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  • 1
    In: Medical Physics, Wiley, Vol. 43, No. 9 ( 2016-09), p. 5028-5039
    Abstract: Rating both a lung segmentation algorithm and a deformable image registration (DIR) algorithm for subsequent lung computed tomography (CT) images by different evaluation techniques. Furthermore, investigating the relative performance and the correlation of the different evaluation techniques to address their potential value in a clinical setting. Methods: Two to seven subsequent CT images (69 in total) of 15 lung cancer patients were acquired prior, during, and after radiochemotherapy. Automated lung segmentations were compared to manually adapted contours. DIR between the first and all following CT images was performed with a fast algorithm specialized for lung tissue registration, requiring the lung segmentation as input. DIR results were evaluated based on landmark distances, lung contour metrics, and vector field inconsistencies in different subvolumes defined by eroding the lung contour. Correlations between the results from the three methods were evaluated. Results: Automated lung contour segmentation was satisfactory in 18 cases (26%), failed in 6 cases (9%), and required manual correction in 45 cases (66%). Initial and corrected contours had large overlap but showed strong local deviations. Landmark‐based DIR evaluation revealed high accuracy compared to CT resolution with an average error of 2.9 mm. Contour metrics of deformed contours were largely satisfactory. The median vector length of inconsistency vector fields was 0.9 mm in the lung volume and slightly smaller for the eroded volumes. There was no clear correlation between the three evaluation approaches. Conclusions: Automatic lung segmentation remains challenging but can assist the manual delineation process. Proven by three techniques, the inspected DIR algorithm delivers reliable results for the lung CT data sets acquired at different time points. Clinical application of DIR demands a fast DIR evaluation to identify unacceptable results, for instance, by combining different automated DIR evaluation methods.
    Type of Medium: Online Resource
    ISSN: 0094-2405 , 2473-4209
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 2
    In: ELECTROPHORESIS, Wiley, Vol. 38, No. 24 ( 2017-12), p. 3136-3146
    Abstract: CZE is a well‐established technique for charge heterogeneity testing of biopharmaceuticals. It is based on the differences between the ratios of net charge and hydrodynamic radius. In an extensive intercompany study, it was recently shown that CZE is very robust and can be easily implemented in labs that did not perform it before. However, individual characteristics of some examined proteins resulted in suboptimal resolution. Therefore, enhanced method development principles were applied here to investigate possibilities for further method optimization. For this purpose, a high number of different method parameters was evaluated with the aim to improve CZE separation. For the relevant parameters, design of experiments (DoE) models were generated and optimized in several ways for different sets of responses like resolution, peak width and number of peaks. In spite of product specific DoE optimization it was found that the resulting combination of optimized parameters did result in significant improvement of separation for 13 out of 16 different antibodies and other molecule formats. These results clearly demonstrate generic applicability of the optimized CZE method. Adaptation to individual molecular properties may sometimes still be required in order to achieve optimal separation but the set screws discussed in this study [mainly pH, identity of the polymer additive (HPC versus HPMC) and the concentrations of additives like acetonitrile, butanolamine and TETA] are expected to significantly reduce the effort for specific optimization.
    Type of Medium: Online Resource
    ISSN: 0173-0835 , 1522-2683
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2019
    In:  ELECTROPHORESIS Vol. 40, No. 18-19 ( 2019-09), p. 2375-2381
    In: ELECTROPHORESIS, Wiley, Vol. 40, No. 18-19 ( 2019-09), p. 2375-2381
    Abstract: Generic in‐capillary as well as offline CE‐based enzyme assays were developed for serine‐β‐lactamases and metallo‐β‐lactamases. The hydrolysis of benzylpenicillin to benzylpenicilloic acid was analyzed using 100 mM sodium phosphate solution, pH 6.0, as a background electrolyte. In‐capillary assays employed an uncoated as well as a polyethylene oxide‐coated capillary, while the offline assays employing long end and short end injection were performed in an uncoated capillary. Using procaine hydrochloride or 4‐hydroxybenzoic acid as internal standard, the respective assays were validated with regard to linearity, LOD and LOQ, repeatability, precision, and accuracy. The assays were applied to the determination of the Michaelis‐Menten parameters K m and V max of Bacillus cereus penicillinase as well as New Delhi metallo‐β‐lactamase 1 and Verona integrin‐encoded metallo‐β‐lactamase 2. Furthermore, the inhibition of the enzymes by irreversible and competitive inhibitors was evaluated. Comparable data were obtained with all assays. The use of a simple substrate ensured broad applicability to the various types of β‐lactamases.
    Type of Medium: Online Resource
    ISSN: 0173-0835 , 1522-2683
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 4
    In: European Journal of Immunology, Wiley, Vol. 48, No. 11 ( 2018-11), p. 1892-1903
    Abstract: Tyrosine kinases are checkpoints for multiple cellular pathways and dysregulation induces malignancies, most notably chronic myeloid leukemia (CML). Inhibition of Abl‐tyrosine kinases has evolved as a new concept for the treatment of CML and other malignant diseases. Due to the multiple immune‐modulatory pathways controlled by tyrosine kinases, treatment with tyrosine kinase inhibitors (TKIs) will not only affect the biology of malignant cells but also modulate physiological immune functions. To understand the effects of TKIs on host defense against intracellular bacteria, we investigated the immunological impact of the dual Abl/Src TKI dasatinib on the cellular immune response to Mycobacterium tuberculosis ( Mtb ). Our results demonstrate that dasatinib impaired proliferation, cytokine release (IFN‐γ, TNF‐α, GM‐CSF), expression of granulysin and degranulation of cytotoxic effector molecules of human Mtb ‐specific T‐lymphocytes by inhibition of lymphocyte‐specific protein tyrosine kinase (Lck) phosphorylation. Despite this profound inhibition of T‐cell function, dasatinib suppressed growth of virulent Mtb in human macrophages co‐cultured with autologous Mtb ‐specific T‐cells (49±15%). Functional analysis suggested that growth inhibition is due to dasatinib‐triggered lysosomal acidification in Mtb ‐infected macrophages. These results highlight the significance of innate immune responses, i.e. acidification of lysosomes, which control the multiplication of intracellular bacteria despite the lack of efficient T‐cell support.
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 5
    In: Prenatal Diagnosis, Wiley, Vol. 39, No. 12 ( 2019-11), p. 1136-1147
    Abstract: 17q12 microdeletions containing HNF1B and intragenic variants within this gene are associated with variable developmental, endocrine, and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe prenatal and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to those of previous studies. Methods Prenatal sequencing and postnatal chromosomal microarray analysis were performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B ‐related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants. Results In a prenatal case, we identified a novel in‐frame deletion p.(Gly239del) within the HNF1B DNA‐binding domain, a mutational hot spot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions. Literature screening revealed variable reporting of HNF1B‐ associated clinical traits. Overall, both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up‐to‐date overview of the mutational spectrum. Conclusions We highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants are necessary for a more accurate risk quantification of prenatal and postnatal clinical features, improving genetic counseling and prenatal decision making.
    Type of Medium: Online Resource
    ISSN: 0197-3851 , 1097-0223
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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    detail.hit.zdb_id: 1491217-X
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  • 6
    In: Environmental Microbiology, Wiley, Vol. 21, No. 2 ( 2019-02), p. 603-617
    Abstract: Remane's Artenminimum at the horohalinicum is a fundamental concept in ecology to describe and explain the distribution of organisms along salinity gradients. However, a recent metadata analysis challenged this concept for protists, proposing a species maximum in brackish waters. Due to data bias, this literature‐based investigation was highly discussed. Reliable data verifying or rejecting the species minimum for protists in brackish waters were critically lacking. Here, we sampled a pronounced salinity gradient along a west–east transect in the Baltic Sea and analysed protistan plankton communities using high‐throughput eDNA metabarcoding. A strong salinity barrier at the upper limit of the horohalinicum and 10 psu appeared to select for significant shifts in protistan community structures, with dinoflagellates being dominant at lower salinities, and dictyochophytes and diatoms being keyplayers at higher salinities. Also in vertical water column gradients in deeper basins (Kiel Bight, Arkona and Bornholm Basin) appeared salinity as significant environmental determinant influencing alpha‐ and beta‐diversity patterns. Importantly, alpha‐diversity indices revealed species maxima in brackish waters, that is, indeed contrasting Remane's Artenminimum concept. Statistical analyses confirmed salinity as the major driving force for protistan community structuring with high significance. This suggests that macrobiota and microbial eukaryotes follow fundamentally different rules regarding diversity patterns in the transition zone from freshwater to marine waters.
    Type of Medium: Online Resource
    ISSN: 1462-2912 , 1462-2920
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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    detail.hit.zdb_id: 2020213-1
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  • 7
    In: Mediators of Inflammation, Wiley, Vol. 2017 ( 2017), p. 1-14
    Abstract: Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1 β , we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2018
    In:  Social Policy & Administration Vol. 52, No. 5 ( 2018-09), p. 969-982
    In: Social Policy & Administration, Wiley, Vol. 52, No. 5 ( 2018-09), p. 969-982
    Abstract: The article departs from the argument that research on welfare attitudes is, so far, dominated by large‐scale survey‐studies, which allow for generalizable insights into citizens' preferences and evaluations, but are necessarily limited in their ability to capture the dynamic and contextual aspects of attitude formation. In order to broaden the horizon of welfare attitudes' research, this article introduces a new qualitative method, namely deliberative forums. In these large group discussions—originally developed for participatory decision‐making—attitudes, opinions, and preferences are core aspects of the deliberation process, and the article argues that by observing deliberation, we can observe attitude construction “ in vivo ”. The evidence from a two‐day German deliberation event illustrates in an exploratory manner how information, reasoning, and group processes can influence people's evaluations and expressed policy preferences with regard to redistribution. By linking participants' answers from a survey before and after the event to their statements during the discussions, the article not only shows that the preferences for redistribution people expressed in the survey answers are often higher after the deliberative event, but also seeks to make sense of attitudinal dynamics on the basis of the qualitative material by pointing towards the role of information, reasoning, and group processes.
    Type of Medium: Online Resource
    ISSN: 0144-5596 , 1467-9515
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 9
    In: The FEBS Journal, Wiley, Vol. 285, No. 23 ( 2018-12), p. 4367-4377
    Abstract: The promiscuous activities of a recursive, generalist enzyme provide raw material for the emergence of metabolic pathways. Here, we use a synthetic biology approach to recreate such an evolutionary setup in central metabolism and explore how cellular physiology adjusts to enable recursive catalysis. We generate an Escherichia coli strain deleted in transketolase and glucose 6‐phosphate dehydrogenase, effectively eliminating the native pentose phosphate pathway. We demonstrate that the overexpression of phosphoketolase restores prototrophic growth by catalyzing three consecutive reactions, cleaving xylulose 5‐phosphate, fructose 6‐phosphate, and, notably, sedoheptulose 7‐phosphate. We find that the activity of the resulting synthetic pathway becomes possible due to the recalibration of steady‐state concentrations of key metabolites, such that the in vivo cleavage rates of all three phosphoketolase substrates are similar. This study demonstrates our ability to rewrite one of nature's most conserved pathways and provides insight into the flexibility of cellular metabolism during pathway emergence.
    Type of Medium: Online Resource
    ISSN: 1742-464X , 1742-4658
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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    SSG: 12
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  • 10
    In: Architectural Design, Wiley, Vol. 85, No. 5 ( 2015-09), p. 48-53
    Abstract: Advanced design, simulation and fabrication technologies facilitate the exploration and transferring of the morphological principles of fibrous systems from biology to technology. The ICD/ITKE Research Pavilion 2012 pioneered such an approach for architecture. Jan Knippers, Riccardo La Magna, Achim Menges, Steffen Reichert, Tobias Schwinn and Frédéric Waimer of the Institute for Computational Design (ICD) and Institute of Building Structures and Structural Design (ITKE) research team at the University of Stuttgart describe how they approached the design of the pavilion, which is located on the school's campus.
    Type of Medium: Online Resource
    ISSN: 0003-8504 , 1554-2769
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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