Materials science at Swiss universities of applied sciences

Copyright ©Swiss Chemical Society: CHIMIA, Volume 73, Numbers 7-8, August 2019, pp. 645-655(11)In the Swiss Universities of Applied Sciences, several research institutes are involved in Materials Science, with different approaches and applications fields. A few examples of recent projects from different groups of the University of Applied Sciences and Arts Western Switzerland (HES-SO), the Zurich University of Applied Sciences (ZHAW) and the University of Applied Sciences and Arts Northwestern Switzerland (FHNW) are given

Monitoring the expression of purinoceptors and nucleotide-metabolizing ecto-enzymes with antibodies directed against proteins in native conformation

Following their release from cells, ATP and NAD, the universal currencies of energy metabolism, function as extracellular signalling molecules. Mammalian cells express numerous purinoceptors, i.e., the nucleotide-gated P2X ion channels and the G-protein-coupled P2Y receptors. Signalling through purinoceptors is controlled by nucleotide-metabolizing ecto-enzymes, which regulate the availability of extracellular nucleotides. These enzymes include ecto-nucleoside triphosphate diphosphohydrolases (ENTPD, CD39 family) and ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP, CD203 family). Investigation of these receptors and enzymes has been hampered by the lack of available antibodies, especially ones that recognize these proteins in their native conformation. This study reports the use of genetic immunization to generate such antibodies against P2X1, P2X4, P2X7, ENTPD1, ENPTD2, ENPTD5, ENPTD6, ENPP2, ENPP3, ENPP4, ENPP5, and ENPP6. Genetic immunization ensures expression of the native protein by the cells of the immunized animal and yields antibodies directed against proteins in native conformation (ADAPINCs). Such antibodies are especially useful for immunofluorescence and immunoprecipitation analyses, whereas antibodies against synthetic peptides usually function well only in Western-blot analyses. Here we illustrate the utility of the new antibodies to monitor the cell surface expression of and to purify some key players of purinergic signalling

Regulation of the Activity in the p53 Family Depends on the Organization of the Transactivation Domain.

Despite high sequence homology among the p53 family members, the regulation of their transactivation potential is based on strikingly different mechanisms. Previous studies revealed that the activity of TAp63α is regulated via an autoinhibitory mechanism that keeps inactive TAp63α in a dimeric conformation. While all p73 isoforms are constitutive tetramers, their basal activity is much lower compared with tetrameric TAp63. We show that the dimeric state of TAp63α not only reduces DNA binding affinity, but also suppresses interaction with the acetyltransferase p300. Exchange of the transactivation domains is sufficient to transfer the regulatory characteristics between p63 and p73. Structure determination of the transactivation domains of p63 and p73 in complex with the p300 Taz2 domain further revealed that, in contrast to p53 and p73, p63 has a single transactivation domain. Sequences essential for stabilizing the closed dimer of TAp63α have evolved into a second transactivation domain in p73 and p53.The research was funded by the DFG (DO 545/8 and DO 545/13), the Center for Biomolecular Magnetic Resonance (BMRZ), and the Cluster of Excellence Frankfurt (Macromolecular Complexes). M.T. was supported by a fellowship from the Fonds of the Chemical Industry

The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine

In adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues

Parasitic Absorption in Polycrystalline Si-layers for Carrier-selective Front Junctions

We investigate the optical properties of n- and p-type polycrystalline silicon (poly-Si) layers. We determine the optical constants n and k of the complex refractive index of polycrystalline silicon by using variable-angle spectroscopic ellipsometry. Moreover, we investigate the effect of different doping levels in the poly-Si on free carrier absorption (FCA). Thereby, we demonstrate that the FCA in poly-Si can be described by a model developed for crystalline silicon (c-Si) at a first approximation. The optical properties of hydrogenated amorphous silicon layers (a-Si:H) are also investigated as a reference. With ray tracing simulations the absorption losses of poly-Si and of the a-Si:H layers are quantified with respect to the film thickness. Based on this approach we find that the short-circuit current density losses due to parasitic absorption of poly-Si layers are significantly lower when compared to a-Si:H layers of the same thickness. For example the short-circuit current density loss due to a 20 nm thick p-type poly-Si layer is around 1.1 mA/cm2, whereas a 20 nm thick p-type a-Si:H layer leads to a loss of around 3.5 mA/cm2.BMWi/032570

VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts

Peer reviewe

mensaarRAUM − Walter Schrempf, Otto Herbert Hajek und ihr Studentenhaus

Das Saarbrücker Studentenhaus — die Mensa — ist eines der ikonischsten Gebäude auf dem Campus und auch weit über das Saarland hinaus als brutalistisches Gesamtkunstwerk aus Architektur und Raumplastik bekannt: Die innovative Zusammenarbeit von Walter Schrempf und Otto Herbert Hajek stellt in den 1960er Jahren eine der ersten und spannendsten Kooperationen zwischen Architektur und Bildhauerei der bundesdeutschen Nachkriegszeit dar. Auch heute noch — 50 Jahre nach der Eröffnung im Oktober 1970 — fordert der Bau sowohl im alltäglichen Unileben als auch in kulturwissenschaftlichen Kontexten bewusst zur Auseinandersetzung heraus. Anknüpfend an das Seminar »Spatial turn — Raumperspektiven in den Kulturwissenschaften« haben MA-Studierende diese Herausforderung angenommen und sich in einem Ausstellungsprojekt dem Bau und seinen Räumen u. a. aus kunstwissenschaftlicher, soziologischer und phänomenologischer Perspektive gewidmet

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Controls on the Geometry and Evolution of Deep-water Fold Thrust Belt of the NW Borneo.

The key driving mechanisms for establishing deep-water fold-thrust belt are either lithospheric stress or gravity-driven associated with margin instability or a combination of both. Despite long academic interest, we still lack of detailed understanding of the interaction between the deformation mechanisms (gravity- and tectonic-driven). The results of an evaluation of the interaction between the deformation mechanisms, with focused attention upon the NW Borneo deep-water fold-thrust belt, are reported. A methodology integrating a detailed structural analysis of the deep-water fold-thrust belt from the available subsurface data and equivalent onshore outcrop is utilized in this study. Detailed structural analysis of 2D seismic profiles is used to present a basin-scale seismic-stratigraphic framework and detailed description of the general appearance of the deformational style along the deltaic system. Sub-seismic scale investigation of well-exposed outcrops onshore NW Sabah is used to extract information on onshore tectonic deformation, making it possible to evaluate the differences of structural architecture related to different deformation mechanisms. The result has led to an improved understanding of the regional-scale structural geometry along the NW Borneo margin. Regional scale cross-sections are used to demonstrate a regional-scale analysis of the NW Borneo margin that includes structural restoration. The results allow an assessment of the relative timing of deformation, the domain interaction and the possible processes and parameters that control deformation. This has led to an improved insight relating to the kinematic nature of the allochthon and the interaction between the deformation mechanisms. Structural restorations are also used to evaluate of areas of compressionally and extensionally dominated systems, in order to verify the main proses responsible for the margin evolution. This study illustrates outcrop-scale to seismic-scale analysis and quantitative measurements combined with seismic interpretations, with the aim to identify the interaction between gravity-and tectonic-driven deformation, and their controls on the geometry and evolution of deep-water fold-thrust systems. Additionally, the margin evolution and the implications on NW Borneo are evaluated

Extracellular NAD and ATP: Partners in immune cell modulation

Extracellular NAD and ATP exert multiple, partially overlapping effects on immune cells. Catabolism of both nucleotides by extracellular enzymes keeps extracellular concentrations low under steady-state conditions and generates metabolites that are themselves signal transducers. ATP and its metabolites signal through purinergic P2 and P1 receptors, whereas extracellular NAD exerts its effects by serving as a substrate for ADP-ribosyltransferases (ARTs) and NAD glycohydrolases/ADPR cyclases like CD38 and CD157. Both nucleotides activate the P2X7 purinoceptor, although by different mechanisms and with different characteristics. While ATP activates P2X7 directly as a soluble ligand, activation via NAD occurs by ART-dependent ADP-ribosylation of cell surface proteins, providing an immobilised ligand. P2X7 activation by either route leads to phosphatidylserine exposure, shedding of CD62L, and ultimately to cell death. Activation by ATP requires high micromolar concentrations of nucleotide and is readily reversible, whereas NAD-dependent stimulation begins at low micromolar concentrations and is more stable. Under conditions of cell stress or inflammation, ATP and NAD are released into the extracellular space from intracellular stores by lytic and non-lytic mechanisms, and may serve as ‘danger signals–to alert the immune response to tissue damage. Since ART expression is limited to naïve/resting T cells, P2X7-mediated NAD-induced cell death (NICD) specifically targets this cell population. In inflamed tissue, NICD may inhibit bystander activation of unprimed T cells, reducing the risk of autoimmunity. In draining lymph nodes, NICD may eliminate regulatory T cells or provide space for the preferential expansion of primed cells, and thus help to augment an immune response