Stable flow-induced expression of KLK10 inhibits endothelial inflammation and atherosclerosis

Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (Klk10, a secreted serine protease) as a flow-sensitive gene in mouse arterial endothelial cells, but its role in endothelial biology and atherosclerosis was unknown. Here, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo& mouse models and in vitro studies with cultured endothelial cells (ECs). Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated Klk10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced permeability dysfunction and inflammation in human artery ECs (HAECs), as determined by NFkB activation, expression of vascular cell adhesion molecule 1 (VCAM1) and intracellular adhesion molecule 1 (ICAM1), and monocyte adhesion. Further, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of Klk10-expressing plasmids inhibited atherosclerosis in Apoe-/- mice. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques. KLK10 is a flow-sensitive endothelial protein that serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor.

Integrated Approach to Maximize Production and Improve HSE

Slugging is an ongoing flow assurance risk in some of the ADNOC Onshore production systems, leading to difficulty in operations, inefficiencies, integrity and HSE concerns. For example stagnant water increases the risk of pipeline corrosion, especially with increased levels of H2S and CO2, potentially leading to leaks, pressure rating downgrading and reduction in the overall system capacity. With more reservoirs being under different schemes of secondary and tertiary recovery (WI, WAG, EOR – CO2, etc.), slugging in wells and transfer lines is expected to continue to be a challenge for the efficient and safe production operations across the entire ADNOC Onshore. This paper summarizes an integrated approach to understand the underlying causes of slugging in an onshore production system, reviews the current slug mitigation philosophy and proposes a stepwise approach to improve performance of the system, leading to production acceleration, improved profitability, efficiency and HSE performance. The system under investigation is experiencing slugging in the Transfer Line (TL) leading to liquid surges in the first stage separator (SEP) located at the Central Facilities. The slugging in the Transfer Line is attributable to a combination of wells and terrain induced slugging, and not so much to the hydrodynamic effects of the multiphase flow. In the current slug management philosophy, the pressure (RP) recorded at the TL receiver location is used in an algebraic formula to calculate a level set-point (LSP) that, in relation to the actual oil level in the separator (SEP), is used to act on the Surge Control Valve (SCV) located at the separator inlet. When the LSP is below the actual oil level in the separator, the SCV is tripped to 30% opening. The RP signal acts as a tell-tale sign of the incoming slug. In an initial phase, the system performance is evaluated using real time data available in the Control Room and offices. The initial data driven approach is complemented by complex dynamic multiphase modeling efforts. The models are used for further insights into the system behavior under different operational conditions, with a focus on identifying a more stable operating envelope, where the effects of slugging are mitigated while the production levels are maintained or increased. The focus on this paper is on the interface between the Transfer Line (TL) and inlet separator (SEP), including the Slug Control Valve (SCV). Results indicate a more stable flow regime is achieved at higher fluid velocities in the TL, where the RM pressure is increased to 35 barg from the current 29 barg. (N.B. The 35 barg is the maximum TL operating pressure, as identified in a separate study, and limited by the current HIPPS setpoints. The corresponding increase in production capacity is up to 10,000 bopd, thus accelerating the cumulative oil by up to 3.5 MMBBl / year, and accelerating revenue by up to USD 180 MM / year). However, in the current control scheme, operation at 35 bar is limited by the SCV characteristic and control scheme. To mitigate the problem, a staggered approach is proposed. A reduction in SCV tripping frequency is expected to be achieved in the short term, by modifying the algebraic equation that govern the SCV actions. A slight increase in the B factor by 2.5% is expected to reduce the SCV tripping frequency by up to 10%. Reduction in SCV tripping frequency will further reduce the mechanical stress on the valve and associated piping, thus reducing the risk of structural damage of the system. Also, it will allow for starting to increase the fluid velocities and move towards a more stable flow regime and reduced water holdup in the pipeline (reduced corrosion risk). Additional increase in fluid velocities appears to be limited by the SCV characteristic. In the current control scheme the pressure drop across the valve becomes sizeable at higher flowrates, leading to frequent tripping. As a longer term measure, increasing the SCV capacity is expected to facilitate operation of the system at higher fluid velocities, thus reducing the slugging, mechanical stress and corrosion risk in the TL. As slugging will continue to be a challenge to safe and efficient operations across ADNOC Onshore, it is important to develop in house the ability to understand the underlying causes for such flow instabilities, identify mitigation and optimization workflows. This paper demonstrates that a combination of data driven analytics and integrated physics based modeling, carried out in an integrated approach by a mixed team of subsurface and surface engineers, can help understanding the system behavior under slugging conditions and identify opportunities to improve production system efficiency and profitability, while operating within a safer envelope.

On state instability of the bi-stable flow past a notchback bluff body

The wake of a notchback Ahmed body presenting a bi-stable nature is investigated by performing wind tunnel experiments and large-eddy simulations. Attention is confined to the Reynolds number ( $Re$ ) influence on the wake state instability within $5\times 10^{4}\leq Re \leq 25\times 10^{4}$ . Experimental observations suggest a wake bi-stability with low-frequency switches under low $Re$ . The wake becomes ‘tri-stable’ with the increase of $Re$ with the introduction of a new symmetric state. The higher presence of the symmetric state can be considered as a symmetrization of the wake bi-stability with an increasing $Re$ . The wake symmetry under high $Re$ attributed to the highly frequent switches of the wake is extremely sensitive to small yaw angles, showing the feature of bi-stable flows. The wake asymmetry is confirmed in numerical simulations with both low and high $Re$ . The wake asymmetries are indicated by the wake separation, the reattachment and the wake dynamics identified by the proper orthogonal decomposition. However, the turbulence level is found to be significantly higher with a higher $Re$ . This leads to a higher possibility to break the asymmetric state, resulting in highly frequent switches showing symmetry.

The impact of e-commerce on the sustainable development: case of Ukraine, Poland, and Austria

The COVID-19 pandemic dramatically and irreversibly transformed global e-commerce trends. The process of internationalization has been slowed down considerably, the level of globalization impact has decreased, that, consequently, has led to a strong lag in the development of some countries. The aim of the study is to determine the nature of e-commerce socio and economic effects in Ukraine, Poland, and Austria. For analysis, a modern mathematical apparatus was used – the Cobb-Douglas model and the Markov chain methodology. The study shows a significant positive impact of e-commerce on employment and GDP in the three countries. Thus, with an increase in investment levels in e-commerce and ICT by 1%, employment in Ukraine will increase by 0.02%, in Poland – by 0.14%, and in Austria – by 0.17%. Similarly, Ukraine’s GDP may rise by 0.07%, Poland’s – by 0.2% and Austria’s – by 0.07%. Therefore, a stable flow of investment in e-commerce will provide countries with a faster way out of the crisis, create more jobs and opportunities for business development.

Stable Flow-induced Expression of KLK10 Inhibits Endothelial Inflammation and Atherosclerosis

Introduction: Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (dflow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (KLK10, a secreted serine protease) as a flow-sensitive gene in arterial endothelial cells, but its role in endothelial biology and atherosclerosis was unknown. Methods and Results: Here, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo mouse models and in vitro studies with cultured endothelial cells (ECs). Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated KLK10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced inflammation and permeability dysfunction in human artery ECs (HAECs). Further, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of KLK10- expressing plasmids inhibited atherosclerosis in ApoE-/- mice. Studies using pharmacological inhibitors and siRNAs revealed that the anti-inflammatory effects of KLK10 were mediated by a Protease Activated Receptors (PAR1/2)-dependent manner. However, unexpectedly, KLK10 did not cleave the PARs. Through a proteomics study, we identified HTRA1 (High-temperature requirement A serine peptidase 1), which bound and cleaved KLK10. Further, siRNA knockdown of HTRA1 prevented KLK10's anti-inflammatory and barrier protective function in HAECs, suggesting that HTRA1 regulates KLK10 function. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques. Conclusion: KLK10 is a flow-sensitive endothelial protein and, in collaboration with HTRA1, serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor.

Flow pulsation reduction of a single-piston piezoelectric pump based on elastic cavity group and unloading valve

A piston piezoelectric (PZT) pump has many advantages for the use of light actuators. How to deal with the contradiction between the piston amount and oil delivery quality is an essence when designing the pump. In order to depress the pressure pulsation and flow pulsation in a single-piston PZT pump, a two-stage attenuator is proposed. It involves an elastic cavity group and an unloading valve. Unsteady flow inside the pump is numerically calculated and analyzed to reveal its delivery characteristic in the whole pumping cycle. The distributing process of the passive valves is obtained through the dynamic mesh technique. Influences of key design and operation factors on the delivery performance of the pump are analyzed. The results indicate that the flexible cavity group and the unloading valve arranged at the delivery port can reduce the flow pulsation by 45%. The design can effectively provide stable flow for the actuator in a certain frequency range.

Study of the structural and mechanical properties of biopolymers in order to obtain a capsule-type product

The article presents some theoretical and experimental data on promising technologies, namely, the processes of obtaining artificial food materials such as spheres or "caviar". They are derived from molecular processes: solubilization, spherification, etc. Possible applications are the food industry, the food service industry, biotechnology, and others. There are different features of obtaining artificial products based on alginates. The peculiarities of the alginate structuring are that it is possible to form a gel layer-encapsulation and gel formation over the entire thickness of the product due to the special chemical properties of the fixing salt. Based on the theory of the molecular structure of biopolymers, molecular technologies for the synthesis of artificial food products were developed, using the example of molecular "caviar". As a result of our own experiments, we obtained a satisfactory encapsulated product from a biopolymer crosslinked with Ca2+ salts in terms of organoleptic and physico-chemical properties. The colloidal biopolymer solution for forming "eggs" was characterized using the method of rotational viscometry, which showed the features of the sodium alginate solution as a structured thixotropic material, which is characterized by" difficulty " of shear at low speeds of rotation of the viscometer rotor. Further on the rheogram, such material exhibits a predicted relatively stable flow. As a result, it can be used to produce semi-finished products of a given shape and texture as a food semi-finished product or product. If the technology is refined, it is possible to use colloidal systems based on alginates and other biopolymers in biotechnology, including the cultivation of microorganisms of various taxonomic groups.