280 research outputs found
Quasicontinuum representations of atomic-scale mechanics: From proteins to dislocations
Computation is one of the centerpieces of both the physical and biological sciences. A key thrust in computational science is the explicit mechanistic simulation of the spatiotemporal evolution of materials ranging from macromolecules to intermetallic alloys. However, our ability to simulate such systems is in the end always limited in both the spatial extent of the systems that are considered, as well as the duration of the time that can be simulated. As a result, a variety of efforts have been put forth that aim to finesse these challenges in both space and time through new techniques in which constraint is exploited to reduce the overall computational burden. The aim of this review is to describe in general terms some of the key ideas that have been set forth in both the materials and biological setting and to speculate on future developments along these lines. We begin by developing general ideas on the exploitation of constraint as a systematic tool for degree of freedom thinning. These ideas are then applied to case studies ranging from the plastic deformation of solids to the interactions of proteins and DNA
Self-adaptive Scouting---Autonomous Experimentation for Systems Biology
We introduce a new algorithm for autonomous experimentation. This algorithm uses evolution to drive exploration during scientific discovery. Population size and mutation strength are self-adaptive. The only variables remaining to be set are the limits and maximum resolution of the parameters in the experiment. In practice, these are determined by instrumentation. Aside from conducting physical experiments, the algorithm is a valuable tool for investigating simulation models of biological systems. We illustrate the operation of the algorithm on a model of HIV-immune system interaction. Finally, the difference between scouting and optimization is discussed
Sediment transport over static armour layers and its impact on bed stability
River morphodynamics and sediment transportRiver morphology and morphodynamic
Der Bibliotheksneubau der Hochschule fĂĽr Technik, Wirtschaft und Kultur Leipzig
Der Neubau der Hochschulbibliothek der
Hochschule fĂĽr Technik, Wirtschaft und
Kultur Leipzig (HTWK) ist ein Beispiel fĂĽr
ein durchgefĂĽhrtes Bauprojekt des Vorhabens
„Infrastruktur an Hochschulen“, finanziert mit Mitteln
des Europäischen Fonds für regionale Entwicklung.
Ziel der Förderung ist unter anderem, die baulichen
Voraussetzungen fĂĽr eine bessere Vernetzung
der Forschung innerhalb der Hochschule, aber auch
zu anderen Einrichtungen und Unternehmen zu
schaffen. Die HTWK Leipzig konzentriert sich an
ihrem Hauptstandort im Leipziger SĂĽden auf beiden
Seiten der Karl-Liebknecht-StraĂźe. Ausgehend
von dieser Zielstellung wurde fĂĽr die Hochschul -
bibliothek ein Neubau geschaffen, der sowohl in
seiner Größe als auch in seiner Ausstattung den
gewachsenen AnsprĂĽchen an die Literatur- und
Informationsversorgung der sich im Campus konzentrierenden
Lehre und Forschung gerecht wird
Cell-Free Microfluidic Determination of P-glycoprotein Interactions with Substrates and Inhibitors
ABSTRACT: The membrane protein P-glycoprotein (P-gp) plays key roles in the oral bioavailability of drugs, their blood brain barrier passage as well as in multidrug resistance. For new drug candidates it is mandatory to study their interaction with P-gp, according to FDA and EMA regulations. The vast majority of these tests are performed using confluent cell layers of P-gp overexpressing cell lines that render these tests laborious. In this study, we introduce a cell-free microfluidic assay for the rapid testing of drug- P-gp interactions. Cell-derived vesicles are prepared from MDCKII-MDR1 overexpressing cells and immobilized on the surface of a planar microfluidic device. The drug is delivered continuously to the vesicles and calcein accumulation is monitored by means of a fluorescence assay and total internal reflection fluorescence (TIRF) microscopy. Only small amounts of compounds (~10μl) are required in concentrations of 5, 25 and 50μM for a test that provides within 5min information on the apparent dissociation constant of the drug and P-gp. We tested 10 drugs on-chip, 9 of which are inhibitors or substrates of P-glycoprotein and one negative control. We benchmarked the measured apparent dissociation constants against an alternative assay on a plate reader and reference data from FDA. These comparisons revealed good correlations between the logarithmic apparent dissociation constants (R2 = 0.95 with ATPase assay, R2 = 0.93 with FDA data) and show the reliability of the rapid on-chip test. The herein presented assay has an excellent screening window factor (Z'-factor) of 0.8, and is suitable for high-throughput testing
Skyrmion Lattice Phases in Thin Film Multilayer
Phases of matter are ubiquitous with everyday examples including solids and
liquids. In reduced dimensions, particular phases, such as the two-dimensional
(2D) hexatic phase and corresponding phase transitions occur. A particularly
exciting example of 2D ordered systems are skyrmion lattices, where in contrast
to previously studied 2D colloid systems, the skyrmion size and density can be
tuned by temperature and magnetic field. This allows us to drive the system
from a liquid phase to a hexatic phase as deduced from the analysis of the
hexagonal order. Using coarse-grained molecular dynamics simulations of soft
disks, we determine the skyrmion interaction potentials and we find that the
simulations are able to reproduce the full two-dimensional phase behavior. This
shows that not only the static behavior of skyrmions is qualitatively well
described in terms of a simple two-dimensional model system but skyrmion
lattices are versatile and tunable two-dimensional model systems that allow for
studying phases and phase transitions in reduced dimensions.Comment: Corrected Acknowledgement
- …