464 research outputs found

    Purely peptidic amphiphiles : understanding and controlling their self-assembled structures

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    Amphiphilic molecules spontaneously self-assemble into a variety of structures in solution. The term amphiphilic indicates that one part of the molecule is attracted to the solvent, while the other is not. Interactions such as between solute-solvent and solute-solute thus determine the organization. Understanding the self-assembly means understanding those interactions and their driving forces. In the first chapter an overview of the self-organization of amphiphilic molecules into supermolecuar aggregates of different morphologies is provided, with a focus on purely peptidic amphiphiles, i.e. amphiphiles which consist solely of a different amino acid sequence. In the second chapter the self-assembly of amphiphilic peptides with a specific amino acid sequence into micelles and spherical peptide nanoparticles is described. The undecamer peptide that was used features a repetitive L-tryptophan and D-leucine [LW-DL] motif, representing the hydrophobic block – which is a truncated version of gramicidin A (gA), named gT. The N-terminally attached hydrophilic section was either lysine (K) or acetylated lysine (X) and was optionally terminated with cysteine for post-functionalization of the thiol-group. The uncharged peptide AcC-X3-gT was demonstrated to assemble into micelles and subsequently into peptide particles, termed ‘peptide beads’. We hypothesize that the peptide beads consisted of micelles – a structure described as multicompartment micelles. Peptide beads using AcC-X3-gT and its analogues – including Ac-X3-gT-C, a new peptide with the cysteine residue on the C instead of the N-terminus – are further investigated in Chapter Three. We succeeded in creating highly ordered Ac-X3-gT-C – Au-NP composites, which allowed us to visualize the inner structure of the nanoparticles. The presented composite materials are expected to exhibit exceptional electrical and optical properties. In Chapter Four these amphiphilic peptides are studied with regard to the interaction within a lipid layer but also in pure peptide layers at the air-water interface. Results indicate the formation of a unimolecular, flat film. Peptide layers were successfully transferred onto a solid support or self-assembled peptide monolayers (SAMs) were created equally well via immersion and spin-coating. Preliminary mineralization experiments confirmed the successful creation of calcium phosphate crystals. The topic of the following chapter focuses on a peptide library that has been synthesized to correlate the primary sequence, its secondary structure and the resulting self-assembly. The peptide design includes three parts: (a) a charged lysine part, (b) an acetylated lysine part and (c) a constant hydrophobic rod-like helix, based on gramicidin A (gA). By stepwise replacement of free lysine (K) with acetylated lysine (X) we generated a library of a total of ten peptides Ac-X8-gA and KmX8-m-gA (m ranging from 0 to 8). By using point mutations, we adjusted the degree of acetylation (DA) and thus the overall amphiphilicity of the peptides, which led to a change in the secondary structure in the aqueous environment from a Beta-sheet to an Alpha-helix. This transition generated a significant change in the morphology of the self-assembled structures from fibers to micelles. The study is important precisely because it presents a first step towards molecular switches based on acetylation of a peptide, inspired by the example of phosphorylation of proteins or enzymes, which converts them into the active or inactive state by structural changes. Chapter Sseven focuses on essential parameters to successfully manage membrane formation from a purely peptidic system. A crucial step in the formation of peptide membranes appears to be dimerization, which originates from the introduction of intermolecular interactions, such as H-bonds or Pi-Pi stacking of aromatic rings. The formation of a stabilized membrane subunit, i.e. dimers in the lateral or perpendicular directions (relative to the membrane) produced stable, purely peptidic vesicles and may well apply to other peptidic systems. These novel peptidic systems offer hydrophilic and hydrophobic compartments to encapsulate and integrate different drugs or payloads and could be used for gene delivery, since the design includes charged moieties. In the last chapter, the achievements of the presented work are discussed and summarized. Furthermore, lines of research are suggested, which, from the present point of view, appear to be the most promising and should be the focus of subsequent experiments

    Memetic Graph Clustering

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    It is common knowledge that there is no single best strategy for graph clustering, which justifies a plethora of existing approaches. In this paper, we present a general memetic algorithm, VieClus, to tackle the graph clustering problem. This algorithm can be adapted to optimize different objective functions. A key component of our contribution are natural recombine operators that employ ensemble clusterings as well as multi-level techniques. Lastly, we combine these techniques with a scalable communication protocol, producing a system that is able to compute high-quality solutions in a short amount of time. We instantiate our scheme with local search for modularity and show that our algorithm successfully improves or reproduces all entries of the 10th DIMACS implementation challenge under consideration using a small amount of time

    Embedded disposable functionalized electrochemical biosensor with a 3D-printed flow cell for detection of hepatic oval cells (HOCs)

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    Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection

    Fully automatic segmentation of glottis and vocal folds in endoscopic laryngeal high-speed videos using a deep Convolutional LSTM Network

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    The objective investigation of the dynamic properties of vocal fold vibrations demands the recording and further quantitative analysis of laryngeal high-speed video (HSV). Quantification of the vocal fold vibration patterns requires as a first step the segmentation of the glottal area within each video frame from which the vibrating edges of the vocal folds are usually derived. Consequently, the outcome of any further vibration analysis depends on the quality of this initial segmentation process. In this work we propose for the first time a procedure to fully automatically segment not only the time-varying glottal area but also the vocal fold tissue directly from laryngeal high-speed video (HSV) using a deep Convolutional Neural Network (CNN) approach. Eighteen different Convolutional Neural Network (CNN) network configurations were trained and evaluated on totally 13,000 high-speed video (HSV) frames obtained from 56 healthy and 74 pathologic subjects. The segmentation quality of the best performing Convolutional Neural Network (CNN) model, which uses Long Short-Term Memory (LSTM) cells to take also the temporal context into account, was intensely investigated on 15 test video sequences comprising 100 consecutive images each. As performance measures the Dice Coefficient (DC) as well as the precisions of four anatomical landmark positions were used. Over all test data a mean Dice Coefficient (DC) of 0.85 was obtained for the glottis and 0.91 and 0.90 for the right and left vocal fold (VF) respectively. The grand average precision of the identified landmarks amounts 2.2 pixels and is in the same range as comparable manual expert segmentations which can be regarded as Gold Standard. The method proposed here requires no user interaction and overcomes the limitations of current semiautomatic or computational expensive approaches. Thus, it allows also for the analysis of long high-speed video (HSV)-sequences and holds the promise to facilitate the objective analysis of vocal fold vibrations in clinical routine. The here used dataset including the ground truth will be provided freely for all scientific groups to allow a quantitative benchmarking of segmentation approaches in future

    Lupusnephritis und assoziierte thrombotische Mikroangiopathie

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    Die Lupusnephritis stellt die hĂ€ufigste Manifestation eines systemischen Lupus an den soliden Organen dar und geht mit einem erhöhten Risiko fĂŒr eine chronische Niereninsuffizienz einher. Das gleichzeitige Auftreten einer Lupusnephritis mit einer thrombotischen Mikroangiopathie wird als selten beschrieben, impliziert jedoch das Risiko fataler Organdysfunktionen. Wir berichten von drei Patienten, bei denen diese beiden KrankheitsentitĂ€ten parallel auftraten und eine intensivierte immunsuppressive Therapie auch mittels Komplementblockade notwendig machten

    The Alpine-Carpathian-Dinaridic orogenic system: correlation and evolution of tectonic units

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    A correlation of tectonic units of the Alpine-Carpathian-Dinaridic system of orogens, including the substrate of the Pannonian and Transylvanian basins, is presented in the form of a map. Combined with a series of crustal-scale cross sections this correlation of tectonic units yields a clearer picture of the three-dimensional architecture of this system of orogens that owes its considerable complexity to multiple overprinting of earlier by younger deformations. The synthesis advanced here indicates that none of the branches of the Alpine Tethys and Neotethys extended eastward into the Dobrogea Orogen. Instead, the main branch of the Alpine Tethys linked up with the Meliata-Maliac-Vardar branch of the Neotethys into the area of the present-day Inner Dinarides. More easterly and subsidiary branches of the Alpine Tethys separated Tisza completely, and Dacia partially, from the European continent. Remnants of the Triassic parts of Neotethys (Meliata-Maliac) are preserved only as ophiolitic mélanges present below obducted Jurassic Neotethyan (Vardar) ophiolites. The opening of the Alpine Tethys was largely contemporaneous with the Latest Jurassic to Early Cretaceous obduction of parts of the Jurassic Vardar ophiolites. Closure of the Meliata-Maliac Ocean in the Alps and West Carpathians led to Cretaceous-age orogeny associated with an eclogitic overprint of the adjacent continental margin. The Triassic Meliata-Maliac and Jurassic Western and Eastern Vardar ophiolites were derived from one single branch of Neotethys: the Meliata-Maliac-Vardar Ocean. Complex geometries resulting from out-of-sequence thrusting during Cretaceous and Cenozoic orogenic phases underlay a variety of multi-ocean hypotheses, that were advanced in the literature and that we regard as incompatible with the field evidence. The present-day configuration of tectonic units suggests that a former connection between ophiolitic units in West Carpathians and Dinarides was disrupted by substantial Miocene-age dislocations along the Mid-Hungarian Fault Zone, hiding a former lateral change in subduction polarity between West Carpathians and Dinarides. The SW-facing Dinaridic Orogen, mainly structured in Cretaceous and Palaeogene times, was juxtaposed with the Tisza and Dacia Mega-Units along a NW-dipping suture (Sava Zone) in latest Cretaceous to Palaeogene times. The Dacia Mega-Unit (East and South Carpathian Orogen, including the Carpatho-Balkan Orogen and the Biharia nappe system of the Apuseni Mountains), was essentially consolidated by E-facing nappe stacking during an Early Cretaceous orogeny, while the adjacent Tisza Mega-Unit formed by NW-directed thrusting (in present-day coordinates) in Late Cretaceous times. The polyphase and multi-directional Cretaceous to Neogene deformation history of the Dinarides was preceded by the obduction of Vardar ophiolites onto to the Adriatic margin (Western Vardar Ophiolitic Unit) and parts of the European margin (Eastern Vardar Ophiolitic Unit) during Late Jurassic to Early Cretaceous time

    Noise Reduction for Single-Shot Grating-Based Phase-Contrast Imaging at an X-ray Backlighter

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    X-ray backlighters allow the capture of sharp images of fast dynamic processes due to extremely short exposure times. Moiré imaging enables simultaneously measuring the absorption and differential phase-contrast (DPC) of these processes. Acquiring images with one single shot limits the X-ray photon flux, which can result in noisy images. Increasing the photon statistics by repeating the experiment to gain the same image is not possible if the investigated processes are dynamic and chaotic. Furthermore, to reconstruct the DPC and transmission image, an additional measurement captured in absence of the object is required. For these reference measurements, shot-to-shot fluctuations in X-ray spectra and a source position complicate the averaging of several reference images for noise reduction. Here, two approaches of processing multiple reference images in combination with one single object image are evaluated regarding the image quality. We found that with only five reference images, the contrast-to-noise ratio can be improved by approximately 13% in the DPC image. This promises improvements for short-exposure single-shot acquisitions of rapid processes, such as laser-produced plasma shock-waves in high-energy density experiments at backlighter X-ray sources such as the PHELIX high-power laser facility
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