Impedanzwandler für elektrische Transportmessungen mit kurzen Strompulsen bei tiefen Temperaturen

Zur Reduktion der benötigten Strompulslänge bei der Untersuchung hochohmiger Proben wurde im Rahmen der vorliegenden Arbeit ein Impedanzwandler für den Einsatz im Kryostaten entworfen, gebaut, charakterisiert und getestet. Die Herausforderung dabei war, dass elektrische Bauteile nicht für den Einsatz im Tieftemperaturbereich konzipiert sind. Demzufolge mussten erst geeignete Bauteile gefunden werden, die im Temperaturbereich von 8~K bis Raumtemperatur funktionieren. Eine weitere Randbedingung war, dass im Kryostaten nur wenig Platz war, um die Schaltung für die vier benötigten Kanäle unterzubringen. Die durchgeführten Messungen umspannen das Testen von Operationsverstärkern auf ihre Stabilität im gesamten Temperaturbereich, die Untersuchung der Eigenschaften der verwendeten Komponenten und des fertigen Impedanzwandlers. Außerdem wurde an einer Probe eine Vergleichsmessung durchgeführt welche die Vorteile des Impedanz\-wandlers demonstriert hat. Um möglichst gute Ergebnisse zu erhalten wurden sowohl Varianten mit ohmschem als auch kapazitivem Spannungsteiler und unterschiedlichen Abschwächungsfaktoren gebaut und getestet. Aufgrund der niedrigen Ausgangsspannungen der Operationsverstärker war es notwendig ein Messprogramm zu schreiben, welches die Pulsspannung asymmetrisch regeln kann, um mit den möglichen Ausgangsspannungen für die Messung der Hall-Spannung auszukommen. Die Ergebnisse sind sehr vielversprechend: Die Pulslänge konnte um einen Faktor 25 reduziert werden, die Einflüsse der Proben-Kontaktwiderstände konnten nicht mehr beobachtet werden und sogar die Ergebnisse der Hallmessung waren sehr zufriedenstellend. Bei der Vergleichsmessung hat sich zusätzlich herausgestellt, dass die Probe mit der ursprünglichen Messanordnung nicht mehr untersuchbar war, da der Spannungsabfall über die Kontaktwiderstände die Ergebnisse der Hall-Spannung zu stark verfälschte.In order to reduce the required length of current pulses when measuring highly resistive samples, an impedance converter for use in a cryostat has been designed, built, characterized and tested in the course of this work. The challenge in this matter was that electric parts are not made for cryogenic temperatures. As a consequence, parts that work in the temperature range from 8 K to room temperature had to be found first. Another problem was that there was very little space left in the cryostat where one could place the circuits for the four channels needed. The measurements include testing of operational amplifiers for their stability at cryogenic temperatures as well as measuring the properties of the parts and the voltage follower. For demonstration purposes a comparison measurement on a sample has been performed to demonstrate the advantages of using the impedance converter. For getting better results, several versions with either ohmic or capacitive voltage dividers and different attenuation factors have been built and evaluated. The low output voltage of the operational amplifiers gave rise to the need of a measurement program that could control the voltage pulses in an asymmetrical way, so that the available output voltage range was sufficient for measuring the Hall-voltage. The results are very promising: The needed pulse length could be reduced by a factor of 25, the influences of the sample's contact resistances couldn't be observed any more and even the results of the measurement of the Hall-voltage were very satisfying

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45

Background: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). Case Report: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45. An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of the WDR45 coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls. Discussion: An extended search for deletions should be performed in apparently WDR45-negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia

The electro-chemo-mechanical coupling in lithium alloy electrodes

Die Kopplung von Elektrochemie und Mechanik in Lithium Legierungselektroden kann sowohl durch Oberflächen- als auch Volumeneffekte hervorgerufen werden. Um diese Effekte unterscheiden zu können wurde sowohl eine dynamische elektro-chemo-mechanische Analyse als auch Kippwinkel abhängige Röntgenbeugung während elektrochemischer Zyklen an Gold-Dünnfilmelektroden durchgeführt. Die Ergebnisse wurden dann untereinander als auch mit Literaturergebnissen verglichen. Darüber hinaus enthält die Arbeit das Design und die Spezifikation der geeigneten Messaufbauten genauso wie mechanische und thermodynamische Berechnungen bezüglich des Zusammenhangs der unterschiedlichen Ergebnisse und deren Interpretation.The coupling of electrochemistry and mechanics in lithium alloy electrodes can result from surface as well as bulk mechanisms. In order to distinguish these mechanisms dynamic electro-chemo-mechanical analysis and tilting angle dependent x-ray diffraction measurements were performed during electrochemical cycling on gold thin film electrodes and the results were compared with each other as well as with literature results. The thesis further includes the required design and specification of suitable measurement setups and thermodynamic as well as mechanic evaluations concerning the interrelation and interpretation of the results.Helmholtz Gemeinschaf

The electro-chemo-mechanical coupling in lithium alloy electrodes and its origins

A method to identify and separate the influence of changes in the surface stress from the bulk stress in a model lithium-ion battery electrode during electrochemical cycling was developed. The strategy for this separation is based on the different influence of surface and bulk stresses on the coupling between electrode potential and mechanical strain as measured by dynamic electro-chemo-mechanical analysis and the coupling between the transferred electric charge and the elastic strain as determined by wide angle X-ray scattering. Using both methods, it was possible to uncover the behavior of an apparent surface stress evoked by the bulk stress due to grain boundary alloying of lithium in a gold film. Additionally, the analysis allowed for a determination of a range in surface stress due to underpotential deposition of one monolayer of lithium as the interval between -3.1 to -1.9 N/m

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of <em>WDR45</em>

<p><strong>Background:</strong>&nbsp;Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA).&nbsp;<em>WDR45</em>&nbsp;mutations were recently identified as causal.&nbsp;<em>WDR45</em>&nbsp;encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN).</p><p><strong>Case Report:</strong>&nbsp;Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of&nbsp;<em>WDR45</em>. An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of the&nbsp;<em>WDR45</em>&nbsp;coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls.</p><p><strong>Discussion:</strong>&nbsp;An extended search for deletions should be performed in apparently&nbsp;<em>WDR45-</em>negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.</p

Two-Phase Flow Oxidation of Valeraldehyde with O₂ in a Microstructured Reactor

Microstructured reactors are the ideal device for highly exothermic reactions. In this work, the highly exothermic two-phase reaction of valeraldehyde with oxygen to valeric acid was carried out in a microreactor. The used device from one-A Engineering Austria GmbH is designed for process development and intensification and can be applied in the scale-up process to small-scale commercial production. The atom economic oxidation of valeraldehyde is performed at 0 to 40 °C with a catalytic amount of manganese­(II) acetate. A continuous flow oxidation of aldehydes in such reactors can be a safe and beneficial alternative to commercial batch processes

Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations

International audienceCongenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CA-KUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpho-lino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and cranio-facial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endoge-nous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder

Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome

Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained, Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS. Here, we describe mutations in genes encoding 4 components of the outer rings of the NPC, namely NUP107, NUP85, NUP133, and NUP160, in 13 families with SRNS. Using coimmunoprecipitation experiments, we showed that certain pathogenic alleles weakened the interaction between neighboring NPC subunits. We demonstrated that morpholino knockdown of nup107, nup85, or nup133 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP107, NUP85, or NUP133 in podocytes activated Cdc42, an important effector of SRNS pathogenesis. CRISPR/Cas9 knockout of nup107 or nup85 in zebrafish caused developmental anomalies and early lethality. In contrast, an in-frame mutation of nup107 did not affect survival, thus mimicking the allelic effects seen in humans. In conclusion, we discovered here that mutations in 4 genes encoding components of the outer ring subunits of the NPC cause SRNS and thereby provide further evidence that specific hypomorphic mutations in these essential genes cause a distinct, organ-specific phenotype