Stress Migration Research Articles

Influence of convective air-cooling on hydrostatic stress induced atomic migration characteristics of a thin Cu-line with Cu-Sn IMC under a DC field

The present paper addresses the influential effect of convective air cooling on the stress-migration induced atomic flux divergence in a copper interconnect/line with copper-tin intermetallic compound under a DC field of high current density. Three identical thin copper lines, namely, a pure Cu line, a copper line with Cu-Sn intermetallic and a line with lead-free solder-joint are considered as the basis for conducting the present investigation of current-induced atomic migration. The associated two-dimensional fields of electric potential, temperature, thermal stress as well as atomic distributions are obtained by solving the relevant coupled multi-physics problems using computer-based numerical schemes. Finally, the stressmigration induced atomic-flux divergence characteristics of three Cu lines are compared with those of electromigration as a function of cooling air velocity under natural and forced convection to quantify the relative contribution of stress migration in the perspective of overall atomic diffusion.

Stress Transfer and Migration of Earthquakes from the Western Pacific Subduction Zone Toward the Asian Continent

Stress Transfer and Migration of Earthquakes from the Western Pacific Subduction Zone Toward the Asian Continent

Paxillin controls actin stress fiber formation and migration of vascular smooth muscle cells by directly binding to the active Fyn

Rho-kinase (ROK)-mediated migration of vascular smooth muscle cells plays a crucial role in cardiovascular diseases. Previously we demonstrated Fyn tyrosine kinase as an upstream molecule of ROK to mediate actin stress fiber formation that plays an important role in cell migration, but the molecular mechanism between the two kinases was unclear. To discover a novel signaling molecule that exists between Fyn and ROK, we identified paxillin acting downstream of the active Fyn by combined use of pulldown assay and mass spectrometry. Immunofluorescence staining confirmed co-localization of Fyn and paxillin at the ends of actin stress fibers in human coronary artery smooth muscle cells (CASMCs). Surface plasmon resonance assay demonstrated direct binding between constitutively active Fyn (CA-Fyn) and N-terminus of paxillin (N-pax). The sphingosylphosphorylcholine (SPC)-induced ROK activation, actin stress fiber formation and cell migration were inhibited by paxillin knockdown, which were rescued by full-length paxillin (FL-pax) but not N-pax. N-pax co-localized with CA-Fyn at the cytosol and overexpression of N-pax inhibited the SPC-induced actin stress fiber formation and cell migration, indicating that the direct binding of FL-pax and CA-Fyn at the ends of actin stress fibers is essential for the ROK-mediated actin stress fiber formation and cell migration. Paxillin, as a novel signalling molecule, mediates the SPC-induced actin stress fiber formation and migration in human CASMCs via the Fyn/paxillin/ROK signalling pathway by direct binding of active Fyn.

Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH), group 1 pulmonary hypertension (PH), is a fatal disease that is characterized by vasoconstriction, increased pressure in the pulmonary arteries, and right heart failure. PAH can be described by abnormal vascular remodeling, hyperproliferation in the vasculature, endothelial cell dysfunction, and vascular tone dysregulation. The disease pathomechanisms, however, are as yet not fully understood at the molecular level. Purinergic receptors P2Y within the G-protein-coupled receptor family play a major role in fluid shear stress transduction, proliferation, migration, and vascular tone regulation in systemic circulation, but less is known about their contribution in PAH. Hence, studies that focus on purinergic signaling are of great importance for the identification of new therapeutic targets in PAH. Interestingly, the role of P2Y2 receptors has not yet been sufficiently studied in PAH, whereas the relevance of other P2Ys as drug targets for PAH was shown using specific agonists or antagonists. In this review, we will shed light on P2Y receptors and focus more on the P2Y2 receptor as a potential novel player in PAH and as a new therapeutic target for disease management.

Comprehensive monitoring for rockburst at a pumped storage power station in northeast China

Rockburst is characterised by the wide occurrence areas and the long delayed time at a pumped storage power station in Heilongjiang province of China. For the study, a new method is proposed to identify the induced rockburst based on the combination of microseismic (MS) and electromagnetic radiation (EMR) monitoring methods. EMR monitoring method is introduced to make up for the shortcomings of the monitoring blind area caused by the propagation path of wave velocity during MS monitoring and a beneficial attempt is carried out for the comprehensive application of the two methods to monitor the rockburst. Firstly, a MS monitoring system is established around the underground powerhouse to recognize the propagation of micro-fracture during the deep excavation, while the typical five parameters including the frequency of the microseismic events, the total energy of daily events, energy index (EI), cumulative apparent volume (CAV) and microseismic signal b-value are analyzed to reveal the temporal and spatial evolution law of microseismic events. Secondly, an EMR monitoring system is also established near the MS events clusting area to study the characteristics of EMR produced from the fractured rock mass. The temporal and spatial variation of the two parameters including electromagnetic radiation intensity and pulse number are also analyzed and the distribution of higher values are compared with the geological structure. Finally, the correlation of electromagnetic signals, microseismic signals and local stress is studied based on theories of geophysics, electromagnetism and rock mechanics, and some credible results are obtained. Here are the following resluts: (1) The microseismic events are characterized by spatial clustering, and the joint action of the excavation disturbance and the weak structure body of the surrounding rock mass are the main factors for rockburst. The trend of sharp decrease of energy index and sudden increase of cumulative apparent volume generally indicates the occurrence of rockburst or macro-fracture. The magnitude of b value indicates that the rockburst failure type in the project belongs to fracture-slip rockburst. (2) The sudden change of electromagnetic radiation intensity in the fault fracture zone of the underground powerhouse can be used as the precursor information of rockburst or large-scale rupture events.(3) The micro-fracture activities revealed by EMR and MS methods are consistent in spatial distribution. The distribution of the peak values of electromagnetic radiation pulse number are basically consistent with the direction of the apparent stress migration disturbed by the field construction situation. So we can infer that it will play an important role to improve the accuracy of rockburst prediction based on the analysis of the multi-source singals.

Numerical analysis of the stress‐strain behaviour in statically determinate composite steel‐concrete beam after 100 years creep phenomena process using Volterra Integral Equations

AbstractThe paper presents a precise analysis of the stress‐strain behaviour due to creep in statically determinate composite steel‐concrete beam according to numerical method in comparison with EM method of Dischinger. The analysis is based on the results obtained by numerical solution with Volterra integral equations, derived for determining the redistribution of stresses in beam section between concrete plate and steel beam with respect to time “t”. The creep law of concrete, according EC2 provisions is used. On the basis of the theory of the viscoelastic body of Arutyunian– Trost‐Bažant it is analyzed the migration of stresses from concrete plate to steel beam using two independent Volterra integral equations of the second kind. The duration of the course of study was adopted 100 years. Developed method will allow soon be confronted methods for calculating the composite beams according to EC4 considering rheology of concrete, based on the reduced elastic modulus of concrete.

Elabela prevents angiotensin II-induced apoptosis and inflammation in rat aortic adventitial fibroblasts via the activation of FGF21-ACE2 signaling.

Apoptosis, inflammation, and fibrosis contribute to vascular remodeling and injury. Elabela (ELA) serves as a crucial regulator to maintain vascular function and has been implicated in the pathogenesis of hypertensive vascular remodeling. This study aims to explore regulatory roles and underlying mechanisms of ELA in rat aortic adventitial fibroblasts (AFs) in response to angiotensin II (ATII). In cultured AFs, exposure to ATII resulted in marked decreases in mRNA and protein levels of ELA, fibroblast growth factor 21 (FGF21), and angiotensin-converting enzyme 2 (ACE2) as well as increases in apoptosis, inflammation, oxidative stress, and cellular migration, which were partially blocked by the exogenous replenishment of ELA and recombinant FGF21, respectively. Moreover, treatment with ELA strikingly reversed ATII-mediated the loss of FGF21 and ACE2 levels in rat aortic AFs. FGF21 knockdown with small interfering RNA (siRNA) significantly counterbalanced protective effects of ELA on ATII-mediated the promotion of cell migration, apoptosis, inflammatory, and oxidative injury in rat aortic AFs. More importantly, pretreatment with recombinant FGF21 strikingly inhibited ATII-mediated the loss of ACE2 and the augmentation of cell apoptosis, oxidative stress, and inflammatory injury in rat aortic AFs, which were partially prevented by the knockdown of ACE2 with siRNA. In summary, ELA exerts its anti-apoptotic, anti-inflammatory, and anti-oxidant effects in rat aortic AFs via activation of the FGF21–ACE2 signaling. ELA may represent a potential candidate to predict vascular damage and targeting the FGF21–ACE2 signaling may be a promising therapeutic intervention for vascular adventitial remodeling and related disorders.

The use of bioabsorbable materials in orthopaedics

Bioabsorbable materials manufactured into fracture fixation devices dissolve slowly in the physiological environment, allowing gradual transfer of stresses to the healing tissue. This removes the need for implant removal surgery and reduces the risks of long term complications seen with bioinert materials, such as: stress shielding, migration, late infection and interference with imaging. When choosing a bioabsorbable material it is important to consider its mechanical properties and its biocompatibility. The three main categories of bioabsorbable materials available for use in trauma and orthopaedic surgery are: polymers, metals and ceramics. Bioabsorbable polymers are well established, with a number of commercially available orthopaedic devices including screws, bone anchors, sutures and drug delivery system. Polymers are limited in their capacity for use as bone fixation devices due to their weaker mechanical properties. Metals more closely align to the mechanical properties of bone. Bioabsorbable metal screws are commercially available but have unpredictable degradation profiles and are still largely in the early stages of development. To date, there have only been a few limited case series reporting their outcomes. Bioabsorbable ceramics have been used successfully as implant coatings and drug delivery systems. Their use in load bearing is limited by their brittle nature. The aim of this article is to provide an overview of the material science of bioabsorbable materials and to summarize their advantages, disadvantages, current clinical uses and potential future applications in orthopaedic surgery.

MiR-31-5p Promotes Oxidative Stress and Vascular Smooth Muscle Cell Migration in Spontaneously Hypertensive Rats via Inhibiting FNDC5 Expression.

Oxidative stress and the migration of vascular smooth muscle cells (VSMCs) are important for vascular remodeling in a variety of vascular diseases. miR-31-5p promotes cell migration in colorectal cancer cells but inhibits cell migration in renal cell carcinoma. However, whether miR-31-5p is involved in oxidative stress and VSMC migration remains unknown. This study shows the crucial roles of miR-31-5p in oxidative stress and VSMC migration, as well as underlying mechanisms. Experiments were carried out in primary VSMCs from aortic media of Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), as well as the A7r5 cell line. Oxidative stress was assessed by NADPH oxidase (NOX) expression, NOX activity, and reactive oxygen species (ROS) production. Cell migration was evaluated with a Boyden chamber assay and a wound healing assay. The miR-31-5p mimic and inhibitor promoted and attenuated oxidative stress and cell migration in the VSMCs of SHR, respectively. A dual-luciferase reporter assay indicated that miR-31-5p targeted the 3’UTR domain of FNDC5. The miR-31-5p level was raised and FNDC5 expression was reduced in the VSMCs of SHR compared with those of WKY. The miR-31-5p mimic reduced FNDC5 expression in the A7r5 cells and the VSMCs of both WKY and SHR, while the miR-31-5p inhibitor only increased FNDC5 expression in the VSMCs of SHR. Exogenous FNDC5 attenuated not only the oxidative stress and VSMC migration in SHR but also the roles of the miR-31-5p mimic in inducing oxidative stress and VSMC migration. These results indicate that miR-31-5p promotes oxidative stress and VSMC migration in SHR via inhibiting FNDC5 expression. The increased miR-31-5p and reduced FNDC5 in the VSMCs of SHR contribute to enhanced oxidative stress and cell migration.

Physics-based simulation of stress-induced and electromigration-induced voiding and their interactions in on-chip interconnects

A novel physics-based simulation model of electromigration (EM) and stress-migration (SM) induced degradation of electrical characteristics of on-chip interconnects is developed based on the coupled evolution of stress and voiding resolved by means of finite element simulations (FEM). The void evolution tracked with the phase field methodology, is linked with the evolution of EM/SM induced stress, which are generated in the metal segments by the interaction of the inelastic deformations due to divergences of atomic fluxes with the rigid confinement. Accounted atomic exchange between the metal and void surface removes a limitation on the void volume conservation. Developed simulation methodology allows to predict effects of the metal segment architecture and geometry, metal morphology and texture, as well as atomic diffusivities along the variety of migration venues on voiding-induced degradation of interconnect electrical conductance. Results of performed simulation indicate that the pre-existed stress induced voids (SIV) can evolve under the action of applied electric current and affect interconnect reliability. The developed physics-based simulation methodology can help to address reliability concerns by optimizing the properties of interconnect materials and modifying the physical design of the interconnect layouts in order to achieve EM resistant on-chip interconnects.

What process causes the slowdown of pressure solution creep

The slowdown of pressure solution creep has been thought to be caused by stress redistribution. This study presents a fresh view towards this creep behaviour. Basically, two rate-limiting mechanisms come into play amid pressure solution creep: (1) stress redistribution across expanding inter-granular contacts and (2) solute accumulation in the water film. Because non-hydrostatic dissolution occurs under open system conditions, solute accumulation in the water film is constrained by the ensuing solute transport process. Relying on the matter exchange across the contact surface boundary, the active processes in the voids, e.g., solute migration and deposition, affect pressure solution creep. Based upon the above, we sum up two requirements that have to be met for achieving chemical compaction equilibrium: (1) the Gibbs free energy of reaction, i.e., the driving force of non-hydrostatic dissolution process, gets depleted and (2) the concentration gradient between the water film and surrounding pore water vanishes.HighlightsThe slowdown of pressure solution creep is a combined result of stress migration across contacts and solute accumulation in the water film.Matter exchange with the surroundings inhibits solute accumulation in the water film.This article identifies two prerequisites that need to be fulfilled for achieving chemical compaction equilibrium.

Delivery of Cinnamic Aldehyde Antioxidant Response Activating nanoParticles (ARAPas) for Vascular Applications.

Selective delivery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators to the injured vasculature at the time of vascular surgical intervention has the potential to attenuate oxidative stress and decrease vascular smooth muscle cell (VSMC) hyperproliferation and migration towards the inner vessel wall. To this end, we developed a nanoformulation of cinnamic aldehyde (CA), termed Antioxidant Response Activating nanoParticles (ARAPas), that can be readily loaded into macrophages ex vivo. The CA-ARAPas-macrophage system was used to study the effects of CA on VSMC in culture. CA was encapsulated into a pluronic micelle that was readily loaded into both murine and human macrophages. CA-ARAPas inhibits VSMC proliferation and migration, and activates Nrf2. Macrophage-mediated transfer of CA-ARAPas to VSMC is evident after 12 h, and Nrf2 activation is apparent after 24 h. This is the first report, to the best of our knowledge, of CA encapsulation in pluronic micelles for macrophage-mediated delivery studies. The results of this study highlight the feasibility of CA encapsulation and subsequent macrophage uptake for delivery of cargo into other pertinent cells, such as VSMC.

1,2,3-Triazole tethered 1,2,4‑trioxane trimer induces apoptosis in metastatic cancer cells and inhibits their proliferation, migration and invasion

Artemisinin (ART) has been in use against different cancer cells and its derivatives and conjugates are more cytotoxic to iron-rich cancer cells. It is desirable to develop easily achievable synthetic 1,2,4-trioxanes having the same pharmacophore as that of ART. To explore more efficient compounds, a 1,2,3-triazole tethered 1,2,4‑trioxane trimer (4T) was synthesized and the anti-cancer effects of ART and 4T on MDA-MB-435 and MDA-MB-231 cells were investigated concerning regulation of osteopontin (OPN) expression, which is associated with cancer progression and malignancy. 1H NMR and 13C NMR, oxidative stress analysis, flow cytometry, western blot, Real-Time PCR, transfections, luciferase assay, cell viability, proliferation, migration and chemotactic invasion assays were used in this study. It was observed that the 4T induced apoptosis by inhibiting Bcl-2 (~0.6-fold) and cleavage of caspase-3 (intrinsic pathway) in these metastatic cancer cells, and also reduced colony formation, migration and invasion of these cancer cells. The treatment of 4T decreased the reduced glutathione level and increased the activities of glucose-6-phosphate dehydrogenase and glutathione reductase in the 4T treated cancer cells as compared to their respective controls. Further, the expression of OPN was diminished (~0.5-fold) by the 4T in these cell lines. It was also observed that the key mitogen-activated protein kinase pathway proteins, mitogen-activated protein kinase kinase1/2 (~1.8-fold) and extracellular signal-regulated kinase1/2 (~16-fold), were also activated following the treatment of the 4T. However, the phosphorylated c-Jun level, a component of activator protein-1, was significantly reduced in these cancer cells upon 4T treatment. Taken together, we hypothesize that 4T may be useful for controlling cancer progression and malignancy.

Abstract P729: Glp-1 Receptor Nitration Contributes to Brain Pericytes Dysfunction in Diabetes

Brain pericytes are unique, multi-functional mural cells located at the center of the NVU. Pericytes maintain the blood-brain barrier (BBB), promote vascular stability, and control the capillary blood flow. We have previously shown that diabetes alters the functions of the pericytes causing BBB damage and increased cerebrovascular pathological neovascularization. GLP-1 agonists, used in the management of diabetes, showed vascular protective effects. However, the underlying mechanisms are unclear. We hypothesis that GLP-1 receptor nitration contributes to the loss of pericytes functions in diabetes. Methods: Expression of GLP-1R in pericytes was assessed in the brain of control and diabetic mice and human brain microvascular pericytes using IHC, RT-PCR, and Western blots. BBB was assessed using Western blot/IHC of Occludin, VEGF, and MMPs gelatinase. Vascular integrity was determined by measuring cerebrovascular neovascularization indices (vascular density, tortuosity, and branching density). GLP-1R nitration was determined by immunoprecipitation and slot blotting. Results: In the present study, we provide novel evidence that the human brain pericytes express the GLP-1R (P<0.05). Moreover, diabetes increased GLP-1R expression in pericytes (P<0.05). Diabetes caused BBB dysfunction, loss of cerebrovascular integrity, and increased all pathological neovascularization indices (P<0.05). Diabetes increased nitration of GLP-1R. Treatment of pericytes with Exendin-4, a GLP-1 agonist, under diabetic conditions, decreased diabetes-induced inflammation, oxidative stress, and pericytes migration, which ameliorated the integrity of the BBB, and prevented the pathological neovascularization (P<0.05). Conclusion: Our results provide novel evidence that pericytes express GLP-1R and that diabetes increased receptor expression and nitration. Treatment of pericytes with GLP-1R agonist exerts neurovascular protective effects, making it a promising strategy in preventing diabetes- mediated cerebrovascular microangiopathy.

Electromigration behavior of silver thin film fabricated by electron-beam physical vapor deposition

Electromigration (EM) is considered as a serious issue that threatens the reliability of electronic packaging. For the long-term reliability of the application of pure silver thin films, it is important to investigate its EM effect; however, there are limited studies focused on this aspect. In this study, the EM of a silver thin film deposited on a glass substrate was examined at a current density of 8.89 × 105 A/cm2 and room temperature of 15 °C. During the EM test, the new phenomenon of the thin-thread silver structures with a unique direction was noted. To explain this, finite element analysis was applied to simulate the temperature and direction of the current flow. The effect of thermal and stress migration could be ignored in this experiment based on the temperature distribution results. The electron wind force played an important role in the formation of the thin-thread silver with nucleation structure following the direction and strength of the electron flow. By analyzing the failure location, melting was observed near the cathode since the generation of the thin-thread silver decreased the contact area for passing current. Finally, reducing the grain boundaries was proposed as an approach to improve the reliability of the pure silver sample, which is paramount for manufactures.

Multiparameter seismic behavior of castellated beam-to-column connections based on stress migration

This paper presents a study on the castellated beam-to-column connections with four regular hexagonal web openings and one solid web beam-to-column connection that considering the opening rate and whether there is a combination of floor slabs (composite action) while subjected to the cyclic loading. Furthermore, the initial geometric imperfection was carefully incorporated in the FE model and the models have been validated against published experimental results. There is a slightly different about 5% between FE and test results including ultimate bearing capacity and other hysteresis behaviors. Investigation of 38 FE models subjected to cyclic loading focuses in the variation regularity of the failure mode, plastic development, stress migration, and seismic behaviors under the coupling effect of various factors, including the composite action of the floor slab, opening rate, the distance from the first opening to the face of the column, depth-to-thickness ratio of the web, and opening spacing. It is found that the composite action can improve the stress distribution around the first opening and raise the bearing capacity and ductility of the connections to a certain extent. Further, when the opening rate is either smaller than 0.5 or higher than 0.7, the plastic hinge of the connections with the floor slab occurs at the beam-to-column connection weld, which is completely different from the failure mode that without composite action. When the distance from the first opening to the face of the column is equal to or greater than 1.375 times the depth of beam, the plastic hinge formed in the beam-to-column weld while the composite action is taken into account; when disregarding the composite action causes the plastic hinge emerged in the beam section. Also, the ultimate bearing capacity of the castellated beam-to-column connections with closely spaced web openings significantly decreases; however, widely spaced web openings make stress concentration around the first opening and hinder the migration of stress to other openings, which has an adverse effect on the ultimate bearing capacity and ductility of the connections. The depth-to-thickness ratio of the web is also an important factor affecting the damage mode either web buckling or beam plastic hinge.

SMYD3–PARP16 axis accelerates unfolded protein response and mediates neointima formation

Neointimal hyperplasia after vascular injury is a representative complication of restenosis. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is involved in the pathogenesis of vascular intimal hyperplasia. PARP16, a member of the poly(ADP-ribose) polymerases family, is correlated with the nuclear envelope and the ER. Here, we found that PERK and IRE1α are ADP-ribosylated by PARP16, and this might promote proliferation and migration of smooth muscle cells (SMCs) during the platelet-derived growth factor (PDGF)-BB stimulating. Using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) analysis, PARP16 was identified as a novel target gene for histone H3 lysine 4 (H3K4) methyltransferase SMYD3, and SMYD3 could bind to the promoter of Parp16 and increased H3K4me3 level to activate its host gene's transcription, which causes UPR activation and SMC proliferation. Moreover, knockdown either of PARP16 or SMYD3 impeded the ER stress and SMC proliferation. On the contrary, overexpression of PARP16 induced ER stress and SMC proliferation and migration. In vivo depletion of PARP16 attenuated injury-induced neointimal hyperplasia by mediating UPR activation and neointimal SMC proliferation. This study identified SMYD3–PARP16 is a novel signal axis in regulating UPR and neointimal hyperplasia, and targeting this axis has implications in preventing neointimal hyperplasia related diseases.

On-axis fatigue behaviors and failure characterization of 3D5D braided composites with yarn-reduction using X-ray computed tomography

This paper mainly provides a thorough experimental investigation of tension-tension fatigue (R = 0.1) failure mechanisms in 3D5D braided carbon/epoxy composites without/with yarn-reduction (No-YR/In-YR) subjected to different stress levels of ultimate tensile stress (40%-75%UTS). X-ray computed tomography (Micro-CT) was conducted to visualize and quantify the damage generated in the fatigued samples. More significantly, a novel two-steps segmentation approach was proposed to classify and locate the cracks. The results indicated that the two types of specimens showed similar fatigue behavior, i.e. the extensive debonding of the braided yarns might give rise to the premature significant stiffness degradation of the fatigued samples. However, the tensile strength and the fatigue limit of In-YR 3D5D braided composites were reduced by 28.3% and 22.8% relative to No-YR 3D5D braided composites, respectively, which might be attributed to the variation of failure modes. Particularly, the failure modes of the axial yarns surround the yarn-reduction point evolved from mode I to mode II due to the deformation generated during the fabrication. It is noteworthy that the cracks presented a typical wedge distribution near the yarn reduction point due to the in-plane stress migration.

Shear stress improves the endothelial progenitor cell function via the CXCR7/ERK pathway axis in the coronary artery disease cases

BackgroundDysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients.MethodsThe human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR.ResultCompared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs.ConclusionUp-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.

Understanding Vectorial Migration Patterns of Wastewater-Induced Earthquakes in the United States

ABSTRACTThe recent surge of earthquakes in the central United States is linked to the disposal of large volumes of wastewater. Even if injection rates have been decreasing since 2015, the seismic hazard remains elevated. Moreover, some events in Kansas occur far from disposal wells. We applied a multidimensional cross-correlation technique to analyze the spatiotemporal relation between fluid injection and earthquakes. While a strong correlation is observed in east-northeastern direction of the disposal wells for the majority of events, some earthquakes occur in northeastern direction far from the disposal wells. We explain this pattern and the large-scale evolution of borehole pressure observations by directional migration of poroelastic stresses and pore pressure diffusion. This follows from our principal 2D poroelastic finite-element model that has a predicting power and identifies controlling parameters of the process. These are the permeability of the basement and its anisotropic character as well as the distribution of critical fault strengths. Our results suggest that remote locations may be destabilized even when injection rates are declining. Thus, a volume reduction may only provide an immediate effect to lower the seismicity locally. It follows that a state-wide reduction in earthquakes may require longer waiting times and that the hazard of induced seismicity may remain elevated for tens of years.