How to get proteomics to the clinic? Issues in clinical proteomics,exemplified by CE‐MS

Clinical proteomics is defined as application of proteome analysis aiming at improving the current clinical situation. As such, the success of clinical proteomics should be assessed based on the clinical impact following implementation of the findings. While we have experienced significant technological advancements in mass spectrometry in the last years, based on the above measure, this has not at all resulted in similar advancements in clinical proteomics. Although a large number of proteomic biomarkers have been described, most of them were not subsequently validated, and certainly have had no impact in clinical decision making as yet. Under the current conditions, it appears likely that the situation will not change significantly: we will be flooded by reports on biomarkers, but not see any implementation. In this article, some key issues in proteomic biomarker research are pinpointed, based on the experience with CE‐MS, likely also holding true for biomarkers resulting from other analysis domains.     

CFD-Simulation eines direkt befeuerten Ofens zur Vorbehandlung feuerverzinkter Stahlbänder

For the production of high-quality goods in industrial furnaces using minimal expenditure of energy, optimization of the process parameters is required. One tool for improving the processes economically is the simulation of the furnaces by using Computational Fluid Dynamics (CFD). The pre-heating process of a steel strip in a section of an annealing furnace for surface treatment in a hot-dip galvanizing process was simulated using the commercial CFD software Ansys Fluent 15.0. For combustion, the Equilibrium model is used, turbulence is modeled by the realizable-k-ε model, and radiation is taken into account by using the Discrete Ordinate Method (DOM).     

Training echo state networks for rotation-invariant bone marrow cell classification

The main principle of diagnostic pathology is the reliable interpretation of individual cells in context of the tissue architecture. Especially a confident examination of bone marrow specimen is dependent on a valid classification of myeloid cells. In this work, we propose a novel rotation-invariant learning scheme for multi-class echo state networks (ESNs), which achieves very high performance in automated bone marrow cell classification. Based on representing static images as temporal sequence of rotations, we show how ESNs robustly recognize cells of arbitrary rotations by taking advantage of their short-term memory capacity. The performance of our approach is compared to a classification random forest that learns rotation-invariance in a conventional way by exhaustively training on multiple rotations of individual samples. The methods were evaluated on a human bone marrow image database consisting of granulopoietic and erythropoietic cells in different maturation stages. Our ESN approach to cell classification does not rely on segmentation of cells or manual feature extraction and can therefore directly be applied to image data.

     

Porous protein-based scaffolds prepared through freezing as potential scaffolds for tissue engineering

Successful tissue engineering with the aid of a polymer scaffold offers the possibility to produce a larger construct and to mould the shape after the defect. We investigated the use of cryogelation to form protein-based scaffolds through different types of formation mechanisms; enzymatic crosslinking, chemical crosslinking, and non-covalent interactions. Casein was found to best suited for enzymatic crosslinking, gelatin for chemical crosslinking, and ovalbumin for non-covalent interactions. Fibroblasts and myoblasts were used to evaluate the cryogels for tissue engineering purposes. The stability of the cryogels over time in culture differed depending on formation mechanism. Casein cryogels showed best potential to be used in skeletal tissue engineering, whereas gelatin cryogels would be more suitable for compliable soft tissues even though it also seemed to support a myogenic phenotype. Ovalbumin cryogels would be better suited for elastic tissues with faster regeneration properties due to its faster degradation time. Overall, the cryogelation technique offers a fast, cheap and reproducible way of creating porous scaffolds from proteins without the use of toxic compounds.     

A method to characterize asymmetrical three-stage creep of ordinary refractory ceramics and its application for numerical modelling

During operation, thermomechanical stresses occur in refractory linings. Under elevated stress and temperatures, these ceramics experience primary creep, which can further proceed to the secondary and tertiary creep stages. This necessitates a characterization of their three-stage creep behavior. Hence, two advanced uniaxial tensile and compressive creep testing devices are utilized. The Norton-Bailey creep equations and an inverse identification procedure are applied for the evaluation of the creep curves. To account for the full three-stage creep behavior in thermomechanical modelling activities, a creep-stage transition criterion is identified and subsequently implemented together with the Norton-Bailey creep-strain rate representations in a new developed creep model. The finite element simulation results from different creep testing procedures are in accordance with the corresponding experimental results of a magnesia-chromite refractory ceramic. The study also reveals the temperature-dependent asymmetrical creep behavior of the material in terms of the creep-strain rates and critical creep strains.     

SPHERES, Jülich's high-flux neutron backscattering spectrometer at FRM II

SPHERES is a third-generation neutron backscattering spectrometer, located at the 20 MW German neutron source FRM II and operated by the Ju?lich Centre for Neutron Science. It offers an energy resolution (fwhm) better than 0.65 μeV, a dynamic range of ±?31 μeV, and a signal-to-noise ratio of up to 1750:1.     

Engineering of Saccharomyces cerevisiae for the production of (+)-ambrein

The triterpenoid (+)-ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)-ambrein, several fragrance molecules are formed, amongst them (−)-ambrox, one of the highest valued compounds in the perfume industry. In order to generate a Saccharomyces cerevisiae whole-cell biocatalyst for the production of (+)-ambrein, intracellular supply of the squalene was enhanced by overexpression of two central enzymes in the mevalonate and sterol biosynthesis pathway, namely the N-terminally truncated 3-hydroxy-3-methylglutaryl-CoA reductase 1 (tHMG) and the squalene synthase (ERG9). In addition, another key enzyme in sterol biosynthesis, squalene epoxidase (ERG1) was inhibited by an experimentally defined amount of the inhibitor terbinafine in order to reduce flux of squalene towards ergosterol biosynthesis while retaining sufficient activity to maintain cell viability and growth. Heterologous expression of a promiscuous variant of Bacillus megaterium tetraprenyl-β-curcumene cyclase (BmeTC-D373C), which has been shown to be able to catalyse the conversion of squalene to 3-deoxyachillol and then further to (+)-ambrein resulted in production of these triterpenoids in S. cerevisiae for the first time. Triterpenoid yields are comparable with the best microbial production chassis described in literature so far, the methylotrophic yeast Pichia pastoris. Consequently, we discuss similarities and differences of these two yeast species when applied for whole-cell (+)-ambrein production.     

Diamine oxidase supplementation improves symptoms in patients with histamine intolerance

Food Science and Biotechnology - Histamine intolerance (HIT) is thought to be caused by a disproportionate amount of histamine in the body. The enzyme diamine oxidase (DAO) is considered for the...