Increased Fluid Shear Research Articles

Comparison of engineered nanoparticle transport in columns of three different lengths: Transport experiments and multi-observation point modeling

This study focuses on the effectiveness of commonly-used 15 cm column lengths for investigating nanoparticle transport in porous media. Experimental tests examined the transport and retention behaviors of two types of nanoparticles, graphene oxide (GO) and titanium dioxide (TiO2) nanoparticles, in saturated sand columns of different lengths (15, 30 and 45 cm), while considering key environmental factors like ionic strength (IS, 1–50 mM), flow rate (1–3 mL min−1), and grain size (150–850 μm). In the 15 cm columns, both GO and TiO2 transport decreased with higher IS and lower flow rate; grain size affected GO and TiO2 differently. Smaller grain size increased GO retention in the sand columns through straining, thus weakening GO mobility, whereas increased fluid shear force suppressed the ripening of TiO2, enhancing its migration. Similar environmental effects were noted in longer columns (30 and 45 cm), but fitted transport parameters (Smax and k) and predicted long-term mobility (Lmax) indicated that 15 cm columns might underestimate nanoparticle mobility. Blocking and ripening models based on single and multiple observation points to simulate nanoparticle transport and retention showed that predictions aligned well with experimental data. These results indicate that using combinations of columns of different lengths to achieve multiple observation points improves model prediction accuracy; in single-column experiments, the 45 cm and 30 cm columns respectively better predict the mobility range of GO and TiO2 compared to 15 cm columns.

Examining the impact of fluid shear stress on cancer-fighting immune cells

Natural killer cells hunt rogue cancer cells in the bloodstream aided by increased fluid shear stress.

Force-Regulated Calcium Signaling of Lymphoid Cell RPMI 8226 Mediated by Integrin α4β7/MAdCAM-1 in Flow.

MAdCAM-1 binds to integrin α4β7, which mediates the rolling and arrest of circulating lymphocytes upon the vascular endothelia during lymphocytic homing. The calcium response by adhered lymphocytes is a critical event for lymphocyte activation and subsequent arrest and migration under flow. However, whether the interaction of integrin α4β7 /MAdCAM-1 can effectively trigger the calcium response of lymphocytes remains unclear, as well as whether the fluid force affects the calcium response. In this study, we explore the mechanical regulation of integrin α4β7-induced calcium signaling under flow. Flou-4 AM was used to examine the calcium response under real-time fluorescence microscopy when cells were firmly adhered to a parallel plate flow chamber. The interaction between integrin α4β7 and MAdCAM-1 was found to effectively trigger calcium signaling in firmly adhered RPMI 8226 cells. Meanwhile, increasing fluid shear stress accelerated the cytosolic calcium response and enhanced signaling intensity. Additionally, the calcium signaling of RPMI 8226 activated by integrin α4β7 originated from extracellular calcium influx instead of cytoplasmic calcium release, and the signaling transduction of integrin α4β7 was involved in Kindlin-3. These findings shed new light on the mechano-chemical mechanism of calcium signaling in RPMI 8226 cells induced by integrin α4β7.

Acquired Von Willebrand Disease Associated with Hematologic Malignancies: Case Series and Literature Review

Objective: To describe a single institution experience of AvWD of the spectrum of presentation in hematologic malignancies. Introduction: Acquired von Willebrand disease (AvWD) is a rare acquired bleeding disorder characterized by mucocutaneous bleeding and functional alterations in von Willebrand factor (vWF). AvWD can be caused by numerous conditions but we are going to focus on those associated with hematologic malignancies. The pathogenic mechanisms responsible for the vWF abnormalities can include abnormal clearance due to binding of paraproteins, inhibition of vWF, adsorption to the surface of platelets, proteolysis from increased fluid shear stress, and decreased synthesis. Methods: Clinical review of 4 cases of AvWD at a tertiary academic medical center from January 2016 to January 2022. Results: Case 1: 57-year-old female with history of chronic thrombocytosis of 1.6 million and was diagnosed with a JAK2 V617F mutation positive essential thrombocythemia and concurrent iron deficiency anemia. She was placed on low dose aspirin for thromboprophylaxis and presented with hematochezia with a drop in hemoglobin from 9.7g/dL to 4.3g/dL, platelets were 857k/uL. At that time her aPTT was mildly elevated at 37.0 (normal 36.5) This prompted testing for von Willebrand disease which showed low vWF activity 50% and vWF GP I binding activity 47% with normal vWF antigen activity 82% and factor VIII clotting activity of 100 IU/ml. Aspirin was held and hydroxyurea initiated at 1000mg daily with clinical response. Coagulation testing including aPTT and vWF antigen, Activity and multimers normalized after cytoreduction of her platelets with hydrea. Case 2: 75-year-old male with history of stroke on aspirin. We saw the patient for erythrocytosis and made the diagnosis of JAK 2 V617F mutation positive polycythemia rubra vera. Phlebotomy was initiated however, he presented with large ecchymoses at the venipuncture sites following phlebotomy. Testing showed quantitative vWF and factor VIII were normal, abnormal GPIbM: vWF ratio and loss of highest molecular weight multimers. He was maintained on hydroxyurea 1500mg daily for target hematocrit of 40 g/dL and low dose aspirin thromboprophylaxis without recurrent bleeding. Case 3: A 68-year-old female who we were following with a history of an IgM monoclonal gammopathy of undetermined significance (MGUS) reported mild ecchymosis on the extremities. Testing showed low factor VIII level of 34% and low vWF antigen and activity at 29% and 22%, and normal vWF multimers. She has been observed without any therapy given lack of clinically significant bleeding. Three years later, she has now developed of cytopenias and bone marrow biopsy showed 30 - 40% lymphoplasmacytic infiltrate consistent with progression to Waldenström Macroglobulinemia. Case 4 60 year-old-male with history of an IgG lambda MGUS who presented with new onset recurrent melena without a source of bleeding found on endoscopy. Testing showed decreased vWF antigen 30% and vWF activity 21%, normal factor VIII activity 69% and all multimers decreased consistent with AvWD from his known MGUS. His recurrent mucosal bleeding was managed with weekly Humate P. Revlimid 10mg per day was initiated for MGUS. Two months later, his indices improved with normalized VWF multimers and VWF antigen 70% and factor VIII activity 142%, and with now only mildly decreased VWF activity at 48%. Recurrent bleeding ceased. Conclusions: Patients with hematologic malignancies may present with mucocutaneous bleeding which may mimic congenital vWD however, AvWD should be considered in this population of patients. In addition, patients with AvWD can present with varying degrees of bleeding which might be mistaken for platelet dysfunction due to the underlying malignancies or the addition of aspirin or anticoagulation. One must maintain high clinical suspicion for AvWD with new onset bleeding in setting of known myeloproliferative or lymphoproliferative disorder. vWF antigen, activity, factor VIII activity and multimer testing should be obtained to secure the diagnosis. Treatment of the underlying disorder will result in clinical and laboratory improvement.

Human dermal microvascular endothelial cell morphological response to fluid shear stress

As the cells that line the vasculature, endothelial cells are continually exposed to fluid shear stress by blood flow. Recent studies suggest that the morphological response of endothelial cells to fluid shear stress depends on the endothelial cell type. Thus, the present study characterizes the morphological response of human dermal microvascular endothelial cells (HMEC-1) and nuclei to steady, laminar, and unidirectional fluid shear stress. Cultured HMEC-1 monolayers were exposed to shear stress of 0.3 dyn/cm2, 16 dyn/cm2, or 32 dyn/cm2 for 72 h with hourly live-cell imaging capturing both the nuclear and cellular morphology. Despite changes in elongation and alignment occurring with increasing fluid shear stress, there was a lack of elongation and alignment over time under each fluid shear stress condition. Conversely, changes in cellular and nuclear area exhibited dependence on both time and fluid shear stress magnitude. The trends in cellular morphology differed at shear stress levels above and below 16 dyn/cm2, whereas the nuclear orientation was independent of fluid shear stress magnitude. These findings show the complex morphological response of HMEC-1 to fluid shear stress.

Exosomes as Intercellular Messengers in Hypertension.

People living with hypertension have a higher risk of developing heart diseases, and hypertension remains a top cause of mortality. In hypertension, some detrimental changes occur in the arterial wall, which include physiological and biochemical changes. Furthermore, this disease is characterized by turbulent blood flow, increased fluid shear stress, remodeling of the blood vessels, and endothelial dysfunction. As a complex disease, hypertension is thought to be caused by an array of factors, its etiology consisting of both environmental and genetic factors. The Mosaic Theory of hypertension states that many factors, including genetics, environment, adaptive, neural, mechanical, and hormonal perturbations are intertwined, leading to increases in blood pressure. Long-term efforts by several investigators have provided invaluable insight into the physiological mechanisms responsible for the pathogenesis of hypertension, and these include increased activity of the sympathetic nervous system, overactivation of the renin–angiotensin–aldosterone system (RAAS), dysfunction of the vascular endothelium, impaired platelet function, thrombogenesis, vascular smooth muscle and cardiac hypertrophy, and altered angiogenesis. Exosomes are extracellular vesicles released by all cells and carry nucleic acids, proteins, lipids, and metabolites into the extracellular environment. They play a role in intercellular communication and are involved in the pathophysiology of diseases. Since the discovery of exosomes in the 1980s, numerous studies have been carried out to understand the biogenesis, composition, and function of exosomes. In this review, we will discuss the role of exosomes as intercellular messengers in hypertension.

Effect of oscillatory flow conditions on crystalliser fouling investigated through non-invasive imaging

Conditions that lead to undesired fouling events in oscillatory flow crystallisers are investigated. The moving fluid oscillatory baffled crystalliser is used to mimic the operating conditions of continuous oscillatory baffled crystallisers, while reducing materials and energy consumption. A non-invasive imaging method is deployed to determine fouling induction times as a function of oscillatory flow conditions and supersaturation in crystallisation of glycine and L-glutamic acid from aqueous solutions. Heterogeneous nucleation kinetics are extracted from the distribution of fouling induction times, showing that higher fouling nucleation rates are observed when the frequency and amplitude of the oscillatory flow are increased. Higher oscillatory Reynolds numbers result in increased fluid shear in the crystalliser, promoting heterogeneous nucleation at the glass-solution interface and leading to subsequent fouling. It is therefore essential to consider the dependence of fouling kinetics on operating conditions to enable rational design of continuous crystallisers that ensure smooth and robust operation.

Orange juice ultrafiltration: characterisation of deposit layers and membrane surfaces after fouling and cleaning

Abstract The influence of feed condition and membrane cleaning during the ultrafiltration (UF) of orange juice for phytosterol separation was investigated. UF was performed using regenerated cellulose acetate (RCA) membranes at different molecular weight cut-off (MWCO) values with a 336 cm2 membrane area and a range of temperatures (10–40 °C) and different feed volumes (3–9 L). Fluid dynamic gauging (FDG) was applied to assess the fouling and cleaning behaviours of RCA membranes fouled by orange juice and cleaned using P3-Ultrasil 11 over two complete cycles. During the FDG testing, fouling layers were removed by fluid shear stress caused by suction flow. The cleanability was characterised by using ImageJ software analysis. A Liebermann-Buchard-based method was used to quantify the phytosterol content. The results show that RCA 10 kDa filters exhibited the best separation of phytosterols from protein in orange juice at 20 °C using 3 L feed with a selectivity factor of 17. Membranes that were fouled after two cycles showed higher surface coverage compared to one fouling cycle. The surface coverage decreased with increasing fluid shear stress from 0 to 3.9 Pa. FDG achieved 80–95% removal at 3.9 Pa for all RCA membranes. Chemical cleaning using P3-Ultrasil 11 altered both the membrane surface hydrophobicity and roughness. These results show that the fouling layer on RCA membranes can be removed by fluid shear stress without affecting the membrane surface modification caused by chemical cleaning.

Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron

Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.

Novel in vitro microfluidic platform for osteocyte mechanotransduction studies.

Osteocytes are the major mechanosensing cells in bone remodeling. Current in vitro bone mechanotransduction research use macroscale devices such as flow chambers; however, in vitro microfluidic devices provide an optimal tool to better understand this biological process with its flexible design, physiologically relevant dimensions and high-throughput capabilities. This project aims to design and fabricate a multi-shear stress, co-culture platform to study the interaction between osteocytes and other bone cells under varying flow conditions. Standard microfluidic design utilizing changing geometric parameters is used to induce different flow rates that are directly proportional to the levels of shear stress, with devices fabricated from standard polydimethylsiloxane (PDMS)-based softlithography processes. Each osteocyte channel (OCY) is connected to an adjacent osteoclast channel (OC) by 20-μm perfusion channels for cellular signaling molecule transport. Significant differences in RANKL levels are observed between channels with different shear stress levels, and we observed that pre-osteoclast differentiation was directly affected by adjacent flow-stimulated osteocytes. Significant decrease in the number of differentiating osteoclasts is observed in the OC channel adjacent to the 2-Pa shear stress OCY channel, while differentiation adjacent to the 0.5-Pa shear stress OCY channel is unaffected compared with no-flow controls. Addition of zoledronic acid showed a significant decrease in osteoclast differentiation, compounding to effect instigated by increasing fluid shear stress. Using this platform, we are able to mimic the interaction between osteocytes and osteoclasts in vitro under physiologically relevant bone interstitial fluid flow shear stress. Our novel microfluidic co-culture platform provides an optimal tool for bone cell mechanistic studies and provides a platform for the discovery of potential drug targets for clinical treatments of bone-related diseases.

Extracellular RNA released due to shear stress controls natural bypass growth by mediating mechanotransduction in mice

AbstractFluid shear stress in the vasculature is the driving force for natural bypass growth, a fundamental endogenous mechanism to counteract the detrimental consequences of vascular occlusive disease, such as stroke or myocardial infarction. This process, referred to as “arteriogenesis,” relies on local recruitment of leukocytes, which supply growth factors to preexisting collateral arterioles enabling them to grow. Although several mechanosensing proteins have been identified, the series of mechanotransduction events resulting in local leukocyte recruitment is not understood. In a mouse model of arteriogenesis (femoral artery ligation), we found that endothelial cells release RNA in response to increased fluid shear stress and that administration of RNase inhibitor blocking plasma RNases improved perfusion recovery. In contrast, treatment with bovine pancreatic RNase A or human recombinant RNase1 interfered with leukocyte recruitment and collateral artery growth. Our results indicated that extracellular RNA (eRNA) regulated leukocyte recruitment by engaging vascular endothelial growth factor receptor 2 (VEGFR2), which was confirmed by intravital microscopic studies in a murine cremaster model of inflammation. Moreover, we found that release of von Willebrand factor (VWF) as a result of shear stress is dependent on VEGFR2. Blocking VEGFR2, RNase application, or VWF deficiency interfered with platelet–neutrophil aggregate formation, which is essential for initiating the inflammatory process in arteriogenesis. Taken together, the results show that eRNA is released from endothelial cells in response to shear stress. We demonstrate this extracellular nucleic acid as a critical mediator of mechanotransduction by inducing the liberation of VWF, thereby initiating the multistep inflammatory process responsible for arteriogenesis.

Validated model of platelet slip at stenosis and device surfaces

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres–modeling platelets–slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200–400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20–90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective) and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm−1]×mean velocity [cm×sec−1]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses.

Secondary Nucleation from Nuclei Breeding and Its Quantitative Link with Fluid Shear Stress in Mixing: A Potential Approach for Precise Scale-up in Industrial Crystallization

The development of robust process scale-up involves a clear understanding of mixing hydrodynamics in crystallization. In the present work, particle imaging velocimetry (PIV) was used to determine the fluid turbulent shear stress (TSS) as a function of scale-up involving cooling crystallization experiments at different agitation rates. At a given scale, with increased agitation rate from 300 to 370 rpm, the secondary nucleation threshold (SNT) and product mean particle size were observed to decrease due to increased TSS. In nuclei breeding, the nucleated crystals at the seed surface are readily sheared off by the increased fluid shear stress. This catalytic process enhanced the rate of secondary nucleation, and hence a decrease in SNT. The SNT and mean particle size increased with scale size due to a decrease in average turbulent dissipation rate which resulted from a decrease in TSS. Secondary nucleation due to nuclei breeding was found to have a quantitative link with TSS. This resulted in a constant SNT...

Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function

The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit(+)/CXCR-4(+) cells stimulate arteriogenesisby recruiting additional neutrophils as well as growth-promoting monocytes and Tcells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.

Phenotype and function of dendritic cells in chronic epididymitis

The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.

Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4.

Placental growth factor (PLGF), a potent stimulator of arteriogenesis, is upregulated during outward arterial remodeling. Increased fluid shear stress (FSS) is a key physiological stimulus for arteriogenesis. However, the role of FSS in regulating PLGF expression is unknown. To test the hypothesis that FSS regulates PLGF expression in vascular cells and to identify the signaling pathways involved, human coronary artery endothelial cells (HCAEC) and human coronary artery smooth muscle cells were cultured on either side of porous Transwell inserts. HCAEC were then exposed to pulsatile FSS of 0.07 Pa ("normal," mimicking flow through quiescent collaterals), 1.24 Pa ("high," mimicking increased flow in remodeling collaterals), or 0.00 Pa ("static") for 2 h. High FSS increased secreted PLGF protein ∼1.4-fold compared with static control (n = 5, P < 0.01), while normal FSS had no significant effect on PLGF. Similarly, high flow stimulated PLGF mRNA expression nearly twofold in isolated mouse mesenteric arterioles. PLGF knockdown using siRNA revealed that HCAEC were the primary source of PLGF in cocultures (n = 5, P < 0.01). Both H2O2 and nitric oxide production were increased by FSS compared with static control (n = 5, P < 0.05). N(G)-nitro-l-arginine methyl ester (100 μM) had no significant effect on the FSS-induced increase in PLGF. In contrast, both catalase (500 U/ml) and diphenyleneiodonium (5 μM) attenuated the effects of FSS on PLGF protein in cocultures. Diphenyleneiodonium also blocked the effect of high flow to upregulate PLGF mRNA in isolated arterioles. Further studies identified NADPH oxidase 4 as a source of reactive oxygen species for this pathway. We conclude that FSS regulates PLGF expression via NADPH oxidase 4 and reactive oxygen species signaling.

Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response.

Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collateral arterial endothelium to transduce the extrinsic shear stimulus into an arteriogenic remodeling response. MSX1 was specifically up-regulated in remodeling collateral arteries. MSX1 induction in collateral endothelial cells (ECs) was shear stress driven and downstream of canonical bone morphogenetic protein-SMAD signaling. Flow recovery and collateral remodeling were significantly blunted in EC-specific Msx1/2 knockout mice. Mechanistically, MSX1 linked the arterial shear stimulus to arteriogenic remodeling by activating the endothelial but not medial layer to a proinflammatory state because EC but not smooth muscle cellMsx1/2 knockout mice had reduced leukocyte recruitment to remodeling collateral arteries. This reduced leukocyte infiltration in EC Msx1/2 knockout mice originated from decreased levels of intercellular adhesion molecule 1 (ICAM1)/vascular cell adhesion molecule 1 (VCAM1), whose expression was also in vitro driven by promoter binding of MSX1.

Agglomeration of Ni-Rich Hydroxide in Reaction Crystallization: Effect of Taylor Vortex Dimension and Intensity

The effect of a Taylor vortex flow on the agglomeration of Ni-rich hydroxide (Ni0.90Co0.05Mn0.05)(OH)2 was investigated in a Couette–Taylor (CT) crystallizer. The agglomeration process was found to be significantly affected by the rotation speed of the inner cylinder (hydrodynamic intensity) and gap size between the inner and outer cylinders of the CT crystallizer (vortex dimension), as these parameters affected the fluid shear and stability of the Taylor vortex flow. Thus, the agglomerate size was reduced when increasing the rotation speed and decreasing the gap size due to the increased fluid shear. A high rotation speed also improved the agglomerate size distribution and tap density. However, the agglomerate size distribution became broader and the tap density lower when decreasing the gap size, despite the increased fluid shear. This was due to an increase in the axial dispersion effect in the CT crystallizer when decreasing the gap size. As a result, the effective fluid motion of the Taylor vortex pr...

Proteomic analysis of Staphylococcus aureus biofilm cells grown under physiologically relevant fluid shear stress conditions.

BackgroundThe biofilm forming bacterium Staphylococcus aureus is responsible for maladies ranging from severe skin infection to major diseases such as bacteremia, endocarditis and osteomyelitis. A flow displacement system was used to grow S. aureus biofilms in four physiologically relevant fluid shear rates (50, 100, 500 and 1000 s-1) to identify proteins that are associated with biofilm.ResultsGlobal protein expressions from the membrane and cytosolic fractions of S. aureus biofilm cells grown under the above shear rate conditions are reported. Sixteen proteins in the membrane-enriched fraction and eight proteins in the cytosolic fraction showed significantly altered expression (p < 0.05) under increasing fluid shear. These 24 proteins were identified using nano-LC-ESI-MS/MS. They were found to be associated with various metabolic functions such as glycolysis / TCA pathways, protein synthesis and stress tolerance. Increased fluid shear stress did not influence the expression of two important surface binding proteins: fibronectin-binding and collagen-binding proteins.ConclusionsThe reported data suggest that while the general metabolic function of the sessile bacteria is minimal under high fluid shear stress conditions, they seem to retain the binding capacity to initiate new infections.

Diagnosis and treatment of acquired von Willebrand syndrome

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is characterized by structural or functional alterations in von Willebrand factor (VWF) caused by a range of lymphoproliferative, myeloproliferative, cardiovascular, autoimmune, and other disorders. The pathogenic mechanisms responsible for the VWF abnormalities depend on the underlying condition, but include clearance due to binding of paraproteins, inhibition of VWF, adsorption to the surface of platelets, increased fluid shear stress, and resultant proteolysis or, more rarely, decreased synthesis. The diagnosis and treatment of AVWS are complicated by the need for multiple laboratory tests and the management of bleeding risk in a typically elderly population with serious underlying conditions that predispose towards thrombosis. Recently developed diagnostic algorithms, based on standard laboratory assays, may assist clinicians with the diagnostic workup and help differentiate between AVWS and von Willebrand disease (VWD) types 1 and 2. AVWS should be considered in all patients with new-onset bleeding whenever laboratory findings suggest VWD, particularly in the presence of an AVWS-associated disorder. AVWS testing is also recommended prior to surgery or an intervention with a high risk of bleeding in any individual with an AVWS-associated disorder. Treatment of the underlying condition using immunosuppressants, surgery, or chemotherapy, can lead to remission of AVWS in some individuals and should always be considered. Strategies to prevent and/or treat bleeding episodes should also be in place, including the use of VWF-containing factor VIII concentrates, desmopressin and tranexamic acid. Treatment success will depend largely on the underlying pathogenesis of the disorder.