Adhesive Interactions Research Articles

Экспериментальные исследования адгезионного взаимодействия в зоне контакта стекла и алюминия в стеклометаллокомпозитном элементе

При создании стекло-металлических соединений, в том числе нового конструкционного материала стеклометаллокомпозита, используется способность стекла надежно соединяться с металлами при определенном уровне температур стекла и металла. Адгезия горячего стекла тесно связана с физико-химическими процессами, протекающими на границе раздела «стекло – металл». Соединение зависит от температуры металлических обшивок и расплава стекла, времени выдержки, давления, состава стекла и металла. В данной работе экспериментально исследуется влияние технологических параметров центробежного литья на прочностные свойства конструкционного элемента стеклометаллокомпозита, как результата контактного взаимодействия слоев, сила сцепления которых определяет основные механические свойства соединения. Предлагается экспериментальный метод определения адгезионной силы при исследовании конструктивных цилиндрических образцов стеклометаллокомпозита на сдвиг. When creating glass-metal compounds, including a new structural material of glassmetal composite, the ability of glass to reliably connect with metals at a certain temperature level of glass and metal is used. The adhesion of hot glass is closely related to the physico-chemical processes occurring at the glass–metal interface. The connection depends on the temperature of the metal sheaths and the melt of the glass, the holding time, the pressure, the composition of the glass and metal. In this paper, the influence of technological parameters of centrifugal casting on the strength properties of a structural element of a glass-metal composite is experimentally investigated as a result of the contact interaction of layers, the adhesion strength of which determines the basic mechanical properties of the compound. An experimental method for determining the adhesive force in the study of structural cylindrical samples of glass-metal composite for shear is proposed.

Wetting and Adhesive Properties of Biopolymer-Based Organized Condensed Phases as Drug Delivery Systems

Lyotropic liquid crystalline systems are of great interest as carriers of biological substances for targeted delivery, mainly for transdermal administration of drugs and their application to the skin and mucous membranes. The wetting and adhesive interactions of lyomesophases and gel based on a chitosan polysaccharide in lactic acid solution on a glass substrate (base surface) and the surface of a semi-permeable polytetrafluoroethylene membrane (model of epidermis horny layer) were studied. The effect of the riboflavin drug (vitamin B2) on the surface tension of studied samples and the amount of adhesion work has been established. It is shown that biocompatible chitosan-containing systems can be used as drug carriers for various biomedical purposes, including transdermal drug delivery.

Non-slipping adhesive contact between dissimilar elastic solids under normal and tangential loads

In this paper, a model of two-dimensional non-slipping adhesive contact between dissimilar elastic solids under normal and tangential loads is proposed, and the general analytical solution is derived. The interaction of adhesion and friction along the contacting interface is studied. Specifically, (i) the shear-off force of adhesive contact is proposed; (ii) the effect of tangential load on the puff-off force is presented; (iii) the influence of the normal load on the shear-off force is obtained; (iv) in the context of these results, the nominal static friction coefficient is defined and analyzed, and it is shown that the static friction coefficient is a function of external normal load, which can well explain some experimental results in the literature. The proposed model appears to be consistent with the available experimental data, which offers new insight into the interplay mechanism between friction and adhesion. These results provide the foundation for understanding and modelling some tribological phenomena at the macro-, micro- and nano- scales.

Adhesive contact mechanics of penta-twinned nanowires

Penta-twinned nanowires, made of silver, gold, or copper, are envisioned to enable many applications, most notably stretchable and flexible electronics. In several instances of analysis of their behavior for device design, such as heat transfer due to current-induced heating, adhesion to substrates, or adhesion of nanowires to each other in conductive networks, knowledge of variables related to the mechanics of their contact is needed, for example the contact area (or radius). Due to the nanowires’ change in cross section, from circular to rounded-pentagonal as diameter increases, adhesive contact analysis is complex, and up to now has been simplified to assume either circular or perfect pentagonal cross sections. Here, we analyze the adhesive contact of the nanowires, fully considering the complexity of the cross section. We present equations to describe the geometry of the cross-section as it decreases in roundness with increasing diameter, finite element simulations that include elastic anisotropy and Lennard-Jones adhesive interactions, and observations on the adequacy of simplified contact models in describing the behavior. Calculations are presented for contact to typical stiff (silicon) and compliant (PDMS) substrates. The results reveal that, contrary to previous assumptions, the nanowires do not conform to the behavior of a perfect pentagon for the diameters typically encountered experimentally, and the roundness of the cross-section remains a factor that reduces the contact area. This reduction depends on the stiffness of the contact, being greater for stiff substrates.

A Reversible, Versatile Skin‐Attached Haptic Interface Platform with Bioinspired Interconnection Architectures Capable of Resisting Sweat and Vibration

AbstractA stable conformal interface technology for rough and sweaty complex skin is essential for a haptic interface capable of delivering sophisticated mechanical stimuli. However, conventional polymeric/hydrogel‐based skin adhesives cannot maintain adequate adhesion interaction performance at the haptic interface due to repetitive vibrations or sweaty skin. This study reports a reversible, versatile skin‐attached haptic interface platform, which embeds the hybrid architecture of a water‐drainable hexagonal array of frog toe pads and the energy‐dissipation matrix of snail pedal muscles with interconnected structures. The hybrid frog–snail‐inspired adhesive patch exhibits remarkable adhesion in pulling and shear directions under both dry and sweaty conditions. Furthermore, the microchannels between the hexagonal array can effectively drain liquid under sweaty conditions while also enhancing skin‐conformal contacts. The adhesion force enhanced by energy‐dissipation is analyzed considering a simple theory based on the adhesion, elastic, dissipation energies, and geometric features, resulting in the vibration‐resistant characteristics against diverse dry and wet vibration environments (vibrational frequency: 1–150 Hz). Bioinspired integrated skin‐attached haptic interface platform demonstrates the versatility of being reversibly applicable to various skin surfaces such as fingers, arms, and legs, yielding the feasibility of dynamic handling a basketball with multiple contacts and impacts in virtual reality (VR).

Ag2O-Containing Biocidal Interpolyelectrolyte Complexes on Glass Surfaces-Adhesive Properties of the Coatings.

Biocidal coatings are of great interest to the healthcare system. In this work, the biocidal activity of coatings based on a complex biocide containing polymer and inorganic active antibacterial components was studied. Silver oxide was distributed in a matrix of a positively charged interpolyelectrolyte complex (IPEC) of polydiallyldimethylammonium chloride (PDADMAC) and sodium polystyrene sulfonate (PSS) using ultrasonic dispersion, forming nanoparticles with an average size of 5-6 nm. The formed nanoparticles in the matrix are not subject to agglomeration and changes in morphology during storage. It was found that the inclusion of silver oxide in a positively charged IPEC allows a more than 4-fold increase in the effectiveness of the complex biocide against E. coli K12 in comparison with the biocidal effect of PDADMAC and IPEC. Polycation, IPEC, and the IPEC/Ag2O ternary complex form coatings on the glass surface due to electrostatic adsorption. Adhesive and cohesive forces in the resulting coatings were studied with micron-scale coatings using dynamometry. It was found that the stability of the coating is determined primarily by adhesive interactions. At the macro level, it is not possible to reliably identify the role of IPEC formation in adhesion. On the other hand, use of the optical tweezers method makes it possible to analyze macromolecules at the submicron scale and to evaluate the multiple increase in adhesive forces when forming a coating from IPEC compared to coatings from PDADMAC. Thus, the application of ternary IPEC/Ag2O complexes makes it possible to obtain coatings with increased antibacterial action and improved adhesive characteristics.

Pull-off dynamics of mushroom-shaped adhesive structures

Dynamic adhesion characteristics of synthetic adhesives have attracted massive attention recently. Specific to the mushroom-shaped adhesive structures with outperformed adhesion properties, a clear understanding of the pull-off dynamics, especially the role of retraction velocity, has not been addressed yet. In this paper, based on a custom-built adhesion test apparatus allowing in-situ high-speed measurement of the interface failure, we conducted detachment tests on hundreds-micrometer-scale mushroom-shaped adhesive structures with different cap thicknesses at a retraction velocity range spanning 4 orders of magnitude. It is found that the crack propagation mode for a thin or thick cap remains the same at different retraction velocities, whereas for an intermediate cap the transition from the edge-crack mode to the center-crack mode is observable. Notably, for center-crack mode, the crack area at pull-off remains relatively constant at different velocities. The variation of the pull-off forces with velocity exhibits a scaling law at high velocity regardless of the propagation mode. Dynamic detachment models are developed by considering the rate-dependent work of adhesion to demonstrate the critical-crack-dimension invariance at different velocities and the scaling law of pull-off force with the velocity with the same scaling exponent for center- and edge-crack mode. The theoretical scaling agrees well with experiments. Furthermore, finite element analysis of the viscoelastic detachment demonstrates the stress redistribution against retraction velocities. A prominent feature is the increasing length of the cohesive zone at pull-off with the increasing velocity, indicating a potential trend of a transition to a long-range adhesive interaction. At a sufficiently large velocity, the stress spike at the crack tip disappears and a theoretical strength is almost obtained at the region beneath the stalk.

Elucidating the Effects of Chemisorbed Water Molecules on the Adhesive Interactions of Epoxy Resin to γ-Alumina Surfaces.

The adhesion mechanism of epoxy resin to the γ-alumina (110) surface was investigated using first-principles density functional theory (DFT). Aluminum materials are lightweight and are used in a wide range of industrial fields. Its surface is oxidized to alumina, and the stable surface is known as the γ-alumina (110) surface. The coverage of hydroxy groups by chemisorbed water molecules on this surface varied depending on the pretreatment temperature. In this study, we investigated the adhesive interactions of epoxy resin on four alumina surfaces with different densities of surface hydroxy groups (0, 3, 6, and 9 OH/nm2) and have discussed their effects. At each interface, the energy curves of the vertically displaced epoxy resin were calculated and the adhesive forces were estimated by differentiating these curves. As the coverage of the surface hydroxy groups increased from 0 to 6 OH/nm2, the adhesive strength gradually decreased. However, the adhesive strength at 9 OH/nm2 was relatively large and almost equal to that at 3 OH/nm2. This inverse volcano-type behavior was analyzed via the decomposition of adhesive forces and the crystal orbital Hamilton population (COHP). The decomposition of adhesive forces into DFT and dispersion components revealed that the inverse volcano-type behavior is derived from the DFT component, and the interfacial interactions owing to the DFT component are accompanied by charge transfer. These were investigated using a COHP analysis, which revealed that this behavior was caused by changes in the activity of the aluminum atoms on the surface and surface reconstruction by chemisorbed water molecules. It is noteworthy that the adhesive strength for 9 OH/nm2 was only 6.9% lower than that for 0 OH/nm2 wherein the chemisorbed water molecules were completely removed from the surface. These results are expected to provide a guideline for the adhesion of epoxy resin to aluminum materials.

Removal of fine solids from bitumen by hetero-aggregation and magnetic separation using surface-modified magnetite nanoparticles. Part 2: Role of surface modification

Stearylamine acetate (SAA) modified magnetite nanoparticles (MNPs) have been previously proven to significantly improve the efficiency of fine solids removal from cyclohexane-diluted non-aqueous extracted (NAE) bitumen following magnetic separation. In this work, asphaltene-modified magnetite nanoparticles (Asp-MNPs) were prepared, and their ability to remove fine solids from NAE bitumen was evaluated. The influence of the surface modification with SAA or asphaltene on MNPs in their interactions with NAE fine solids was studied through quartz crystal microbalance with dissipation monitoring and atomic force microscopy studies. It was demonstrated that modification by SAA increased the adhesion interaction between the MNPs and NAE fine solids through a bridging effect. The use of an external magnetic field also strengthened the hetero-aggregation between surface-modified MNPs and the NAE fine solids. Though the asphaltene modification of MNPs resulted in a repulsive behavior in the interaction between MNPs and NAE fine solids due to steric effect, the applied external magnetic field could drive the Asp-MNPs together and induce the bridging among the Asp-MNPs through an interdigitation process, and the NAE fine solids could be captured through a sweeping effect by the networked Asp-MNPs.

Artificial patterns in spatially discrete models of cell migration and how to mitigate them

Several discrete models for diffusive motion are known to exhibit checkerboard artifacts, absent in their continuous analogues. We study the origins of the checkerboard artifact in the discrete heat equation and show that this artifact decays exponentially in time when following either of two strategies: considering the present state of each lattice site to determine its own future state (self-contributions), or using non-square lattice geometries. Afterwards, we examine the effects of these strategies on nonlinear models of biological cell migration with two kinds of cell-cell interactions: adhesive and polar velocity alignment. In the case of adhesive interaction, we show that growing modes related to pattern formation overshadow artifacts in the long run; nonetheless, artifacts can still be completely prevented following the same strategies as in the discrete heat equation. On the other hand, for polar velocity alignment we show that artifacts are not only strengthened, but also that new artifacts can arise in this model which were not observed in the previous models. We find that the lattice geometry strategy works well to alleviate artifacts. However, the self-contribution strategy must be applied more carefully: lattice sites should contribute to both their own density and velocity values, and their own velocity contribution should be high enough. With this work, we show that these two strategies are effective for preventing artifacts in spatial models based on the discrete continuity equation.

Homemade: building the structure of the neurogenic niche.

Neural stem/progenitor cells live in an intricate cellular environment, the neurogenic niche, which supports their function and enables neurogenesis. The niche is made of a diversity of cell types, including neurons, glia and the vasculature, which are able to signal to and are structurally organised around neural stem/progenitor cells. While the focus has been on how individual cell types signal to and influence the behaviour of neural stem/progenitor cells, very little is actually known on how the niche is assembled during development from multiple cellular origins, and on the role of the resulting topology on these cells. This review proposes to draw a state-of-the art picture of this emerging field of research, with the aim to expose our knowledge on niche architecture and formation from different animal models (mouse, zebrafish and fruit fly). We will span its multiple aspects, from the existence and importance of local, adhesive interactions to the potential emergence of larger-scale topological properties through the careful assembly of diverse cellular and acellular components.

Construction of xylan-based wood adhesive via tailoring crosslinking and interfacial chemical covalent bonding

Currently, low adhesion and poor water resistance are the main factors limiting the application of biomass adhesives. Based on these factors, in this study, branched epoxy compounds were synthesized from erythritol, xylitol and sorbitol, which were further reacted with the synthesized aminated xylan to obtain biomass adhesives. It is noteworthy that amino-rich activated wood surfaces were constructed and a "sandwich" type multiple cross-linked network was formed by chemical bonding between the adhesive and the activated wood surfaces. The dry/hot water/boiling water bond strength of the activated wood plywood were 3.13/1.54/1.18 MPa, which were 42.9%/108.1%/156.5% higher than those of the natural wood plywood, respectively. The plywood prepared from the activated wood interface showed excellent bond strength and water resistance. In this study, the wood surface was modified with orientated functional groups based on the mechanism of cross-linked network formation in the adhesive, resulting in the formation of stable chemical bonds between the adhesive and wood interfaces. This is the key to improving the interfacial adhesive interactions and ultimately the properties of the plywood.

Cell polarity: How to build an asymmetric bridge

A new study provides key insights into planar cell polarity (PCP) establishment through the discovery of molecular asymmetries in the homotypic adhesive interactions of the PCP cadherin, Flamingo, resulting in the formation of asymmetric, intercellular bridges.

A Dual Role of SOX11 Expression in the Formation of T-Cell Acute Lymphoblastic Leukemia in Mouse Models

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that accounts for 10%-15% of pediatric and 25% of adult ALL cases. Intensified chemotherapy and bone marrow transplants have improved the survival of T-ALL patients. However, around 20% of patients still suffer from primary resistant or relapsed T-ALL. Therefore, improving our knowledge of T-ALL biology and developing precision oncology therapeutics is essential for further progress in T-ALL treatment. SRY-related HMG-box 11 (SOX11) is a transcription factor that regulates the development and survival of multiple embryonic tissues and is crucial for the nervous system. SOX11 is expressed in a multitude of tumor types, where it has been associated with either increased or decreased cell proliferation, metastatic potential, and with either good or bad prognosis, depending on cancer type. Despite being absent in the T-cell lineage, SOX11 is expressed in a subset of T-ALLs, where it plays an unknown role. Based on having a malignantly restricted expression, we hypothesize that SOX11 might be oncogenic in T-ALL. Aim: Identify the role of aberrant SOX11 expression in (pre)leukemic T-cells. Methods: Using a conditional Rosa26-SOX11 overexpression mouse model, we generated mice with T-cell specific (using Lck-cre) SOX11 expression (SOX11 Lck). To assess the self-renewal potential of SOX11 Lck thymocytes, we performed thymic transplantations on sublethally irradiated mice expressing a different allele of CD45. To study SOX11 in a leukemic context, we crossed the SOX11 Lck mice with two established T-ALL mouse models that are either driven by the overexpression of Lmo2 (SOX11 Lck-Lmo2 CD2) or by the loss of the tumor suppressor Pten (SOX11/Pten Lck). An aging cohort of these T-ALL models was followed, and tumor samples were collected. Thymi of 8-weeks old mice were used to study the impact of SOX11 in a pre-leukemic context, and T-cell tumors arising in these models were also used for RNA-sequencing. Using a retroviral strategy, we overexpressed SOX11 in human cord blood stem cells, which we differentiated towards the T-cell lineage ex vivo by co-culturing them on OP9 stromal cells expressing Delta-like Notch ligand 4. Furthermore, we transduced Jurkat cells with a SOX11 expression vector, or with an empty vector, and injected the cells into immunocompromised mice to assess the effect of SOX11 on tumor growth in vivo. Results: In SOX11 Lck mice, we found a significant increase in the immature double-negative 3 (DN3) thymic fraction, with a concomitant decrease in the amount of more mature double-positive CD4 +CD8 + (DP) thymocytes (Fig. A). A possible explanation for this phenotype would be the establishment of a stem-like self-renewal program similar to the one driven by Lmo2. However, by performing thymic transplantations into sublethally irradiated mice, we concluded that SOX11 does not confer self-renewal properties to thymocytes. Additionally, we aged a cohort of SOX11 Lck mice and did not observe formation of T-cell malignancies up to 500 days of age. Given that the expression of SOX11 does not suffice to produce T-cell tumors, we generated the SOX11 Lck-Lmo2 CD2 and SOX11/Pten Lck T-ALL mouse models. In SOX11 Lck-Lmo2 CD2 mice, we found a synergistic effect of the co-expression of both genes on the expansion of DN3 thymocytes (Fig. A), which led to accelerated leukemia formation (Fig. B). By sequencing the RNA of pre-leukemic and leukemic DN3 cells, we observed that SOX11 is mostly regulating cell adhesion, morphology, and cell-cell interactions to promote this oncogenic phenotype in Lmo2-driven T-ALL. On the other hand, SOX11/Pten Lck mice suffered from delayed leukemogenesis (Fig. B), and this tumor suppressor role might be associated with the decrease in DP cells observed in the pre-leukemic stage. Lastly, we set out to validate these findings in a human context. The ex vivo differentiation of human hematopoietic stem cells toward the T-cell lineage showed that SOX11 strongly accelerates early commitment to double-negative T-cell precursors. Also, we observed that Jurkat T-ALL cells engraft faster in immunocompromised mice when expressing SOX11. Conclusions: By generating multiple models of SOX11 expression in the T-cell lineage, we showed that SOX11 impacts T-cell differentiation, both in mice and humans, and that it can promote or hinder T-ALL formation depending on the oncogenic driver.

Assessment of Novel Erythroid Signaling Pathways Modulating Hydroxyurea-Mediated Reduction of Vaso-Occlusive Adhesive Interactions in Early Precursors of Sickle Red Blood Cells (RBCs)

Sickle cell disease (SCD) affects ~100,000 Americans and millions worldwide, with healthcare costs in the U.S. exceeding $1 billion annually to treat frequent and unpredictable vaso-occlusive episodes (VOEs). In addition to fetal hemoglobin induction, hydroxyurea (HU) reduces the frequency of VOEs by increasing nitric oxide (NO) bioavailability and decreasing adhesion receptor expression and RBC-endothelial interactions. Very late antigen-4 (VLA-4), the best characterized adhesion receptor in SCD, is highly expressed on circulating reticulocytes (immature RBCs) and white blood cells (WBCs) during VOEs and in SCD patients with severe disease phenotypes and, decreased in response to HU therapy. Like other integrins, VLA-4 is functionally regulated by cell signaling pathways to modulate activity and binding affinity to a wide variety of ligands that are elevated in the SCD micro-environment. There is highly intriguing evidence showing HU modulates adhesion by upregulating a NO/cGMP-dependent pathway to decrease adhesion receptor activity however specific mechanisms remain unclear. The objective of this study was to assess rapid cell signaling pathways involved in HU-mediated reduction in VLA-4 binding to endothelial vascular cell adhesion molecule-1 (VCAM-1). Whole blood (WB) was obtained from patients with SCD at benign clinic visits according to IRB-approved protocols. WB density-gradient centrifugation was used to isolate hematopoietic stem cells (HSCs) and WBCs from the buffy coat layer and, a CD71 monoclonal antibody (Ab) coupled with magnetic beads to isolate reticulocytes from the packed RBC layer. HSCs were matured to erythroblasts (EBs) in appropriate cell culture media and flow cytometric analyses assessed purity of blood samples using CD235a (exclusive WBC marker) and CD45 (exclusive RBC marker) Abs . Blood samples were pretreated with and without a therapeutically relevant hydroxyurea concentration (50mcM) followed by perfusion through micro-fluidic channels coated with VCAM-1 during pulsatile, shear flow (1.67Hz, 1.0 dyne/cm 2). Additionally, EBs were treated with HU combined and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1- one (ODQ; NO-dependent guanylate cyclase inhibitor). Adhered cells were quantified to establish an adhesion index. The non-parametric Wilcoxon matched pairs signed rank test was used to test the statistical differences between groups. Data are presented as mean ± standard error of mean. A p-value < 0.05 was considered statistically significant. There was a significant decrease in WB (p=0.01) and reticulocyte (p<0.0001) adhesion to VCAM-1 in HU-treated samples however, there was no effect on WBC (p>0.99) adhesion suggesting reticulocytes reduce the adhesive burden of blood cells in WB adhesion assays and modulation of VLA-4 binding differs in sickle RBCs when compared to WBCs. More recently, preliminary data from my lab demonstrated that EBs pretreated with HU reduces VLA-4 binding to VCAM-1 (from 126.5 ± 29.42 to 109.5 ± 29.09) by cGMP-dependent mechanisms (HU + ODQ; from 109.5 ± 29.09 to 120.2 ± 42.80). Laboratory-based static and flow adhesion assays have been used for decades to describe adhesion in SCD since earlier studies established that sickle RBCs are more adherent than non-sickle blood cells and, adhesion correlates with SCD severity. For example, the adhesion assay described above has been used to demonstrate that VLA-4 binding can stratify SCD patients based on disease severity and predict impending VOEs. Additionally, reticulocyte and HbF levels strongly correlate with VLA-4 binding to VCAM-1 and, VLA-4-mediated adhesion is increased during patient-reported VOEs and decreased in HU-treated SCD patients. This is the first SCD study demonstrating the role of HU in modulating VLA-4 binding to endothelial VCAM-1 through rapid erythroid signaling pathways. There is also compelling evidence involving downregulation of VLA-4 activity/binding affinity through NO/cGMP dependent mechanisms and enhancement of VLA-4 binding by kinase-dependent pathways. HU has also been shown to modulate adhesion by upregulating a NO/cGMP-dependent pathway to decrease adhesion receptor activity. Collectively, these data suggest that VLA-4 mechanisms may be targeted to therapeutically inhibit vaso-occlusive adhesive events that promote VOEs in SCD.

New Insights into Cellular Defects during Haematopoiesis of Sickle Cell Disease Using the Townes Mouse Model

Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β globin gene leading to the synthesis of an abnormal haemoglobin (HbS), that under low oxygen tension polymerises driving the sickling of red blood cells and reducing their lifespan. SCD is characterized by anaemia, vaso-occlusion and haemolysis, progressive multiorgan damage and increased mortality. For decades, peripheral haemolysis has been considered as the sole driver of anaemia in SCD. Recently, we have demonstrated the occurrence of ineffective erythropoiesis (IE) in SCD suggesting that anaemia can be impacted by defects of central origin and hinting to abnormalities in the haematopoietic compartment. To gain insight into SCD haematopoiesis, we investigated the haematopoietic compartment of the humanized transgenic Townes mouse model by conducting an in-depth flow cytometry-based analysis in the bone marrow (BM) and spleen, comparing SS mice to control littermates (AA and AS) at 8 and 16 weeks of age (termed 8-w and 16-w, respectively). BM and spleen are two key hematopoietic tissues in adult mice: BM is involved in maintaining homeostatic haematopoiesis and spleen responds to stress haematopoiesis. First, we assessed haematopoietic differentiation in the BM of SS, AA and AS mice. Total number of BM cells and frequency of Lin Neg and Lin NegKit Pos (LK) were identical between SS and control littermates whereas a minor increase in the percentages of Lin NegSca PosKit Pos (LSK) was observed in 16-w SS mice. Within the LSK compartment, we found a 1.81- and 2.5-fold reduction of long-term haematopoietic stem cell (lt-HSC) frequency in 8-w and 16-w SS mice, respectively (Fig1 A). HSCs differentiate into multipotent progenitors (MPPs), which have decreased self-renewal capacity and progressively engage in the megakaryocytic (MPP2), myeloid-biased (MPP3), or lymphoid-biased (MPP4) lineage. The MPP3 compartment showed a 1.6-fold increased frequency in 8-w and 16-w SS mice indicating a skewing toward myeloid cell production and the onset of extramedullary haematopoiesis as early as 8 weeks after birth (Fig1 A). Next, we analysed the downstream lineages of the committed progenitors (lymphoid, granulo-macrophagic, megakaryocytic, and erythroid) and found a 1.4 and 2.3-fold increase of th megakaryocyte-erythroid progenitor cells (MEPs) and pre-CFU-Es in 8-w and 16-w SS mice, respectively (Fig1 A,B). We assessed the potential of SS hematopoietic progenitors (HSPCs) to differentiate into myelomonocytic and erythroid lineages by performing methylcellulose colony forming unit (CFU) assays with LSK and LK cells sorted from 8-w mice. Although no difference was observed in the number and type of colonies formed in vitro from SS and control HSPCs, SS colonies were much smaller than the AA/AS ones. Furthermore, serial replating showed a phenotype of stemness exhaustion in SS mice, with a dramatic decrease in the number of colonies formed by LSK cells (27.5 SS CFUs vs 51.6 AA/AS CFUs), suggesting lower self-renewal capacities of SS HSPCs. In spleen, in addition to the expected splenomegaly of SS mice, we found a trend toward a decreased frequency of the LSK compartment and an increase of the LK compartment. There was a 2.25- and 1.42-fold increase in the percentage of MPP-2 and MPP-3 cells, respectively, and a 2.1-fold increase in the pre-CFU-Es confirming an intense splenic haematopoiesis in SS mice (Fig 1B). HSPCs are known to be retained by the BM stromal cells through the chemotactic interaction of CXCL12 and CXCR4 and the adhesive interaction of VCAM-1 and VLA-4. Measuring HSC-related cytokines in BM supernatants, we found severely diminished levels of CXCL12 in SS mice as compared to control littermates (18 pg.mL -1 in SS vs 84 pg.mL -1 in AA; N=80), suggesting HSC mobilization from the BM to the spleen with disease onset. In addition to the well-established stress erythropoiesis phenotype reported in SCD mice, our study describes cellular abnormalities in the haematopoietic compartment shedding light on potential new mechanisms that contribute to SCD pathology in relation to anaemia and bone marrow stemness.

Assessment of Biomarker Response to Clinical Administration of Adakveo in a “Real World” Clinical Setting: A Model for Therapeutic Monitoring in Sickle Cell Disease (SCD)

Background Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive episodes (VOEs) often associated with microvascular blood cell adhesion. P-selectin adhesion has been shown to be a mediator of pathologic adhesive interactions involved in VOEs and is a therapeutic target for SCD-modifying therapies. Adakveo is an FDA-approved (2019) P-selectin monoclonal antibody (mAB) therapy shown to reduce the annualized frequency of VOEs in patients with SCD. Due to the lack of clinically available blood-based biomarkers to define an individual's cellular-level response to therapeutic p-selectin inhibition, providers often rely on the clinical assessment of VOE frequency and intensity to assess an individual's response to anti-p-selectin therapy. This may have contributed to the recently failed Phase 3 clinical trial. In this report, we monitored the cellular-level response to therapeutic p-selectin inhibition by Adakveo administered in a real-world clinical setting using the flow adhesion of whole blood to P-selectin (FA-WB-Psel) assay. Methods This study was a retrospective assessment of FA-WB-Psel biomarker levels before and after clinical administration of Adakveo between January 2019 through June 2022. Flow adhesion of whole blood to p-selectin (FA-WB-Psel ) assays were performed using pulsatile, shear flow (1.67Hz, 1.0 dyne/cm2). SCD patients that received at least 3 biomarker evaluations within 1-year pre-Adakveo and up to 1-year post-Adakveo treatment were included in this analysis. Clinical site received an IRB waiver to confirm therapy start/stop dates. The non-parametric Wilcoxon matched pairs signed rank test was used to test the statistical differences between groups. Data are presented as mean ± standard error of mean. A p-value < 0.05 was considered statistically significant. Results There were 15 patients that met the study criteria described above. All patients included were African American with a confirmed HbSS genotype and mean age of 31 years (93% female and 7% male). Of 475 biomarker evaluations, 169 were obtained pre-Adakveo administration, 247 obtained 1-year post-adakveo, and 59 obtained 2-years post-adakveo. Most patients (87%) had FA-WB-Psel biomarker levels above the critical threshold (46 cells/mm 2). Adakveo significantly reduced and stabilized P-selectin activity (FA-WB-PSEL) 12-months (mean pre=84.32 ± 8.44 cells/mm 2, mean post=48.02 ± 4.54 cells/mm2, p=0.001) and up to 24-months (p=0.0003) following Adakveo initiation. Higher pre-Adakveo FA-WB-Psel levels correlate with greater inhibition of cellular-level response to clinically administered Adakveo (r 2=0.4133). Discussion This study provides the first report of FA-WB-Psel adhesion levels in a real-world SCD population initiated on Adakveo therapy. We observed a statistically significant decrease in FA-WB-Psel following Adakveo initiation, suggesting that FA-WB-Psel may be an effective monitoring biomarker for anti-p-selectin therapy in clinical trials and clinical therapy. Patients with low pre-Adakveo FA-WB-Psel levels may be less likely to experience therapeutic p-selectin inhibition, and in fact may be at risk for increased FA-WB-Psel. Studies are underway to assess a potential role for FA-WB-Psel as a predictive biomarker to identify potential Adakveo responders, a monitoring biomarker to serially assess the pharmaco-dynamic response to Adakveo, and a potential surrogate endpoint for therapeutic p-selectin inhibition.

Nanostructured Effect on Antifouling Conducting Polymers through Interfacial Adhesive Interaction and Protein Adsorption

Nanostructured Effect on Antifouling Conducting Polymers through Interfacial Adhesive Interaction and Protein Adsorption

Integrative analysis of immune-related signature profiles in eosinophilic chronic rhinosinusitis with nasal polyposis.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi-omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed (DE) proteins, including 119 upregulated and 241 downregulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and extracellular matrix (ECM)-receptor interactions. Additionally, a protein-protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data and identified a total of 1077 DE genes. Pathways enriched by the DE genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune-related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.

The role of rolling resistance in the rheology of wizarding quidditch ball suspensions

To elucidate the effect of particle shape on the rheology of a dense, viscous suspension of frictional, non-Brownian particles, experimental measurements are presented for suspensions of polystyrene particles with different shapes in the same solvent. The first suspension is made of spheres whereas the particles which compose the second suspension are globular but with flattened faces. We present results from steady shear and shear-reversal rheological experiments for the two suspensions over a wide range of stresses in the viscous regime. Notably, we show that the rheology of the two suspensions is characterised by a shear-thinning behaviour, which is stronger in the case of the suspension of globular particles. Since the shear-reversal experiments indicate an absence of adhesive particle interactions, we attribute the shear thinning to a sliding friction coefficient which varies with stress as has been observed previously for systems similar to the first suspension. We observe that the viscosity of the two suspensions is similar at high shear stress where small sliding friction facilitates particle relative motion due to sliding. At lower shear stress, however, the sliding friction is expected to increase and the particle relative motion would be associated with rolling. The globular particles attain a higher viscosity at low shear stress than the spherical particles. We attribute this difference to a shape-induced resistance to particle rolling that is enhanced by the flattened faces. Image analysis is employed to identify features of the particle geometry that contribute to the resistance to rolling. It is shown that the apparent rolling friction coefficients inferred from the rheology are intermediate between the apparent dynamic and static rolling friction coefficients predicted on the basis of the image analysis. All three rolling resistance estimates are larger for the globular particles with flat faces than for the spherical particles and we argue that this difference yields the stronger shear thinning of the globular particle suspension.