Velocity and Stress Autocorrelation Decay in Isothermal Dissipative Particle Dynamics

The velocity and stress autocorrelation decay in a dissipative particle dynamics ideal fluid model is analyzed in this paper. The autocorrelation functions are calculated at three different friction parameters and three different time steps using the well-known Groot/Warren algorithm and newer algorithms including selfconsistent leap-frog, self-consistent velocity Verlet and Shardlow first and second order integrators. At low friction values, the velocity autocorrelation function decays exponentially at short times, shows slower-than exponential decay at intermediate times, and approaches zero at long times for all five integrators. As friction value increases, the deviation from exponential behavior occurs earlier and is more pronounced. At small time steps, all the integrators give identical decay profiles. As time step increases, there are qualitative and quantitative differences between the integrators. The stress correlation behavior is markedly different for the algorithms. The self-consistent velocity Verlet and the Shardlow algorithms show very similar stress autocorrelation decay with change in friction parameter, whereas the Groot/Warren and leap-frog schemes show variations at higher friction factors. Diffusion coefficients and shear viscosities are calculated using Green-Kubo integration of the velocity and stress autocorrelation functions. The diffusion coefficients match well-known theoretical results at low friction limits. Although the stress autocorrelation function is different for each integrator, fluctuates rapidly, and gives poor statistics for most of the cases, the calculated shear viscosities still fall within range of theoretical predictions and nonequilibrium studies

Low Mach Number Fluctuating Hydrodynamics for Electrolytes

We formulate and study computationally the low Mach number fluctuating hydrodynamic equations for electrolyte solutions. We are interested in studying transport in mixtures of charged species at the mesoscale, down to scales below the Debye length, where thermal fluctuations have a significant impact on the dynamics. Continuing our previous work on fluctuating hydrodynamics of multicomponent mixtures of incompressible isothermal miscible liquids (A. Donev, et al., Physics of Fluids, 27, 3, 2015), we now include the effect of charged species using a quasielectrostatic approximation. Localized charges create an electric field, which in turn provides additional forcing in the mass and momentum equations. Our low Mach number formulation eliminates sound waves from the fully compressible formulation and leads to a more computationally efficient quasi-incompressible formulation. We demonstrate our ability to model saltwater (NaCl) solutions in both equilibrium and nonequilibrium settings. We show that our algorithm is second-order in the deterministic setting, and for length scales much greater than the Debye length gives results consistent with an electroneutral/ambipolar approximation. In the stochastic setting, our model captures the predicted dynamics of equilibrium and nonequilibrium fluctuations. We also identify and model an instability that appears when diffusive mixing occurs in the presence of an applied electric field.Comment: 37 pages, 5 figure

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Thermal Modeling and Verification of a Quasi-Poloidal Stellarator Modular Coil

Controlled nuclear fusion has been the subject of experimental and analytical studies for more than forty years. A focus of research in this area has been plasma confinement using a toroidal magnetic field. The two important fusion devices used for this purpose are Tokamaks and Stellarators. The Quasi Poloidal Stellerator (QPS) is a low-aspect ratio toroidal magnetic confinement device used to contain the plasma so that Controlled Thermonuclear Reactions (CTR) can take place. An integral part of an Oak Ridge National Laboratory QPS design is the modular coil, which provides the primary magnetic field in the configuration. Since the coils are not actively cooled, the stellarator must be operated in short steps or pulses with sufficient time given to the copper conductors within the modular coils to cool down. This short pulse causes thermal stresses and deformations, which need to be carefully studied and understood in the design process. A prototype modular coil named UT Racetrack coil, was developed in the Mechanical, Aerospace, and Biomedical Engineering Department, at the University of Tennessee, to test and use in verification of thermal computer simulation models. The simulation models were developed to use in studying thermal cooling requirements, need and location for auxiliary cooling methods such as liquid nitrogen lines, use of copper chill plates as heat sinks, and temperature response of the conductor cable. Various other issues related to the physical properties of epoxy and insulations used in the QPS design, and thermal analysis of the welding and fabrication of the modular coils were also addressed and resolved in this study. It was found through the computer simulation of the welding process that the modular coils will not be damaged in the welding of the steel can during the fabrication of the QPS design. In addition, through direct experiments important thermal properties of metals and the epoxy used in the Vacuum Impregnation Process were measured and compared with the available data. Also, a specific simulation method was developed to ascertain the thermal conductivity of a composite material similar to the epoxy-packed copper cables used in the modular coils. The experimentally measured thermal properties were used in the computer simulation of the proposed QPS conductor coils as well as in the simulation of the fabricated UT Racetrack coil. All computer simulations in this thesis were done in FEMLAB®. The developed and verified computer model can now be used in prediction of the thermal stresses and deformations in the modular coil, and in the improvement of the thermal features of the proposed design, including optimization of the location of cooling cryogenic lines

Dissipative particle dynamics for mesoscopic particle-based thermal-fluid simulations

The primary objective of this dissertation is to develop theoretical and computational tools to simulate engineering problems in fluid mechanics and heat transfer using a mesoscopic framework Phase change phenomena are ubiquitous in day to day technological and engineering applications. They are amongst the most complex transport processes and involve the interplay of multiple time and length scales, nonequilibrium and interfacial effects. Previous work on phase change phenomena at the continuum level has focused mainly on semi-theoretical models and correlations with experiments. Studies at the atomistic level using molecular dynamics have been limited to smaller nanoscopic length and time scales. Grid-based mesoscopic methods such as lattice Boltzmann have been very useful for problems in fluid mechanics but suffer from an inadequate multiphase thermal model. Problems associated with grids and lattices can be avoided by using particle-based methods. In addition, boundary conditions can be easily applied and thermal fluctuations can be incorporated easily using particle-based methods. The focus of this work will be on the dissipative particle dynamics mesoscopic method and its use in modeling problems in the thermal-fluids area. Previous work on dissipative particle dynamics has focused primarily on an isothermal model and had inconsistencies in notation and nondimensionalization. In this work, a new and consistent notation is introduced for multicomponent systems and scaling factors for unknown parameters are determined. The dynamic properties of an ideal dissipative particle dynamics fluid are characterized by varying the integration algorithm, time step and friction factor. The energy-conserving model is studied in great depth and is shown to work very well for higher dimensional heat conduction problems for the first time. The model is further extended to investigate the Rayleigh Bénard convective instability problem in a single phase fluid for the first time and can easily be used to study other problems in convection. To develop a multiphase thermal framework, a phase change model is incorporated into the energy-conserving model using the density functional theory formulation of inhomogeneous fluids and is used to study the homogeneous vapor nucleation phenomena at mesoscopic length and time scales

Coarse-Grained Modeling of the Self-Association of Therapeutic Monoclonal Antibodies

Coarse-grained computational models of two therapeutic monoclonal antibodies are constructed to understand the effect of domain-level charge–charge electrostatics on the self-association phenomena at high protein concentrations. The coarse-grained representations of the individual antibodies are constructed using an elastic network normal-mode analysis. Two different models are constructed for each antibody for a compact Y-shaped and an extended Y-shaped configuration. The resulting simulations of these coarse-grained antibodies that interact through screened electrostatics are done at six different concentrations. It is observed that a particular monoclonal antibody (hereafter referred to as MAb1) forms three-dimensional heterogeneous structures with dense regions or clusters compared to a different monoclonal antibody (hereafter referred to as MAb2) that forms more homogeneous structures (no clusters). These structures, together with the potential mean force (PMF) and radial distribution functions (RDF) between pairs of coarse-grained regions on the MAbs, are qualitatively consistent with the experimental observation that MAb1 has a significantly higher viscosity compared to MAb2, especially at concentrations >50 mg/mL, even though the only difference between the MAbs lies with a few amino acids at the antigen-binding loops (CDRs). It is also observed that the structures in MAb1 are formed due to stronger Fab–Fab interactions in corroboration with experimental observations. Evidence is also shown that Fab–Fc interactions can be equally important in addition to Fab–Fab interactions. The coarse-grained representations are effective in picking up differences based on local charge distributions of domains and make predictions on the self-association characteristics of these protein solutions. This is the first computational study of its kind to show that there are differences in structures formed by two different monoclonal antibodies at high concentrations