Betriebsmessdatenvisualisierung und -erfassung mit OPAL (OPC-Panel-Livegraph). (KIT Scientific Reports ; 7558)

Das OPAL-Programm dient auf einem Windows-PC zur Visualisierung und Speicherung von Messdaten, die von einem OPC-Server, Datasocket-Server o. ä. über die Netzwerkumgebung geliefert werden. Dabei können sowohl Einzelmessstellen, als auch Messstellen-Arrays eingelesen werden. Die Konfiguration der Messstellenquellen und ggf. der Werteumrechnung erfolgt bequem über eine einfache Oberfläche mit Messstellen-Browser. Die Akquirierung und Speicherung erfolgt im Sekundentakt

Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1

The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) that seems to extend the RNA-binding surface to six nucleotides for SF1 (Homo sapiens) and seven nucleotides for GLD-1 (Caenorhabditis elegans). To understand the structural basis of this probable difference in specificity, we determined the solution structure of GLD-1 KH-QUA2 with the complete consensus sequence identified in the tra-2 gene. Compared to SF1, the GLD-1 KH-QUA2 interface adopts a different conformation resulting indeed in an additional sequence-specific binding pocket for a uracil at the 5′end. The functional relevance of this binding pocket is emphasized by our bioinformatics analysis showing that GLD-1 binding sites with this 5′end uracil are more predictive for the functional response of the messenger RNAs to gld-1 knockout. We further reveal the importance of the KH-QUA2 interface in vitro and that its alteration in vivo affects the level of translational repression dependent on the sequence of the GLD-1 binding motif. In conclusion, we demonstrate that the QUA2 domain distinguishes GLD-1 from other members of the STAR family and contributes more generally to the modulation of RNA-binding affinity and specificity of KH domain containing protein

Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition

Serine/arginine (SR) proteins, one of the major families of alternativesplicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one a-helix and does not involve the β-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo- RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound a-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function

Quo Vadis HTA for medical devices in Central and Eastern Europe? Recommendations to address methodological challenges

Objectives: Methodological challenges in the evaluation of medical devices (MDs) may be different for early and late technology adopter countries, as well as the potential health technology assessment (HTA) solutions to tackle them. This study aims to provide guidance to Central and Eastern European (CEE) countries on how to address key challenges of HTA for MDs with special focus on the transferability of scientific evidence. Methods: As part of the COMED Horizon 2020 project, a comprehensive list of issues related to MD HTA were identified based on a targeted literature review. Health technology assessment issues which pose a greater challenge or require different solutions in late technology adopter countries were selected. Draught recommendations to address these issues were developed and discussed in a focus group. The recommendations were then validated with a wider group of experts, including HTA and reimbursement decision makers from CEE countries in May and June 2020. Results: A consolidated list of 11 recommendations were developed in 3 major areas: (1) clinical value assessment, focusing on the use of joint EU work, relying on real-world evidence, use of coverage with evidence development schemes, transferring evidence from foreign countries and addressing the challenges of learning curve and centre effect; (2) economic value assessment, covering cost calculation of complex medical devices and transferability of economic evaluations of MDs; (3) HTA processes, related to the frequent product modifications and various indications of MDs. Conclusions: Central and Eastern European countries with limited resources for conducting HTA, can benefit from HTA methods and evidence generated in early technology adopter countries. Considering the appropriate reuse of international HTA materials, late technology adopter countries can still implement HTA, even for MDs, which have a more limited evidence base compared with pharmaceuticals