Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)

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Blood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1)
Chappell, John C.; Darden, Jordan; Payne, Laura Beth; Fink, Kathryn; Bautch, Victoria L. (MDPI, 2019-09-07)
Feedback mechanisms are critical components of many pro-angiogenic signaling pathways that keep vessel growth within a functional range. The Vascular Endothelial Growth Factor-A (VEGF-A) pathway utilizes the decoy VEGF-A receptor Flt-1 to provide negative feedback regulation of VEGF-A signaling. In this study, we investigated how the genetic loss of flt-1 differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated flt-1 in the post-natal retina and found that maximum induction of flt-1 loss resulted in alterations in endothelial sprouting and filopodial extension, ultimately yielding hyper-branched networks in the absence of changes in retinal astrocyte architecture. The mosaic deletion of flt-1 revealed that sprouting endothelial cells flanked by flt-1⁻^/− regions of vasculature more extensively associated with underlying astrocytes and exhibited aberrant sprouting, independent of the tip cell genotype. Overall, our data support a model in which tissue patterning features, such as retinal astrocytes, integrate with flt-1-regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.
Compressive Mechanical Properties of Porcine Brain: Experimentation and Modeling of the Tissue Hydration Effects
Prabhu, Raj K.; Begonia, Mark T.; Whittington, Wilburn R.; Murphy, Michael A.; Mao, Yuxiong; Liao, Jun; Williams, Lakiesha N.; Horstemeyer, Mark F.; Sheng, Jianping (MDPI, 2019-05-07)
Designing protective systems for the human head—and, hence, the brain—requires understanding the brain’s microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on the brain’s biomechanics. Here, native ‘wet’ brain samples contained ~80% (mass/mass) water content and ‘dry’ brain samples contained ~0% (mass/mass) water content. First, the wet brain incurred a large initial peak stress that was not exhibited by the dry brain. Second, stress levels for the dry brain were greater than the wet brain. Third, the dry brain stress–strain behavior was characteristic of ductile materials with a yield point and work hardening; however, the wet brain showed a typical concave inflection that is often manifested by polymers. Finally, finite element analysis (FEA) of the brain’s high strain rate response for samples with various proportions of water and dry brain showed that water played a major role in the initial hardening trend. Therefore, hydration level plays a key role in brain tissue micromechanics, and the incorporation of this hydration effect on the brain’s mechanical response in simulated injury scenarios or virtual human-centric protective headgear design is essential.
Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation
Strauss, Randy E.; Gourdie, Robert G. (MDPI, 2020-12-10)
Barrier function is a vital homeostatic mechanism employed by epithelial and endothelial tissue. Diseases across a wide range of tissue types involve dynamic changes in transcellular junctional complexes and the actin cytoskeleton in the regulation of substance exchange across tissue compartments. In this review, we focus on the contribution of the gap junction protein, Cx43, to the biophysical and biochemical regulation of barrier function. First, we introduce the structure and canonical channel-dependent functions of Cx43. Second, we define barrier function and examine the key molecular structures fundamental to its regulation. Third, we survey the literature on the channel-dependent roles of connexins in barrier function, with an emphasis on the role of Cx43 and the actin cytoskeleton. Lastly, we discuss findings on the channel-independent roles of Cx43 in its associations with the actin cytoskeleton and focal adhesion structures highlighted by PI3K signaling, in the potential modulation of cellular barriers. Mounting evidence of crosstalk between connexins, the cytoskeleton, focal adhesion complexes, and junctional structures has led to a growing appreciation of how barrier-modulating mechanisms may work together to effect solute and cellular flux across tissue boundaries. This new understanding could translate into improved therapeutic outcomes in the treatment of barrier-associated diseases.
The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner
Strauss, Randy E.; Mezache, Louisa; Veeraraghavan, Rengasayee; Gourdie, Robert G. (MDPI, 2021-08-12)
The Cx43 carboxyl-terminus (CT) mimetic peptide, αCT1, originally designed to bind to Zonula Occludens 1 (ZO1) and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing (ECIS), a TRITC-dextran Transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell–cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular chiral orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell–cell border localization of endothelial VE-cadherin, the tight junction protein Zonula Occludens 1 (ZO1), and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1 binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema.
Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies
Graybill, Philip M.; Davalos, Rafael V. (MDPI, 2020-04-30)
Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.
A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and Structure
Bracey, Daniel N.; Seyler, Thorsten M.; Jinnah, Alexander H.; Lively, Mark O.; Willey, Jeffrey S.; Smith, Thomas L.; Van Dyke, Mark E.; Whitlock, Patrick W. (MDPI, 2018-07-12)
Background: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species. Xenografts are available in unlimited supply from healthy animal donors with controlled biology, avoiding the risk of human disease transmission, and may satisfy current demand for bone graft products. Methods: In the current study, cancellous bone was harvested from porcine femurs and subjected to a novel decellularization protocol to derive a bone scaffold. Results: The scaffold was devoid of donor cellular material on histology and DNA sampling (p < 0.01). Microarchitectural properties important for osteoconductive potential were preserved after decellularization as shown by high resolution imaging modalities. Proteomics data demonstrated similar profiles when comparing the porcine bone scaffold against commercially available human demineralized bone matrix approved for clinical use. Conclusion: We are unaware of any porcine-derived bone graft products currently used in orthopaedic surgery practice. Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute.
Dynamic Analysis and Design Optimization of a Drag-Based Vibratory Swimmer
Tahmasian, Sevak; Jafaryzad, Arsam; Bulzoni, Nicolas L.; Staples, Anne E. (MDPI, 2020-03-22)
Many organisms achieve locomotion via reciprocal motions. This paper presents the dynamic analysis and design optimization of a vibratory swimmer with asymmetric drag forces and fluid added mass. The swimmer consists of a floating body with an oscillatory mass inside. One-dimensional oscillations of the mass cause the body to oscillate with the same frequency as the mass. An asymmetric rigid fin attached to the bottom of the body generates asymmetric hydrodynamic forces, which drive the swimmer either backward or forward on average, depending on the orientation of the fin. The equation of motion of the system is a time-periodic, piecewise-smooth differential equation. We use simulations to determine the hydrodynamic forces acting on the fin and averaging techniques to determine the dynamic response of the swimmer. The analytical results are found to be in good agreement with vibratory swimmer prototype experiments. We found that the average unidirectional speed of the swimmer is optimized if the ratio of the forward and backward drag coefficients is minimized. The analysis presented here can aid in the design and optimization of bio-inspired and biomimetic robotic swimmers. A magnetically controlled microscale vibratory swimmer like the one described here could have applications in targeted drug delivery.
Effects of Nonlinear Propagation of Focused Ultrasound on the Stable Cavitation of a Single Bubble
Bakhtiari-Nejad, Marjan; Shahab, Shima (MDPI, 2018-12-06)
Many biomedical applications such as ultrasonic targeted drug delivery, gene therapy, and molecular imaging entail the problems of manipulating microbubbles by means of a high-intensity focused ultrasound (HIFU) pressure field; namely stable cavitation. In high-intensity acoustic field, bubbles demonstrate translational instability, the well-known erratic dancing motion, which is caused by shape oscillations of the bubbles that are excited by their volume oscillations. The literature of bubble dynamics in the HIFU field is mainly centered on experiments, lacking a systematic study to determine the threshold for shape oscillations and translational motion. In this work, we extend the existing multiphysics mathematical modeling platform on bubble dynamics for taking account of (1) the liquid compressibility which allows us to apply a high-intensity acoustic field; (2) the mutual interactions of volume pulsation, shape modes, and translational motion; as well as (3) the effects of nonlinearity, diffraction, and absorption of HIFU to incorporate the acoustic nonlinearity due to wave kinematics or medium—all in one model. The effects of acoustic nonlinearity on the radial pulsations, axisymmetric modes of shape oscillations, and translational motion of a bubble, subjected to resonance and off-resonance excitation and various acoustic pressure, are examined. The results reveal the importance of considering all the involved harmonics and wave distortion in the bubble dynamics, to accurately predict the oscillations, translational trajectories, and the threshold for inertial (unstable) cavitation. This result is of interest for understanding the bubble dynamical behaviors observed experimentally in the HIFU field.
Emergency Response to Vehicle Collisions: Feedback from Emergency Medical Service Providers
Valente, Jacob T.; Perez, Miguel A. (MDPI, 2020-10-20)
(1) Background: The purpose of this study is to identify emergency medical technicians’ perceptions of the most pressing issues that they experience when responding to motor vehicle collisions and record their opinions about what information is needed to improve the efficiency and effectiveness of the care they provide. (2) Methods: Emergency medical technicians participated in one-on-one structured interviews about their experiences responding to motor vehicle collisions. Their feedback on dispatching procedures and protocols, travel to and from the scene, and the response process was collected. (3) Results: Participants reported experiencing difficulties related to lack of or inaccuracies in information, interactions with traffic, incompatibility in communication technology, scene safety, resource management, and obtaining timely notifications of motor vehicle collisions. Regarding the type of information most needed to improve emergency medical response, respondents indicated a desire for additional data related to the vehicle and its occupants. (4) Conclusions: The early and widespread availability of this information is expected to aid emergency responders in coordinating necessary resources faster and more optimally, help service optimization in situations with multiple motor vehicle collisions in close temporal proximity, and improve on-scene safety for first responders and other necessary personnel.
Extracting Interactions between Flying Bat Pairs Using Model-Free Methods
Roy, Subhradeep; Howes, Kayla; Müller, Rolf; Butail, Sachit; Abaid, Nicole (MDPI, 2019-01-09)
Social animals exhibit collective behavior whereby they negotiate to reach an agreement, such as the coordination of group motion. Bats are unique among most social animals, since they use active sensory echolocation by emitting ultrasonic waves and sensing echoes to navigate. Bats’ use of active sensing may result in acoustic interference from peers, driving different behavior when they fly together rather than alone. The present study explores quantitative methods that can be used to understand whether bats flying in pairs move independently of each other or interact. The study used field data from bats in flight and is based on the assumption that interactions between two bats are evidenced in their flight patterns. To quantify pairwise interaction, we defined the strength of coupling using model-free methods from dynamical systems and information theory. We used a control condition to eliminate similarities in flight path due to environmental geometry. Our research question is whether these data-driven methods identify directed coupling between bats from their flight paths and, if so, whether the results are consistent between methods. Results demonstrate evidence of information exchange between flying bat pairs, and, in particular, we find significant evidence of rear-to-front coupling in bats’ turning behavior when they fly in the absence of obstacles.
Hybrid Composites Based on Carbon Fiber/Carbon Nanofilament Reinforcement
Tehrani, Mehran; Yari Boroujeni, Ayoub; Luhrs, Claudia; Phillips, Jonathan; Al-Haik, Marwan S. (MDPI, 2014-05-28)
Carbon nanofilament and nanotubes (CNTs) have shown promise for enhancing the mechanical properties of fiber-reinforced composites (FRPs) and imparting multi-functionalities to them. While direct mixing of carbon nanofilaments with the polymer matrix in FRPs has several drawbacks, a high volume of uniform nanofilaments can be directly grown on fiber surfaces prior to composite fabrication. This study demonstrates the ability to create carbon nanofilaments on the surface of carbon fibers employing a synthesis method, graphitic structures by design (GSD), in which carbon structures are grown from fuel mixtures using nickel particles as the catalyst. The synthesis technique is proven feasible to grow nanofilament structures—from ethylene mixtures at 550 °C—on commercial polyacrylonitrile (PAN)-based carbon fibers. Raman spectroscopy and electron microscopy were employed to characterize the surface-grown carbon species. For comparison purposes, a catalytic chemical vapor deposition (CCVD) technique was also utilized to grow multiwall CNTs (MWCNTs) on carbon fiber yarns. The mechanical characterization showed that composites using the GSD-grown carbon nanofilaments outperform those using the CCVD-grown CNTs in terms of stiffness and tensile strength. The results suggest that further optimization of the GSD growth time, patterning and thermal shield coating of the carbon fibers is required to fully materialize the potential benefits of the GSD technique.
Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput
Maloney, Erin; Clark, Casey; Sivakumar, Hemamylammal; Yoo, KyungMin; Aleman, Julio; Rajan, Shiny A. P.; Forsythe, Steven; Mazzocchi, Andrea R.; Laxton, Adrian W.; Tatter, Stephen B.; Strowd, Roy E.; Votanopoulos, Konstantinos I.; Skardal, Aleksander (MDPI, 2020-02-18)
The current drug development pipeline takes approximately fifteen years and $2.6 billion to get a new drug to market. Typically, drugs are tested on two-dimensional (2D) cell cultures and animal models to estimate their efficacy before reaching human trials. However, these models are often not representative of the human body. The 2D culture changes the morphology and physiology of cells, and animal models often have a vastly different anatomy and physiology than humans. The use of bioengineered human cell-based organoids may increase the probability of success during human trials by providing human-specific preclinical data. They could also be deployed for personalized medicine diagnostics to optimize therapies in diseases such as cancer. However, one limitation in employing organoids in drug screening has been the difficulty in creating large numbers of homogeneous organoids in form factors compatible with high-throughput screening (e.g., 96- and 384-well plates). Bioprinting can be used to scale up deposition of such organoids and tissue constructs. Unfortunately, it has been challenging to 3D print hydrogel bioinks into small-sized wells due to well–bioink interactions that can result in bioinks spreading out and wetting the well surface instead of maintaining a spherical form. Here, we demonstrate an immersion printing technique to bioprint tissue organoids in 96-well plates to increase the throughput of 3D drug screening. A hydrogel bioink comprised of hyaluronic acid and collagen is bioprinted into a viscous gelatin bath, which blocks the bioink from interacting with the well walls and provides support to maintain a spherical form. This method was validated using several cancerous cell lines, and then applied to patient-derived glioblastoma (GBM) and sarcoma biospecimens for drug screening.
Intercomparison of Small Unmanned Aircraft System (sUAS) Measurements for Atmospheric Science during the LAPSE-RATE Campaign
Barbieri, Lindsay; Kral, Stephan T.; Bailey, Sean C. C.; Frazier, Amy E.; Jacob, Jamey D.; Reuder, Joachim; Brus, David; Chilson, Phillip B.; Crick, Christopher; Detweiler, Carrick; Doddi, Abhiram; Elston, Jack; Foroutan, Hosein; González-Rocha, Javier; Greene, Brian R.; Guzman, Marcelo I.; Houston, Adam L.; Islam, Ashraful; Kemppinen, Osku; Lawrence, Dale; Pillar-Little, Elizabeth A.; Ross, Shane D.; Sama, Michael P.; Schmale, David G. III; Schuyler, Travis J.; Shankar, Ajay; Smith, Suzanne W.; Waugh, Sean; Dixon, Cory; Borenstein, Steve; de Boer, Gijs (MDPI, 2019-05-10)
Small unmanned aircraft systems (sUAS) are rapidly transforming atmospheric research. With the advancement of the development and application of these systems, improving knowledge of best practices for accurate measurement is critical for achieving scientific goals. We present results from an intercomparison of atmospheric measurement data from the Lower Atmospheric Process Studies at Elevation—a Remotely piloted Aircraft Team Experiment (LAPSE-RATE) field campaign. We evaluate a total of 38 individual sUAS with 23 unique sensor and platform configurations using a meteorological tower for reference measurements. We assess precision, bias, and time response of sUAS measurements of temperature, humidity, pressure, wind speed, and wind direction. Most sUAS measurements show broad agreement with the reference, particularly temperature and wind speed, with mean value differences of 1.6 ± 2.6 ∘ C and 0.22 ± 0.59 m/s for all sUAS, respectively. sUAS platform and sensor configurations were found to contribute significantly to measurement accuracy. Sensor configurations, which included proper aspiration and radiation shielding of sensors, were found to provide the most accurate thermodynamic measurements (temperature and relative humidity), whereas sonic anemometers on multirotor platforms provided the most accurate wind measurements (horizontal speed and direction). We contribute both a characterization and assessment of sUAS for measuring atmospheric parameters, and identify important challenges and opportunities for improving scientific measurements with sUAS.
Lagrangian Reduced Order Modeling Using Finite Time Lyapunov Exponents
Xie, Xuping; Nolan, Peter J.; Ross, Shane D.; Mou, Changhong; Iliescu, Traian (MDPI, 2020-10-23)
There are two main strategies for improving the projection-based reduced order model (ROM) accuracy—(i) improving the ROM, that is, adding new terms to the standard ROM; and (ii) improving the ROM basis, that is, constructing ROM bases that yield more accurate ROMs. In this paper, we use the latter. We propose two new Lagrangian inner products that we use together with Eulerian and Lagrangian data to construct two new Lagrangian ROMs, which we denote α-ROM and λ-ROM. We show that both Lagrangian ROMs are more accurate than the standard Eulerian ROMs, that is, ROMs that use standard Eulerian inner product and data to construct the ROM basis. Specifically, for the quasi-geostrophic equations, we show that the new Lagrangian ROMs are more accurate than the standard Eulerian ROMs in approximating not only Lagrangian fields (e.g., the finite time Lyapunov exponent (FTLE)), but also Eulerian fields (e.g., the streamfunction). In particular, the α-ROM can be orders of magnitude more accurate than the standard Eulerian ROMs. We emphasize that the new Lagrangian ROMs do not employ any closure modeling to model the effect of discarded modes (which is standard procedure for low-dimensional ROMs of complex nonlinear systems). Thus, the dramatic increase in the new Lagrangian ROMs’ accuracy is entirely due to the novel Lagrangian inner products used to build the Lagrangian ROM basis.
Mass Transport and Turbulent Statistics within Two Branching Coral Colonies
Hossain, Md Monir; Staples, Anne E. (MDPI, 2020-09-04)
Large eddy simulations were performed to characterize the flow and mass transport mechanisms in the interior of two Pocillopora coral colonies with different geometries, one with a relatively loosely branched morphology (P. eydouxi), and the other with a relatively densely branched structure (P. meandrina). Detailed velocity vector and streamline fields were obtained inside both corals for the same unidirectional oncoming flow, and significant differences were found between their flow profiles and mass transport mechanisms. For the densely branched P. meandrina colony, a significant number of vortices were shed from individual branches, which passively stirred the water column and enhanced the mass transport rate inside the colony. In contrast, vortices were mostly absent within the more loosely branched P. eydouxi colony. To further understand the impact of the branch density on internal mass transport processes, the non-dimensional Stanton number for mass transfer, St, was calculated based on the local flow time scale and compared between the colonies. The results showed up to a 219% increase in St when the mean vortex diameter was used to calculate St, compared to calculations based on the mean branch diameter. Turbulent flow statistics, including the fluctuating velocity components, the mean Reynolds stress, and the variance of the velocity components were calculated and compared along the height of the flow domain. The comparison of turbulent flow statistics showed similar Reynolds stress profiles for both corals, but higher velocity variations, in the interior of the densely branched coral, P. meandrina.
A Method for Detecting Atmospheric Lagrangian Coherent Structures Using a Single Fixed-Wing Unmanned Aircraft System
Nolan, Peter J.; McClelland, Hunter G.; Woolsey, Craig A.; Ross, Shane D. (MDPI, 2019-04-03)
The transport of material through the atmosphere is an issue with wide ranging implications for fields as diverse as agriculture, aviation, and human health. Due to the unsteady nature of the atmosphere, predicting how material will be transported via the Earth’s wind field is challenging. Lagrangian diagnostics, such as Lagrangian coherent structures (LCSs), have been used to discover the most significant regions of material collection or dispersion. However, Lagrangian diagnostics can be time-consuming to calculate and often rely on weather forecasts that may not be completely accurate. Recently, Eulerian diagnostics have been developed which can provide indications of LCS and have computational advantages over their Lagrangian counterparts. In this paper, a methodology is developed for estimating local Eulerian diagnostics from wind velocity data measured by a single fixed-wing unmanned aircraft system (UAS) flying in a circular arc. Using a simulation environment, driven by realistic atmospheric velocity data from the North American Mesoscale (NAM) model, it is shown that the Eulerian diagnostic estimates from UAS measurements approximate the true local Eulerian diagnostics and also predict the passage of LCSs. This methodology requires only a single flying UAS, making it easier and more affordable to implement in the field than existing alternatives, such as multiple UASs and Dopler LiDAR measurements. Our method is general enough to be applied to calculate the gradient of any scalar field.
Numerical Simulations of Two-Phase Flow in a Dorr-Oliver Flotation Cell Model
Salem-Said, Abdel-Halim; Fayed, Hassan; Ragab, Saad A. (MDPI, 2013-08-09)
Two-phase (water and air) flow in the forced-air mechanically-stirred Dorr-Oliver machine has been investigated using computational fluid dynamics (CFD). A 6 m3 model is considered. The flow is modeled by the Euler-Euler approach, and transport equations are solved using software ANSYS-CFX5. Unsteady simulations are conducted in a 180-degree sector with periodic boundary conditions. Air is injected into the rotor at the rate of 2.63 m3/min, and a uniform bubble diameter is specified. The effects of bubble diameter on velocity field and air volume fraction are determined by conducting simulations for three diameters of 0.5, 1.0, and 2.0 mm. Air volume fraction contours, velocity profiles, and turbulent kinetic energy profiles in different parts of the machine are presented and discussed. Results have been compared to experimental data, and good agreement is obtained for the mean velocity and turbulent kinetic energy profiles in the rotor-stator gap and in the jet region outside stator blades.
Numerical Simulations of Two-Phase Flow in a Self-Aerated Flotation Machine and Kinetics Modeling
Fayed, Hassan; Ragab, Saad A. (MDPI, 2015-03-30)
A new boundary condition treatment has been devised for two-phase flow numerical simulations in a self-aerated minerals flotation machine and applied to a Wemco 0.8 m³ pilot cell. Airflow rate is not specified a priori but is predicted by the simulations as well as power consumption. Time-dependent simulations of two-phase flow in flotation machines are essential to understanding flow behavior and physics in self-aerated machines such as the Wemco machines. In this paper, simulations have been conducted for three different uniform bubble sizes (d_b = 0.5, 0.7 and 1.0 mm) to study the effects of bubble size on air holdup and hydrodynamics in Wemco pilot cells. Moreover, a computational fluid dynamics (CFD)-based flotation model has been developed to predict the pulp recovery rate of minerals from a flotation cell for different bubble sizes, different particle sizes and particle size distribution. The model uses a first-order rate equation, where models for probabilities of collision, adhesion and stabilization and collisions frequency estimated by Zaitchik-2010 model are used for the calculation of rate constant. Spatial distributions of dissipation rate and air volume fraction (also called void fraction) determined by the two-phase simulations are the input for the flotation kinetics model. The average pulp recovery rate has been calculated locally for different uniform bubble and particle diameters. The CFD-based flotation kinetics model is also used to predict pulp recovery rate in the presence of particle size distribution. Particle number density pdf and the data generated for single particle size are used to compute the recovery rate for a specific mean particle diameter. Our computational model gives a figure of merit for the recovery rate of a flotation machine, and as such can be used to assess incremental design improvements as well as design of new machines.
Patterning the Stiffness of Elastomeric Nanocomposites by Magnetophoretic Control of Cross-linking Impeder Distribution
Ghosh, Suvojit; Tehrani, Mehran; Al-Haik, Marwan S.; Puri, Ishwar K. (MDPI, 2015-01-30)
We report a novel method to pattern the stiffness of an elastomeric nanocomposite by selectively impeding the cross-linking reactions at desired locations while curing. This is accomplished by using a magnetic field to enforce a desired concentration distribution of colloidal magnetite nanoparticles (MNPs) in the liquid precursor of polydimethysiloxane (PDMS) elastomer. MNPs impede the cross-linking of PDMS; when they are dispersed in liquid PDMS, the cured elastomer exhibits lower stiffness in portions containing a higher nanoparticle concentration. Consequently, a desired stiffness pattern is produced by selecting the required magnetic field distribution a priori. Up to 200% variation in the reduced modulus is observed over a 2 mm length, and gradients of up to 12.6 MPa·mm⁻¹ are obtained. This is a significant improvement over conventional nanocomposite systems where only small unidirectional variations can be achieved by varying nanoparticle concentration. The method has promising prospects in additive manufacturing; it can be integrated with existing systems thereby adding the capability to produce microscale heterogeneities in mechanical properties.
Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine
Marsh, Spencer R.; Williams, Zachary J.; Pridham, Kevin J.; Gourdie, Robert G. (MDPI, 2021-05-05)
Connexin (Cx43)-formed channels have been linked to cardiac arrhythmias and diseases of the heart associated with myocardial tissue loss and fibrosis. These pathologies include ischemic heart disease, ischemia-reperfusion injury, heart failure, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and Duchenne muscular dystrophy. A number of Cx43 mimetic peptides have been reported as therapeutic candidates for targeting disease processes linked to Cx43, including some that have advanced to clinical testing in humans. These peptides include Cx43 sequences based on the extracellular loop domains (e.g., Gap26, Gap 27, and Peptide5), cytoplasmic-loop domain (Gap19 and L2), and cytoplasmic carboxyl-terminal domain (e.g., JM2, Cx43tat, CycliCX, and the alphaCT family of peptides) of this transmembrane protein. Additionally, RYYN peptides binding to the Cx43 carboxyl-terminus have been described. In this review, we survey preclinical and clinical data available on short mimetic peptides based on, or directly targeting, Cx43, with focus on their potential for treating heart disease. We also discuss problems that have caused reluctance within the pharmaceutical industry to translate peptidic therapeutics to the clinic, even when supporting preclinical data is strong. These issues include those associated with the administration, stability in vivo, and tissue penetration of peptide-based therapeutics. Finally, we discuss novel drug delivery technologies including nanoparticles, exosomes, and other nanovesicular carriers that could transform the clinical and commercial viability of Cx43-targeting peptides in treatment of heart disease, stroke, cancer, and other indications requiring oral or parenteral administration. Some of these newly emerging approaches to drug delivery may provide a path to overcoming pitfalls associated with the drugging of peptide therapeutics.

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