A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to summarize the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

Larrea tridentata is an endemic plant from the Mexican highlands used in traditional medicine to treat hypertension and kidney stones, among many ailments. This study evaluated a vasorelaxant compound: 5- Hydroxy-2-(4-hydroxy-3-methoxyphenyl)-6,7,8-trimethoxy-4H-1-benzopyran-4-one (also known as 8-Methoxycirsilineol: 8-M) which we purified from an extract of this plant. Mesenteric artery rings were isolated from male guinea pigs for isometric force measurements. Freshly isolated smooth muscle cells from mesenteric artery were used for ionic current measurement for calcium and potassium. 10 μM 8-M completely relaxed vascular rings contracted with phenylephrine in a dose-dependent fashion with an EC50 = 4.26 ± 1.16 10-6 M and 4.56 ± 1.64 10-6 M for endothelium intact and endothelium-free tissue, respectively. The relaxant effect of 8-M was not affected by maximal doses of nifedipine, verapamil or iberiotoxin. Nevertheless, the relaxant effect was partially abolished by addition of 10 mM Tetraethylammonium (TEA). In accordance to this, calcium currents evoked by depolarization were not affected by 8-M, whereas TEA-sensitive potassium currents, were increased upon its addition. Vasorelaxation due to 8-M is partly due to activation of KV currents in an endothelium independent mode.

Epigenetic modifications play a significant role in determining the fate of AFSC in terms of differentiation into multiple lineages. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells differentiation. The present study investigates the role of miRNAs in differentiation of AFSC and addresses how their unique signatures contribute to lineage-specific differentiation. miRNAs profile was assessed in AFSC after 4 weeks of endothelial and muscular differentiation. Our results showed a decreased expression of for 5 miRNAs (miR-125b-5p, hsa-miR-18a-5p, hsa-miR-137, hsa-miR-21-5p and hsa-let-7a-5p) and an increased expression for 12 miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, hsa-let-7e-5p) in EPC compared with undifferentiated AFSC. Smooth muscle differentiation of AFSC revealed significant changes in 9 miRNAs from total of 84 tested; 3 were downregulated (miR-18a-5p, miR-137, sa-miR-21-5p) and 6 were upregulated (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, hsa-miR-375). miRNAs are molecular regulators of cell fate and differentiation, recent advances in molecular biology techniques revealed miRNA regulatory networks that can provide us information of endothelial and muscle cell biology in terms of homeostasis, growth, differentiation, and vascular function.

The homeostasis of cellular calcium is fundamental for many physiological activities, while calcium levels maintain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet derived growth factor (PDGF), inducing proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulations at different compartments of ASM cells. PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed from both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by PLC-IP3R pathway. Interestingly, removal of extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effect on calcium-dependent activation of ER ryanodine receptor. Inhibition of L-type calcium channel on plasma membrane, or SERCA pump on ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. Inhibited SERCA pump caused immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating an active calcium exchange between cytosol and ER storage in resting cells. PDGF-induced calcium at outer mitochondrial membrane sub-region showed similar regulatory response to cytosolic calcium, not influenced by inhibition of mitochondrial calcium uniporter channel. Therefore, our work identified calcium flow pathways among extracellular medium, cell cytosol, and ER by regulatory calcium channels. Particularly, extracellular calcium flow has an essential function to fully activate ER calcium release.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Changes during this period could contribute to inflammation and be associated with variations in the vascular smooth muscle (VSMC) phenotype. We studied changes in inflammatory pathways that could underlie the expressions of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. We analyzed histological changes in the aorta and expressions of the COX-2, TLR4, iNOS, eNOS, MMP-2, -9, β-, α-actin, and TNF-α, IL-6 and IL-1β expressions, and fatty acids by gas chromatography. The aortic wall presented disorganization, decellularization, wavy elastic fibers and increase in the lumen area. The COX-2, TLR4 expressions, TNF-α and IL-6 were increased, but iNOS, MMP-2 and -9 tended to increase and eNOS and arachidonic acid tended to decrease, con increase in oleic acid in CP in comparison with control group. There is a transient hypertension at the end of the CP that is accompanied by an inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the hypertension development during adulthood.

In this review paper, we present a pellucid proof of how x tanh(x/µ) approximates |x|and is better than √x² +µ  when we are concernedwith accuracy.

This research paper aimed to examine the impact of exchange rate volatility on South Africa's exports from 1994 Q1 to 2023 Q2. The study used the Augmented Dickey-Fuller (ADF) and Phillips-Perron (PP) tests to test for stationarity. The nonlinear autoregressive distributed lag (NARDL) model and smooth threshold regression (STR) are employed to analyse the relationship between exchange rate volatility and exports. The GARCH (1.1) technique is used to construct the exchange rate volatility data. The results of the stationarity tests reveal that variables are either integrated in order I(0) or I(1). This implies that the variables used in this study are stationary, which is crucial for conducting accurate analyses. Moreover, the NARDL test approach provided insights into the long-run effects of exchange rate volatility on South Africa's exports. Based on the NARDL test, positive shocks have a greater but statistically insignificant effect on exports than negative shocks. Therefore, a greater level of exchange rate volatility may lead to increased exports from South Africa. Furthermore, the STR also reveals that the impact of exchange rate volatility is insignificant. These findings provide valuable insights for policymakers and firms to make informed decisions regarding exchange rate management and export strategies in South Africa.

One of the most important subjects of hydraulic engineering is the reliable estimation of the transverse distribution in rectangular channel of bed and wall shear stresses. This study makes use of the Tsallis entropy, Genetic Programming (GP) and (ANFIS) methods to assess the shear stress distribution (SSD) in rectangular channel. To evaluate the results of the Tsallis entropy, GP and ANFIS models, laboratory observations were used in which shear stress was measured using an optimized Preston tube. This is then used to measure the SSD in various aspect ratios in the rectangular channel. To investigate the shear stress percentage, 10 data series with a total of 112 different data for were used. The results of the sensitivity analysis show that the most influential parameter for the SSD in smooth rectangular channel is the dimensionless parameter B/H, Where the transverse co-ordinate is B, and the flow depth is H. With the parameters (b/B), (B/H) for the bed and (z/H), (B/H) for the wall as inputs, the modeling of the GP was better than the other one. Based on the analysis, it can be concluded that the use of GP and ANFIS algorithms is more effective in estimating shear stress in smooth rectangular channels than the Tsallis entropy-based equations.

We present smooth approximations to $ \vert{x} \vert $ using sigmoid functions. In particular $ x\,erf(x/\mu) $ is proved to be better smooth approximation for $ \vert{x} \vert $ than $ x\,tanh(x/\mu) $ and $ \sqrt{x^2 + \mu} $ with respect to accuracy. To accomplish our goal we also provide sharp hyperbolic bounds for error function.

Nonnegative matrix factorization (NMF) has been shown to be a strong data representation technique, with applications in text mining, pattern recognition, image processing, clustering and other fields. In this paper, we propose a hypergraph regularized Lp smooth nonnegative matrix factorization (HGSNMF), by incorporating hypergraph regularization and Lp smoothing constraint terms into the standard NMF. The hypergraph regularization term can capture the intrinsic geometry structure of the high dimension space data more comprehensively than simple graph, the Lp smoothing constraint may yield a smooth and more accurate solution to the optimization problem. The updating rules are given using multiplicative update techniques, and the convergence of HGSNMF is theoretically investigated. The experimental results on four different data sets show that the proposed method has better clustering effect than the related state-of-the-art methods in the vast majority of cases.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

The role of fractional calculus in circuit systems has received increased attention in recent years. In order to evaluate the effectiveness of time-domain calculation methods in the analysis of fractional-order piecewise smooth circuit systems, an experimental prototype is developed and the effects of three typical calculation methods in different test scenarios are compared and studied in this paper. It is proved that Oustaloup’s rational approximation method usually overestimates the peak-to-peak current and brings in pulse-voltage phenomenon in piecewise smooth test scenarios, while the results of two iterative recurrence-form numerical methods are in good agreement with the experimental results. The study results are dedicated to provide a reference for efficiently deploying calculation methods in fractional-order piecewise smooth circuit systems. Some quantitative analysis results are concluded in this paper.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

A methodology for both accurate and smooth contour line generation from Light Detection and Ranging (LiDAR) point clouds is proposed in this paper. In order to improve the accuracy of contour lines in the area of forests, constrained triangulation networks with break lines are then constructed to generate contour lines. In break line extraction, a bi-threshold method for edge line detection is used to extract both complete and reliable break lines. A point clouds elevation adjustment with constrain of break lines and an interpolator considering a contour interval is proposed to improve the smoothness of contour lines. The proposed interpotator is also can avoid contour line intersection when contour lines are interpolated. Statistical parameters and shape index are then used to evaluate quantitatively the accuracy and smoothness of the resultant contour lines, which fill in the blank of contour lines evaluation in theory. The experiments show that high-quality contours in terms of smoothness and accuracy can be generated from LiDAR point clouds.

Currently, the design of the concrete mix is an important part of the environmental problem. In front of this question, engineers face a major challenge that is addressed in two ways. On one hand, how do they use its component materials to improve its mechanical properties, on the other hand how do they use less polluting materials? Hence, in an environmental and economical view, laboratory tests were carried out on samples of concrete reinforced with smooth steel fiber extracted from the waste tires, in order to assess its impact and to prove its mechanical feasibility for these purposes. Consequently, laboratory results have shown satisfactory improvement in the behavior of concrete under compression loads in the elastic stage and an increase in ductility and toughness of the matrix in the plastic stage. Besides, taking into account the discontinuity and the structural disturbances observed during the loading of samples in the post-elastic state, a method has been proposed to calculate "the effective toughness and toughness Index of fiber concrete; on the other hand, this method has helped to better optimize length and slenderness of fibers for better use of this recycled material

3D printing with earth-based mortar is still under development and faces challenges. Optimizing the mortar mixture, improving structural strength, determining the relationship between printing speed and the amount of extruded material, and ensuring long-term durability are areas that are still being refined. Additionally, regulatory and certification issues must also be considered to ensure the safety and compliance of 3D printed structures. This paper presents for discussion the records, analyses, studies, and considerations regarding the initial initiatives involving 3D printing with the extrusion of earth-based mortar developed at the Faculty of Engineering of the University of Porto - FEUP. Through this work, it is possible to strengthen and reaffirm that 3D printing with earth-based mortar has significant potential in the construction industry and that the incorporation of dispersed kraft paper fibres from the recycling of cement bags is an excellent resource to achieve good constructability in 3D printing with earth-based mortar.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in some sections we present concerning numerical examples and the respective softwares.

Unidentified abortion, of which leptospirosis, brucellosis and ovine enzootic abortion are important factors, is the main cause of disease spread between animals and humans in all agricultural systems in most developing countries. Although there are well-defined risk factors for these diseases, these characteristics do not represent the prevalence of the disease in different regions. This study predicts the unidentified abortion burden from multi-microorganisms in ewes based on artificial neural networks approach and GLM. Methods: A two-stage cluster survey design was conducted to estimate the seroprevalence of abortifacient microorganisms, and to identify putative factors of infectious abortion. Results: Overall seroprevalence of Brucella was 70.7%, while Leptospira spp. was 55.2%, C. abortus 21.9% and B. ovis 7.4%. Serological detection with the 4 abortion-causing microorganisms was determined only in 0.87% of sheep sampled. The best GLM is integrated by serological detection of serovar Hardjo and Brucella ovis in animals of the slopes with elevation between 2600 to 2800 meters above sea level from municipality of Xalatlaco, as well water supply, sheep pen built with materials of metal grids and untreated wood, with dirt and concrete floors, and bed of straw that remained independently associated with infectious abortion in ewes. Approximately 80% of those respondents did not wear gloves or masks to prevent the transmission of the abortifacient zoonotic microorganisms. Conclusions: Sensitizing stakeholders on good agricultural practices could improve public health surveillance. Further studies on the effect of animal-human transmission in such a setting are worthwhile to further support the One Health initiative.

This paper aims to implement histogram pyramids with marching cubes method for 3D medical volumetric rendering. The histogram pyramids are used for feature extraction by segmenting the image into the hierarchical order like the pyramid shape. The histogram pyramids can decrease the number of sparse matrixes that will occur during voxel manipulation. The important feature of the histogram pyramids is the direction of segments in the image. This feature will be then used for connecting pixels (2D) to form up voxel (3D) during marching cubes implementation. The proposed method is fast and easy to implement and it also produces a smooth result (compared to the traditional marching cubes technique). The experimental results show that time consuming for generating 3D model can be reduced by 15.59% in average. The paper also shows the comparison between the surface rendering using the traditional marching cubes and the marching cubes with histogram pyramids. Therefore, for the volumetric rendering such as 3D medical models and terrains where a large number of lookups in 3D grids are performed, this method is a particularly good choice for generating the smooth surface of 3D object.

In this paper we review a proposal to represent the geometric degrees of freedom of the gravitational field as a branched covering space, and introduce a new application of this in which the branch loci are 1- or 2-knots. This allows one to construct arbitrary smooth, closed 3- and 4-manifolds with enough geometric and topological information to write down a partition function and calculate statistical quantities in the thermodynamic limit. Further, we find clear evidence for a dimensional reduction of the spacetime geometry from four to two. As an example, we choose a family of smooth 4-manifolds presented in this way, and calculate the entropy of the system.

The finite-time turnpike property describes the situation in an optimal control problem where an optimal trajectory reaches the desired state before the end of the time interval and remains there. We consider a machine learning problem with a neural ordinary differential equation that can be seen as a homogenization of a deep ResNet. We show that with appropriate scaling of the quadratic control cost and the non-smooth tracking term the optimal control problem has the finite-time turnpike property, that is the desired state is reached in the interior of the time interval and the optimal state remains there until the terminal time $T$. This property is useful to achieve a compromise between the depth of the network and the size of the optimal system parameters which we hope will be useful to determine optimal depths for neural network architectures in the future.

This paper focus on the modeling and time-domain analyzing method of piecewise-smooth fractional-order circuit systems. Firstly, an analytical framework is constructed based on a generalized piecewise-smooth two-port impedance network model, which takes the topological characteristics of Dickson type switched-capacitor converters (SCCs) as examples, and considers the fractional-order characteristics of class-2 X7R ceramic capacitors, which are widely used in SCCs. Secondly, the time-domain analyzing method for such a piecewise-smooth fractional-order circuit system is developed, numerical solutions are obtained, and the influence of the fractional-order capacitor on the power conversion efficiency of the system are revealed. Finally, in order to validate the analysis, both numerical simulation and experiments are provided in the work, the results of which confirm that, the proposed fractional-order analytical framework can capture the power loss mechanism of piecewise-smooth fractional-order circuit systems more effectively than the traditional integer-order based approach, thus benefiting the design of circuit systems.

The concepts of fractional calculus and the related techniques have been gaining momentum in circuit system fields, and an increasing body of evidence suggests that fractional-order characteristics are widely distributed in electronic components. In this paper, we consider the fractional characteristics of non-solid aluminum electrolytic capacitors and focus on the nonlinear dynamic characteristics of peak-current-mode controlled (PCMC) dc-dc boost converters with such components. In the work, we establish a piecewise smooth non-commensurate fractional-order model to describe the converter, in which the fractional-order equivalent impedance model of capacitors is adopted and the detailed control loop is considered. In order to analyze the converter, we use the fractional Adams-Bashforth-Moulton typed method (F-ABM) and stroboscopic map technique to obtain the time-domain solutions and the bifurcation diagram. The results of bifurcation diagrams indicate that, with the change of different parameters, the converter enters chaotic state through period doubling bifurcation. In order to provide empirical evidence for the nonlinear dynamic analysis, we consider both circuit-level simulation and experiments in the work, the results of which further confirm the results of theoretical analysis.

Additive manufacturing enables the realization of complex component designs that can not be achieved with conventional processes, such as the integration of lattice structures for weight reduction. To include lattice structures in component designs, an automated algorithm compatible to conventional CAD is required that is able to handle various lattice topologies as well as variable local shape parameters such as strut radii. Furthermore, smooth node transitions are desired since previous studies indicate advantages regarding reduced stress concentrations and the structural response to loadings such as fatigue performance. The surface patch-based algorithm developed in this work is able to solidify given lattice frames to smooth lattice structures without manual construction steps. The algorithm requires only a few seconds of sketching time for each node and favours paralellization. Automated special case workarounds as well as fallback mechanisms are considered for non-standard inputs. It is demonstrated on irregular lattice topologies and applied for the construction of a lattice infill of an aircraft component that was additively manufactured.

Robotic path planning is a field of research which is gaining traction given the broad domains of interest to which path planning is an important systemic requirement; the aim being to optimise the efficacy of robotic movements in a defined operational environment. For example, robots have been employed in many domains including: cleaning robots (such as vacuum cleaners), automated paint spraying robots, window cleaning robots, forest monitoring robots, agricultural robots (often driven using satellite and geostationary positional satellite data). Additionally, mobile robotic systems have been utilised in disaster areas and locations hazardous to humans (such as war zones in mine clearance). The coverage path planning problem describes an approach which is designed to determine the path that traverses all points in a defined operational environment while avoiding static and dynamic (moving) obstacles. In this paper we present our proposed Smooth-STC model, the aim of the model being to identify an optimal path, avoid all obstacles, prevent (or at least minimise) backtracking, and maximise the coverage in any defined operational environment. The experimental results in a simulation show that, in uncertain environments, our proposed smooth STC method achieves an almost absolute coverage rate and demonstrates improvement when measured against alternative conventional algorithms.

For the set of probability measures ${\sf I}(X)$, where $X$ is a compact Hausdorff space, we propose a new way to introduce the topology by using open subsets of the space $X$. Then, among other things, we give a new proof that for a compact Hausdorff space $X$ the space ${\sf I}(X)$ is also a compact Hausdorff space. For a Tychonoff space $X$, we consider the topological space ${\sf I_{\tau}}(X)$ of $\tau$-smooth idempotent probability measures on $X$,and show that the space ${\sf I_{\tau}}(X)$ is \v{C}ech-complete if and only if the given space $X$ is \v{C}ech-complete.

Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, the latter termed cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) within the cerebrovasculature and its potential associations with CAA, gender, and ApoE4 genotype. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher colocalization of HS with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebral vasculature was detected in AD patients with severe CAA, suggesting a potential role in CAA development. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings shed light on the intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further exploring the underlying mechanisms may present novel therapeutic avenues for AD treatment.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

Stenting is a common method for treating atherosclerosis. A metal or polymer stent is deployed to open the stenosed artery or vein. After the stent is deployed, the blood flow dynamics influence the mechanics by compressing and expanding the structure. If the stent does not respond properly to the resulting stress, vascular wall injury or re-stenosis can occur. In this work, Discrete Multiphysics is used to study the mechanical deformation of the coronary stent and its relationship with the blood flow dynamics. The major parameters responsible for deforming the stent are sort in terms of dimensionless numbers and a relationship between the elastic forces in the stent and pressure forces in the fluid is established. The blood flow and the stiffness of the stent material contribute significantly to the stent deformation and affect the rate of deformation. The stress distribution in the stent is not uniform with the higher stresses occurring at the nodes of the structure.

The article considers a way to compare large bulks of experimental data with theoretical calculations, in which the quality of theoretical models is clearly demonstrated graphically. Published theoretical data of the three-fluid dynamic model (3FD) applied to the experimental data from heavy-ion collisions at the energy range \sqrt{s_{NN}} = 2.7 - 63 GeV are used as example of application of the developed methodology. When analyzing the results, the quantum nature of the fireball, created at heavy ion collisions, was taken into account.

In this paper, we investigate the accuracy and robustness of three classes of methods for solving two-phase incompressible flows on a staggered grid. Here, the unsteady two-phase flow equations are simulated by finite volumes and penalty methods using implicit and monolithic approaches (such as the augmented Lagrangian and the fully coupled methods), where all velocity components and pressure variables are solved simultaneously (as opposed to segregated methods). The interface tracking is performed with a Volume-of-Fluid (VOF) method, using the Piecewise Linear Interface Construction (PLIC) technique. The home code Fugu is used for implementing the various methods. Our target application is the simulation of two-phase flows at high density and viscosity ratios, which are known to be challenging to simulate. The resulting strategies of monolithic approaches will be proven to be considerably better suited for these two-phase cases, they also allow to use larger time step than segregated methods.

The potentially active A subunit of coagulation factor XIII (FXIII-A) is an intracellular transglutaminase expressed in various cell types including platelets and monocytes/macrophages. It is involved in stabilizing protein structures by cross-linking through Nε-(?-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque and are important in determining its structural/functional features. Two of their important functions are the accumulation of oxidized LDL in the lipid core, and by cross-linking structural proteins they may stabilize the plaque and protect the thrombi of atherogenic origin against fibrinolytic degradation. It is important to know whether these functions operate in parallel utilizing the same cellular compartments. First, we showed that monocyte-derived human macrophages significantly increase their FXIII-A content when up-taking oxidized LDL. This phenomenon is very likely independent of the process of transformation into foam cells, as the transformation of vascular smooth muscle cells into foam cells fails to result in the expression of FXIII-A. FXIII containing macrophage-like cells are abundant in the plaque and FXIII-A is also present in the extracellular core. Several cells co-stained for FXIII-A and for Oil Red O suggest that expression of FXIII-A and lipid up-take are common features of macrophages present in the atherosclerotic plaque.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

This paper gives a new unified formula for the Newtonian fluids valid for all pipe flow regimes from laminar to the fully rough turbulent. It includes laminar, unstable sharp jump from laminar to turbulent, and all types of the turbulent regimes: smooth turbulent regime, partial non-fully developed turbulent and fully developed rough turbulent regime. The formula follows the inflectional form of curves as suggested in Nikuradse’s experiment rather than monotonic shape proposed by Colebrook and White. The composition of the proposed unified formula consists of switching functions and of the interchangeable formulas for laminar, smooth turbulent and fully rough turbulent flow. The proposed switching functions provide a smooth and a computationally cheap transition among hydraulic regimes. Thus, the here presented formulation represents a coherent hydraulic model suitable for engineering use. The model is compared to existing literature models, and shows smooth and computationally cheap transitions among hydraulic regimes.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

This paper studies the evaporative heat transfer characteristics of R744 at low temperatures in a horizontal smooth tube as a cascade refrigeration system (CRS) among hybrid cascade refrigeration systems (HCRSs). There is a lack of research on the low-temperature evaporative heat transfer characteristics of R744 under the operating conditions of evaporators used in actual CRSs used in supermarkets. Therefore, this study aims to provide basic data on the evaporative heat transfer characteristics of R744 in the evaporators of refrigerators used in supermarkets. The tube used in the evaporation experiment conducted herein was a smooth horizontal copper tube with an inner diameter and length of 11.46 mm and 8000 mm, respectively. The experimental pa-rameters were as follows: heat fluxes of 12–21.5 kW/m2, mass fluxes of 75–225 kg/(m2·s), and saturation temperatures of −50–−30 °C. The main results are summarized as follows. (1) When designing the R744 evaporator, the mass and heat fluxes must be maximized within the operating conditions, and the saturation temperature must be designed to be as low as possible. (2) The evaporative heat transfer coefficient of R744 can be predicted well by using the correlation formula of Chen at the evaporation temperature of −40 °C in the CRS.