A particle method for two‐phase flows with compressible air pocket

When using particle methods to simulate water–air flows with compressible air pockets, a major challenge is to deal with the large differences in physical properties (e.g., density and viscosity) between water and air. In addition, the accurate modeling of air compressibility is essential. To this end, a new two‐phase strategy is proposed to simulate incompressible and compressible fluids simultaneously without iterations between the solvers for incompressible and compressible flows. Water is modeled by the recently developed 2‐phase Consistent Particle Method for incompressible flows. For air modeling, a new compressible solver is proposed based on the ideal gas law and thermodynamics. The formulation avoids the problem of determining the actual sound speed that is dependent on the temperature and is therefore not necessarily constant. In addition, the compressible air solver is seamlessly integrated with the incompressible solver 2‐phase Consistent Particle Method because they both use the same predictor–corrector scheme to solve the governing equations. The performance of the proposed method is demonstrated by three benchmark problems as well as an experimental study of sloshing impact with entrapped air pockets in an oscillating tank. Copyright © 2016 John Wiley & Sons, Ltd.     

Parallel load‐balanced simulation for short‐range interaction particle methods with hierarchical particle grouping based on orthogonal recursive bisection

We describe an efficient load‐balancing algorithm for parallel simulations of particle‐based discretization methods such as the discrete element method or smoothed particle hydrodynamics. Our approach is based on an orthogonal recursive bisection of the simulation domain that is the basis for recursive particle grouping and assignment of particle groups to the parallel processors. Particle grouping is carried out based on sampled discrete particle distribution functions. For interaction detection and computation, which is the core part of particle simulations, we employ a hierarchical pruning algorithm for an efficient exclusion of non‐interacting particles via the detection of non‐overlapping bounding boxes. Load balancing is based on a hierarchical PI‐controller approach, where the differences of processor per time step waiting times serve as controller input. Copyright © 2007 John Wiley & Sons, Ltd.     

Biomechanical Strain Exacerbates Inflammation on a Progeria‐on‐a‐Chip Model

Organ‐on‐a‐chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson‐Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues. Here, a progeria‐on‐a‐chip model is developed and the effects of biomechanical strain are examined in the context of vascular aging and disease. Physiological strain induces a contractile phenotype in primary smooth muscle cells (SMCs), while a pathological strain induces a hypertensive phenotype similar to that of angiotensin II treatment. Interestingly, SMCs derived from human induced pluripotent stem cells of HGPS donors (HGPS iPS‐SMCs), but not from healthy donors, show an exacerbated inflammatory response to strain. In particular, increased levels of inflammation markers as well as DNA damage are observed. Pharmacological intervention reverses the strain‐induced damage by shifting gene expression profile away from inflammation. The progeria‐on‐a‐chip is a relevant platform to study biomechanics in vascular biology, particularly in the setting of vascular disease and aging, while simultaneously facilitating the discovery of new drugs and/or therapeutic targets.     

A particle method for two‐phase flows with large density difference

A new numerical approach for solving incompressible two‐phase flows is presented in the framework of the recently developed Consistent Particle Method (CPM). In the context of the Lagrangian particle formulation, the CPM computes spatial derivatives based on the generalized finite difference scheme and produces good results for single‐phase flow problems. Nevertheless, for two‐phase flows, the method cannot be directly applied near the fluid interface because of the abrupt discontinuity of fluid density resulting in large change in pressure gradient. This problem is resolved by dealing with the pressure gradient normalized by density, leading to a two‐phase CPM of which the original singlephase CPM is a special case. In addition, a new adaptive particle selection scheme is proposed to overcome the problem of ill‐conditioned coefficient matrix of pressure Poisson equation when particles are sparse and non‐uniformly spaced. Numerical examples of Rayleigh–Taylor instability, gravity current flow, water‐air sloshing and dam break are presented to demonstrate the accuracy of the proposed method in wave profile and pressure solution. Copyright © 2015 John Wiley & Sons, Ltd.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

In Situ Observation of Single‐Phase Lithium Intercalation in Sub‐25‐nm Nanoparticles

Many lithium‐storage materials operate via first‐order phase transformations with slow kinetics largely restricted by the nucleation and growth of a new phase. Due to the energy penalties associated with interfaces between coexisting phases, the tendency for a single‐phase solid‐solution pathway with exceptional reaction kinetics has been predicted to increase with decreasing particle size. Unfortunately, phase evolutions inside such small particles (tens of nanometers) are often shrouded by electrode‐scale inhomogeneous reactions containing millions of particles, leading to intensive debate over the size‐dependent microscopic reaction mechanisms. This study provides a generally applicable methodology capable of tracking lithiation pathways in individual nanoparticles and unambiguously reveals that lithiation of anatase TiO₂, previously long believed to be biphasic, converts to a single‐phase reaction when particle size reaches ≈25 nm. These results imply the prevalence of such a size‐dependent transition in lithiation mechanism among intercalation compounds and provide important guidelines for designing high‐power electrodes, especially cathodes.     

Insulin‐Responsive Glucagon Delivery for Prevention of Hypoglycemia

Hypoglycemia, the state of abnormally low blood glucose level, is an acute complication of insulin and sulfonylurea therapy in diabetes management. Frequent insulin dosing and boluses during daily diabetes care leads to an increased risk of dangerously low glucose levels, which can cause behavioral and cognitive disturbance, seizure, coma, and even death. This study reports an insulin‐responsive glucagon delivery method based on a microneedle (MN)‐array patch for the prevention of hypoglycemia. The controlled release of glucagon is achieved in response to elevated insulin concentration by taking advantage of the specific interaction between insulin aptamer and target insulin. Integrating a painless MN‐array patch, it is demonstrated that this insulin‐triggered glucagon delivery device is able to prevent hypoglycemia following a high‐dose insulin injection in a chemically induced type 1 diabetic mouse model.     

Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end‐stage renal disease patients

Dyslipidemias may account for the excess of cardiovascular mortality in end‐stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride‐rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle‐aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE‐rich particles, lower high‐density lipoprotein (HDL) largest subclasses, and a smaller low‐density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL‐cholesterol levels, and a raise of small very‐low‐density lipoprotein, intermediate‐density lipoproteins (IDL), apoE‐rich particles, and non‐HDL‐cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation.     

Self‐Powered Real‐Time Arterial Pulse Monitoring Using Ultrathin Epidermal Piezoelectric Sensors

Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self‐powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near‐surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa^?1), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self‐powered and real‐time pulse monitoring system.     

The particle finite element method: a powerful tool to solve incompressible flows with free‐surfaces and breaking waves

Particle Methods are those in which the problem is represented by a discrete number of particles. Each particle moves accordingly with its own mass and the external/internal forces applied to it. Particle Methods may be used for both, discrete and continuous problems. In this paper, a Particle Method is used to solve the continuous fluid mechanics equations. To evaluate the external applied forces on each particle, the incompressible Navier–Stokes equations using a Lagrangian formulation are solved at each time step. The interpolation functions are those used in the Meshless Finite Element Method and the time integration is introduced by an implicit fractional‐step method. In this manner classical stabilization terms used in the momentum equations are unnecessary due to lack of convective terms in the Lagrangian formulation. Once the forces are evaluated, the particles move independently of the mesh. All the information is transmitted by the particles. Fluid–structure interaction problems including free‐fluid‐surfaces, breaking waves and fluid particle separation may be easily solved with this methodology. Copyright © 2004 John Wiley & Sons, Ltd.     

Generation of High‐Order All‐Aqueous Emulsion Drops by Osmosis‐Driven Phase Separation

Droplets containing ternary mixtures can spontaneously phase‐separate into high‐order structures upon a change in composition, which provides an alternative strategy to form multiphase droplets. However, existing strategies always involve nonaqueous solvents that limit the potential applications of the resulting multiple droplets, such as encapsulation of biomolecules. Here, a robust approach to achieve high‐order emulsion drops with an all‐aqueous nature from two aqueous phases by osmosis‐induced phase separation on a microfluidic platform is presented. This technique is enabled by the existence of an interface of the two aqueous phases and phase separation caused by an osmolality difference between the two phases. The complexity of emulsion drops induced by phase separation could be controlled by varying the initial concentration of solutes and is systematically illustrated in a state diagram. In particular, this technique is utilized to successfully achieve high‐order all‐aqueous droplets in a different aqueous two‐phase system. The proposed method is simple since it only requires two initial aqueous solutions for generating multilayered, organic‐solvent‐free all‐aqueous emulsion drops, and thus these multiphase emulsion drops can be further tailored to serve as highly biocompatible material templates.     

Moving‐least‐squares‐particle hydrodynamics—I. Consistency and stability

The Smooth‐Particle‐Hydrodynamics (SPH) method is derived in a novel manner by means of a Galerkin approximation applied to the Lagrangian equations of continuum mechanics as in the finite‐element method. This derivation is modified to replace the SPH interpolant with the Moving‐Least‐Squares (MLS) interpolant of Lancaster and Saulkaskas, and define a new particle volume which ensures thermodynamic compatibility. A variable‐rank modification of the MLS interpolants which retains their desirable summation properties is introduced to remove the singularities that occur when divergent flow reduces the number of neighbours of a particle to less than the minimum required. A surprise benefit of the Galerkin SPH derivation is a theoretical justification of a common ad hoc technique for variable‐h SPH. The new MLSPH method is conservative if an anti‐symmetric quadrature rule for the stiffness matrix elements can be supplied. In this paper, a simple one‐point collocation rule is used to retain similarity with SPH, leading to a non‐conservative method. Several examples document how MLSPH renders dramatic improvements due to the linear consistency of its gradients on three canonical difficulties of the SPH method: spurious boundary effects, erroneous rates of strain and rotation and tension instability. Two of these examples are non‐linear Lagrangian patch tests with analytic solutions with which MLSPH agrees almost exactly. The examples also show that MLSPH is not absolutely stable if the problems are run to very long times. A linear stability analysis explains both why it is more stable than SPH and not yet absolutely stable and an argument is made that for realistic dynamic problems MLSPH is stable enough. The notion of coherent particles, for which the numerical stability is identical to the physical stability, is introduced. The new method is easily retrofitted into a generic SPH code and some observations on performance are made. Copyright © 1999 John Wiley & Sons, Ltd.     

Disease‐Triggered Drug Release Effectively Prevents Acute Inflammatory Flare‐Ups,Achieving Reduced Dosing

For conditions with inflammatory flare‐ups, fast drug‐release from a depot is crucial to reduce cell infiltration and prevent long‐term tissue destruction. While this concept has been explored for chronic diseases, preventing acute inflammatory flares has not been explored. To address this issue, a preventative inflammation‐sensitive system is developed and applied to acute gout, a condition where millions of inflammatory cells are recruited rapidly, causing excruciating and debilitating pain. Rapid drug release is first demonstrated from a pH‐responsive acetalated dextran particle loaded with dexamethasone (AcDex‐DXM), reducing proinflammatory cytokines in vitro as efficiently as free drug. Then, using the air pouch model of gout, mice are pretreated 24 h before inducing inflammation. AcDex‐DXM reduces overall cell infiltration with decreased neutrophils, increases monocytes, and diminishes cytokines and chemokines. In a more extended prophylaxis model, murine joints are pretreated eight days before initiating inflammation. After quantifying cell infiltration, only AcDex‐DXM reduces the overall joint inflammation, where neither free drug nor a conventional drug‐depot achieves adequate anti‐inflammatory effects. Here, the superior efficacy of disease‐triggered drug‐delivery to prevent acute inflammation is demonstrated over free drug and slow‐release depots. This approach and results promise exciting treatment opportunities for multiple inflammatory conditions suffering from acute flares.     

Cancer‐Cell‐Specific Induction of Apoptosis Using Mesoporous Silica Nanoparticles as Drug‐Delivery Vectors

Targeted delivery of the chemotherapeutic agent methotrexate (MTX) to cancer cells using poly(ethyleneimine)‐functionalized mesoporous silica particles as drug‐delivery vectors is reported. Due to its high affinity for folate receptors, the expression of which is elevated in cancer cells, MTX serves as both a targeting ligand and a cytotoxic agent. Enhanced cancer‐cell apoptosis (programmed cell death) relative to free MTX is thus observed at particle concentrations where nonspecific MTX‐induced apoptosis is not observed in the nontargeted healthy cell line, while corresponding amounts of free drug affect both cell lines equally. The particles remain compartmentalized in endo‐/lysosomes during the time of observation (up to 72 h), while the drug is released from the particle only upon cell entry, thereby inducing selective apoptosis in the target cells. As MTX is mainly attached to the particle surface, an additional advantage is that the presented carrier design allows for adsorption (loading) of additional drugs into the pore network for therapies based on a combination of drugs.     

Shape‐ and Nitric Oxide Flux‐Dependent Bactericidal Activity of Nitric Oxide‐Releasing Silica Nanorods

Silica nanorods (SNRs) are synthesized and then functionalized with aminoalkoxysilanes to prepare a new class of nitric oxide (NO)‐releasing materials. The aspect ratio and size of the SNRs are tuned by varying the temperature, pH, and silane concentration used during the surfactant‐templated synthesis. N‐Diazeniumdiolate nitric oxide (NO) donors are formed on the secondary amine‐functionalized SNRs by reaction with NO gas under basic conditions. Particle surface modifications are employed to manipulate the NO release kinetics. The diverse morphology (i.e., aspect ratio ～1–8), NO‐release kinetics (2000–14 000 ppb NO/mg particle) and similar sizes (i.e., particle volume ～0.02 μm³) of the resulting NO‐releasing SNRs facilitates further studies of how particle shape and NO flux impacts bactericidal activity against Gram–positive Staphylococcus aureus (S. aureus) and Gram–negative Pseudomonas aeruginosa (P. aeruginosa) bacteria. The bactericidal efficacies of these materials improves with increasing particle aspect ratio and initial NO flux. Both chemical (i.e., NO‐release kinetics) and physical (i.e., morphology) properties greatly influenced the bactericidal activity of these materials.     

An upscale theory of particle simulation for two‐dimensional quasi‐static problems

An upscale theory of the particle simulation, which is based on the distinct element method, is presented for two‐dimensional quasi‐static problems. Since the present upscale theory is comprised of four similarity criteria between different length‐scale particle‐simulation models, it reveals the intrinsic relationship between the particle‐simulation solution obtained from a small length‐scale (e.g. a laboratory length‐scale) model and that obtained from a large length‐scale (e.g. a geological length‐scale) one. The present upscale theory is of significant theoretical value in the particle simulation of two‐dimensional systems, at least from the following two points of view. (1) If the mechanical response of a particle model of a small length‐scale is used to indirectly investigate that of a large length‐scale, then the present upscale theory provides the necessary conditions, under which the particle model of the small length‐scale needs to be satisfied so that a similarity between the mechanical responses of two different length‐scale particle models can be maintained. (2) If a particle model of a large length‐scale is used to directly investigate the mechanical response of the model, then the present upscale theory can be used to determine the necessary particle‐scale mechanical properties from the macroscopic mechanical properties that are obtained from either a laboratory test or an in situ measurement. The related simulation results from two typical examples of significantly different length‐scales (i.e. a metre‐scale and a kilometre‐scale) have demonstrated the usefulness and correctness of the proposed upscale theory for simulating different length‐scale problems in quasi‐static geological systems. Copyright © 2007 John Wiley & Sons, Ltd.     

Highly Sensitive and Selective Field‐Effect‐Transistor NonEnzyme Dopamine Sensors Based on Pt/Conducting Polymer Hybrid Nanoparticles

Dopamine (DA), as one of catecholamine family of neurotransmitters, is crucially important in humans owing to various critical effects on biometric system such as brine circuitry, neuronal plasticity, organization of stress responses, and control of cardiovascular and renal organizations. Abnormal level of dopamine in the central nervous system causes several neurological diseases, e.g., schizophrenia, Parkinson's disease, and attention deficit hybperactivity disorder (ADHD)/attention deficit disorder (ADD). In this report, we suggest the fabrication of nonenzyme field effect transistor (FET) sensor composed of immobilized Pt particle decorated conducting‐polymer (3‐carboxylate polypyrrole) nanoparticles (Pt_CPPy) to detect dopamine. The hybrid nanoparticles (NPs) are produced by means of facile chemical reduction of pristine CPPyNP‐contained Pt precursor (PtCl₄) solution. The Pt_CPPys are then immobilized on an amine‐functionalized (–NH₂) interdigitated‐array electrode substrate, through the formation of covalent bonds with amine groups (–CONH). The resulting Pt_CPPy‐based FET sensors exhibit high sensitivity and selectivity toward DA at unprecedentedly low concentrations (100 × 10^?15m ) and among interfering biomolecules, respectively. Additionally, due to the covalent bonding involved in the immobilization process, a longer lifetime is expected for the FET sensor.     

Sliding wear and solid particle erosion response of aluminium reinforced with tungsten carbide nanoparticles and aluminide particles

In the present effort, aluminium matrix composites (AMCs) were produced by the addition of submicron‐sized WC particles of low (up to 2.5 vol%) content into a melt of Al1050. Casting was assisted by the use of K₂TiF₆ as a wetting agent and mechanical stirring in order to limit particle clustering. Particle distribution was reasonably uniform comprising both clusters and isolated particles. Various different reinforcing particles' phases were identified, both in situ (Al‐W, Al‐Ti, and Al‐W‐Ti intermetallic phases) and ex situ (WC particles) of various morphologies shapes and sizes. Increase of the reinforcing particle content led to an increase of the tendency for clustering. The wear properties of the composite were examined by dry sliding wear. The worn surfaces and the produced debris were examined by SEM‐EDX, and an effort to correlate the wear response of the produced materials with the matrix and the reinforcing phase characteristics was attempted. In general, the increase of the reinforcing phase content led to an improvement of the sliding wear response. Solid particle erosion experiments were carried out for impact angles of 30°, 60°, and 90°. Τhe eroded surfaces were examined with SEM‐EDX, and possible erosion mechanisms were proposed based on morphological and other material characteristics. Intensive particle clustering seemed to deteriorate the erosion resistance of the systems. Medium concentrations of the reinforcing particles (1.0‐1.5 vol% WC) are proposed as a recipe for optimum sliding wear and solid particle erosion resistance behavior.