Vessel Stability Research Articles

Study on dynamic post-buckling stability of fast reactor vessels subjected to vertical vibration

Abstract As a lesson learned from the Fukushima nuclear accident, the importance of accident mitigation for Beyond Design Basis Events (BDBEs) is recognized. Excessive earthquake is a typical BDBE. During such events, the Fast Reactor Vessel (FRV) is vulnerable to buckling. The safety goal of FRV under excessive earthquake is to achieve a stable post-buckling state. Our previous study on bending buckling confirmed a global response stability under horizontal vibration. As a parallel study, this paper focuses on axial compression buckling under vertical vibration. Shaking table experiments using thin-walled cylindrical models (R/t=260) are carried out. Similar methodology is applied to investigate the buckling and post-buckling behavior. It is found that axial compression buckling shares an extensive similarity with bending buckling in both buckling mode and post-buckling behavior. Similar global response stability is confirmed due to phase-inverse phenomenon. After buckling, buckling failure becomes stable and does not progress further even when an intense input amplitude is continuously applied. The vibrational load acts as a displacement-controlled load in the out-of-phase domain such that immediate collapse is prevented. Most input energy is dissipated in hysteresis loops rather than being carried by the mass. These mechanisms are independent of input waveform and can be applied to an arbitrary seismic input. In addition, a conservative limit displacement for global response stability is identified. Moreover, the effect of the input frequency ratio, the initial geometrical imperfection and the gravitational force on the post-buckling behavior are clarified.

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.

Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.

Human iPSC-derived pericyte-like cells carrying APP Swedish mutation overproduce beta-amyloid and induce cerebral amyloid angiopathy-like changes

BackgroundPatients with Alzheimer's disease (AD) frequently present with cerebral amyloid angiopathy (CAA), characterized by the accumulation of beta-amyloid (Aβ) within the cerebral blood vessels, leading to cerebrovascular dysfunction. Pericytes, which wrap around vascular capillaries, are crucial for regulating cerebral blood flow, angiogenesis, and vessel stability. Despite the known impact of vascular dysfunction on the progression of neurodegenerative diseases, the specific role of pericytes in AD pathology remains to be elucidated.MethodsTo explore this, we generated pericyte-like cells from human induced pluripotent stem cells (iPSCs) harboring the Swedish mutation in the amyloid precursor protein (APPswe) along with cells from healthy controls. We initially verified the expression of classic pericyte markers in these cells. Subsequent functional assessments, including permeability, tube formation, and contraction assays, were conducted to evaluate the functionality of both the APPswe and control cells. Additionally, bulk RNA sequencing was utilized to compare the transcriptional profiles between the two groups.ResultsOur study reveals that iPSC-derived pericyte-like cells (iPLCs) can produce Aβ peptides. Notably, cells with the APPswe mutation secreted Aβ1-42 at levels ten-fold higher than those of control cells. The APPswe iPLCs also demonstrated a reduced ability to support angiogenesis and maintain barrier integrity, exhibited a prolonged contractile response, and produced elevated levels of pro-inflammatory cytokines following inflammatory stimulation. These functional changes in APPswe iPLCs correspond with transcriptional upregulation in genes related to actin cytoskeleton and extracellular matrix organization.ConclusionsOur findings indicate that the APPswe mutation in iPLCs mimics several aspects of CAA pathology in vitro, suggesting that our iPSC-based vascular cell model could serve as an effective platform for drug discovery aimed to ameliorate vascular dysfunction in AD.

Adoption of lib (Lithium Batteries) for hybrid propulsion on small passenger vessel and consequences on damage stability

Nowadays the Hybrid Propulsion is a reality, increasing its diffusion. The main principle is the storing of energy in battery packs to provide energy for the propulsion system of the vessel, aiming the fundament of hybrid propulsion is the use of Li-Ion or Li-Po batteries, with high capability of energy storage (MWh). This good capability has the disadvantage of the explosion risk if exposed to heat. The solutions adopted can impact on damage stability. This paper will analyze the aspects connected with hybrid propulsion in small passenger vessels, considering the State of Art of Rules regarding the fire safety and the possible solutions adopted regarding Lithium batteries. The paper refers to the consequences of adoption of new technology of Lithium batteries developed to be used in maritime application, batteries indicated as “LiB”. The paper is not referring to Lithium metal batteries with the Lithium used as metallic anode and all the consequences on fire risks. The paper is not about the risk of fire due to the battery technology, but is related to the consequences on stability of small vessels if, for security reason a large amount of water is used to cool down the battery packs. The paper will consider the case study of a small passenger ship, examining the general arrangement adopted and the position of the batteries, and the consequences caused by the installation on board of the battery packs. The results will show how the fire safety is important and requires special attention, also in consideration of the various possibilities to contain the fire or prevent the risk of explosion. The aim is to give a suggestion for set new standards for firefighting in presence of large batteries and also to focus on possible problems arising in case of fire on hybrid vessels.

THE ROLE OF PERICYTES IN BONE TISSUE REGENERATION AND THERAPEUTIC APPLICATIONS

The regeneration of massive bone defects poses a significant challenge in traumatology and orthopedics, often requiring bone grafting procedures following tumor resection, surgery, or severe injury. Current treatment methods include autologous and allogeneic bone grafts, as well as bone substitutes. While autologous transplantation is considered the standard, it is limited by donor site morbidity and availability. Allogeneic transplantation presents risks such as graft rejection and disease transmission. Bone substitutes may not fully restore bone defects. Tissue-engineered biomaterials offer promise for effective regeneration, utilizing stem cells, growth factors, and scaffolds. Adipose tissue, rich in mesenchymal stem cells and perivascular stem cells (pericytes), is a promising cell source for tissue engineering. This thesis explores the therapeutic potential of pericytes combined with various biological carriers and stimulating factors to enhance bone tissue regeneration. Pericytes, contractile cells surrounding small blood vessels, are crucial for vessel integrity and blood flow regulation. They express markers like α-SMA and PDGFR-β and participate in angiogenesis, immune function, and tissue repair. Interactions with endothelial cells via signaling pathways involving molecules like VEGF and TGF-β are vital for vessel formation and stability. With their multipotent nature, pericytes show promise for regenerative medicine. Ongoing research is essential to address challenges in pericyte biology, including identification and understanding their roles in tissue regeneration. Studies highlight the potential of adipose tissue-derived pericytes in bone regeneration, particularly CD146+ pericytes, showing efficacy in spinal fusion and nonunion fracture treatment when combined with DBM. Preclinical studies confirm their effectiveness, especially when incorporated into various scaffold materials. Clinical studies using adipose-derived stem cells and autologous microfragmented adipose tissue have shown promise, with pericyte-enriched fractions holding potential for improved outcomes. Future research into pericyte application, combined with growth factors and scaffolds, could significantly advance bone tissue regeneration and regenerative medicine. Human pericytes show promise for bone tissue regeneration due to their mesenchymal stem cell properties and role in vascular stabilization. Injectable hydrogels are crucial for bone tissue engineering, with various biomaterials developed for this purpose. Studies using injectable hydrogels with pericytes have demonstrated their efficacy in accelerating bone regeneration in different models. Further advancements in injectable hydrogel technology incorporating stem cells and osteoinductive factors are needed for more efficient bone tissue restoration.

Exploring Innovative Methods in Maritime Simulation: A Ship Path Planning System Utilizing Virtual Reality and Numerical Simulation

In addressing the high costs, inefficiencies, and limitations of purely digital simulations in maritime trials for unmanned vessel path planning, this paper introduces a ship virtual path planning simulation test system. This system, unbound by temporal and spatial constraints, vividly showcases the navigational performance of vessels. After analyzing the virtual testing requirements for the autonomous navigation performance of unmanned surface vehicles (USVs), we established the overall framework of this system. Data-driven by a numerical simulation platform, the system achieves synchronized operation between physical and virtual platforms and supports interactive path planning simulations between USVs and the virtual testing system. Furthermore, to address the limitations of traditional ship trajectory planning evaluation, this paper develops a global path planning fitness evaluation function that comprehensively considers trajectory safety, navigation distance, and vessel stability, achieving optimal comprehensive routes through the particle swarm optimization algorithm. Test results indicate an average roll reduction of 14.31% in the planned routes, with a slight increase in navigation distance. By integrating two-dimensional curve simulation with three-dimensional visualization, this paper not only overcomes the limitations of purely physical and purely virtual simulations but also enhances the overall credibility and intuitiveness of the simulation. Experimental results validate the system’s effectiveness, providing a novel method for autonomous navigation testing and evaluation of USVs.

Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach.

Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.

Insulin-like growth factor-binding protein 7 (IGFBP7): A microenvironment-dependent regulator of angiogenesis and vascular remodeling.

Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) is an extracellular matrix (ECM) glycoprotein, highly enriched in activated vasculature during development, physiological and pathological tissue remodeling. Despite decades of research, its role in tissue (re-)vascularization is highly ambiguous, exhibiting pro- and anti-angiogenic properties in different tissue remodeling states. IGFBP7 has multiple binding partners, including structural ECM components, cytokines, chemokines, as well as several receptors. Based on current evidence, it is suggested that IGFBP7's bioactivity is strongly dependent on the microenvironment it is embedded in. Current studies indicate that during physiological angiogenesis, IGFBP7 promotes endothelial cell attachment, luminogenesis, vessel stabilization and maturation. Its effects on other stages of angiogenesis and vessel function remain to be determined. IGFBP7 also modulates the pro-angiogenic properties of other signaling factors, such as VEGF-A and IGF, and potentially acts as a growth factor reservoir, while its actual effects on the factors' signaling may depend on the environment IGFBP7 is embedded in. Besides (re-)vascularization, IGFBP7 clearly promotes progenitor and stem cell commitment and may exhibit anti-inflammatory and anti-fibrotic properties. Nonetheless, its role in inflammation, immunomodulation, fibrosis and cellular senescence is again likely to be context-dependent. Future studies are required to shed more light on the intricate functioning of IGFBP7.

P-424 Placental extracellular matrix remodelling in pregnancies by oocyte donation shows similarities with preeclamptic placenta: a pilot study

Abstract Study question Do stromal alterations occur during placentation upon heterologous assisted reproductive techniques (ART) and are they associated with a higher risk of developing preeclampsia? Summary answer The remodelling of extracellular matrix molecules, key for vascularization and immunity, is altered in pregnancies from oocyte donation and resembles the miss-regulations observed in preeclampsia. What is known already Preeclampsia represents one of the main causes of maternal and perinatal morbidity, affecting 2-8% of spontaneous pregnancies. Its incidence increases two times upon homologous ART and up to four times upon oocyte donation, however the underlying factors are still unknown. Preeclampsia is characterized by high blood pressure and endothelial cell dysfunction, but its pathogenesis is multifactorial relying on vascular, metabolic and immune alterations. All these elements are tightly influenced by the extracellular matrix (ECM) that, during an uneventful pregnancy, is remodelled to support an efficient placentation and immunotolerance. Despite its key functions, little is known regarding ECM remodelling in preeclampsia. Study design, size, duration This is an observational pilot study conducted over a 12 months period. Four groups were included: 1) pregnant women that underwent homologous ART (n = 7; HOM); 2) pregnant women that underwent oocyte donation (n = 10; OD); 3) women that conceived spontaneously affected by PE (n = 7); and 4) uneventful spontaneous pregnancies (n = 8; control group CTRL). Participants/materials, setting, methods For each patient placental samples have been collected upon delivery and processed to perform molecular and proteomic analysis by real time PCR and immunohistochemistry The statistical differences among the groups have been evaluated by the ANOVA and Mann-Whitney tests. Main results and the role of chance We focused our study on specific ECM elements known to modulate angiogenesis and immunity, two key players in preeclampsia occurrence. Our data indicated first that collagen I, collagen IV and Multimerin-2, important components of the vessel wall that contribute to vessel stabilization and efficiency, are significantly decreased in OD compared to HOM group (coll I P = 0.04; coll IV P = 0.043; Multimerin-2 P = 0.036). Next, we analyzed EMILIN-2 and versican, two ECM components exerting not only angiogenic but also immunomodulatory functions. We found that EMILIN-2 is decreased in OD compared to CTRL placentas (P = 0.043), whereas versican undergoes an opposite regulation, being slightly increased in the OD placentas (P = 0.045). We observed an analogous mis-regulation when comparing PE to the CTRL group, suggesting that these stromal alterations may take part in the establishment of a microenvironment more prone to preeclampsia onset and associate with the higher risk related to OD pregnancies. We also found that some features of ECM remodelling seem to be strongly associated with OD. Precisely, our data denoted that the glycoprotein tenascin-C decreased specifically in OD patients, while was comparable between HOM, PE and CTRL groups (P = 0.042). Limitations, reasons for caution The main limitation of this pilot study is the restricted number of patients. Further investigations on a larger sample and prospective cohort of patients might provide more robust data. Wider implications of the findings Our data highlighted for the first time that the placental stroma undergoes an altered remodelling in OD and PE pregnancies. We envision that a deep characterization of ECM will help better understanding of the mechanisms behind the pathogenesis of preeclampsia with possible implications for prediction and prevention. Trial registration number N/A

Outcomes of off-the-shelf preloaded inner branch device for urgent endovascular thoraco-abdominal aortic repair in the ItaliaN Branched Registry of E-nside EnDograft

ObjectiveThe aim of this study was to report the outcomes of endovascular urgent thoracoabdominal aortic (TAAA) repair, using an off-the-shelf preloaded inner branch device (E-nside; Artivion). MethodsData from a physician-initiated national multicenter registry, including patients treated with E-nside endograft (INBREED) were prospectively collected (2020-2024); only urgent cases were included in this study. Primary outcomes were technical success and mortality at 30 days. Secondary outcomes were spinal cord ischemia rate, stroke rate, major adverse events (MAE) as also branch instability at 12 months. ResultsOf 185 patients enrolled in the INBREED, 64 (34.5%) were treated in a urgent setting and were included in the study. Reason for urgent repair was presence of aneurysm-related symptoms in 31 patients (48.4%), a contained rupture in eight (12.5%), and a large aneurysm >80 mm in 25 (39.1%). Extent of repair was I to III in 32 patients (50%) and IV in 32 (50%); 18 (28%) had a narrow (<25 mm) paravisceral aortic lumen. An adjunctive proximal thoracic endograft was deployed in 29 patients (45.3%); a distal bifurcated abdominal endograft was used in 33 (51.5%). Two hundred forty-nine target vessels (97.2%) were successfully incorporated through an inner branch from an upper arm (81.2%) or femoral (18.8%) access. A balloon expandable stent was used in 184 (75.7%) target vessels, a self-expandable stent in 59 (24.3%). Mean time for target vessel bridging was 39.9 ± 28.4 minutes per target vessel. Thirty-day cumulative major adverse event (MAE) rate was 28%, and mortality occurred in five patients (9.1%). There was one postoperative stroke (1.6%), and the spinal cord ischemia (SCI) rate was 8% (n = 5). For the 249 target vessels successfully incorporated through an inner branch, 1-year freedom from target vessel instability was 93% ± 3% after 1 year. ConclusionsThe E-nside represents a valid solution for the urgent treatment of TAAAs, including symptomatic and ruptured TAAAs, as well as large asymptomatic TAAAs that cannot wait for a custom-made device. The preloaded inner branches and available proximal and distal graft diameters might be useful in urgent settings and provided satisfactory early and 1-year results, in terms of both endograft and target vessel stability. Further studies are required to assess the clinical role of E-nside for urgent TAAA repair.

Experimental investigation and intelligent control of the magnus anti-rolling device for ship stability at zero speed

Under zero-speed conditions, ships are particularly susceptible to the effects of waves, which directly impact the safety of the vessel. A ship anti-rolling device based on the Magnus effect is designed to mitigate rolling motions across a full range of speeds, thereby enhancing the vessel's stability. This study presents an experimental investigation and intelligent control of Magnus anti-rolling devices aimed at enhancing ship stability at zero speed. The test setup, intelligent control algorithm, and experimental procedures specifically tailored for evaluating the Magnus anti-rolling device were designed. Following this, a comprehensive analysis was conducted to assess the effects of different cylinder geometries, swinging speeds, initial roll angles, and control methods on the anti-rolling characteristics of the device. Results demonstrate that the intelligent control method achieves an average anti-rolling efficiency of 89%. Additionally, the optimised geometric model of the Magnus anti-rolling device exhibits improved anti-rolling efficiency relative to the original model. The study confirms the stability and robustness of the intelligent Magnus anti-rolling device and suggests future research directions for practical applications aboard full-scale vessels in complex marine environments.

Digital sailmate: enhancing safety through low-cost stability monitoring in artisanal fishing

Despite overall mortality decreasing, offshore fishing remains one of the riskiest work-based activities worldwide. For example, fishing communities in East Africa have a 43-fold higher rate of drowning than the general population. A lack of safety culture and knowledge around vessel stability contributes to this issue. Formal safety measures can be difficult to enforce, especially in small scale and subsistence fishing activities dominated by small artisanal boats. Digital technologies hold potential to effectively improve fishing safety. A digital safety device based on commonly held and relatively low-cost consumer products such as smartphones can provide increasing information to fishers enabling more informed safety decisions to be taken during vessel use. This paper proposes the algorithms for a prototype device to monitor stability of fishing vessels, with focus on the capabilities of low-fidelity data in stability assessment. The findings of experimental results at model and full scale are presented. The research indicates that an inclining test can be carried out with minimal training or knowledge base to allow an adequate stability assessment of a vessel before departure on a fishing trip. This baseline measure can then be used to track stability whilst underway as vessel motion is recorded and processed continually updating the stability assessment.

Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents.

Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFβ and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment.

FOXF1 promotes tumor vessel normalization and prevents lung cancer progression through FZD4

Cancer cells re-program normal lung endothelial cells (EC) into tumor-associated endothelial cells (TEC) that form leaky vessels supporting carcinogenesis. Transcriptional regulators that control the reprogramming of EC into TEC are poorly understood. We identified Forkhead box F1 (FOXF1) as a critical regulator of EC-to-TEC transition. FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). Low FOXF1 correlated with poor overall survival of NSCLC patients. In mice, endothelial-specific deletion of FOXF1 decreased pericyte coverage, increased vessel permeability and hypoxia, and promoted lung tumor growth and metastasis. Endothelial-specific overexpression of FOXF1 normalized tumor vessels and inhibited the progression of lung cancer. FOXF1 deficiency decreased Wnt/β-catenin signaling in TECs through direct transcriptional activation of Fzd4. Restoring FZD4 expression in FOXF1-deficient TECs through endothelial-specific nanoparticle delivery of Fzd4 cDNA rescued Wnt/β-catenin signaling in TECs, normalized tumor vessels and inhibited the progression of lung cancer. Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/β-catenin signaling in TECs. Nanoparticle delivery of FZD4 cDNA has promise for future therapies in NSCLC.

Investigating the relationship between residual stress and micromechanical properties of blood vessels using atomic force microscopy.

The magnitude of vascular residual stress, an inherent characteristic exclusive to the vasculature, exhibits a strong correlation with vascular compliance, tensile resistance, vascular rigidity, and vascular remodeling subsequent to vascular transplantation. Vascular residual stress can be quantified by evaluating the magnitude of the opening angle within the vascular ring. For decellularized vessels, the vascular ring's opening angle diminishes, consequently reducing residual stress. The decellularization process induces a laxity in the vascular fiber structure within decellularized vessels. To investigate the interrelation between the magnitude of residual stress and the microstructure as well as mechanical properties of elastin and collagen within blood vessels, this study employed fresh blood vessels, stress-relieved vessels, and sections of decellularized blood vessels. Structural scanning and force map experiments on the surface of the sections were conducted using atomic force microscopy (AFM). The findings revealed well-organized arrangements of elastin and collagen within fresh vessels, wherein the regularity of collagen and elastin exhibited variability as residual stress declined. Furthermore, both stress-relieved and decellularized vessel sections exhibited a reduction in the mean Young's modulus to varying extents in comparison to fresh vessels. The validity of our experimental results was further corroborated through finite element simulations. Hence, residual stress assumes a crucial role in upholding the structural stability of blood vessels, and the intricate association between residual stress and the microstructural and micromechanical properties of blood vessels holds significant implications for comprehending the impact of vascular diseases on vascular structure and advancing the development of biomimetic artificial blood vessels that replicate residual stress. RESEARCH HIGHLIGHTS: In this inquiry, we scrutinized the interconnection amid vascular residual stress and the microscale and nanoscale aspects of vascular structure and mechanical function, employing AFM. We ascertained that residual stress assumes a pivotal role in upholding vascular microstructure and mechanical attributes. The experimental outcomes were subsequently validated through finite element simulation.

The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.

Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, and cardiovascular system function; despite these functional overlaps, little is known about Wnt/β-catenin-S1P cross-talk. In the vascular system, both Wnt/β-catenin and S1P signals affect vessel maturation, stability, and barrier function, but information regarding their potential coordination is scant. We report an instance of functional interaction between the two pathways, including evidence that S1P receptor 1 (S1PR1) is a transcriptional target of β-catenin. By studying vascular smooth muscle cells and arterial injury response, we find a specific requirement for the β-catenin carboxyl terminus, which acts to induce S1PR1, and show that this interaction is essential for vascular remodeling. We also report that pharmacological inhibition of the β-catenin carboxyl terminus reduces S1PR1 expression, neointima formation, and atherosclerosis. These findings provide mechanistic understanding of how Wnt/β-catenin and S1P systems collaborate during vascular remodeling and inform strategies for therapeutic manipulation.

Mechanobiological tortuosity of blood vessels with stress-modulated growth and remodeling

The stability of blood vessels is essential for maintaining their functions, while severe blood vessel tortuosity leads to various clinical complications. The growth and remodeling of blood vessels, which are regulated by mechanical and biochemical cues, cause residual stresses that affect vessel stability. In this paper, we combine theory and simulations to study the mechanobiological behavior of blood vessels with stress-modulated growth and remodeling. Effects of the volumetric growth of the matrix and the turnover and reorientation of collagen fibers are accounted for. Linear stability analysis is first carried out to investigate the mechanobiological stability of blood vessels. By developing a finite element method that incorporates stress-modulated growth and remodeling, we validate the theoretical solution of the critical state and further capture the postbuckling evolution of blood vessels. Our results show that an increased internal pressure can lead to the thickening of the vessel wall, which stabilizes the blood vessels mechanically, whereas the effect of internal pressure on the mechanobiological buckling is nonmonotonic. Compared to the mechanical instability, the mechanobiological buckling results in a larger mode number and a shorter wavelength, as usually observed in varicose veins. Vessels during postbuckling may exhibit non-uniform wall thicknesses, in consistency with the experimental observation on tortuous aortas. These findings highlight the crucial role of mechanical remodeling in tissue morphogenesis and could deepen the understanding of mechanobiological mechanisms underlying the formation and development of blood vessel tortuosity.

The Effects of SARS-CoV-2 on the Angiopoietin/Tie Axis and the Vascular Endothelium

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyperinflammation, vasculitis, and multi-organ failure. SARS-CoV-2 causes the deterioration of numerous systems, with increasing evidence implying that COVID-19 affects the endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietin/Tie balance affects the vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects the Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically on the Angiopoietin/Tie pathway.

Mooring Design and Fatigue Damage on Variant Fairlead Positions During FPSO Operation – Case Study

This comprehensive case study delves into the intricate dynamics of deepwater mooring systems, specifically focusing on Floating Production Storage and Offloading (FPSO) operations. Our investigation centers on the Anoa Natuna FPSO, situated in the Arafura Sea. We examine how varying fairlead positions, employing a 4x3 chain configuration, influence structural integrity, operational stability, and fatigue damage. The research meticulously analyzes the response of the FPSO to environmental forces, providing a detailed understanding of the vessel's behavior under different fairlead positions. The results showcase the vessel's stability, elucidate variations in its motion response, and highlight the effects of fairlead positioning on structural fatigue, offering valuable insights for safe and efficient deepwater FPSO operations.

Sensitivity assessment of the crack propagation behavior in welded stiffened panels

ABSTRACT Welded stiffened panels play an integral role in maintaining the strength, stability, and lightweight characteristics of marine vessels. The stiffeners also affect the service life of the structure under propagating cracks. In this context, properly quantifying the effect of various input parameters on the fatigue crack propagation behavior is crucial to accurately predict the service life. This paper quantifies the influence of relevant input parameters, covering geometric and mechanical properties, on the crack propagation and fatigue service life of welded stiffened panels. Three-dimensional finite element analysis, artificial neural networks, and an elastic-plastic crack advancement rule are integrated to predict the crack propagation. Variance-based sensitivity analysis is conducted to evaluate the effect of variability in the considered input parameters on the variance of the fatigue service life of these panels. It was found that neglecting the uncertainties associated with the geometric parameters can lead to unconservative estimates of the fatigue reliability.