An indole-binding site is a major determinant of the ligand specificity of the GABA type A receptor-associated protein GABARAP

The role of tryptophan as a key residue for ligand binding to the ubiquitin-like modifier GABA(A) receptor associated protein (GABARAP) was investigated. Two tryptophan-binding hydrophobic patches were identified on the conserved face of the GABARAP structure by NMR spectroscopy and molecular docking. GABARAP binding of indole and indole derivatives, including the free amino acid tryptophan was quantified. The two tryptophan binding sites can be clearly distinguished by mapping the NMR spectroscopy-derived residue-specific apparent dissociation constant, K(d), onto the three-dimensional structure of GABARAP. The biological relevance of tryptophan-binding pockets of GABARAP was supported by a highly conserved tryptophan residue in the GABARAP binding region of calreticulin, clathrin heavy chain, and the gamma2 subunit of the GABA(A) receptor. Replacement of tryptophan by alanine abolished ligand binding to GABARAP.     

Biomechanical functional and sensory modelling of the gastrointestinal tract

The aim of this review is to describe the biomechanical, functional and sensory modelling work that can be used to integrate the physiological, anatomical and medical knowledge of the gastrointestinal (GI) system. The computational modelling in the GI tract was designed, implemented and evaluated using a series of information and communication technologies-based tools. These tools modelled the morphometry, biomechanics, functions and sensory aspects of the human GI tract. The research presented in this review is based on the virtual physiological human concept that pursues a holistic approach to representation of the human body. Such computational modelling combines imaging data, GI physiology, the gut-brain axis, geometrical and biomechanical reconstruction, and computer graphics for mechanical, electronic and pain analysis. The developed modelling will aid research and ensure that medical professionals benefit through the provision of relevant and precise information about a patient's condition. It will also improve the accuracy and efficiency of the medical procedures that could result in reduced cost for diagnosis and treatment.     

Stepwise current-driven release of attogram quantities of copper iodide encapsulated in carbon nanotubes

Encapsulated nanograins of copper iodide have been sequentially discharged from individual carbon nanotubes. Using a high resolution electron microscope equipped with a two-terminal electrical measurements unit, it was possible to manipulate the filling contents with precisions of a few attograms at a time. Changes in electrical resistance and filling ratio were followed in tandem and in real-time. It is shown that the pulsed release of the halide is directly related to the overall conductance of the filled nanotube.     

Development of New Combined Manufacturing Technologies ‐ Influence of the Cutting Process on Workpiece Properties

Properties of materials for high‐strength structure components are influenced by production processes. These influences can be augmented by a combination of two presently consecutively executed process steps. The presented work shows first results in the development of novel combined manufacturing technologies, which along with prospective tools use this effect to adjust the material properties locally, adapted to the requirements. The combination consists of a merging of the process steps ‘material separation’ (metal cutting) and ‘changing properties’ (rubbing, rolling) to one single process step. For this purpose novel combined tools have to be developed. For the estimation of the possibilities of properties changes by combined processes at first the influences of single processes have to be determined. This contribution presents results of a “material separation” process. The investigated material is the industrially important aluminium wrought alloy AI7075‐T6, the applied process is orthogonal turning, the process parameters varied are cutting speed and feed as well as the tool geometry. Cutting force and feed force are measured, and the process influences on surface and subsurface properties are determined.     

Liver TAG Transiently Decreases While PL n-3 and n-6 Fatty Acids are Persistently Elevated in Insulin Resistant Mice

Changes in fatty acid metabolism associated with insulin resistance have been described in rats and humans but have not been well characterized in the frequently used mouse model of diet-induced obesity. To analyse the early phase as well as established insulin resistance, C57BL/6 mice were placed for 1 or 16 weeks on a high fat diet (1w-HFD, 16w-HFD). Endocrine and metabolic parameters indicated that 1w-HFD mice showed a moderate but significant induction of insulin resistance while 16w-HFD mice exhibited profound obesity-associated insulin resistance and dyslipidemias. Significant alterations in fatty acid composition were observed in plasma and liver in both groups. Liver phospholipid-associated arachidonate and docosahexaenoate were increased in both 1w-HFD and 16w-HFD mice, possibly due to increased expression of the desaturases Fads1 and Fads2. Unexpectedly, SCD1 activity and gene expression in liver were decreased in the 1w-HFD group accompanied by diminished total hepatic lipid levels, while they were increased in chronically fed mice. Our data indicate that the early phase of HFD-induced insulin resistance is not associated with elevated liver lipid concentration. Furthermore, the early and persistent rise of arachidonate and docosahexaenoate indicates that insulin resistance is not due to insufficient availability (or concentrations) of polyunsaturated fatty acids as postulated previously. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Influence of twin-screw extrusion conditions on the dispersion of multi-walled carbon nanotubes in a poly(lactic acid) matrix

Twin-screw extrusion using a co-rotating Berstorff ZE25 extruder was applied to disperse multi-walled carbon nanotubes (MWNT) in poly(lactic acid) (PLA). The masterbatch dilution technique was used whereas four different masterbatches were produced under variation of MWNT content, screw profile, temperature profile, and rotation speed which then were diluted to composites with 0.75 wt% MWNT under varied process conditions. The state of dispersion was investigated by light microscopy from which a dispersion index was quantified. Transmission electron microscopy was performed to observe the MWNT dispersion and network formation in the sub-micron scale.The state of MWNT dispersion within the diluted composites was predominated by the state of filler dispersion in the masterbatches. High rotation speed (500 rpm) that still ensures a certain residence time of the melt combined with a screw profile containing mainly mixing elements were found to be highly convenient to disperse and distribute the MWNT in the PLA matrix as well during masterbatch production as the dilution step. The temperature profile showed less influence, however, an increasing profile resulted in slightly better nanotube dispersions. By means of these processing conditions a percolation set was performed indicating an electrical percolation threshold below 0.5 wt% MWNT content as measured on compression molded samples.     

Improving the load flexibility of industrial air separation units using a pressure-driven digital twin

Air separation units are one of the prime examples for studies on demand side management and (non-)linear model predictive control due to their high power consumption and energy storage potential. These plants separate ambient air into its main components, nitrogen, oxygen, and argon, by means of cryogenic distillation at different pressure levels. Approximately two thirds of the industrially operated air separation units consider the separation of argon either as a value product or for reasons of energy efficiency. However, most of the studies in literature neglect the separation of argon since this requires additional equipment, increases the heat and process integration and, thus, the complexity of process control. In this work, a digital twin of an air separation unit with argon system is used to analyze and to improve load change procedures. Moreover, the potential of applying the digital twin as a soft sensor is demonstrated.     

Multipass cell design for Stark-modulation spectroscopy

A multipass cell for absorption measurements with an additionally applied homogeneous electric field for Stark effect measurements is described. The configuration is based on two ring mirrors, where the laser beam propagates between two nested cylindrical-wall electrodes. The total optical path length achieved is 40 m. The beam pointing stability of this setup is investigated and compared to a confocal-type Herriott cell of the same base length, employing numerical simulations. The exit beam pointing stability is found to be very good. The response measurements show fast exchange times, which agree well with theoretical values.