Bestimmung der Parameter einer Regressionsellipse in allgemeiner Raumlage

Dreidimensionale Koordinaten von diskreten Punkten eines zu untersuchenden Objektes können mit verschiedenen geodätischen Messsystemen erfasst werden. Um jedoch eine qualitative Aussage bezüglich der Größe, Form oder Lage dieses Objektes treffen zu können, werden Algorithmen zur Schätzung von Approximationsformen benötigt. Das Ableiten von Formmaßen mithilfe der Methode der kleinesten Quadrate bildet die Grundlage bei der Qualitätsüberwachung und -analyse z.B. im Anlagen- und Maschinenbau. Am Beispiel der Ellipsenausgleichung werden in diesem Beitrag zunächst Bestimmungsverfahren in der Ebene beschrieben, die anschließend auf den allgemeinen räumlichen Fall übertragen werden und in einem einfach zu implementierenden funktionalen Modell zur Parameterschätzung münden

Wireless Low-Power Transfer for Galvanically Isolated High-Voltage Applications

For various applications, such as gate drivers for transistors, wireless chargers for mobile devices and cars, and isolated measurement equipment, an isolated DC power supply for electronic components is required. In this work, a new concept for an isolated power supply with insulation strength of 50 kV and power transmission of up to 60 W to supply measurement equipment with 12 or 24 V is presented. Furthermore, high overall efficiency of 82.5% at 55 W is achieved. Feasibility is demonstrated in a real application powering data acquisition electronics at high reference potential. Our new concept uses a coreless printed circuit board (PCB) transformer (15 cm × 10 cm × 4 cm and a weight of 480 g) designed for maximum efficiency via a coil layout and close proximity of adjacent coils on one PCB while reaching high isolation strength via the PCB material and potted coils. To increase efficiency, we investigated different coil geometries at different frequencies. A low-cost design consisting of two Qi charging coils mounted on one PCB is compared with our integrated PCB transformers manufactured from a four-layer PCB with ferrites applied on the outside. With this new design, high isolation voltages are possible while reaching high transformer efficiency of up to 90%. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

The ineluctable requirement for the trans-iron elements molybdenum and/or tungsten in the origin of life

An evolutionary tree of key enzymes from the Complex-Iron-Sulfur-Molybdoenzyme (CISM) superfamily distinguishes “ancient” members, i.e. enzymes present already in the last universal common ancestor (LUCA) of prokaryotes, from more recently evolved subfamilies. The majority of the presented subfamilies and, as a consequence, the Molybdo-enzyme superfamily as a whole, appear to have existed in LUCA. The results are discussed with respect to the nature of bioenergetic substrates available to early life and to problems arising from the low solubility of molybdenum under conditions of the primordial Earth

Multifunctional supramolecular polymer networks as next-generation consolidants for archaeological wood conservation.

The preservation of our cultural heritage is of great importance to future generations. Despite this, significant problems have arisen with the conservation of waterlogged wooden artifacts. Three major issues facing conservators are structural instability on drying, biological degradation, and chemical degradation on account of Fe(3+)-catalyzed production of sulfuric and oxalic acid in the waterlogged timbers. Currently, no conservation treatment exists that effectively addresses all three issues simultaneously. A new conservation treatment is reported here based on a supramolecular polymer network constructed from natural polymers with dynamic cross-linking formed by a combination of both host-guest complexation and a strong siderophore pendant from a polymer backbone. Consequently, the proposed consolidant has the ability to chelate and trap iron while enhancing structural stability. The incorporation of antibacterial moieties through a dynamic covalent linkage into the network provides the material with improved biological resistance. Exploiting an environmentally compatible natural material with completely reversible chemistries is a safer, greener alternative to current strategies and may extend the lifetime of many culturally relevant waterlogged artifacts around the world.This is the author's accepted manuscript. The final version is available from PNAS at http://www.pnas.org/content/111/50/17743.long

Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): rationale and study design

Background: The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial's impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort. Methods: The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG-/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov . Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication's target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials. Results: We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36). Conclusions: The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved

The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth

Cilia are specialized organelles that play an important role in several biological processes, including mechanosensation, photoperception, and osmosignaling. Mutations in proteins localized to cilia have been implicated in a growing number of human diseases. In this study, we demonstrate that the von Hippel-Lindau (VHL) protein (pVHL) is a ciliary protein that controls ciliogenesis in kidney cells. Knockdown of pVHL impeded the formation of cilia in mouse inner medullary collecting duct 3 kidney cells, whereas the expression of pVHL in VHL-negative renal cancer cells rescued the ciliogenesis defect. Using green fluorescent protein–tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. Furthermore, pVHL interacts with the Par3–Par6–atypical PKC complex, suggesting a mechanism for linking polarity pathways to microtubule capture and ciliogenesis

NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network

Mouse B cells lacking NFATc1 exhibit defective proliferation, survival, isotype class switching, cytokine production, and T cell help

Bio-inspired CO₂ conversion by iron sulfide catalysts under sustainable conditions

The mineral greigite presents similar surface structures to the active sites found in many modern-day enzymes. We show that particles of greigite can reduce CO2 under ambient conditions into chemicals such as methanol, formic, acetic and pyruvic acid. Our results also lend support to the Origin of Life theory on alkaline hydrothermal vents

Mouse models for pseudoxanthoma elasticum: Genetic and dietary modulation of the ectopic mineralization phenotypes

Pseudoxanthoma elasticum (PXE), a heritable ectopic mineralization disorder, is caused by mutations in the ABCC6 gene. Null mice ( Abcc6 -/-) recapitulate the genetic, histopathologic and ultrastructural features of PXE, and they demonstrate early and progressive mineralization of vibrissae dermal sheath, which serves as a biomarker of the overall mineralization process. Recently, as part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have vibrissae dermal mineralization similar to Abcc6-/- mice. These two strains were shown to harbor a single nucleotide polymorphism (rs32756904) in the Abcc6 gene, which resulted in out-of-frame splicing and marked reduction in ABCC6 protein expression in the liver of these mice. The same polymorphism is present in two additional mouse strains, DBA/2J and C3H/HeJ, with similar reduction in Abcc6 protein levels, yet these mice did not demonstrate tissue mineralization when kept on standard rodent diet. However, all four mouse strains, when placed on experimental diet enriched in phosphate and low in magnesium, developed extensive ectopic mineralization. These results indicate that the genetic background of mice and the mineral composition of their diet can profoundly modulate the ectopic mineralization process predicated on mutations in the Abcc6 gene. These mice provide novel model systems to study the pathomechanisms and the reasons for strain background on phenotypic variability of PXE. © 2014 Li et al

Analysis of Pseudoxanthoma Elasticum-Causing Missense Mutants of ABCC6 In Vivo; Pharmacological Correction of the Mislocalized Proteins

Mutations in the ABCC6 gene cause soft-tissue calcification in pseudoxanthoma elasticum (PXE) and, in some patients, generalized arterial calcification of infancy (GACI). PXE is characterized by late onset and progressive mineralization of elastic fibers in dermal, ocular, and cardiovascular tissues. GACI patients present a more severe, often prenatal arterial calcification. We have tested 10 frequent disease-causing ABCC6 missense mutants for the transport activity by using Sf9 (Spodoptera frugiperda) cells, characterized the subcellular localization in MDCKII (Madin-Darby canine kidney (cell line)) cells and in mouse liver, and tested the phenotypic rescue in zebrafish. We aimed at identifying mutants with preserved transport activity but with improper plasma membrane localization for rescue by the chemical chaperone 4-phenylbutyrate (4-PBA). Seven of the mutants were transport-competent but mislocalized in mouse liver. The observed divergence in cellular localization of mutants in MDCKII cells versus mouse liver underlined the limitations of this 2D in vitro cell system. The functionality of ABCC6 mutants was tested in zebrafish, and minimal rescue of the morpholino-induced phenotype was found. However, 4-PBA, a drug approved for clinical use, restored the plasma membrane localization of four ABCC6 mutants (R1114P, S1121W, Q1347H, and R1314W), suggesting that allele-specific therapy may be useful for selected patients with PXE and GACI.Journal of Investigative Dermatology advance online publication, 19 December 2013; doi:10.1038/jid.2013.482