNS in case of the new model. Significant differences are seen in case of the basic k-ϵ model.

It is time-consuming for acquiring complete data by fully phase encoding in two orthogonal directions along with one frequency encoding direction. Undersampling in the 3D k-space is promising in accelerating such 3D MRI process. Though 3D undersampling can be conducted according to predefined probability density, the density based method is not optimal. Because of the large amount of 3D data and computational cost, it is challenging to perform data-driven and learning-based 3D undersampling and subsequent 3D reconstruction. To tackle this challenge, this paper proposes a deep neural network called EEUR-Net, realized by optimizing specific undersampling patterns for the fully-sampled 3D k-space data. Innovatively, our undersampling algorithm employs an end-to-end deep learning approach to optimize phase encoding patterns and uses a 3D U-Net for image reconstruction of undersampled data. Through end-to-end training, we obtain an optimized 3D undersampling pattern, which significantly enhances the quality of the reconstructed image under the same acceleration factor. A series of experiments on a knee MRI dataset demonstrated that, in comparison to standard random uniform, radial, Poisson and equispaced Cartesian undersampling schemes, our end-to-end learned undersampling pattern considerably improves the reconstruction quality of undersampled MRI images.

The Covid-19 crisis has been one of the most relevant economic shocks in the history of the modern economy, mainly due to the restrictions on travel and social interaction taken by the authorities (quarantines, closure of schools, artistic activities, bars, and restaurants, capacity in stores), to reduce the transmission of the virus (Sars-Cov2), having consequences on the national productions of all countries (about 7% for the loss of GDP worldwide). In our study, we analyze, through clustering methods, the effects of the level of contagion, economic projections, and economic mitigation measures taken by governments for managing the pandemic. According to the analyses, it can be concluded that a low infection rate implies a lower loss of product and economic savings when applying economic mitigation measures, taking relevance in the management of sanitary measures to reduce the transmission of the virus (and the temporality of these).

This article is a study on the (k,s)-Riemann-Liouville fractional integral, a generalization of the Riemann-Liouville fractional integral. Firstly, we introduce several properties of the extended integral of continuous functions. Furthermore, we make the estimation of the Box dimension of the graph of continuous functions after the extended integral. It presents that the upper Box dimension of the (k,s)-Riemann-Liouville fractional integral for any continuous functions is no more than the upper Box dimension of the functions on the unit interval I=[0,1], which indicates that the upper Box dimension of the integrand f(x) will not be increased by the σ-order (k,s)-Riemann-Liouville fractional integral ksD−σf(x) where σ&gt;0 on I. Additionally, we prove that the fractal dimension of ksD−σf(x) of one-dimensional continuous functions f(x) is still one.

In this study, based on frost formation data provided by Harbin Meteorological Bureau, combined with geographical factors, temperature and population density, linear fitting, Mann-Kendall mutation test, pettitt method and sliding T test were used to analyze the spatio-temporal variation characteristics of frost date in Harbin Municipality and the effects of geographical factors, temperature and population density on frost regularity. The results showed that (1) The earliest year of FSD appeared was 1966 and 1967, on the 255th, i.e., August 18th, and the latest was 283 days, i.e., October 10th, 2006. The earliest year in which the FED appeared was April 24th of 2015, the 114th day of that year, and the latest was April 21st of 1974, the 141st day of that year. The year with the most frost was 2012, with 161 days, and the year with the shortest was 1966, with 123 days. (2) Throughout the study period, FSD increased by 7.8 days at a rate of -1.27d/10a, FED increased by 10.9 days at a rate of 1.77d/10a, and FFS increased by 18.9 days at a rate of 3.05d/10a. The tendency rate of FSD and FFS at each site in Harbin showed an increasing trend. For FED, the tendency rate of some sites showed an increasing trend. In general, FSD showed a delayed trend, FED showed an advanced trend, and FFS showed a prolonged trend. Using the method of unary linear regression, FSD of each site showed an increasing trend, FFS showed an increasing trend, and FED showed a decreasing trend in general. (3) Throughout the study period, FSD was mutated in 2000, and the arrival time of it in the study area averaged the 265th, i.e., September 22nd, and after that, the arrival time of it changed to the 272nd, i.e., September 29th of that year. FED was mutated in 2006, and the arrival time of it in the study area averaged 128th, i.e., April 8th. After the mutation, the arrival time of FED changed to 121st, i.e., April 1st of that year. FFS was mutated in 2004. Before the mutation, with an average arrival time of 137days in the study area .But after that, the time changed to 150 days.(4) FSD and FFS in Harbin Municipality were negatively correlated with latitude and positively correlated with temperature, while FED was positively correlated with latitude and negatively correlated with temperature. The FSD, FED and FFS in the central part of Harbin Municipality were the earliest, the latest and the longest, respectively, so the Pearson correlation coefficient method and the influence of longitude could not be reflected in the multiple regression. Several factors were judged by grey correlation analysis method. The longitude is significantly related to FSD, FED and FFS.

Synthetic Aperture Radar (SAR) is an active sensor that uses microwave for sense, it is unrestricted by weather and illumination conditions, and it can observe targets all day and weather. Aircraft targets are important monitoring objects in military and civilian fields, and how to efficiently detect and recognize aircraft targets is an important topic in the field of SAR image interpretation. Based on the features of SAR images, such as complex background, high resolution, and multi-scale, we proposed an improved method based on YOLOv5s. Firstly, this paper proposed the structure of the multi-scale receptive field and channel attention fusion, which is applied to the shallow layer of the backbone of YOLOv5s, it can adjust the weights of the multi-scale receptive field during the training process to enhance the extraction ability of feature information. Secondly, we proposed four de-coupled detection heads to replace the original part in YOLOv5s, which can improve the efficiency and accuracy of SAR image interpretation for small targets. Thirdly, in the case of the limited amount of SAR images, this paper proposed multi methods of data augmentation, which can enhance the diversity and generalization of the network. Fourthly, this paper proposed the K-means++ to re-place the original K-means to improve the network convergence speed and detection accuracy. Finally, Experiments demonstrate that the improved YOLOv5s can enhance the accuracy of SAR image interpretation by 9.3%, and the accuracy of small targets is improved more obviously, reaching 13.1%.

In this work, we explore the extreme searching of multidimensional functions by natural gradient descent based on Dirichlet and generalized Dirichlet distributions. The natural gradient is based on describing multidimensional surface with probability distributions, which allows us to reduce changing the accuracy of gradient and step-size. In this article, we propose an algorithm of natural gradient descent based on Dirichlet and generalized Dirichlet distributions. We demonstrate that the natural gradient descent with step-size adaptation with Dirichlet and generalized Dirichlet distributions has higher accuracy and does not take a large number of iterations for minimizing test functions than gradient descent and Adam.

The membrane potential or resting potential of the neuron has been the subject of many studies. Although this theory explains the generation and maintenance of the membrane potential by direct or even facilitated diffusion, there are too many contradictions to doubt that these forces are sufficient or even at work in a process whose initial conditions are of rare complexity. The aim of this article is to show that already in the past, a competing theory has been developed whose hypothesis seems more scientifically sound. To confirm this last theory, Hirohisa Tamagawa carried out an experiment of great simplicity which makes it possible to invalidate the current theory and to question the teaching and the knowledge in Biology and Biophysics.

The generation and maintenance of membrane potential is a fundamental part of Membrane Pump Theory. One of the key points of this hypothesis is based on a natural or facilitated molecular diffusion through several types of ion channels and pumps like the Na/K ATPase. Following the principles of chemistry, electrostatics and geometry, it becomes clear that ion channels cannot function in this way. The ions channels cannot by their location have both a filter function and be ion concentrators, and the Na/K pump by its position in the membrane and by the proposed assumptions is not able to perform its regulatory function. The current model must absolutely be revised according to the current state of our knowledge and allow an advance in the understanding of the phenomena opening new research perspectives.

Premature ventricular contraction (PVC) is one of the common ventricular arrhythmias, which may cause stroke or sudden cardiac death. Automatic long-term electrocardiogram (ECG) analysis algorithms could provide diagnosis suggestion even early warning for physicians, however, they are mutually-exclusive in terms of robustness, generalization and low complexity. In this study, a novel PVC recognition algorithm that combines deep learning-based heartbeat template clusterer and expert system-based heartbeat classifier is proposed. Long short-term memory-based auto-encoder (LSTM-AE) network was used to extract features from ECG heartbeats for K-means clustering. Thus, the templates were constructed and determined based on clustering results. Finally, the PVC heartbeats were recognized based on a combination of multiple rules, including template matching and rhythm characteristics. Three quantitative parameters, sensitivity (Se), positive predictive value (P+) and accuracy (ACC), were used to evaluate the performances of the proposed method on the MIT-BIH Arrhythmia database and the St. Petersburg Institute of Cardiological Technics database. Se on the two test databases was 87.51% and 87.92%, respectively; P+ was 92.47% and 93.18%, respectively; and ACC was 98.63% and 97.89%, respectively. The PVC scores on the 3rd China Physiological Signal Challenge 2020 training set and hidden test set were 36,256 and 46,706, respectively, which could rank first in the open-source codes. The results showed that the combination strategy of expert system and deep learning can provide new insights for robust and generalized PVC identification from long-term single-lead ECG recordings.

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Thus, specific breeding programs to incorporate these natural defences, that are common within the Solanum genus, might improve a more sustainable management. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. Two F2 mapping populations using two different parents have been developed, characterized and genotyped using a new genotype methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 markers with an average distance between markers of 0.2 cM that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium that increases by a factor of 9 the density of trichomes.

Banks are normally offered two kinds of deposit accounts. It consists of deposits like current/saving account and term deposits like fixed or recurring deposits. For enhancing the maximized profit from bank as well as customer perspective, term deposit can accelerate uplifting of finance fields. This paper focuses on likelihood of term deposit subscription taken by the customers. Bank campaign efforts and customer detail analysis can influence term deposit subscription chances. An automated system is approached in this paper that works towards prediction of term deposit investment possibilities in advance. This paper proposes deep learning based hybrid model that stacks Convolutional layers and Recurrent Neural Network (RNN) layers as predictive model. For RNN, Gated Recurrent Unit (GRU) is employed. The proposed predictive model is later compared with other benchmark classifiers such as k-Nearest Neighbor (k-NN), Decision tree classifier (DT), and Multi-layer perceptron classifier (MLP). Experimental study concludes that proposed model attains an accuracy of 89.59% and MSE of 0.1041 which outperform well other baseline models.

There are no studies that quantitatively compare life histories among scorpion species. Statistical procedures applied to 94 scorpion species indicate that those with larger bodies do not necessarily have larger litters or longer life cycles, opposite to some theoretical predictions.

General characteristics of K changes together with their fine structure associated with ground flashes in Sri Lanka in the tropics are presented. It is found that on average there are about 2 K changes associated with each return stroke. Analysis of the fine structure of the K changes shows that the K change is a chaotic pulse burst. Some of these chaotic pulse bursts start and the others end as a regular pulse bursts. Sometimes the chaotic part occurs in between two regular pulse bursts. This is in agreement with the recent published results that claim that chaotic pulse bursts are a random superposition of regular pulse bursts. The results show that the small step fields identified in the literature as K changes are the static fields associated with these pulse bursts.

This paper presents the results of an experimental investigation about target detecting with passive sonar in Persian Gulf. Detecting propagated sounds in the water is one of the basic challenges of the researchers in sonar field. This challenge will be complex in shallow water (like Persian Gulf) and noise less vessels. Generally, in passive sonar the targets are detected by sonar equation (with constant threshold) which increase the detection error in shallow water. Purpose of this study is proposed a new method for detecting targets in passive sonars using adaptive threshold. In this method, target signal (sound) is processed in time and frequency domain. For classifying, Bayesian classification is used and prior distribution is estimated by Maximum Likelihood algorithm. Finally, target was detected by combining the detection points in both domains using LMS adaptive filter. Results of this paper has showed that proposed method has improved true detection rate about 27% compare other the best detection method.

Today, various dietary supplements are taken to improve endurance performance during physical activity. These supplements have proven to be very successful in controlling and balancing various hormone levels and have contributed to the prevention and healing of metabolic disorders and physical injuries. In this study, we sought to investigate the effects of the ACTN3 gene and nutrient supplementation, including beta-alanine, ashwagandha, L-carnitine, and iron, on athletic performance. The ACTN3 gene has been identified as a potential genetic determinant of athletic performance, particularly in activities that require high levels of power and strength. This study investigated the interaction between the ACTN3 gene and supplementation and highlighted the potential for personalized approaches to improve athletic performance. 24 subjects per group, were randomized in a parallel-group design to examine the effects of supplementation on the ACTN3 gene and athletic performance over a 21-day intervention period. Participants in the intervention were divided into four groups of six members each. The same subjects who did not take supplements formed the control group. In addition, the subjects were divided into 4 groups (G1, G2, G3, and G4), each consisting of subgroups of control and a treated. All treated groups (TG1, TG2, TG3, and TG4) received 4 supplements for 21 days, namely S1 (ashwagandha), S2 (iron), S3 (beta-alanine) and S4 (L-carnitine), together with the 4 control groups, i.e. CG1, CG2, CG3 and CG4, who received no supplements during the same period. In particular, this study determines the effect of these 4 supplements on actn3 gene expression, testosterone, cholesterol and BUN levels of the participants. The P-values determined for all parameters showed statistically significant values and the final result showed that all supplements had positive effects on the tested parameters. The result showed a highly significant difference between the intake of supplements before and after the intake of 24 athletes per group on the ACTN3 gene expression level and biochemical indicators.

Alteration in heparan sulfate (HS) biosynthesis has been described to impact a range of pivotal processes involved in cancer progression. HS 3-O-sulfotransferase 3B1 (HS3ST3B1) catalyzes the reaction of 3-O-sulfation within HS chains. Over the past few years, a growing number of studies has reported a tumor-promoting effect of this HS-modifying enzyme in various cancers. Consistent with these studies, we previously reported that HS3ST3B1 overexpression increased survival and resistance to apoptosis in MDA-MB-231 breast cancer (BrCa) cells. In the present study, we further investigated the biological and clinical significance of HS3ST3B1 expression in BrCa. Interrogation of public databases revealed that high expression levels of HS3STB1 are associated with invasive and mesenchymal-like phenotype in BrCa cells and predict poor clinical outcome in BrCA patients with chemotherapy. In vitro, HS3ST3B1 overexpression increased the invasive properties of MDA-MB-231 cells and enhanced chemo-resistance to conventional anticancer drugs. Mechanistically, we found that the advantage given by HS3ST3B1 was linked to the expression and activation of PDGF-Rβ. Silencing the expression of this receptor reversed the effects driven by HS3ST3B1 overexpression. Altogether, our results suggest that HS3ST3B1 may play an important role in the progression of aggressive BrCa and offer a potentially druggable target for therapeutic application.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing the composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium (Tropaeolum majus) is known for its antimicrobial activity and is used for the treatment against infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question whether 14 d nasturtium intervention (3 g daily, N=30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak, but significant antibacterial effect against Escherichia coli. A significant increase in human beta defensin 1 as parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did circulating serum metabolome. On an individual level, partly large changes were observed between sampling points, though. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species.

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p &lt; 0.05 ~ p &lt; 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

Probabilistic and parsimony-based arguments regarding available genetics data are used to propose that Hardy and Higgin’s amyloid cascade hypothesis is valid but is commonly interpreted too narrowly to support, incorrectly, the primacy of the amyloid beta peptide (Aβ) in driving Alzheimer’s disease pathogenesis. Instead, increased activity of the βCTF (C99) fragment of APP is likely the critical pathogenic determinant altered by mutations in the APP gene. This model is consistent with the regulation of APP mRNA translation via its 5’ iron responsive element (IRE). Similar arguments support that the pathological effects of familial Alzheimer’s disease mutations in the genes PSEN1 and PSEN2 are not exerted directly via changes in APP cleavage to produce different ratios of Aβ length. Rather, these mutations likely affect the stability of presenilin holoprotein and/or γ-secretase multimers with consequences for γ-secretase activity and other important cellular functions. All fAD mutations in APP, PSEN1, and PSEN2 likely find unity of pathological mechanism in their actions on endolysosomal acidification and mitochondrial function, with detrimental effects on iron homeostasis and promotion of “pseudo-hypoxia” being of central importance. Aβ production is enhanced and distorted by oxidative stress and accumulates due to decreased lysosomal function. It may act as a disease-associated molecular pattern (DAMP) enhancing oxidative stress-driven neuroinflammation during the cognitive phase of the disease. We also discuss fascinating, but largely ignored, data on presenilin biology that may be important in understanding presenilins’ central role in familial Alzheimer’s disease.

The mutton quality of Chinese Tan lambs (Ovis aries) has declined as feeding patterns have shifted from pasturing to pen rationing. Mutton quality is affected by fatty acids, and rumen microorganisms play a role in the synthesis of short-chain fatty acids, long-chain fatty acids, and conjugated linoleic acids. We used 16S rDNA sequencing to analyze the effects of two feeding patterns on the rumen bacteria of Tan lambs. In a randomized block design with 24 newborn Tan lambs, 12 lambs were fed by ewes in pasture and 12 were fed by pen-fed ewes. At 2 months, the biceps femoris and the longissimus dorsi were analyzed by gas chromatography for intramuscular fat content and fatty acid composition, and DNA in the rumen contents was extracted and used to analyze the structure of the bacterial community. Different feeding patterns had no significant effect on the intramuscular fat content of the biceps femoris and longissimus dorsi of the lambs, but there was a significant effect on fatty acid composition. Rumen bacteria were significantly more diverse in the pasture group than in the pen-ration group (P < 0.01). Twenty-one phyla were identified in the pasture group, and 14 phyla were identified in the pen-ration group. The dominant phyla in the pasture group were Bacteroidetes and Fibrobacteres; the dominant phyla in the pen-ration group were Proteobacteria and Bacteroidetes. The relative abundance of Proteobacteria was significantly higher in the pen-ration group than in the pasture group (P < 0.01). Diversity at the genus level was also higher in the pasture group, with 176 genera in the pasture group and 113 genera in the pen-ration group. The dominant genera in the pasture group were Prevotella_1, Rikenellaceae_RC9_gut_group, and Bacteroidales_BS11_gut_group_Na; the dominant genera in the pen-ration group were Prevotella_1, Prevotella_7, Succinivibrionaceae_UCG-001, and Succinivibrionaceae_NA.

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Searching for neutrinoless double beta decay is a top priority in particle and astroparticle physics, being the most sensitive test of lepton number violation and the only suitable process to probe the Majorana nature of neutrinos. In order to increase the experimental sensitivity for this particular search, ton-scale detectors operated at nearly zero-background conditions with a few keV energy resolution are required. In this scenario, cryogenic detectors have proven effective in addressing many of these issues simultaneously. After long technical developments, the CUORE experiment established the possibility to operate large scale detectors based on this technology. Parallel studies pointed out that scintillating cryogenic detectors represent a suitable upgrade for the CUORE design, directed towards higher sensitivities. In this work, we review the recent development of cryogenic detectors, starting from the status of the art and outlying the path toward next-generation experiments.

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 & diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide & PCPRI laboratory findings after BCG vaccination for a 9 years’ patient. The patient was re-vaccinated based on a negative tuberculin test & no scar at the site of injection of the 1st BCG vaccination at birth. Furthermore, the authors in the present article described a prospective BCG multi-dose clinical study in full details that they will apply in case of acceptance of their submitted grant & the ethical committee approval. The aim of the clinical study is to check if double dose BCG (4 weeks apart) will show a significant difference in the protection of health care professionals in Egypt. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions & exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.

Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

1) Background: Neotropical montane forests represent one of the most diverse ecosystems; however, they are also the most threatened for deforestation. Our main goal is to evaluate the change in Basal Area (BA), Density and Species Composition of montane forests in the southern Ecuador and to determine the influence on some critical ecological and geomorphological factors. 2) Methods: One hundred thirty-two temporary plots of 400 m² each were installed; we identified and measured all trees> 10 cm DBH. We modeled species diversity (Fisher’s alpha) change in relation to climatic, elevational and geomorphological gradients with GLM and Kruskall-Wallis analyses. The change in composition was determined using Cluster Analyses (BIOENV analysis followed by a LINKTREE procedure). Non-metric multidimensional scaling (NMDS) was used to analyze changes across climatic and geomorphological gradients. Finally, we used SIMPER analysis to identify the species that contributed most to the dissimilarity among the different elevations. 3) Results: Formation of floristic groups was influenced by altitude, temperature and Isothermality; physiographic province, great landscape, geological landscape and lithology. Plots located in low hills have higher alpha diversity with respect to the high hills and dissected mountains. 4) Conclusions: The elevation is first hierarchical factor responsible of the division of structural and floristic groups. Plots located on the whitish tuff have a higher alpha value diversity compared with plots in andesitic tuffs. Wettest quarter (> 839 mm) and Isothermality (> 90.5) are the climatic factors that driven de floristic divisions.

Understanding the optimal strategy for a real estate investment and how performance changes based on characteristics is crucial for optimising the achievable return. This is prominent in tourist areas such as Paphos where there is no clear distinction as to whether short or long-term approaches are optimal. The study aimed to develop a model for predicting the optimal rental strategy whilst assessing which model performed best and which property attributes impacted its return the greatest. Short-term data was collected from AirDNA and long-term data was manually collected from real estate agents websites. Furthermore, Random Forest, K-Nearest Neighbour and Multiple Linear Regression models were created to predict the highest and best use for each property. Model accuracy varied between data sets with the best performing model for short-term properties being Random Forest (R-Squared: 0.843), and Distance-Based Multiple Linear Regression for long-term approach (R-Squared: 0.843). The study demonstrated that accurate models could be created to predict the optimal rental strategy with the number of bedrooms being the main driver for rental income, followed by luxury finishes and the presence of a pool. It found that locational characteristics didn’t impact the returns significantly assuming that the property was located within a tourist area.

Slave Province in Canada is an Archean granite-supracrustal terrane at the northwestern corner of the Canadian Shield. It is bordered by the Thelon–Taltson orogen (2.0 to 1.9 Ga) to the south-east and the Wopmay orogen (1.9 to 1.8 Ga) to the west. Acasta gneisses exposed in the western-most Slave province and the Wopmay rocks close to the gneisses were collected systematically for K-Ar and laser step-heating 40Ar /39Ar analyses of the biotite and amphibole. The K-Ar biotite ag-es of the four Wopmay samples range from 1816 ± 18 Ma to 1854 ± 26 Ma, which is within the reported U-Pb zircon age range of the Wopmay orogen. The K-Ar biotite ages of the fifteen Acasta gneisses range from 1779 ± 25 Ma to 1877 ± 26 Ma, except for a younger sample (1711 ± 25 Ma). The 40Ar/39Ar biotite analyses of the three samples from the Wopmay orogen give the plateau ages of 1826 ± 21 Ma, 1886 ± 13 Ma, and 1870 ± 18 Ma. On the other hand, the 40Ar/39Ar analyses of the biotite crystals from the Acasta gneiss show a variety of ages. Three samples show the plateau ages of 1877 ± 8 Ma, 1935 ± 14 Ma, and 1951 ± 11 Ma. These plateau ages are a little older than the total gas ages. The 40Ar/39Ar analyses of the amphibole crystals show more varied age rela-tions. The two samples show consistent age relations between the plateau ages (1814 ± 22 Ma and 1964 ± 12 Ma) and the total gas ages (1789 ± 23 Ma and 1967 ± 11 Ma), respectively. Some sam-ples have the apparent old age of 2000 Ma in the middle temperature fractions. These old frac-tions are due to that the originally existed amphibole crystals formed in Archean were affected by the thermal events during the Wopmay orogeny. but did not fully reset. The results suggest that the K-Ar system ages of the biotite and amphibole of the Archean Acasta gneiss that is aged from 4200 to 2600 Ma of zircon U-Pb ages were rejuvenated in the Paleo–Proterozoic ages. The heat source that rejuvenated the K-Ar system ages may have arisen due to the asthenospheric intrusion into the wedge mantle, which took place because of the subduction rollback.

Finding the ideal statistical method for grouping phenological data is always an important step for breeders to draw correct conclusions from it possibly. In this paper, K-cluster analysis is presented as a perfect tool for grouping phenological data. The present research was performed based on the phenological data of 61 strawberries (Fragaria × ananassa) cultivars of different geo-graphical origins grown in Estonian conditions. Groups of strawberry cultivars were deter-mined according to flowering and ripening time: early, middle and late, based on the sum of ef-fective temperatures above +5°C. The result of the K-cluster analysis carried out in this way makes it possible to precisely plan the ripening time of berries of different strawberry cultivars. Using such analysis data, it is possible to combine with different early, mid or late strawberry cultivars to extend the picking period. Also, this technique can be used to study the effect of cli-matic changes occurring over the years on the phenology of strawberry cultivars grown in the region.

In the particular configuration of the scalar field K-essence in the Wheeler-DeWitt quantum equation, for some age in the Bianchi type I anisotropic cosmological model, a fractional differential equation for the scalar field arises naturally. The order of the fractional differential equation is $\beta=\frac{2\alpha}{2\alpha - 1}$. This fractional equation belongs to different intervals, depending on the value of the barotropic parameter; when $\omega_{X} \in [0,1]$, the order belongs to the interval $1\leq \beta \leq 2$, and when $\omega_{X}\in[-1,0)$, the order belongs to the interval $0<\beta \leq 1$. In the quantum scheme, we introduce the factor ordering problem in the variables $(\Omega,\phi)$ and its corresponding momenta $(\Pi_\Omega, \Pi_\phi)$, obtaining a linear fractional differential equation with variable coefficients in the scalar field equation, then the solution is found using a fractional power series expansion. The corresponding quantum solutions are also given. We found the classical solution in the usual gauge N obtained in the Hamiltonian formalism and without a gauge. In the last case, the general solution is presented in a transformed time $T(\tau)$, however in the dust era we found a closed solution in the gauge time $\tau$.

Abstract: The surge of diabetes poses a significant global health challenge, particularly in Oman and the Middle East. Early detection of diabetes is crucial for proactive intervention and improved patient outcomes. This research leverages the power of machine learning, specifically, Convolutional Neural Networks (CNNs), to develop an innovative 4D CNN model dedicated to early diabetes prediction. A region-specific dataset from Oman is utilized to enhance health outcomes for individuals at risk of developing diabetes. The proposed model showcases remarkable accuracy, achieving an average accuracy of 98.49% to 99.17% across various epochs. Additionally, it demonstrates excellent F1 score, recall, and sensitivity, highlighting its ability to identify true positive cases. The findings contribute to the ongoing effort to combat diabetes and pave the way for future research in using deep learning for early disease detection and proactive healthcare.

This paper explores the dynamic interplay of K-12 education, the Fourth Industrial Revolution (IR 4.0), and internationalization in the Philippines. Through qualitative content analysis, key themes emerged, shedding light on the impact of K-12 education on global competitiveness, challenges in embracing IR 4.0 technologies, and opportunities arising from internationalization efforts. The findings underscore the significance of curriculum alignment with international standards, comprehensive digital literacy training, and fostering a global mindset to prepare students for the digitally-driven, interconnected world. Understanding the implications of these themes is crucial for the Philippines' education system, as it navigates towards a transformative and globally competitive future. Further, this research offers evidence-based recommendations and addresses research gaps, contributing to a broader understanding of how the convergence of these forces shapes the future of Philippine education. Future research avenues may explore long-term impacts on workforce preparedness, innovative IR 4.0 integration, and the effectiveness of internationalization efforts on educational outcomes. Eventually, this study inspires an education system that nurtures learners equipped to thrive in an ever-evolving global landscape.

Forensic document examiners can determine the authenticity of questioned documents by analyzing the ink used to create them. If an ink mismatch is found, it could be a sign of scam, backdating, or forgery. In this research a Hyperspectral Images of iVision HHID dataset is used to detect number of possible inks used in document. By using Hyperspectral Images, it’s possible to detect ink mismatch in a given document. In this research unsupervised learning method K-means is used to detect number of inks. Approximate number of clusters are determined by Elbow and Silhouette method before implementation of K-means.

Address parsing is a crucial task in natural language processing, particularly for Chinese addresses. The complex structure and semantic features of Chinese addresses present challenges due to their inherent ambiguity. Additionally, different task scenarios require varying levels of granularity in address components, further complicating the parsing process. To address these challenges and adapt to low-resource environments, we propose CapICL, a novel Chinese address parsing model based on the In-Context Learning (ICL) framework. CapICL leverages a sequence generator, regular expression matching, BERT semantic similarity computation, and GPT modeling to enhance parsing accuracy by incorporating contextual information. We construct the sequence generator using a small annotated dataset, capturing distribution patterns and boundary features of address types to model address structure and semantics, mitigating interference from unnecessary variations. We introduce the REB-KNN algorithm, which selects similar samples for ICL-based parsing using regular expression matching and BERT semantic similarity computation. The selected samples, raw text, and explanatory text are combined to form prompts, and inputted into the GPT model for prediction and address parsing. Experimental results demonstrate significant achievements of CapICL in low-resource environments, reducing dependency on annotated data and computational resources. Our model's effectiveness, adaptability, and broad application potential are validated, showcasing its positive impact in natural language processing and geographical information systems.

The Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes, such as cellular cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro for determining the changes induced by Ouabain in concentration of 10-5 M, 10-6 M, 10-8 M, 10-9 M on these cellular types, employing specific methods: SEM for morphological evaluation; immunocytochemistry, flowcytometry to assess immunophenotypical markers expression, cell cycle and Annexin V/PI assay for cellular proliferation and viability testing; flowchamber assay to evaluate functional adhesion behavior; RT-PCR for Na+/K+ ATPase subunits molecular expression. Being indicative of the pro-apoptotic and inhibitory effect of Ouabain on tumor invasion and metastasis, the results support the addition of Ouabain to the oncological therapeutic arsenal, trailing the “repurposing drugs” approach.