Neue Methoden zur Charakterisierung von Fraktionellen Josephson Kontakten und Majorana Anregungen

In this thesis we propose and discuss new ways to probe and characterize fractional Josephson junctions and Majorana excitations forming inside of such junctions. First we propose a Josephson junction based on silicene. By using the buckled structure of silicene, topological edge states can be defined using electric fields. When mediating the Josephson effect with such edge states, the resulting Josephson junction can be tuned electrically between a fractional junction hosting two Majorana excitations and a nonfractional junction hosting no Majorana excitations. An experimental setup to use this effect as an indicator for the topology of the junction is proposed and discussed. Such signatures will typically only be visible in measurements if the quasiparticle poisoning is slow in these junctions. We analyze the effects that such poisoning events have on the dynamics of fractional Josephson junctions. Experimental schemes to measure the poisoning rate through voltage measurements are proposed for different parameter regimes. Many of the proposed setups use the fact that the Josephson junction is in the long junction regime. We propose a setup in which the topological edge states mediating the fractional Josephson effect are coupled to additional states. As an example we consider the cases where the edge states either couple to an additional nondispersive channel or to a single level quantum dot. Due to this coupling, the electrons and holes forming the Andreev bound states pick up an additional phase during one round trip, which alters their energy phase relation. The resulting setups mimic junctions with an effective length that is longer than the physical length of the junction. We characterize these junctions including coupling to additional states by an effective junction length and consider multiple limiting cases. By employing such coupling short junctions can potentially be tuned to the long junction regime, which would make many of the proposed measurements possible even in junctions that are physically in the short junction regime. This thesis also contains a brief overview of the current experimental situation surrounding this field of study as well as a short review of the Kane-Mele model as an example model featuring a quantum spin Hall insulating phase including spin-helical topological edge states.In dieser Dissertation schlagen wir neue Methoden zur Untersuchung und Charakterisierung sowohl von fraktionalen Josephson Kontakten als auch von Majorana Anregungen, welche sich in solchen Kontakten bilden, vor und diskutieren diese. Als erstes schlagen wir einen Josephson Kontakt in Silicen vor. Aufgrund der wellenförmigen Struktur von Silicen können wir topologische Randkanäle mit Hilfe von elektrische Feldern definieren. Wenn der Josephson Effekt über diese topologischen Randkanäle vermittelt wird, kann der resultierende Josephson Kontakt elektrisch zwischen einem fraktionalen Josephson Kontakt, in welchem sich zwei Majorana Anregungen bilden, und einem nicht fraktionalen Josephson Kontakt, in welchem sich keine Majorana Anregungen bilden, geschaltet werden. Ein experimenteller Aufbau, in welchem dieser Effekt als Indikator für die Topologie des Kontaktes genutzt wird, wird vorgeschlagen und diskutiert. Solche Signaturen sind in Messungen typischerweise nur sichtbar, falls die Quasiteilchenvergiftung langsam ist. Wir untersuchen den Effekt, der eine solche Vergiftung auf die Dynamik von fraktionalen Josephson Kontakten hat. Experimentelle Konstruktionen zum Messen der Quasiteilchenvergiftungsrate über Spannungsmessungen werden für verschiedene Parameterbereiche vorgeschlagen. Viele dieser vorgeschlagenen Konstruktionen basieren darauf, dass sich die Josephson Kontakte in dem langen Kontakt Regime befinden. Wir schlagen einen Aufbau vor, in dem die topologischen Randkanäle, welche den fraktionalen Josephson Effekt vermitteln, an weitere Zustände gekoppelt werden. Die resultierenden Kontakte ähneln solchen, welche länger sind als die ihnen unterliegenden Kontakte physisch sind. Wir charakterisieren diese Kontakte mit Kopplungen an weitere Zustände über eine effektive Länge und betrachten verschiedene Grenzfälle. Mit Hilfe solcher Kopplungen können kurze Kontakte potentiell in den langen Kontakt Regime gebracht werden, was viele der vorgeschlagenen Messungen selbst in Kontakten, welche sich physisch im kurzen Kontakt Regime befinden, möglich machen würde. Diese Dissertation enthält ebenfalls sowohl einen kurzen Überblick über die experimentelle Lage des umliegenden Forschungsfeldes als auch eine kleine Übersicht des Kane-Mele Modells als ein Beispiel für ein Modell, welches eine Quanten-Spin-Hall isolierende Phase inklusive Spin helikalen topologischen Randkanälen besitzt

The Psychometric Properties of a Self-Administered, Open-Source Module for Valuing Metastatic Epidural Spinal Cord Compression Utilities.

INTRODUCTION: Web surveys are often used for utility valuation. Typically, custom utility valuation tools that have not undergone psychometric evaluation are used. OBJECTIVES: This study aimed to determine the psychometric properties of a metastatic epidural spinal cord compression (MESCC) module run on a customizable open-source, internet-based, self-directed utility valuation platform (Self-directed Online Assessment of Preferences [SOAP]). METHODS: Individuals accompanying patients to the emergency department waiting room in Ottawa, Canada, were recruited. Participants made SOAP MESCC health state valuations in the waiting room and 48 h later at home. Validity, agreement reliability, and responsiveness were measured by logical consistency of responses, smallest detectable change, the interclass correlation coefficient, and Guyatt\u27s responsiveness index, respectively. RESULTS: Of 285 participants who completed utility valuations, only 113 (39.6%) completed the re-test. Of these 113 participants, 92 (81.4%) provided valid responses on the first test and 75 (66.4%) provided valid responses on the test and re-test. Agreement for all groups of health states was adequate, since their smallest detectable change was less than the minimal clinically important difference. The mean interclass correlation coefficients for all health states were \u3e 0.8, indicating at least substantial reliability. Guyatt\u27s responsiveness indices all exceeded 0.80, indicating a high level of responsiveness. CONCLUSIONS: To our knowledge, this is the first validated open-source, web-based, self-directed utility valuation module. We have demonstrated the SOAP MESCC module is valid, reproducible, and responsive for obtaining ex ante utilities. Considering the successful psychometric validation of the SOAP MESCC module, other investigators can consider developing modules for other diseases where direct utility valuation is needed

Myofibrillar Characteristics of Porcine Stress Syndrome

Porcine Stress Syndrome (PSS) is a genetic trait causing considerable economic loss to the swine industry through stress related death and the poor quality meat known as pale, soft, exudative (PSE) pork . A scanning and transmission electron microscopic examination of muscle biopsies from stress susceptible pigs revealed contracture bands , wide separation of myofibers and focal distortion and dissolution of myofibril s . The changes affecting myofibrillar characteristics and intra and intercellular accumulation of material suspected to be myoplasmic fluid in biopsies of halothane reactors suqqest that the myopathic alterations presaging the carcass deterioration into pale, soft , exudative pork are integrants of this syndrome and that the PSE trait may not be a postmortem change triggered by the environmental factors just prior to or during slaughter

Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers

Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development. View Full-Tex

Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree

: The transcription factor p63 shares a high sequence identity with the tumour suppressor p53 which manifests itself in high structural similarity and preference for DNA sequences. Mutations in the DNA binding domain (DBD) of p53 have been studied in great detail, enabling a general mechanism-based classification. In this study we provide a detailed investigation of all currently known mutations in the p63 DBD, which are associated with developmental syndromes, by measuring their impact on transcriptional activity, DNA binding affinity, zinc binding capacity and thermodynamic stability. Some of the mutations we have further characterized with respect to their ability to convert human dermal fibroblasts into induced keratinocytes. Here we propose a classification of the p63 DBD mutations based on the four different mechanisms of DNA binding impairment which we identified: direct DNA contact, zinc finger region, H2 region, and dimer interface mutations. The data also demonstrate that, in contrast to p53 cancer mutations, no p63 mutation induces global unfolding and subsequent aggregation of the domain. The dimer interface mutations that affect the DNA binding affinity by disturbing the interaction between the individual DBDs retain partial DNA binding capacity which correlates with a milder patient phenotype

Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion’s size and polydispersity

The aim of the present study was to optimize the size and polydispersity of a lipid nanoemulsion as a function of the oil (Labrafac® WL1349), surfactant (Kolliphor® HS 15) and cosurfactant (Span® 80) phase composition and temperature. The nanoemulsions were prepared using a low-energy self-emulsification method. The Z-average diameter and the polydispersity index (PDI) were modeled with mixture experiments. Nanoemulsions from 20 nm to 120 nm with PDI < 0.2 were obtained at the three different tested temperatures (30 °C, 50 °C and 90 °C). The nanoemulsion size was able to be controlled with the oil, surfactant and cosurfactant concentrations. Interestingly, the smallest PDIs were obtained at 30 °C, and the cosurfactant concentration was able to be adjusted to optimize the formulation and to obtain nanoemulsions in the 20–120 nm range with a PDI smaller than 0.14. These nanoemulsions have shown a good stability at 4 °C in storage conditions and at 37 °C in diluted conditions

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo