Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation

Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Clinical studies demonstrate a reduction of the mentioned diseases’ symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs. In this study, we, therefore, evaluated the anti-inflammatory capacities of the two novel coumarin-based compounds, KIT C and KIT H, in human neuroblastoma cells and primary murine microglia. Both compounds reduced PGE₂-concentrations likely via the inhibition of COX-2 synthesis in SK-N-SH cells but only KIT C decreased PGE₂-levels in primary microglia. The examination of other pro- and anti-inflammatory parameters showed varying effects of both compounds. Therefore, the differences in the effects of KIT C and KIT H might be explained by functional selectivity as well as tissue- or cell-dependent expression and signal pathways coupled to GPR55. Understanding the role of chemical residues in functional selectivity and specific cell- and tissue-targeting might open new therapeutic options in pharmacological drug development and might improve the treatment of the mentioned diseases by intervening in an early step of their pathogenesis.     

T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model

To better understand the role of sphingolipids in the multifactorial process of inflammatory bowel disease (IBD), we elucidated the role of CerS4 in colitis and colitis-associated cancer (CAC). For this, we utilized the azoxymethane/dextran sodium sulphate (AOM/DSS)-induced colitis model in global CerS4 knockout (CerS4 KO), intestinal epithelial (CerS4 Vil/Cre), or T-cell restricted knockout (CerS4 LCK/Cre) mice. CerS4 KO mice were highly sensitive to the toxic effect of AOM/DSS, leading to a high mortality rate. CerS4 Vil/Cre mice had smaller tumors than WT mice. In contrast, CerS4 LCK/Cre mice frequently suffered from pancolitis and developed more colon tumors. In vitro, CerS4-depleted CD8+ T-cells isolated from the thymi of CerS4 LCK/Cre mice showed impaired proliferation and prolonged cytokine production after stimulation in comparison with T-cells from WT mice. Depletion of CerS4 in human Jurkat T-cells led to a constitutively activated T-cell receptor and NF-κB signaling pathway. In conclusion, the deficiency of CerS4 in T-cells led to an enduring active status of these cells and prevents the resolution of inflammation, leading to a higher tumor burden in the CAC mouse model. In contrast, CerS4 deficiency in epithelial cells resulted in smaller colon tumors and seemed to be beneficial. The higher tumor incidence in CerS4 LCK/Cre mice and the toxic effect of AOM/DSS in CerS4 KO mice exhibited the importance of CerS4 in other tissues and revealed the complexity of general targeting CerS4.     

Impact of macro-structural reforms on the productivity growth of regions: Distance to the frontier matters

Using a panel of 265 regions from 24 OECD countries from 1997 to 2007, we explore the impact of nation-wide macroeconomic and structural policies on the productivity growth of subnational regions. We find that average relationships between nation-wide policies and regional productivity growth can hide strong differentiated effects according to the distance to the frontier: relaxing employment protection legislation on temporary contracts, lowering barriers to trade and investment and increasing trade openness enhances productivity growth in lagging regions, whereas reducing barriers to entrepreneurship or higher levels of government debt has a positive effect on regions closer to the productivity frontier.     

Rapid Biophysical Characterization and NMR Spectroscopy Structural Analysis of Small Proteins from Bacteria and Archaea

Proteins encoded by small open reading frames (sORFs) have a widespread occurrence in diverse microorganisms and can be of high functional importance. However, due to annotation biases and their technically challenging direct detection, these small proteins have been overlooked for a long time and were only recently rediscovered. The currently rapidly growing number of such proteins requires efficient methods to investigate their structure–function relationship. Herein, a method is presented for fast determination of the conformational properties of small proteins. Their small size makes them perfectly amenable for solution-state NMR spectroscopy. NMR spectroscopy can provide detailed information about their conformational states (folded, partially folded, and unstructured). In the context of the priority program on small proteins funded by the German research foundation (SPP2002), 27 small proteins from 9 different bacterial and archaeal organisms have been investigated. It is found that most of these small proteins are unstructured or partially folded. Bioinformatics tools predict that some of these unstructured proteins can potentially fold upon complex formation. A protocol for fast NMR spectroscopy structure elucidation is described for the small proteins that adopt a persistently folded structure by implementation of new NMR technologies, including automated resonance assignment and nonuniform sampling in combination with targeted acquisition.     

Influence of Spray Drying Parameters on the Formation of β-Phase Poly(vinylidene fluoride)

A simple one-step spraying method to produce poly(vinylidene fluoride) (PVDF) in the desired conformation is presented. The content of the piezoelectric β-phase is measured at different spray drying conditions and during electrospray. The influence of a strong electrical field and charges on the droplet are investigated separately from the electrospray setup with a pneumatic atomizer. For this purpose, the electric field is integrated into a pneumatic atomization process by a plate capacitor and the charge of the droplets by corona discharge. To investigate the drying properties, the drying temperature and the flow rate of dry air are examined. The presented process offers the possibility to deposit PVDF films or to produce PVDF powders, in their piezoelectric β- and γ-phases or in the nonpolar α-phase.     

Assessment of MR imaging during one-lung flooding in a large animal model

Magnetic Resonance Materials in Physics, Biology and Medicine - Magnetic resonance imaging (MRI) of the lung remains challenging due to the low tissue density, susceptibility artefacts,...     

Visual Analytics in Dental Aesthetics

Dental healthcare increasingly employs computer-aided design software, to provide patients with high-quality dental prosthetic devices. In modern dental reconstruction, dental technicians address the unique anatomy of each patient individually, by capturing the dental impression and measuring the mandibular movements. Subsequently, dental technicians design a custom denture that fits the patient from a functional point of view. The current Workflow does not include a systematic analysis of aesthetics, and dental technicians rely only on an aesthetically pleasing mock-up that they discuss with the patient, and on their experience. Therefore, the final denture aesthetics remain unknown until the dental technicians incorporate the denture into the patient. In this Work, we present a solution that integrates aesthetics analysis into the functional Workflow of dental technicians. Our solution uses a video recording of the patient, to preview the denture design at any stage of the denture design process. We present a teeth pose estimation technique that enables denture preview and a set of linked visualizations that support dental technicians in the aesthetic design of dentures. These visualizations assist dental technicians in choosing the most aesthetically fitting preset from a library of dentures, in identifying the suitable denture size, and in adjusting the denture position. We demonstrate the utility of our system with four use cases, explored by a dental technician. Also, we performed a quantitative evaluation for teeth pose estimation, and an informal usability evaluation, with positive outcomes concerning the integration of aesthetics analysis into the functional Workflow.     

Kinetic Modeling of Rhodium-Catalyzed Reductive Amination of Undecanal in Different Solvent Systems

The homogenously rhodium-catalyzed reductive amination of 1-undecanal was performed in two different thermomorphic solvent systems with the ligand Xantphos. The influences of partial pressure, temperature, methanol and catalyst concentration on the reaction were investigated. Based on a network analysis a kinetic model was derived and successfully parametrized for all studied solvent systems. Simulation results were found to be in good agreement with the experiments and allow a further process development and optimization.     

Triphenylamine and some of its derivatives as versatile building blocks for organic electronic applications

This review article gives an overview of past and current activities in the Linear Conjugated Systems Group of Angers and in the IPOC – Functional Polymers Group of the Institute of Polymer Chemistry of Stuttgart on the use of triphenylamine (TPA) as versatile building block for organic electronics. In the first part, the properties of TPA itself are introduced including geometrical and energy level considerations. Dimerization of TPA to tetraphenylbenzidine upon electrochemical oxidation is highlighted. The blocking of TPA para‐positions and its implications in terms of electroactivity is further discussed. The second part shows that dimerization of TPA as pendant redox‐active moieties in polymers is a versatile strategy to crosslink polymer films. Coming from redox homopolymers the crosslinking strategy is extended towards conjugated redox polymers based on polythiophenes and block copolymers. Conductivity mechanisms and the influence of doping level on conductivity are probed with cyclic voltammetry coupled with in situ conductance and four‐point probe measurements. The last part is dedicated to the use of TPA as an electron‐donating block in the design of donor‐π‐acceptor chromophores and their use as active material in organic photovoltaics. An overview of some relevant TPA‐based push–pull molecules from the literature and our contribution to this field is presented emphasizing the progress of the photovoltaic performance of organic solar cells made over the last decade. © 2018 Society of Chemical Industry     

Textile-Based Sensors for Inspection of Composite Materials

The monitoring of mechanical deformation and damage of composite materials is normally performed by established analytical methods,such as strain gauges and opt...