Vessel Stability Research Articles

Dynamic Interactions of a Cable-Laying Vessel with a Submarine Cable during Its Landing Process

The rapid development of offshore electricity grid construction has led to a great demand for submarine cable deployment. In this study, a numerical model is established based on the commercial software ANSYS-AQWA to investigate the dynamic interactions between a cable-laying vessel and a submarine cable during its landing process, which has not yet been reported and is critical to the safety of the cable. The numerical model was validated by an experimental test on the mooring stability of a vessel conducted in a wave tank. The effects of the cable length, the current velocity, the incident wave, and the wind direction on vessel stability and the tensions in the mooring lines and cable were investigated. When the cable length is short, the submarine cable acts as a mooring cable that can stabilize the hull, but it is not safe to apply force to the submarine cable. At the same time, an increase in the current speed also increases the tensile force of the submarine cable. The influence of different incident wave directions and wind directions on the stability and tension of ships in mooring lines and cables was studied, and the most unfavorable environmental conditions for submarine cable laying were determined under different environmental conditions.

Влияние перепроектирования конструкции корпуса судна под аддитивное производство на характеристики остойчивости

The article considers the problem of changing vessel stability characteristics due to the optimization of the hull design and the increase in mass due to the choice of polylactide as a hull material for manufacturing by additive technologies. The stability characteristics of a small vessel hull of the "Nerl" kayak type was calculated in two approximations: in the first - for a standard prototype vessel made of fiberglass weighing 35 kg, in the second - for a project under development for additive manufacturing using polylactide weighing 70 kg. Stability was calculated according to the requirements of the Russian River Register using the FreeShip+ and Hydromax software. It was found that not all stability characteristics of the prototype vessel (maximum restoring moment arm) meet the requirements of this register, while for the projected vessel of additive manufacturing all requirements are met. The results of the study may be useful to shipbuilding enterprises planning to organize manufacturing products by 3D printing.

CD146+ Pericytes Subset Isolated from Human Micro-Fragmented Fat Tissue Display a Strong Interaction with Endothelial Cells: A Potential Cell Target for Therapeutic Angiogenesis.

Pericytes (PCs) are mesenchymal stromal cells (MSCs) that function as support cells and play a role in tissue regeneration and, in particular, vascular homeostasis. PCs promote endothelial cells (ECs) survival which is critical for vessel stabilization, maturation, and remodeling. In this study, PCs were isolated from human micro-fragmented adipose tissue (MFAT) obtained from fat lipoaspirate and were characterized as NG2+/PDGFRβ+/CD105+ cells. Here, we tested the fat-derived PCs for the dispensability of the CD146 marker with the aim of better understanding the role of these PC subpopulations on angiogenesis. Cells from both CD146-positive (CD146+) and negative (CD146−) populations were observed to interact with human umbilical vein ECs (HUVECs). In addition, fat-derived PCs were able to induce angiogenesis of ECs in spheroids assay; and conditioned medium (CM) from both PCs and fat tissue itself led to the proliferation of ECs, thereby marking their role in angiogenesis stimulation. However, we found that CD146+ cells were more responsive to PDGF-BB-stimulated migration, adhesion, and angiogenic interaction with ECs, possibly owing to their higher expression of NCAM/CD56 than the corresponding CD146− subpopulation. We conclude that in fat tissue, CD146-expressing cells may represent a more mature pericyte subpopulation that may have higher efficacy in controlling and stimulating vascular regeneration and stabilization than their CD146-negative counterpart.

Notch Signaling in Vascular Endothelial and Mural Cell Communications.

The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. It is known that vascular endothelial cells and mural cells interact to regulate vessel formation, cell maturation, and stability of the vascular network. Defective endothelial-mural cell interactions are a common phenotype in diseases characterized by impaired vascular integrity. Further refinement of the role of Notch signaling in the vascular junctions will be critical to attempts to modulate Notch in the context of human vascular disease. In this review, we aim to consolidate and summarize our current understanding of Notch signaling in the vascular endothelial and mural cells during development and in the adult vasculature.

Modeling Structural Adaptation and Pruning of Blood Vessels Connected in Parallel: Implications for Control of Capillary Density

Blood vessels are capable of structural adaptation in response to changes in physiological conditions including blood flow rates and oxygen levels. A theoretical model is developed to simulate the changes in diameter of two neighboring microvessels connected in parallel. The model is used to examine the conditions leading to stability of this configuration or to pruning of one of the vessels. When two adjacent vessels supply blood to the same region of tissue, structural adaptation is governed by two competing mechanisms: the elimination of a redundant vessel to minimize the energy cost of sustaining blood flow, and the stabilization of both vessels to distribute oxygen more broadly. Therefore, the behavior of the system depends on both the strength of the metabolic oxygen demand from the tissue and the distance between the vessels. In the simulation, the diameters of two vessels connected in parallel vary based on the mechanical shear and pressure forces acting on the endothelial wall, an oxygen‐dependent metabolic stimulus, and a constant tendency for vessels to shrink. The distribution of oxygen throughout the tissue is calculated using a Green’s function method. An initial condition is assumed in which the vessels have near equal diameters. The strength of the metabolic response needed to stabilize both vessels with equal diameters is determined as a function of the distance between the vessels. In cases where equal diameters are unstable, the condition for pruning of one of the vessels, defined as a diameter below 3 μm, is found. For a given spacing between the vessels, two critical values are found for the strength of the metabolic signal. Above the higher critical value, the two vessels are stable with equal diameters. Between the critical values, the two vessels approach a state with unequal diameters. The ability of vessels to stabilize at unequal vessel diameters may contribute to the heterogeneity of physiological vasculatures. Below the lower critical value, one of the vessels is pruned. Under the assumed conditions, both critical values decrease with increasing spacing up to about 70 μm, and are independent of spacing for larger distances. For a given strength of the metabolic signal, smaller spacing favors pruning of one of the vessels because their proximity allows one vessel to meet the metabolic demand of the tissue. The pruning of closely spaced vessels may contribute to the control of capillary density in tissues such as skeletal muscle. Further work is needed to determine whether similar behavior occurs in arrays of multiple capillaries as in muscle vasculature.

Endothelial ETS1 inhibition exacerbate blood–brain barrier dysfunction in multiple sclerosis through inducing endothelial-to-mesenchymal transition

Blood–brain barrier (BBB) dysfunction has been recognized as an early pathological feature and contributing factor in multiple sclerosis. Endothelial-to-mesenchymal transition is a process associated with endothelial dysfunction leading to the disruption of vessel stability and barrier function, yet its functional consequence in multiple sclerosis remains unclear. Here, we demonstrated that endothelial-to-mesenchymal transition accompanied the blood–brain barrier dysfunction in several neurological disorders, especially in multiple sclerosis. The activity of transcription factor ETS1, which is highly expressed in endothelial cells (ECs) and responded to an inflammatory condition, is suppressed in the central nervous system (CNS) ECs in MS and its animal model experimental autoimmune encephalomyelitis. We identify ETS1 as a central regulator of endothelial-to-mesenchymal transition (EndMT) associated with the compromise of barrier integrity. These phenotypical and functional alterations can further induce high permeability, immune infiltration, and organ fibrosis in multiple sclerosis, thus promoting disease progression. Together, these results demonstrate a functional role of EndMT in blood–brain barrier dysfunction and propose ETS1 as a potential transcriptional switch of EndMT to target the development of multiple sclerosis.

Analysis of Domestic Fishing Vessel Stability Regulations and Research on their Criteria Amendment for Improvement

Analysis of Domestic Fishing Vessel Stability Regulations and Research on their Criteria Amendment for Improvement

Excess load on ships and its effects on stability performance in Nigerian waterways

This research has been carried out to examine the impact of excess shipload on ship performance and stability. The objectives are to analyse the trend of sinking ships in Nigeria occasioned to ship excess load. Secondly, to examine the relationship between load size and ship stability and identify the various factors responsible for ship instability. Data were gathered from operators in the maritime industry using structured questionnaires and interviews as data collection instruments. Four significant stakeholders that can provide information based on their involvement across three strata of management, operation and general cadre were sampled. Pearson Moment Correlation technique has been used to examine the relationship between load size and ship stability, and Analysis of Variance-one was used to identify the various factors responsible for ship instability. The Pearson Moment Correlation technique analysis shows a significant relationship between load size and stability. The analysis of variance revealed that "hogging and sagging" is the most crucial factor among the factors identified for ship instability. It has the highest value of F-ratio of 17.837 with a significance at p<0.05. The research concluded that resultant accidents from the instability of vessels are caused majorly by hogging and sagging of vessels, and notably, the occurrence is much in riverine areas in Nigeria. Loading the vessel has a relationship with the vessel's stability, as depicted from the analysis in this research. Recommendations on how to enhance stability through boat construction, shipbuilding, loading and passenger's use of life jackets, among others were made.

Dynamic stability of vessels with a suspended load

The transverse stability of a sample vessel with a suspended load in regular beam waves is investigated and quantified. Incorporating several series of experimental and numerical model tests in calm water and in waves, three aspects of influence from the suspended load are identified: GM (metacentric height) variation, lever effects, and swinging pull. As from the result of scale-model tests, a suspended load of 0.66% (nondimensionalised by the model's mass displacement) alters the GM value by about 2% corresponding to a change of the roll natural period of about 4%. In calm water, the suspended load alone at a position with the longest lever stretching out at side heels the model up to 8° and reduces the GZ (righting lever) value by about 40%. In waves, the suspended load with a longer connecting ‘rope’ does not seem to increase or decrease the roll amplitude of the vessel as opposed to the one with a shorter ‘rope’. But it changes the behaviour of the roll motion – from regular sinusoidal-like roll to irregular behaviour at higher wave excitation frequencies but not for lower ones.

Adaptive event-triggered global asymptotic full-state stabilization of under-actuated surface vessels with unknown model parameters

This paper studies an adaptive event-triggered controller (ETC) for global asymptotic full-state stabilization of under-actuated surface vessels (USVs) with unknown model parameters. Applying an inner–outer loop structure, desired linear and angular velocities regarded as control inputs of the outer loop subsystem are designed free of any model parameters, such that the outer loop subsystem is globally asymptotically stabilized. The generated desired velocities are assigned as the reference signals for the inner loop subsystem, thereby the actual adaptive ETC is designed to track the reference velocities and to compensate for the effect of the unknown model parameters. The proposed scheme guarantees global asymptotic stability of the closed-loop system proved by the Lyapunov-based analysis. The switching threshold event-triggering mechanism (SWT-ETM) is introduced to alleviate the system’s burden requiring less resources for communication and actuator execution. Simulation results show the effectiveness of the proposed method.

NLGP regulates RGS5-TGFβ axis to promote pericyte-dependent vascular normalization during restricted tumor growth.

Altered RGS5-associated intracellular pericyte signaling and its abnormal crosstalk with endothelial cells (ECs) result chaotic tumor-vasculature, prevent effective drug delivery, promote immune-evasion and many more to ensure ultimate tumor progression. Moreover, the frequency of lethal-RGS5high pericytes within tumor was found to increase with disease progression, which signifies the presence of altered cell death pathway within tumor microenvironment(TME). In this study, we checked whether and how neem leaf glycoprotein (NLGP)-immunotherapy-mediated tumor growth restriction is associated with modification of pericytes' signaling, functions and its interaction with ECs. Analysis of pericytes isolated from tumors of NLGP treated mice suggested that NLGP treatment promotes apoptosis of NG2+ RGS5high -fuctionally altered pericytes by downregulating intra-tumoral TGFβ,along with maintenance of more matured RGS5neg pericytes. NLGP-mediated inhibition of TGFβ within TME rescues binding of RGS5 with Gαi and thereby termination of PI3K-AKT mediated survival signaling by downregulating Bcl2 and initiating pJNK mediated apoptosis. Limited availability ofTGFβalso prevents complex-formation between RGS5 and Smad2 and rapid RGS5 nuclear translocation to mitigate alternate immunoregulatory functions of RGS5high tumor-pericytes. We also observed binding of Ang1 from pericytes with Tie2 on ECs in NLGP-treated tumor, which support re-association of pericytes with endothelium and subsequent vessel stabilization. Furthermore, NLGP-therapy- associatedRGS5 deficiency relieved CD4+ and CD8+ T cells from anergy by regulating 'alternate-APC-like' immunomodulatory characters of tumor-pericytes. Taken together, present study described the mechanisms of NLGP's effectiveness in normalizing tumor-vasculature by chiefly modulating pericyte-biology and EC-pericyte interactions in tumor-host to further strengthen its translational potential as single modality treatment.

Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury.

The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure. To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later. Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

Key Role of Astrocytes in Postnatal Brain and Retinal Angiogenesis.

Angiogenesis is a key process in various physiological and pathological conditions in the nervous system and in the retina during postnatal life. Although an increasing number of studies have addressed the role of endothelial cells in this event, the astrocytes contribution in angiogenesis has received less attention. This review is focused on the role of astrocytes as a scaffold and in the stabilization of the new blood vessels, through different molecules release, which can modulate the angiogenesis process in the brain and in the retina. Further, differences in the astrocytes phenotype are addressed in glioblastoma, one of the most devastating types of brain cancer, in order to provide potential targets involved in the cross signaling between endothelial cells, astrocytes and glioma cells, that mediate tumor progression and pathological angiogenesis. Given the relevance of astrocytes in angiogenesis in physiological and pathological conditions, future studies are required to better understand the interrelation between endothelial and astrocyte signaling pathways during this process.

Antiplatelet Agents Affecting GPCR Signaling Implicated in Tumor Metastasis.

Metastasis requires that cancer cells survive in the circulation, colonize distant organs, and grow. Despite platelets being central contributors to hemostasis, leukocyte trafficking during inflammation, and vessel stability maintenance, there is significant evidence to support their essential role in supporting metastasis through different mechanisms. In addition to their direct interaction with cancer cells, thus forming heteroaggregates such as leukocytes, platelets release molecules that are necessary to promote a disseminating phenotype in cancer cells via the induction of an epithelial–mesenchymal-like transition. Therefore, agents that affect platelet activation can potentially restrain these prometastatic mechanisms. Although the primary adhesion of platelets to cancer cells is mainly independent of G protein-mediated signaling, soluble mediators released from platelets, such as ADP, thromboxane (TX) A2, and prostaglandin (PG) E2, act through G protein-coupled receptors (GPCRs) to cause the activation of more additional platelets and drive metastatic signaling pathways in cancer cells. In this review, we examine the contribution of the GPCRs of platelets and cancer cells in the development of cancer metastasis. Finally, the possible use of agents affecting GPCR signaling pathways as antimetastatic agents is discussed.

Constitutive relation, limited stretchability, and stability of residually stressed Gent materials

We exactly determine the constitutive relation and the strain energy function for an initially stressed material that completely follows the characteristics of the Gent model in the virtual stress-free reference. The parameters of the deduced models are expressed as functions of initial stress. Quite interestingly, we observe that when the stiffening parameter approaches infinity, the present model assumes the form of the (existing) initially stressed neo-Hookean model. We apply the developed model to perform the inflation test for a residually stressed cylinder when the axial stretch is constrained or unconstrained. The residually stressed Gent model does exhibit limited stretchability and rapid strain-stiffening in large strain. Additionally, when the axial stretch unconstrained, the inflation can exhibit either a stable characteristics, or a snap-through instability. However, the maximum allowable stretch, which is generally a function of stiffening parameter only, depends considerably on the residual stress. Furthermore, the stability of inflating the cylinder with unconstrained axial stretch also depends strongly on residual stress. Residual stress influences the critical stiffening parameter, which completely determines the stability and which is a constant for the Gent model. We observe that residual stress improves the stability and pressure-bearing capacity of a pressure vessel. Since this is an exact model, the present results should hold accurately whenever the material has the Gent model characteristics in a stress-free state.

Importance of Pericytes in the Pathophysiology of Cerebral Ischemia.

Various cell types contribute to pathological changes observed in the brain following cerebral ischemia. Pericytes, as a component of neurovascular unit (NVU) and blood brain barrier (BBB), play a key role for cerebral blood flow control and regulation of vessel permeability. It was shown that pericytes can control cerebral blood flow at the level of capillaries, by their contractile property. Their role in BBB development and maintenance are crucial for guidance of brain vessel development, new vessel formation and stabilization of the newly formed vessels. Additionally, they can contribute to inflammation in response to inflammatory stimuli and can differentiate to various cell types by their multipotent differentiation properties. This cell type which is intimately associated with cerebral circulation also plays important roles during cerebral ischemia. Here, we review the properties and physiological functions of pericytes, how these functions change during ischemia to affect the pathophysiology of ischemic stroke and post stroke cognitive impairment. Pericytes are a neglected cell type and they are not unambiguously characterized which in turn led to contradictory findings in the literature. Clear characterization of pericytes by current methods will help better understanding of their role in the pathophysiology of stroke. With the information gained from these efforts it will be possible to develop pericyte specific therapeutic targets and achieve important breakthroughs in clinical recovery in ischemic stroke treatment.

Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition

Vascular mural cells (vMC) play an essential role in the development and maturation of the vasculature by promoting vessel stabilization through their interactions with endothelial cells (EC). Whether endothelial metabolism influences mural cell recruitment and differentiation is unknown. Here, we show that the oxidative Pentose Phosphate Pathway (oxPPP) in EC is required for establishing vMC coverage of the dorsal aorta (DA) during early vertebrate development in zebrafish and mice. We demonstrate that laminar shear stress (LSS) and blood flow maintain oxPPP activity, which, in turn, promotes Elastin (Eln) expression in blood vessels through production of ribose-5-phosphate (R5P). Eln is both necessary and sufficient to drive vMC recruitment and maintenance when the oxPPP is active. In summary, our work demonstrates that endothelial cell metabolism regulates blood vessel maturation by controlling vascular matrix composition and vMC recruitment.

Loss of Endothelial Cell Matrix Metalloproteinase 14 Reduces Melanoma Growth and Metastasis by Increasing Tumor Vessel Stability

Matrix metalloproteinase (MMP) 14 belongs to a large family of zinc-dependent endopeptidases and plays a critical role in skin physiological and pathological processes. Complete loss of the protease resulted in severe developmental defects leading to early death. However, because of the premature death of the mice, the functional significance for endothelial cell (EC) expression of MMP14 in skin physiology and pathology invivo after birth is yet unknown. Using a mouse model with constitutive EC-specific deletion of Mmp14 (Mmp14EC‒/‒), we showed that mice developed and bred normal, but melanoma growth and metastasis were reduced. Although vascularity was unaltered, vessel permeability was decreased. Deletion of MMP14 in ECs led to increased vessel coverage by pericytes and vascular endothelial-cadherin expression in mice invivo and invitro but not in human ECs. Endothelial nitric oxide synthase expression and nitric oxide production were significantly reduced in Mmp14EC‒/‒ ECs and MMP14-silenced human umbilical vein ECs. A direct correlation between endothelial nitric oxide synthase and MMP14 expression was detected in intratumoral vessels of human malignant melanomas. Altogether, we show that endothelial MMP14 controls tumor vessel function during melanoma growth. These data suggest that EC-derived MMP14 direct targeting alone or with vascular stabilizing agents may be therapeutically crucial in inhibiting melanoma growth and metastasis.

ETS-Related Gene Activation Preserves Adherens Junctions and Permeability in Microvascular Endothelial Cells.

ERG (ETS-related gene) is a member of the ETS (Erythroblast-transformation specific) family of transcription factors abundantly present in vascular endothelial cells. Recent studies demonstrate that ERG has important roles in blood vessel stability and angiogenesis. However, it is unclear how ERG is potentially involved in microvascular barrier functions and permeability. A wide variety of diseases and clinical conditions including trauma-hemorrhagic shock and burn injury are associated with microvascular dysfunctions, which causes excessive microvascular permeability, tissue edema and eventually, multiple organ dysfunction and death. The main purpose of this study was to determine the specific role of ERG in regulating microvascular permeability in human lung microvascular endothelial cells (HLMEC) and to evaluate if exogenous ERG will protect the barrier. The HLMECs were grown on Transwell inserts as monolayers and were transfected with ERG CRISPR/cas9 knockdown plasmid, ERG CRISPR activation plasmid, recombinant ERG protein or their respective controls. Recombinant vascular endothelial growth factor (VEGF) was used as an inducer of permeability for evaluating the effect of ERG activation on permeability. Changes in barrier integrity and permeability were studied using monolayer permeability assay and immunofluorescence of adherens junction proteins (VE-cadherin and β-catenin) respectively. CRISPR/cas9-based ERG knockdown as well as VEGF treatment induced monolayer hyperpermeability, VE-cadherin, and β-catenin junctional relocation and cytoskeletal F-actin stress fiber formation. CRISPR based ERG activation and recombinant ERG transfection attenuated VEGF-induced monolayer hyperpermeability. ERG activation preserved the adherens junctions and cytoskeleton. These results demonstrate that ERG is a potent regulator of barrier integrity and permeability in human lung microvascular endothelial cells and endogenously or exogenously enhancing ERG provides protection against barrier dysfunction and hyperpermeability.

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device.

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR.