Computer Simulation of Particle Suspensions

Particle suspensions are ubiquitous in our daily life, but are not well understood due to their complexity. During the last twenty years, various simulation methods have been developed in order to model these systems. Due to varying properties of the solved particles and the solvents, one has to choose the simulation method properly in order to use the available compute resources most effectively with resolving the system as well as needed. Various techniques for the simulation of particle suspensions have been implemented at the Institute for Computational Physics allowing us to study the properties of clay-like systems, where Brownian motion is important, more macroscopic particles like glass spheres or fibers solved in liquids, or even the pneumatic transport of powders in pipes. In this paper we will present the various methods we applied and developed and discuss their individual advantages.Comment: 31 pages, 11 figures, to appear in Lecture Notes in Applied and Computational Mechanics, Springer (2006

A Stability Diagram for Dense Suspensions of Model Colloidal Al2O3-Particles in Shear Flow

In Al2O3 suspensions, depending on the experimental conditions very different microstructures can be found, comprising fluid like suspensions, a repulsive structure, and a clustered microstructure. For technical processing in ceramics, the knowledge of the microstructure is of importance, since it essentially determines the stability of a workpiece to be produced. To enlighten this topic, we investigate these suspensions under shear by means of simulations. We observe cluster formation on two different length scales: the distance of nearest neighbors and on the length scale of the system size. We find that the clustering behavior does not depend on the length scale of observation. If inter-particle interactions are not attractive the particles form layers in the shear flow. The results are summarized in a stability diagram.Comment: 15 pages, 10 figures, revised versio

Phagocytosis and LPS alter the maturation state of β-amyloid precursor protein and induce different Aβ peptide release signatures in human mononuclear phagocytes

<p>Abstract</p> <p>Background</p> <p>The classic neuritic β-amyloid plaque of Alzheimer's disease (AD) is typically associated with activated microglia and neuroinflammation. Similarly, cerebrovascular β-amyloid (Aβ) deposits are surrounded by perivascular macrophages. Both observations indicate a contribution of the mononuclear phagocyte system to the development of β-amyloid.</p> <p>Methods</p> <p>Human CD14-positive mononuclear phagocytes were isolated from EDTA-anticoagulated blood by magnetic activated cell sorting. After a cultivation period of 72 hours in serum-free medium we assessed the protein levels of amyloid precursor protein (APP) as well as the patterns and the amounts of released Aβ peptides by ELISA or one-dimensional and two-dimensional urea-based SDS-PAGE followed by western immunoblotting.</p> <p>Results</p> <p>We observed strong and significant increases in Aβ peptide release upon phagocytosis of acetylated low density lipoprotein (acLDL) or polystyrene beads and also after activation of the CD14/TLR4 pathway by stimulation with LPS. The proportion of released N-terminally truncated Aβ variants was increased after stimulation with polystyrene beads and acLDL but not after stimulation with LPS. Furthermore, strong shifts in the proportions of single Aβ_1-40and Aβ_2-40variants were detected resulting in a stimulus-specific Aβ signature. The increased release of Aβ peptides was accompanied by elevated levels of full length APP in the cells. The maturation state of APP was correlated with the release of N-terminally truncated Aβ peptides.</p> <p>Conclusions</p> <p>These findings indicate that mononuclear phagocytes potentially contribute to the various N-truncated Aβ variants found in AD β-amyloid plaques, especially under neuroinflammatory conditions.</p

Acceptance, Prevalence and Indications for Robot-Assisted Laparoscopy - Results of a Survey Among Urologists in Germany, Austria and Switzerland

Background: Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. Objective: To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. Materials and Methods: To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. Results: The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. Conclusions: This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered

Simulation of Claylike Colloids

We investigate properties of dense suspensions and sediments of small spherical silt particles by means of a combined Molecular Dynamics (MD) and Stochastic Rotation Dynamics (SRD) simulation. We include van der Waals and effective electrostatic interactions between the colloidal particles, as well as Brownian motion and hydrodynamic interactions which are calculated in the SRD-part. We present the simulation technique and first results. We have measured velocity distributions, diffusion coefficients, sedimentation velocity, spatial correlation functions and we have explored the phase diagram depending on the parameters of the potentials and on the volume fraction.Comment: 20 pages, 14 figure

Late-Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3') Kinases

The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug‐resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad‐spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram‐positive and Gram‐negative bacteria is phosphorylation of these amino sugars at the 3’‐position by O‐phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’‐position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi‐step synthesis, which is not appealing for pharma industry in this low‐return‐on‐investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’‐position via palladium‐catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s‐mediated resistance employing only four synthetic steps

Shear Viscosity of Clay-like Colloids in Computer Simulations and Experiments

Dense suspensions of small strongly interacting particles are complex systems, which are rarely understood on the microscopic level. We investigate properties of dense suspensions and sediments of small spherical Al_2O_3 particles in a shear cell by means of a combined Molecular Dynamics (MD) and Stochastic Rotation Dynamics (SRD) simulation. We study structuring effects and the dependence of the suspension's viscosity on the shear rate and shear thinning for systems of varying salt concentration and pH value. To show the agreement of our results to experimental data, the relation between bulk pH value and surface charge of spherical colloidal particles is modeled by Debye-Hueckel theory in conjunction with a 2pK charge regulation model.Comment: 15 pages, 8 figure

Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

Multivalent interactions at biological interfaces occur frequently in nature and mediate recognition and interactions in essential physiological processes such as cell-to-cell adhesion. Multivalency is also a key principle that allows tight binding between pathogens and host cells during the initial stages of infection. One promising approach to prevent infection is the design of synthetic or semisynthetic multivalent binders that interfere with pathogen adhesion1,2,3,4. Here, we present a multivalent binder that is based on a spatially defined arrangement of ligands for the viral spike protein haemagglutinin of the influenza A virus. Complementary experimental and theoretical approaches demonstrate that bacteriophage capsids, which carry host cell haemagglutinin ligands in an arrangement matching the geometry of binding sites of the spike protein, can bind to viruses in a defined multivalent mode. These capsids cover the entire virus envelope, thus preventing its binding to the host cell as visualized by cryo-electron tomography. As a consequence, virus infection can be inhibited in vitro, ex vivo and in vivo. Such highly functionalized capsids present an alternative to strategies that target virus entry by spike-inhibiting antibodies5 and peptides6 or that address late steps of the viral replication cycle