Ion‐Exchange Adsorption of Proteins: Experiments and Molecular Dynamics Simulations

The adsorption of serum albumin and hemoglobin onto Q Sepharose FF was investigated, where the single and binary adsorption were considered. Both experiments and molecular dynamics simulations have been performed to study the adsorption from macroscopic and microscopic points of view. The steric mass‐action model was applied to describe the single adsorption isotherms and to predict the binary isotherms. The results of the experiments and simulations were connected and compared by two parameters of the steric mass‐action model. Both results present a preferential adsorption of serum albumin.     

Formal testing of timed graph transformation systems using metric temporal graph logic

Embedded real-time systems generate state sequences where time elapses between state changes. Ensuring that such systems adhere to a provided specification of admissible or desired behavior is essential. Formal model-based testing is often a suitable cost-effective approach. We introduce an extended version of the formalism of symbolic graphs, which encompasses types as well as attributes, for representing states of dynamic systems. Relying on this extension of symbolic graphs, we present a novel formalism of timed graph transformation systems (TGTSs) that supports the model-based development of dynamic real-time systems at an abstract level where possible state changes and delays are specified by graph transformation rules. We then introduce an extended form of the metric temporal graph logic (MTGL) with increased expressiveness to improve the applicability of MTGL for the specification of timed graph sequences generated by a TGTS. Based on the metric temporal operators of MTGL and its built-in graph binding mechanics, we express properties on the structure and attributes of graphs as well as on the occurrence of graphs over time that are related by their inner structure. We provide formal support for checking whether a single generated timed graph sequence adheres to a provided MTGL specification. Relying on this logical foundation, we develop a testing framework for TGTSs that are specified using MTGL. Lastly, we apply this testing framework to a running example by using our prototypical implementation in the tool AutoGraph.

     

Overcoming hypoxia in 3D culture systems for tissue engineering of bone in vitro using an automated, oxygen-triggered feedback loop

Tissue engineering is an attractive approach to heal bony defects. However, three-dimensional cell-scaffold constructs display uneven oxygen supply resulting in inhomogeneous tissue quality. We assessed different strategies to improve oxygen supply in vitro. Scaffolds with differing inner surface were seeded with preosteoblastic cells and cultivated either statically or in perfusion bioreactors. Oxygen concentration and pH were measured in the center of the scaffolds. An inductive feedback mechanism was build to increase bioreactor pump speed according to the oxygen concentrations measured within the scaffolds. While pH remained stable, oxygen concentration decreased significantly under static conditions within the cell-seeded scaffolds. Reducing the scaffolds’ inner surface as well as increasing perfusion speeds in bioreactors resulted in improved oxygen supply. We conclude that improving oxygen supply to three dimensional culture systems for bone tissue engineering is feasible in an automated manner. Culture conditions have to be adapted to each cell-scaffold system individually.     

Insights into clients’ choice in preventive health care facility location planning

In this contribution we build on the approach proposed by Zhang et al. (OR Spectrum 34:349–370, 2012) to consider clients’ choice in preventive health care facility location planning. The objective is to maximize the participation in a preventive health care program for early detection of breast cancer in women. In order to account for clients’ choice behavior the multinomial logit model is employed. In this paper, we show that instances up to 20 potential locations and 400 demand points can be easily solved (to optimality or at least close to optimality) by a commercial solver in reasonable time if the problem is modeled by an alternative formulation. We present an intelligible approach to derive a lower bound to the problem. Our paper provides interesting insights into the trade-off between minimum workload requirement (to ensure quality of care) and participation (and thus early diagnosis of disease). We present a general definition of clients’ utility (which allows for clients’ characteristics, for example) and discuss some fundamental issues (and pitfalls) concerning the specification of utility functions.     

Engineering a Constrained Peptidic Scaffold towards Potent and Selective Furin Inhibitors

We report the engineering of the monocyclic sunflower trypsin inhibitor (SFTI‐1[1,14]) into a potent furin inhibitor. In a rational approach, we converted the native scaffold of this trypsin‐like serine protease inhibitor into a subtilisin‐like one by substitutions in the canonical and, particularly, in the substrate‐binding loop. Although the substrate sequence for furin is Arg‐X‐Arg/Lys‐Arg↓, the most potent inhibitor had a lysine at position P1. C‐terminally truncated versions demonstrated the strongest activity, thus suggesting a lack of interaction between this motif and the surface of furin. This observation was further supported by molecular modeling. With an inhibition constant of 0.49 nm , the engineered peptide H‐KRCKKSIPPICF‐NH₂ is a promising compound for further development of furin inhibitors aimed at controlling the activity of this protease in vitro and in vivo.