@article{ZoltnerKrienitzFieldetal.2018,
  author    = {Zoltner, Martin and Krienitz, Nina and Field, Mark C. and Kramer, Susanne},
  title     = {Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {12},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {7},
  doi       = {10.1371/journal.pntd.0006679},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177126},
  pages     = {e0006679},
  year      = {2018},
  abstract  = {Poly(A)-binding proteins (PABPs) regulate mRNA fate by controlling stability and translation through interactions with both the poly(A) tail and eIF4F complex. Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate distinct sets of mRNAs. Trypanosomes have five eIF4G paralogs, six of eIF4E and two PABPs, PABP1 and PABP2. Under starvation, polysomes dissociate and the majority of mRNAs, most translation initiation factors and PABP2 reversibly localise to starvation stress granules. To understand this more broadly we identified a protein interaction cohort for both T. brucei PABPs by cryo-mill/affinity purification-mass spectrometry. PABP1 very specifically interacts with the previously identified interactors eIF4E4 and eIF4G3 and few others. In contrast PABP2 is promiscuous, with a larger set of interactors including most translation initiation factors and most prominently eIF4G1, with its two partners TbG1-IP and TbG1-IP2. Only RBP23 was specific to PABP1, whilst 14 RNA-binding proteins were exclusively immunoprecipitated with PABP2. Significantly, PABP1 and associated proteins are largely excluded from starvation stress granules, but PABP2 and most interactors translocate to granules on starvation. We suggest that PABP1 regulates a small subpopulation of mainly small-sized mRNAs, as it interacts with a small and distinct set of proteins unable to enter the dominant pathway into starvation stress granules and localises preferentially to a subfraction of small polysomes. By contrast PABP2 likely regulates bulk mRNA translation, as it interacts with a wide range of proteins, enters stress granules and distributes over the full range of polysomes.},
  language  = {en}
}
@article{ZimmererFischbachLatoschik2018,
  author    = {Zimmerer, Chris and Fischbach, Martin and Latoschik, Marc Erich},
  title     = {Semantic Fusion for Natural Multimodal Interfaces using Concurrent Augmented Transition Networks},
  series = {Multimodal Technologies and Interaction},
  volume    = {2},
  journal   = {Multimodal Technologies and Interaction},
  number    = {4},
  issn      = {2414-4088},
  doi       = {10.3390/mti2040081},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197573},
  year      = {2018},
  abstract  = {Semantic fusion is a central requirement of many multimodal interfaces. Procedural methods like finite-state transducers and augmented transition networks have proven to be beneficial to implement semantic fusion. They are compliant with rapid development cycles that are common for the development of user interfaces, in contrast to machine-learning approaches that require time-costly training and optimization. We identify seven fundamental requirements for the implementation of semantic fusion: Action derivation, continuous feedback, context-sensitivity, temporal relation support, access to the interaction context, as well as the support of chronologically unsorted and probabilistic input. A subsequent analysis reveals, however, that there is currently no solution for fulfilling the latter two requirements. As the main contribution of this article, we thus present the Concurrent Cursor concept to compensate these shortcomings. In addition, we showcase a reference implementation, the Concurrent Augmented Transition Network (cATN), that validates the concept's feasibility in a series of proof of concept demonstrations as well as through a comparative benchmark. The cATN fulfills all identified requirements and fills the lack amongst previous solutions. It supports the rapid prototyping of multimodal interfaces by means of five concrete traits: Its declarative nature, the recursiveness of the underlying transition network, the network abstraction constructs of its description language, the utilized semantic queries, and an abstraction layer for lexical information. Our reference implementation was and is used in various student projects, theses, as well as master-level courses. It is openly available and showcases that non-experts can effectively implement multimodal interfaces, even for non-trivial applications in mixed and virtual reality.},
  language  = {en}
}
@article{ZielewskaBuettnerHeurichMuelleretal.2018,
  author    = {Zielewska-B{\"u}ttner, Katarzyna and Heurich, Marco and M{\"u}ller, J{\"o}rg and Braunisch, Veronika},
  title     = {Remotely Sensed Single Tree Data Enable the Determination of Habitat Thresholds for the Three-Toed Woodpecker (Picoides tridactylus)},
  series = {Remote Sensing},
  volume    = {10},
  journal   = {Remote Sensing},
  number    = {12},
  issn      = {2072-4292},
  doi       = {10.3390/rs10121972},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197565},
  year      = {2018},
  abstract  = {Forest biodiversity conservation requires precise, area-wide information on the abundance and distribution of key habitat structures at multiple spatial scales. We combined airborne laser scanning (ALS) data with color-infrared (CIR) aerial imagery for identifying individual tree characteristics and quantifying multi-scale habitat requirements using the example of the three-toed woodpecker (Picoides tridactylus) (TTW) in the Bavarian Forest National Park (Germany). This bird, a keystone species of boreal and mountainous forests, is highly reliant on bark beetles dwelling in dead or dying trees. While previous studies showed a positive relationship between the TTW presence and the amount of deadwood as a limiting resource, we hypothesized a unimodal response with a negative effect of very high deadwood amounts and tested for effects of substrate quality. Based on 104 woodpecker presence or absence locations, habitat selection was modelled at four spatial scales reflecting different woodpecker home range sizes. The abundance of standing dead trees was the most important predictor, with an increase in the probability of TTW occurrence up to a threshold of 44-50 dead trees per hectare, followed by a decrease in the probability of occurrence. A positive relationship with the deadwood crown size indicated the importance of fresh deadwood. Remote sensing data allowed both an area-wide prediction of species occurrence and the derivation of ecological threshold values for deadwood quality and quantity for more informed conservation management.},
  language  = {en}
}
@phdthesis{Ziegenhals2018,
  author    = {Ziegenhals, Thomas},
  title     = {The role of the miR-26 family in neurogenesis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156395},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {For the differentiation of a embryonic stem cells (ESCs) to neuronal cells (NCs) a complex and coordinated gene regulation program is needed. One important control element for neuronal differentiation is the repressor element 1 silencing transcription factor (REST) complex, which represses neuronal gene expression in non-neuronal cells. Crucial effector proteins of the REST complex are small phosphatases such as the CTDSPs (C-terminal domain small phosphatases) that regulate polymerase II activity by dephosphorylating the C-terminal domain of the polymerase, thereby repressing target genes. The stepwise inactivation of REST, including the CTDSPs, leads to the induction of a neuron-specific gene program, which ultimately induces the formation of neurons. The spatio-temporal control of REST and its effector components is therefore a crucial step for neurogenesis. In zebrafish it was shown that the REST-associated CTDSP2 is negatively regulated by the micro RNA (miR) -26b. Interestingly, the miR-26b is encoded in an intron of the primary transcript of CTDSP2. This gives the fundament of an intrinsic regulatory negative feedback loop, which is essential for the proceeding of neurogenesis. This feedback loop is active during neurogenesis, but inactive in non-neuronal cells. The reason for this is that the maturation of the precursor miR (pre-miR) to the mature miR-26 is arrested in non neuronal cells, but not in neurons. As only mature miRs are actively repressing genes, the regulation of miR-26 processing is an essential step in neurogenesis. In this study, the molecular basis of miR-26 processing regulation in the context of neurogenesis was addressed. The mature miR is processed from two larger precursors: First the primary transcript is cleaved by the enzyme DROSHA in the nucleus to form the pre-miR. The pre-miR is exported from the nucleus and processed further through the enzyme DICER to yield the mature miR. The mature miR can regulate gene expression in association with the RNA-induced silencing complex (RISC). Multiple different scenarios in which miR processing was regulated were proposed and experimentally tested. Microinjection studies using Xenopus leavis oocytes showed that slowdown or blockage of the nucleo-cytoplasmic transport are not the reason for delayed pre-miR-26 processing. Moreover, in vitro and in vivo miR-processing assays showed that maturation is most likely regulated through a in trans acting factor, which blocks processing in non neuronal cells. Through RNA affinity chromatographic assays using zebrafish and murine lysates I was able to isolate and identify proteins that interact specifically with pre-miR-26 and could by this influence its biogenesis. Potential candidates are FMRP/FXR1/2, ZNF346 and Eral1, whose functional characterisation in the context of miR-biogenesis could now be addressed. The second part of my thesis was executed in close colaboration with the laboratory of Prof. Albrecht M{\"u}ller. The principal question was addressed how miR-26 influences neuronal gene expression and which genes are primarily affected. This research question could be addressed by using a cell culture model system, which mimics ex vivo the differentiation of ESCs to NCs via neuronal progenitor. For the functional analysis of miR-26 knock out cell lines were generated by the CRISPR/Cas9 technology. miR-26 deficient ESC keep their pluripotent state and are able to develop NPC, but show major impairment in differentiating to NCs. Through RNA deep sequencing the miR-26 induced transcriptome differences could be analysed. On the level of mRNAs it could be shown, that the expression of neuronal gene is downregulated in miR-26 deficient NCs. Interestingly, the deletion of miR-26 leads to selectively decreased levels of miRs, which on one hand regulate the REST complex and on the other hand are under transcriptional control by REST themself. This data and the discovery that induction of miR-26 leads to enrichment of other REST regulating miRs indicates that miR-26 initiates neurogenesis through stepwise inactivation of the REST complex.},
  subject      = {miRNS},
  language  = {en}
}
@phdthesis{Zenk2018,
  author    = {Zenk, Markus},
  title     = {On Numerical Methods for Astrophysical Applications},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162669},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Diese Arbeit befasst sich mit der Approximation der L{\"o}sungen von Modellen zur Beschreibung des Str{\"o}mungsverhaltens in Atmosph{\"a}ren. Im Speziellen umfassen die hier behandelten Modelle die kompressiblen Euler Gleichungen der Gasdynamik mit einem Quellterm bez{\"u}glich der Gravitation und die Flachwassergleichungen mit einem nicht konstanten Bodenprofil. Verschiedene Methoden wurden bereits entwickelt um die L{\"o}sungen dieser Gleichungen zu approximieren. Im Speziellen geht diese Arbeit auf die Approximation von L{\"o}sungen nahe des Gleichgewichts und, im Falle der Euler Gleichungen, bei kleinen Mach Zahlen ein. Die meisten numerischen Methoden haben die Eigenschaft, dass die Qualit{\"a}t der Approximation sich mit der Anzahl der Freiheitsgrade verbessert. In der Praxis werden deswegen diese numerischen Methoden auf großen Computern implementiert um eine m{\"o}glichst hohe Approximationsg{\"u}te zu erreichen. Jedoch sind auch manchmal diese großen Maschinen nicht ausreichend, um die gew{\"u}nschte Qualit{\"a}t zu erreichen. Das Hauptaugenmerk dieser Arbeit ist darauf gerichtet, die Qualit{\"a}t der Approximation bei gleicher Anzahl von Freiheitsgrade zu verbessern. Diese Arbeit ist im Zusammenhang einer Kollaboration zwischen Prof. Klingenberg des Mathemaitschen Instituts in W{\"u}rzburg und Prof. R{\"o}pke des Astrophysikalischen Instituts in W{\"u}rzburg entstanden. Das Ziel dieser Kollaboration ist es, Methoden zur Berechnung von stellarer Atmosph{\"a}ren zu entwickeln. In dieser Arbeit werden vor allem zwei Problemstellungen behandelt. Die erste Problemstellung bezieht sich auf die akkurate Approximation des Quellterms, was zu den so genannten well-balanced Schemata f{\"u}hrt. Diese erlauben genaue Approximationen von L{\"o}sungen nahe des Gleichgewichts. Die zweite Problemstellung bezieht sich auf die Approximation von Str{\"o}mungen bei kleinen Mach Zahlen. Es ist bekannt, dass L{\"o}sungen der kompressiblen Euler Gleichungen zu L{\"o}sungen der inkompressiblen Euler Gleichungen konvergieren, wenn die Mach Zahl gegen null geht. Klassische numerische Schemata zeigen ein stark diffusives Verhalten bei kleinen Mach Zahlen. Das hier entwickelte Schema f{\"a}llt in die Kategorie der asymptotic preserving Schematas, d.h. das numerische Schema ist auf einem diskrete Level kompatibel mit dem auf dem Kontinuum gezeigten verhalten. Zus{\"a}tzlich wird gezeigt, dass die Diffusion des hier entwickelten Schemas unabh{\"a}ngig von der Mach Zahl ist. In Kapitel 3 wird ein HLL approximativer Riemann L{\"o}ser f{\"u}r die Approximation der L{\"o}sungen der Flachwassergleichungen mit einem nicht konstanten Bodenprofil angewendet und ein well-balanced Schema entwickelt. Die meisten well-balanced Schemata f{\"u}r die Flachwassergleichungen behandeln nur den Fall eines Fluids im Ruhezustand, die so genannten Lake at Rest L{\"o}sungen. Hier wird ein Schema entwickelt, welches sich mit allen Gleichgewichten befasst. Zudem wird eine zweiter Ordnung Methode entwickelt, welche im Gegensatz zu anderen in der Literatur nicht auf einem iterativen Verfahren basiert. Numerische Experimente werden durchgef{\"u}hrt um die Vorteile des neuen Verfahrens zu zeigen. In Kapitel 4 wird ein Suliciu Relaxations L{\"o}ser angepasst um die hydrostatischen Gleichgewichte der Euler Gleichungen mit einem Gravitationspotential aufzul{\"o}sen. Die Gleichungen der hydrostatischen Gleichgewichte sind unterbestimmt und lassen deshalb keine Eindeutigen L{\"o}sungen zu. Es wird jedoch gezeigt, dass das neue Schema f{\"u}r eine große Klasse dieser L{\"o}sungen die well-balanced Eigenschaft besitzt. F{\"u}r bestimmte Klassen werden Quadraturformeln zur Approximation des Quellterms entwickelt. Es wird auch gezeigt, dass das Schema robust, d.h. es erh{\"a}lt die Positivit{\"a}t der Masse und Energie, und stabil bez{\"u}glich der Entropieungleichung ist. Die numerischen Experimente konzentrieren sich vor allem auf den Einfluss der Quadraturformeln auf die well-balanced Eigenschaften. In Kapitel 5 wird ein Suliciu Relaxations Schema angepasst f{\"u}r Simulationen im Bereich kleiner Mach Zahlen. Es wird gezeigt, dass das neue Schema asymptotic preserving und die Diffusion kontrolliert ist. Zudem wird gezeigt, dass das Schema f{\"u}r bestimmte Parameter robust ist. Eine Stabilit{\"a}t wird aus einer Chapman-Enskog Analyse abgeleitet. Resultate numerische Experimente werden gezeigt um die Vorteile des neuen Verfahrens zu zeigen. In Kapitel 6 werden die Schemata aus den Kapiteln 4 und 5 kombiniert um das Verhalten des numerischen Schemas bei Fl{\"u}ssen mit kleiner Mach Zahl in durch die Gravitation geschichteten Atmosph{\"a}ren zu untersuchen. Es wird gezeigt, dass das Schema well-balanced ist. Die Robustheit und die Stabilit{\"a}t werden analog zu Kapitel 5 behandelt. Auch hier werden numerische Tests durchgef{\"u}hrt. Es zeigt sich, dass das neu entwickelte Schema in der Lage ist, die Dynamiken besser Aufzul{\"o}sen als vor der Anpassung. Das Kapitel 7 besch{\"a}ftigt sich mit der Entwicklung eines multidimensionalen Schemas basierend auf der Suliciu Relaxation. Jedoch ist die Arbeit an diesem Ansatz noch nicht beendet und numerische Resultate k{\"o}nnen nicht pr{\"a}sentiert werden. Es wird aufgezeigt, wo sich die Schw{\"a}chen dieses Ansatzes befinden und weiterer Entwicklungsbedarf besteht.},
  subject      = {Str{\"o}mung},
  language  = {en}
}
@article{ZeinerZinkeKowalewskietal.2018,
  author    = {Zeiner, P. S. and Zinke, J. and Kowalewski, D. J. and Bernatz, S. and Tichy, J. and Ronellenfitsch, M. W. and Thorsen, F. and Berger, A. and Forster, M. T. and Muller, A. and Steinbach, J. P. and Beschorner, R. and Wischhusen, J. and Kvasnicka, H. M. and Plate, K. H. and Stefanović, S. and Weide, B. and Mittelbronn, M. and Harter, P. N.},
  title     = {CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival},
  series = {Acta Neuropathologica Communications},
  volume    = {6},
  journal   = {Acta Neuropathologica Communications},
  doi       = {10.1186/s40478-018-0521-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233882},
  year      = {2018},
  abstract  = {Abstract Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity. We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line. We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected. In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.},
  language  = {en}
}
@article{YuVogelFoerstner2018,
  author    = {Yu, Sung-Huan and Vogel, J{\"o}rg and F{\"o}rstner, Konrad U.},
  title     = {ANNOgesic: a Swiss army knife for the RNA-seq based annotation of bacterial/archaeal genomes},
  series = {GigaScience},
  volume    = {7},
  journal   = {GigaScience},
  doi       = {10.1093/gigascience/giy096},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178942},
  year      = {2018},
  abstract  = {To understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or noncoding RNAs, are harder to detect. RNA sequencing (RNA-seq) has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-seq data in order to generate high-resolution annotations is challenging, time consuming, and requires numerous steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-seq and differential RNA-seq and predicts and annotates numerous features, including small noncoding RNAs, with high precision. The software is available under an open source license (ISCL) at https://pypi.org/project/ANNOgesic/.},
  language  = {en}
}
@unpublished{YinWernerHiguchietal.2018,
  author    = {Yin, Yafu and Werner, Rudolf A. and Higuchi, Takahiro and Lapa, Constantin and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.},
  title     = {Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.118.217653},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167594},
  year      = {2018},
  abstract  = {Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9\%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3\%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7\%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0\%) PSMA-RADS-3A lesions and 3/14 (21.4\%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{YankuBitmanLotanZoharetal.2018,
  author    = {Yanku, Yifat and Bitman-Lotan, Eliya and Zohar, Yaniv and Kurant, Estee and Zilke, Norman and Eilers, Martin and Orian, Amir},
  title     = {Drosophila HUWE1 ubiquitin ligase regulates endoreplication and antagonizes JNK signaling during salivary gland development},
  series = {Cells},
  volume    = {7},
  journal   = {Cells},
  number    = {10},
  issn      = {2073-4409},
  doi       = {10.3390/cells7100151},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197630},
  pages     = {151},
  year      = {2018},
  abstract  = {The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development.},
  language  = {en}
}
@article{WurmbSchorscherJusticeetal.2018,
  author    = {Wurmb, T and Schorscher, N and Justice, P and Dietz, S and Schua, R and Jarausch, T and Kinstle, U and Greiner, J and M{\"o}ldner, G and M{\"u}ller, J and Kraus, M and Simon, S and Wagenh{\"a}user, U and Hemm, J and Roewer, N and Helm, M},
  title     = {Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators},
  series = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine},
  volume    = {26},
  journal   = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine},
  number    = {87},
  doi       = {10.1186/s13049-018-0555-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177054},
  year      = {2018},
  abstract  = {Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.},
  language  = {en}
}
@article{WolffWeikampBatinic2018,
  author    = {Wolff, Hans-Georg and Weikamp, Julia G. and Batinic, Bernad},
  title     = {Implicit Motives as Determinants of Networking Behaviors},
  series = {Frontiers in Psychology},
  volume    = {9},
  journal   = {Frontiers in Psychology},
  number    = {411},
  issn      = {1664-1078},
  doi       = {10.3389/fpsyg.2018.00411},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189954},
  year      = {2018},
  abstract  = {In today's world of work, networking behaviors are an important and viable strategy to enhance success in work and career domains. Concerning personality as an antecedent of networking behaviors, prior studies have exclusively relied on trait perspectives that focus on how people feel, think, and act. Adopting a motivational perspective on personality, we enlarge this focus and argue that beyond traits predominantly tapping social content, motives shed further light on instrumental aspects of networking - or why people network. We use McClelland's implicit motives framework of need for power (nPow), need for achievement (nAch), and need for affiliation (nAff) to examine instrumental determinants of networking. Using a facet theoretical approach to networking behaviors, we predict differential relations of these three motives with facets of (1) internal vs. external networking and (2) building, maintaining, and using contacts. We conducted an online study, in which we temporally separate measures (N = 539 employed individuals) to examine our hypotheses. Using multivariate latent regression, we show that nAch is related to networking in general. In line with theoretical differences between networking facets, we find that nAff is positively related to building contacts, whereas nPow is positively related to using internal contacts. In sum, this study shows that networking is not only driven by social factors (i.e., nAff), but instead the achievement motive is the most important driver of networking behaviors.},
  language  = {en}
}
@phdthesis{Wohlfart2018,
  author    = {Wohlfart, Christian},
  title     = {The Yellow River Basin in Transition - Multi-faceted Land Cover Change Analysis in the Yellow River Basin in the Context of Global Change Using Multi-sensor Remote Sensing Imagery},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163724},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {As a cradle of ancient Chinese civilization, the Yellow River Basin has a very long human-environment interrelationship, where early anthropogenic activities re- sulted in large scale landscape modifications. Today, the impact of this relationship has intensified further as the basin plays a vital role for China's continued economic development. It is one of the most densely-populated, fastest growing, and most dynamic regions of China with abundant natural and environmental resources providing a livelihood for almost 190 million people. Triggered by fundamental economic reforms, the basin has witnessed a spectacular economic boom during the last decades and can be considered as an exemplary blueprint region for contemporary dynamic Global Change processes occurring throughout the country, which is currently transitioning from an agrarian-dominated economy into a modern urbanized society. However, this resourcesdemanding growth has led to profound land use changes with adverse effects on the Yellow River social-ecological systems, where complex challenges arise threatening a long-term sustainable development. Consistent and continuous remote sensing-based monitoring of recent and past land cover and land use change is a fundamental requirement to mitigate the adverse impacts of Global Change processes. Nowadays, technical advancement and the multitude of available satellite sensors, in combination with the opening of data archives, allow the creation of new research perspectives in regional land cover applications over heterogeneous landscapes at large spatial scales. Despite the urgent need to better understand the prevailing dynamics and underlying factors influencing the current processes, detailed regional specific land cover data and change information are surprisingly absent for this region. In view of the noted research gaps and contemporary developments, three major objectives are defined in this thesis. First (i), the current and most pressing social-ecological challenges are elaborated and policy and management instruments towards more sustainability are discussed. Second (ii), this thesis provides new and improved insights on the current land cover state and dynamics of the entire Yellow River Basin. Finally (iii), the most dominant processes related to mining, agriculture, forest, and urban dynamics are determined on finer spatial and temporal scales. The complex and manifold problems and challenges that result from long-term abuse of the water and land resources in the basin have been underpinned by policy choices, cultural attitude, and institutions that have evolved over centuries in China. The tremendous economic growth that has been mainly achieved by extracting water and exploiting land resources in a rigorous, but unsustainable manner, might not only offset the economic benefits, but could also foster social unrest. Since the early emergence of the first Chinese dynasties, flooding was considered historically as a primary issue in river management and major achievements have been made to tame the wild nature of the Yellow River. Whereas flooding is therefore largely now under control, new environmental and social problems have evolved, including soil and water pollution, ecological degradation, biodiversity decline, and food security, all being further aggravated by anthropogenic climate change. To resolve the contemporary and complex challenges, many individual environmental laws and regulations have been enacted by various Chinese ministries. However, these policies often pursue different, often contradictory goals, are too general to tackle specific problems and are usually implemented by a strong top-down approach. Recently, more flexible economic and market-based incentives (pricing, tradable permits, investments) have been successfully adopted, which are specifically tailored to the respective needs, shifting now away from the pure command and regulating instruments. One way towards a more holistic and integrated river basin management could be the establishment of a common platform (e.g. a Geographical Information System) for data handling and sharing, possibly operated by the Yellow River Basin Conservancy Commission (YRCC), where available spatial data, statistical information and in-situ measures are coalesced, on which sustainable decision-making could be based. So far, the collected data is hardly accessible, fragmented, inconsistent, or outdated. The first step to address the absence and lack of consistent and spatially up-to-date information for the entire basin capturing the heterogeneous landscape conditions was taken up in this thesis. Land cover characteristics and dynamics were derived from the last decade for the years 2003 and 2013, based on optical medium-resolution hightemporal MODIS Normalized Differenced Vegetation Index (NDVI) time series at 250 m. To minimize the inherent influence of atmospheric and geometric interferences found in raw high temporal data, the applied adaptive Savitzky-Golay filter successfully smoothed the time series and substantially reduced noise. Based on the smoothed time series data, a large variety of intra-annual phenology metrics as well as spectral and multispectral annual statistics were derived, which served as input variables for random forest (RF) classifiers. High quality reference data sets were derived from very high resolution imagery for each year independently of which 70 \% trained the RF models. The accuracy assessments for all regionally specific defined thematic classes were based on the remaining 30 \% reference data split and yielded overall accuracies of 87 \% and 84 \% for 2003 and 2013, respectively. The first regional adapted Yellow River Land Cover Products (YRB LC) depict the detail spatial extent and distribution of the current land cover status and dynamics. The novel products overall differentiate overall 18 land cover and use classes, including classes of natural vegetation (terrestrial and aquatic), cultivated classes, mosaic classes, non-vegetated, and artificial classes, which are not presented in previous land cover studies so far. Building on this, an extended multi-faceted land cover analysis on the most prominent land cover change types at finer spatial and temporal scales provides a better and more detailed picture of the Yellow River Basin dynamics. Precise spatio-temporal products about mining, agriculture, forest, and urban areas were examined from long-trem Landsat satellite time series monitored at annual scales to capture the rapid rate of change in four selected focus regions. All archived Landsat images between 2000 and 2015 were used to derive spatially continuous spectral-temporal, multi-spectral, and textural metrics. For each thematic region and year RF models were built, trained and tested based on a stablepixels reference data set. The automated adaptive signature (AASG) algorithm identifies those pixels that did not change between the investigated time periods to generate a mono-temporal reference stable-pixels data set to keep manual sampling requirements to a minimum level. Derived results gained high accuracies ranging from 88 \% to 98 \%. Throughout the basin, afforestation on the Central Loess Plateau and urban sprawl are identified as most prominent drivers of land cover change, whereas agricultural land remained stable, only showing local small-scale dynamics. Mining operations started in 2004 on the Qinghai-Tibet Plateau, which resulted in a substantial loss of pristine alpine meadows and wetlands. In this thesis, a novel and unique regional specific view of current and past land cover characteristics in a complex and heterogeneous landscape was presented by using a multi-source remote sensing approach. The delineated products hold great potential for various model and management applications. They could serve as valuable components for effective and sustainable land and water management to adapt and mitigate the predicted consequences of Global Change processes.},
  subject      = {Fernerkundung},
  language  = {en}
}
@phdthesis{Wiedenmann2018,
  author    = {Wiedenmann, Jonas},
  title     = {Induced topological superconductivity in HgTe based nanostructures},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162782},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {This thesis describes the studies of topological superconductivity, which is predicted to emerge when pair correlations are induced into the surface states of 2D and 3D topolog- ical insulators (TIs). In this regard, experiments have been designed to investigate the theoretical ideas first pioneered by Fu and Kane that in such system Majorana bound states occur at vortices or edges of the system [Phys. Rev. Lett. 100, 096407 (2008), Phys. Rev. B 79, 161408 (2009)]. These states are of great interest as they constitute a new quasiparticle which is its own antiparticle and can be used as building blocks for fault tolerant topological quantum computing. After an introduction in chapter 1, chapter 2 of the thesis lays the foundation for the understanding of the field of topology in the context of condensed matter physics with a focus on topological band insulators and topological superconductors. Starting from a Chern insulator, the concepts of topological band theory and the bulk boundary corre- spondence are explained. It is then shown that the low energy Hamiltonian of mercury telluride (HgTe) quantum wells of an appropriate thickness can be written as two time reversal symmetric copies of a Chern insulator. This leads to the quantum spin Hall effect. In such a system, spin-polarized one dimensional conducting states form at the edges of the material, while the bulk is insulating. This concept is extended to 3D topological insulators with conducting 2D surface states. As a preliminary step to treating topological superconductivity, a short review of the microscopic theory of superconductivity, i.e. the theory of Bardeen, Cooper, and Shrieffer (BCS theory) is presented. The presence of Majorana end modes in a one dimensional superconducting chain is explained using the Kitaev model. Finally, topological band insulators and conventional superconductivity are combined to effectively engineer p-wave superconductivity. One way to investigate these states is by measuring the periodicity of the phase of the Josephson supercurrent in a topological Josephson junction. The signature is a 4π-periodicity compared to the 2π-periodicity in conventional Josephson junctions. The proof of the presence of this effect in HgTe based Josephson junction is the main goal of this thesis and is discussed in chapters 3 to 6. Chapter 3 describes in detail the transport of a 3D topological insulator based weak link under radio-frequency radiation. The chapter starts with a review of the state of research of (i) strained HgTe as 3D topological insulator and (ii) the progress of induc- ing superconducting correlations into the topological surface states and the theoretical predictions of 3D TI based Josephson junctions. Josephson junctions based on strained HgTe are successfully fabricated. Before studying the ac driven Josephson junctions, the dc transport of the devices is analysed. The critical current as a function of temperature is measured and it is possible to determine the induced superconducting gap. Under rf illumination Shapiro steps form in the current voltage characteristic. A missing first step at low frequencies and low powers is found in our devices. This is a signature of a 4π-periodic supercurrent. By studying the device in a wide parameter range - as a 147148 SUMMARY function of frequency, power, device geometry and magnetic field - it is shown that the results are in agreement with the presence of a single gapless Andreev doublet and several conventional modes. Chapter 4 gives results of the numerical modelling of the I -V dynamics in a Josephson junction where both a 2π- and a 4π-periodic supercurrents are present. This is done in the framework of an equivalent circuit representation, namely the resistively shunted Josephson junction model (RSJ-model). The numerical modelling is in agreement with the experimental results in chapter 3. First, the missing of odd Shapiro steps can be understood by a small 4π-periodic supercurrent contribution and a large number of modes which have a conventional 2π-periodicity. Second, the missing of odd Shapiro steps occurs at low frequency and low rf power. Third, it is shown that stochastic processes like Landau Zener tunnelling are most probably not responsible for the 4π contribution. In a next step the periodicity of Josephson junctions based on quantum spin Hall insulators using are investigated in chapter 5. A fabrication process of Josephson junctions based on inverted HgTe quantum wells was successfully developed. In order to achieve a good proximity effect the barrier material was removed and the superconductor deposited without exposing the structure to air. In a next step a gate electrode was fabricated which allows the chemical potential of the quantum well to be tuned. The measurement of the diffraction pattern of the critical current Ic due to a magnetic field applied perpendicular to the sample plane was conducted. In the vicinity to the expected quantum spin Hall phase, the pattern resembles that of a superconducting quantum interference device (SQUID). This shows that the current flows predominantly on the edges of the mesa. This observation is taken as a proof of the presence of edge currents. By irradiating the sample with rf, missing odd Shapiro steps up to step index n = 9 have been observed. This evidences the presence of a 4π-periodic contribution to the supercurrent. The experiment is repeated using a weak link based on a non-inverted HgTe quantum well. This material is expected to be a normal band insulator without helical edge channels. In this device, all the expected Shapiro steps are observed even at low frequencies and over the whole gate voltage range. This shows that the observed phenomena are directly connected to the topological band structure. Both features, namely the missing of odd Shapiro steps and the SQUID like diffraction pattern, appear strongest towards the quantum spin Hall regime, and thus provide evidence for induced topological superconductivity in the helical edge states. A more direct way to probe the periodicity of the Josephson supercurrent than using Shapiro steps is the measurement of the emitted radiation of a weak link. This experiment is presented in chapter 6. A conventional Josephson junction converts a dc bias V to an ac current with a characteristic Josephson frequency fJ = eV /h. In a topological Josephson junction a frequency at half the Josephson frequency fJ /2 is expected. A new measurement setup was developed in order to measure the emitted spectrum of a single Josephson junction. With this setup the spectrum of a HgTe quantum well based Josephson junction was measured and the emission at half the Josephson frequency fJ /2 was detected. In addition, fJ emission is also detected depending on the gate voltage and detection frequency. The spectrum is again dominated by half the Josephson emission at low voltages while the conventional emission is determines the spectrum at high voltages. A non-inverted quantum well shows only conventional emission over the whole gateSUMMARY 149 voltage and frequency range. The linewidth of the detected frequencies gives a measure on the lifetime of the bound states: From there, a coherence time of 0.3-4ns for the fJ /2 line has been deduced. This is generally shorter than for the fJ line (3-4ns). The last part of the thesis, chapter 7, reports on the induced superconducting state in a strained HgTe layer investigated by point-contact Andreev reflection spectroscopy. For the experiment, a HgTe mesa was fabricated with a small constriction. The diameter of the orifice was chosen to be smaller than the mean free path estimated from magne- totransport measurements. Thus one gets a ballistic point-contact which allows energy resolved spectroscopy. One part of the mesa is covered with a superconductor which induces superconducting correlations into the surface states of the topological insulator. This experiment therefore probes a single superconductor normal interface. In contrast to the Josephson junctions studied previously, the geometry allows the acquisition of energy resolved information of the induced superconducting state through the measurement of the differential conductance dI/dV as a function of applied dc bias for various gate voltages, temperatures and magnetic fields. An induced superconducting order parame- ter of about 70µeV was extracted but also signatures of the niobium gap at the expected value around Δ Nb ≈ 1.1meV have been found. Simulations using the theory developed by Blonder, Tinkham and Klapwijk and an extended model taking the topological surface states into account were used to fit the data. The simulations are in agreement with a small barrier at the topological insulator-induced topological superconductor interface and a high barrier at the Nb to topological insulator interface. To understand the full con- ductance curve as a function of applied voltage, a non-equilibrium driven transformation is suggested. The induced superconductivity is suppressed at a certain bias value due to local electron population. In accordance with this suppression, the relevant scattering regions change spatially as a function of applied bias. To conclude, it is emphasized that the experiments conducted in this thesis found clear signatures of induced topological superconductivity in HgTe based quantum well and bulk devices and opens up the avenue to many experiments. It would be interesting to apply the developed concepts to other topological matter-superconductor hybrid systems. The direct spectroscopy and manipulation of the Andreev bound states using circuit quantum electrodynamic techniques should be the next steps for HgTe based samples. This was already achieved in superconducting atomic break junctions by the group in Saclay [Science 2015, 349, 1199-1202 (2015)]. Another possible development would be the on-chip detection of the emitted spectrum as a function of the phase φ through the junction. In this connection, the topological junction needs to be shunted by a parallel ancillary junction. Such a setup would allow the current phase relation I(φ) directly and the lifetime of the bound states to be measured directly. By coupling this system to a spectrometer, which can be another Josephson junction, the energy dependence of the Andreev bound states E(φ) could be obtained. The experiments on the Andreev reflection spectroscopy described in this thesis could easily be extended to two dimensional topological insulators and to more complex geometries, like a phase bias loop or a tunable barrier at the point-contact. This work might also be useful for answering the question how and why Majorana bound states can be localized in quantum spin Hall systems.},
  subject      = {Quecksilbertellurid},
  language  = {en}
}
@article{WevrettFenwickScuffhametal.2018,
  author    = {Wevrett, Jill and Fenwick, Andrew and Scuffham, James and Johansson, Lena and Gear, Jonathan and Schl{\"o}gl, Susanne and Segbers, Marcel and Sj{\"o}green-Gleisner, Katarina and Soln{\´y}, Pavel and Lassmann, Michael and Tipping, Jill and Nisbet, Andrew},
  title     = {Inter-comparison of quantitative imaging of lutetium-177 (\(^{177}\)Lu) in European hospitals},
  series = {EJNMMI Physics},
  volume    = {5},
  journal   = {EJNMMI Physics},
  doi       = {10.1186/s40658-018-0213-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233658},
  year      = {2018},
  abstract  = {Background This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (\(^{177}\)Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. Results The volumes reported by the participants for the inner section of the source were all within 29\% of the true value and within 60\% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20\% of the true value, whilst those reported for the outer section were up to 83\% different to the true value. Conclusions A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods.},
  language  = {en}
}
@article{WernerWakabyashiChenetal.2018,
  author    = {Werner, Rudolf and Wakabyashi, Hiroshi and Chen, Xinyu and Hirano, Mitsuru and Shinaji, Tetsuya and Lapa, Constantin and Rowe, Steven and Javadi, Mehrbod and Higuchi, Takahiro},
  title     = {Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.203828},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161279},
  year      = {2018},
  abstract  = {Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases. Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05). Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.},
  subject      = {Nierenfunktionsst{\"o}rung},
  language  = {en}
}
@article{WernerWakabayashiBaueretal.2018,
  author    = {Werner, Rudolf and Wakabayashi, Hiroshi and Bauer, Jochen and Sch{\"u}tz, Claudia and Zechmeister, Christina and Hayakawa, Nobuyuki and Javadi, Mehrbod S. and Lapa, Constantin and Jahns, Roland and Erg{\"u}n, S{\"u}leyman and Jahns, Valerie and Higuchi, Takahiro},
  title     = {Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis},
  series = {European Heart Journal Cardiovascular Imaging},
  journal   = {European Heart Journal Cardiovascular Imaging},
  issn      = {2047-2404},
  doi       = {10.1093/ehjci/jey119},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165601},
  pages     = {1-8},
  year      = {2018},
  abstract  = {Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund's adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease). Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.},
  subject      = {Myokarditis},
  language  = {en}
}
@article{WernerSolnesJavadietal.2018,
  author    = {Werner, Rudolf and Solnes, Lilja and Javadi, Mehrbod and Weich, Alexander and Gorin, Michael and Pienta, Kenneth and Higuchi, Takahiro and Buck, Andreas and Pomper, Martin and Rowe, Steven and Lapa, Constantin},
  title     = {SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.206631},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161298},
  year      = {2018},
  abstract  = {Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.},
  subject      = {Standardisierung},
  language  = {en}
}
@article{WernerSchmidHiguchietal.2018,
  author    = {Werner, Rudolf and Schmid, Jan-Stefan and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and M{\"a}rkl, Bruno and Aulmann, Christoph and Fassnacht, Martin and Kroiß, Matthias and Reiners, Christoph and Buck, Andreas and Kreissl, Michael and Lapa, Constantin},
  title     = {Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.199778},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161256},
  year      = {2018},
  abstract  = {Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type). Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation. Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance. Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.},
  subject      = {Medull{\"a}rer Schilddr{\"u}senkrebs},
  language  = {en}
}
@article{WernerHaenscheidLealetal.2018,
  author    = {Werner, Rudolf and H{\"a}nscheid, Heribert and Leal, Jeffrey P. and Javadi, Mehrbod S. and Higuchi, Takahiro and Lodge, Martin A. and Buck, Andreas K. and Pomper, Martin G. and Lapa, Constantin and Rowe, Steven P.},
  title     = {Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170280},
  pages     = {1-9},
  year      = {2018},
  abstract  = {Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden. Procedures: Of the 44 included patients, 36/44 (82\%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2\%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3\%) vs. higher TBU (>7\%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerWeichKircheretal.2018,
  author    = {Werner, Rudolf A. and Weich, Alexander and Kircher, Malte and Solnes, Lilja B. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Pomper, Martin G. and Rowe, Steven and Lapa, Constantin},
  title     = {The theranostic promise for neuroendocrine tumors in the late 2010s - Where do we stand, where do we go?},
  series = {Theranostics},
  volume    = {8},
  journal   = {Theranostics},
  number    = {22},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170264},
  pages     = {6088-6100},
  year      = {2018},
  abstract  = {More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerMarcusSheikhbahaeietal.2018,
  author    = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Solnes, Lilja B. and Leal, Jeffrey P. and Du, Yong and Rowe, Steven P. and Higuchi, Takahiro and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.},
  title     = {Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging},
  series = {Clinical Nuclear Medicine},
  volume    = {44},
  journal   = {Clinical Nuclear Medicine},
  number    = {1},
  issn      = {1536-0229},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168181},
  year      = {2018},
  abstract  = {PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5\%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7\%, ĸ = 0.75) compared to semiquantification (86.2\%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.},
  subject      = {SPECT},
  language  = {en}
}
@inproceedings{WernerMarcusSheikhbahaeietal.2018,
  author    = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Higuchi, Takahiro and Solnes, Lilja B. and Rowe, Steven P. and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.},
  title     = {Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method},
  series = {Journal of Nuclear Medicine},
  volume    = {59},
  booktitle = {Journal of Nuclear Medicine},
  number    = {Supplement No. 1},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162208},
  pages     = {626},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Parkinson-Krankheit},
  language  = {en}
}
@inproceedings{WernerMarcusSheikhbahaeietal.2018,
  author    = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Higuchi, Takahiro and Solnes, Lilja B. and Rowe, Steven P. and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.},
  title     = {The Impact of Ageing on Dopamine Transporter Imaging},
  series = {Journal of Nuclear Medicine},
  volume    = {59},
  booktitle = {Journal of Nuclear Medicine},
  number    = {Supplement No 1},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162213},
  pages     = {1646},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Parkinson-Krankheit},
  language  = {en}
}
@article{WernerKobayashiJavadietal.2018,
  author    = {Werner, Rudolf A. and Kobayashi, Ryohei and Javadi, Mehrbod Som and K{\"o}ck, Zoe and Wakabayashi, Hiroshi and Unterecker, Stefan and Nakajima, Kenichi and Lapa, Constantin and Menke, Andreas and Higuchi, Takahiro},
  title     = {Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.206045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161280},
  year      = {2018},
  abstract  = {Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results. Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 \% for desipramine, 25.5 \% for venlafaxine, 11.7 \% for bupropion and 0.72 \% for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake. Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.},
  subject      = {Antidepressants},
  language  = {en}
}
@unpublished{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {https://doi.org/10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164624},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167168},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerEisslerHayakawaetal.2018,
  author    = {Werner, Rudolf A. and Eissler, Christoph and Hayakawa, Nobuyuki and Arias-Loza, Paula and Wakabayashi, Hiroshi and Javadi, Mehrbod S. and Chen, Xinyu and Shinaji, Tetsuya and Lapa, Constantin and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {17631},
  doi       = {10.1038/s41598-018-35986-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171765},
  year      = {2018},
  abstract  = {In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5\%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.},
  language  = {en}
}
@article{WernerChenRoweetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Rowe, Steven P. and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers},
  series = {The International Journal of Cardiovascular Imaging},
  journal   = {The International Journal of Cardiovascular Imaging},
  issn      = {1569-5794},
  doi       = {10.1007/s10554-018-1469-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169134},
  year      = {2018},
  abstract  = {The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.},
  subject      = {Positronenemissionstomografie},
  language  = {en}
}
@article{WernerChenMayaetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Maya, Yoshifumi and Eissler, Christoph and Hirano, Mitsuru and Nose, Naoko and Wakabayashi, Hiroshi and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {11120},
  issn      = {2281-5872},
  doi       = {10.1038/s41598-018-29509-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164826},
  year      = {2018},
  abstract  = {We aimed to explore the impact of ageing on 11C-Hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (-)-metaraminol as the free base (radiochemical purity >95\%) and a wide range of specific activities (0.2-141.9 GBq/μmol) were prepared. \(^{11}\)C-HED (48.7±9.7MBq, ranged 0.2-60.4μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (\%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11CHED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerChenHiranoetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Hirano, Mitsuru and Rowe, Steven P. and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {SPECT vs. PET in Cardiac Innervation Imaging: Clash of the Titans},
  series = {Clinical and Translational Imaging},
  journal   = {Clinical and Translational Imaging},
  issn      = {2281-5872},
  doi       = {10.1007/s40336-018-0289-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163628},
  year      = {2018},
  abstract  = {Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers. Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@inproceedings{WernerChenHiranoetal.2018,
  author    = {Werner, Rudolf A. and Chen, Xinyu and Hirano, Mitsuru and Nose, Naoko and Lapa, Constantin and Javadi, Mehrbod S. and Higuchi, Takahiro},
  title     = {The Impact of Ageing on [\(^{11}\)C]meta-Hydroxyephedrine Uptake in the Rat Heart},
  series = {Journal of Nuclear Medicine},
  volume    = {59},
  booktitle = {Journal of Nuclear Medicine},
  number    = {Supplement No 1},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162228},
  pages     = {100},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerBundschuhHiguchietal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and Zs{\´o}t{\´e}r, Norbert and Kroiss, Matthias and Fassnacht, Martin and Buck, Andreas K. and Kreissl, Michael C. and Lapa, Constantin},
  title     = {Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib},
  series = {Endocrine},
  journal   = {Endocrine},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-018-1749-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167910},
  year      = {2018},
  abstract  = {Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerBundschuhBundschuhetal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Leal, Jeffrey P. and Higuchi, Takahiro and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.},
  title     = {Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.118.217588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167788},
  year      = {2018},
  abstract  = {Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4\%) instances, three readers in 40/125 (32\%) and two observers in 27/125 (21.6\%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerBundschuhBundschuhetal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Higuchi, Takahiro and Weich, Alexander and Sheikhbahaei, Sara and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.},
  title     = {MI-RADS: Molecular Imaging Reporting and Data Systems - A Generalizable Framework for Targeted Radiotracers with Theranostic Implications},
  series = {Annals of Nuclear Medicine},
  journal   = {Annals of Nuclear Medicine},
  issn      = {0914-7187},
  doi       = {10.1007/s12149-018-1291-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166995},
  year      = {2018},
  abstract  = {Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader's confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerAndreeJavadietal.2018,
  author    = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.},
  title     = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging},
  series = {Urology - The Gold Journal},
  journal   = {Urology - The Gold Journal},
  issn      = {0090-4295},
  doi       = {10.1016/j.urology.2018.03.030},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161103},
  year      = {2018},
  abstract  = {No abstract available.},
  subject      = {Virchow Node},
  language  = {en}
}
@article{WernerAndreeJavadietal.2018,
  author    = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.},
  title     = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging},
  series = {Urology - The Gold Journal},
  volume    = {117},
  journal   = {Urology - The Gold Journal},
  issn      = {0090-4295},
  doi       = {10.1016/j.urology.2018.03.030},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164632},
  pages     = {18-21},
  year      = {2018},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{Werner2018,
  author    = {Werner, Rudolf A.},
  title     = {Editorial: Cardiac Innervation Imaging as a Risk Stratification Tool for Potential Device Therapy Candidates},
  series = {Journal of Nuclear Cardiology},
  journal   = {Journal of Nuclear Cardiology},
  issn      = {1071-3581},
  doi       = {10.1007/s12350-018-01475-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168465},
  year      = {2018},
  abstract  = {As a scintigraphic approach evaluating cardiac nerve integrity, \(^{123}\)I-metaiodobenzylguanidine (123I-mIBG) has been recently Food and Drug Administration approved. A great deal of progress has been made by the prospective ADMIRE-HF trial, which primarily demonstrated the association of denervated myocardium assessed by \(^{123}\)I-mIBG and cardiac events. However, apart from risk stratification, myocardial nerve function evaluated by molecular imaging should also be expanded to other clinical contexts, in particular to guide the referring cardiologist in selecting appropriate candidates for specific therapeutic interventions. In the present issue of the Journal of Nuclear Cardiology, the use of 123I-mIBG for identifying cardiomyopathy patients, which would most likely not benefit from ICD due low risk of arrhythmias, is described. If we aim to deliver on the promise of cardiac innervation imaging as a powerful tool for risk stratification in a manner similar to nuclear oncology, studies such as the one reviewed here may imply an important step to lay the proper groundwork for a more widespread adoption in clinical practice.},
  subject      = {SPECT},
  language  = {en}
}
@article{WeisShanKuhlmannetal.2018,
  author    = {Weis, Matthias and Shan, Junwen and Kuhlmann, Matthias and Jungst, Tomasz and Tessmar, J{\"o}rg and Groll, J{\"u}rgen},
  title     = {Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting},
  series = {Gels},
  volume    = {4},
  journal   = {Gels},
  number    = {4},
  issn      = {2310-2861},
  doi       = {10.3390/gels4040082},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197600},
  pages     = {82},
  year      = {2018},
  abstract  = {In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers.},
  language  = {en}
}
@article{WeigelSchmitzPfisteretal.2018,
  author    = {Weigel, Tobias and Schmitz, Tobias and Pfister, Tobias and Gaetzner, Sabine and Jannasch, Maren and Al-Hijailan, Reem and Sch{\"u}rlein, Sebastian and Suliman, Salwa and Mustafa, Kamal and Hansmann, Jan},
  title     = {A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {14545},
  doi       = {10.1038/s41598-018-32790-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177368},
  year      = {2018},
  abstract  = {Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system's natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven.},
  language  = {en}
}
@phdthesis{Weidner2018,
  author    = {Weidner, Magdalena Theodora},
  title     = {Brain serotonin throughout development - for better and for worse},
  publisher = {Magdalena T. Weidner},
  address   = {Maastricht, the Netherlands},
  isbn      = {978-94-6233-940-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163345},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The work presented in this thesis covers the effects of early-life adversity in the context of altered serotonin (5-HT; 5-hydroxytryptamine) system functioning in mice. The main body is focussing on a screening approach identifying molecular processes, potentially involved in distinct behavioural manifestations that emerge from or are concomitant with early adversity and, with regard to some behavioural manifestations, dependent on the functioning of the 5-HT system.},
  subject      = {Gehirn},
  language  = {en}
}
@article{WeiBlaschke2018,
  author    = {Wei, Chunzhu and Blaschke, Thomas},
  title     = {Pixel-wise vs. object-based impervious surface analysis from remote sensing: correlations with land surface temperature and population density},
  series = {Urban Science},
  volume    = {2},
  journal   = {Urban Science},
  number    = {1},
  issn      = {2413-8851},
  doi       = {10.3390/urbansci2010002},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197829},
  pages     = {2},
  year      = {2018},
  abstract  = {Impervious surface areas (ISA) are heavily influenced by urban structure and related structural features. We examined the effects of object-based impervious surface spatial pattern analysis on land surface temperature and population density in Guangzhou, China, in comparison to classic per-pixel analyses. An object-based support vector machine (SVM) and a linear spectral mixture analysis (LSMA) were integrated to estimate ISA fraction using images from the Chinese HJ-1B satellite for 2009 to 2011. The results revealed that the integrated object-based SVM-LSMA algorithm outperformed the traditional pixel-wise LSMA algorithm in classifying ISA fraction. More specifically, the object-based ISA spatial patterns extracted were more suitable than pixel-wise patterns for urban heat island (UHI) studies, in which the UHI areas (landscape surface temperature >37 °C) generally feature high ISA fraction values (ISA fraction >50\%). In addition, the object-based spatial patterns enable us to quantify the relationship of ISA with population density (correlation coefficient >0.2 in general), with global human settlement density (correlation coefficient >0.2), and with night-time light map (correlation coefficient >0.4), and, whereas pixel-wise ISA did not yield significant correlations. These results indicate that object-based spatial patterns have a high potential for UHI detection and urbanization monitoring. Planning measures that aim to reduce the urbanization impacts and UHI intensities can be better supported.},
  language  = {en}
}
@article{WegenerSauer2018,
  author    = {Wegener, Sonja and Sauer, Otto A.},
  title     = {Electrometer offset current due to scattered radiation},
  series = {Journal of Applied Clinical Medical Physics},
  volume    = {19},
  journal   = {Journal of Applied Clinical Medical Physics},
  number    = {6},
  doi       = {10.1002/acm2.12458},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176137},
  pages     = {274-281},
  year      = {2018},
  abstract  = {Relative dose measurements with small ionization chambers in combination with an electrometer placed in the treatment room ("internal electrometer") show a large dependence on the polarity used. While this was observed previously for percent depth dose curves (PDDs), the effect has not been understood or preventable. To investigate the polarity dependence of internal electrometers used in conjunction with a small-volume ionization chamber, we placed an internal electrometer at a distance of 1 m from the isocenter and exposed it to different amounts of scattered radiation by varying the field size. We identified irradiation of the electrometer to cause a current of approximately -1 pA, regardless of the sign of the biasing voltage. For low-sensitivity detectors, such a current noticeably distorts relative dose measurements. To demonstrate how the current systematically changes PDDs, we collected measurements with nine ionization chambers of different volumes. As the chamber volume decreased, signal ratios at 20 and 10 cm depth (M20/M10) became smaller for positive bias voltage and larger for negative bias voltage. At the size of the iba CC04 (40 mm\(^{3}\)) the difference of M20/M10 was around 1\% and for the smallest studied chamber, the iba CC003 chamber (3 mm\(^{3}\)), around 7\% for a 10 × 10 cm² field. When the electrometer was moved further from the source or shielded, the additional current decreased. Consequently, PDDs at both polarities were brought into alignment at depth even for the 3 mm\(^{3}\) ionization chamber. The apparent polarity effect on PDDs and lateral beam profiles was reduced considerably by shielding the electrometer. Due to normalization the effect on output values was low. When measurements with a low-sensitivity probe are carried out in conjunction with an internal electrometer, we recommend careful monitoring of the particular setup by testing both polarities, and if deemed necessary, we suggest shielding the electrometer.},
  language  = {en}
}
@phdthesis{Wedel2018,
  author    = {Wedel, Carolin},
  title     = {The impact of DNA sequence and chromatin on transcription in \(Trypanosoma\) \(brucei\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173438},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {For cellular viability, transcription is a fundamental process. Hereby, the DNA plays the most elemental and highly versatile role. It has long been known that promoters contain conserved and often well-defined motifs, which dictate the site of transcription initiation by providing binding sites for regulatory proteins. However, research within the last decade revealed that it is promoters lacking conserved promoter motifs and transcribing constitutively expressed genes that constitute the majority of promoters in eukaryotes. While the process of transcription initiation is well studied, whether defined DNA sequence motifs are required for the transcription of constitutively expressed genes in eukaryotes remains unknown. In the highly divergent protozoan parasite Trypanosoma brucei, most of the proteincoding genes are organized in large polycistronic transcription units. The genes within one polycistronic transcription unit are generally unrelated and transcribed by a common transcription start site for which no RNA polymerase II promoter motifs have been identified so far. Thus, it is assumed that transcription initiation is not regulated but how transcription is initiated in T. brucei is not known. This study aimed to investigate the requirement of DNA sequence motifs and chromatin structures for transcription initiation in an organism lacking transcriptional regulation. To this end, I performed a systematic analysis to investigate the dependence of transcription initiation on the DNA sequence. I was able to identify GT-rich promoter elements required for directional transcription initiation and targeted deposition of the histone variant H2A.Z, a conserved component during transcription initiation. Furthermore, nucleosome positioning data in this work provide evidence that sites of transcription initiation are rather characterized by broad regions of open and more accessible chromatin than narrow nucleosome depleted regions as it is the case in other eukaryotes. These findings highlight the importance of chromatin during transcription initiation. Polycistronic RNA in T. brucei is separated by adding an independently transcribed miniexon during trans-splicing. The data in this work suggest that nucleosome occupancy plays an important role during RNA maturation by slowing down the progressing polymerase and thereby facilitating the choice of the proper splice site during trans-splicing. Overall, this work investigated the role of the DNA sequence during transcription initiation and nucleosome positioning in a highly divergent eukaryote. Furthermore, the findings shed light on the conservation of the requirement of DNA motifs during transcription initiation and the regulatory potential of chromatin during RNA maturation. The findings improve the understanding of gene expression regulation in T. brucei, a eukaryotic parasite lacking transcriptional Regulation.},
  subject      = {Transkription},
  language  = {en}
}
@article{WeberLassalleHaukeRamseretal.2018,
  author    = {Weber-Lassalle, Nana and Hauke, Jan and Ramser, Juliane and Richters, Lisa and Groß, Eva and Bl{\"u}mcke, Britta and Gehrig, Andrea and Kahlert, Anne-Karin and M{\"u}ller, Clemens R. and Hackmann, Karl and Honisch, Ellen and Weber-Lassalle, Konstantin and Niederacher, Dieter and Borde, Julika and Thiele, Holger and Ernst, Corinna and Altm{\"u}ller, Janine and Neidhardt, Guido and N{\"u}rnberg, Peter and Klaschik, Kristina and Schroeder, Christopher and Platzer, Konrad and Volk, Alexander E. and Wang-Gohrke, Shan and Just, Walter and Auber, Bernd and Kubisch, Christian and Schmidt, Gunnar and Horvath, Judit and Wappenschmidt, Barbara and Engel, Christoph and Arnold, Norbert and Dworniczak, Bernd and Rhiem, Kerstin and Meindl, Alfons and Schmutzler, Rita K. and Hahnen, Eric},
  title     = {BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer},
  series = {Breast Cancer Research},
  volume    = {20},
  journal   = {Breast Cancer Research},
  doi       = {10.1186/s13058-018-0935-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233433},
  year      = {2018},
  abstract  = {Background Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. Methods To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. Results BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95\% confidence interval (CI) = 12.02-36.57, P < 0.0001) and in the subgroup of index patients with late-onset OC (OR = 29.91, 95\% CI = 14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR = 1.81 95\% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95\% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95\% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. Conclusions To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.},
  language  = {en}
}
@phdthesis{Wannagat2018,
  author    = {Wannagat, Wienke Charlotte},
  title     = {Cognitive Processes of Discourse Comprehension in Children and Adults - Comparisons between Written, Auditory, and Audiovisual Modes of Presentation -},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162515},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {In drei Studien wurde untersucht, wie sich unterschiedliche Darbietungsformate (schriftlich, auditiv, audiovisuell (auditiv + Bilder) auf das Verst{\"a}ndnis semantisch identischer Inhalte auswirken. Dabei interessierte insbesondere der Entwicklungsverlauf von der ersten Klasse bis zum Erwachsenenalter. Dass sich Bilder f{\"o}rderlich auf die Verst{\"a}ndnisleistung auswirken k{\"o}nnen, gilt als gut untersucht (z.B. Carney \& Levin, 2002). Anders als viele bisherige Studien erfassen wir Textverstehen mit impliziten Maßen, die differenziertere R{\"u}ckschl{\"u}sse auf die, g{\"a}ngigen Theorien zufolge, zugrundeliegenden Prozesse zulassen: Textverstehen geht mit der Konstruktion von drei Ebenen mentaler Repr{\"a}sentationen einher (vgl. Kintsch, 1998). Weiterhin bedeutet erfolgreiches Textverstehen, eine auf lokaler und globaler Ebene koh{\"a}rente mentale Repr{\"a}sentation zu konstruieren (z.B. Schnotz \& Dutke, 2004). Mit einem Satz-Rekognitionstest (vgl. Schmalhofer \& Glavanov, 1986) untersuchten wir, ob sich das Ged{\"a}chtnis f{\"u}r die Textoberfl{\"a}che, die Textbasis und das Situationsmodell bei 103 8- und 10-J{\"a}hrigen zwischen schriftlicher, auditiver und audiovisueller (Studie 1) und bei 106 7-, 9- und 11-J{\"a}hrigen zwischen auditiver und audiovisueller Darbietung narrativer Texte (Studie 2) unterscheidet. Weiterhin (Studie 3) untersuchten wir mit 155 9- und 11-J{\"a}hrigen, inwieweit sich die F{\"a}higkeit der Inferenzbildung zur Herstellung lokaler und globaler Koh{\"a}renz zwischen schriftlicher, auditiver und audiovisueller Darbietung unterscheidet. Als Indikator dienten die Reaktionszeiten auf W{\"o}rter, die mit einem {\"u}ber (global)- oder untergeordneten (lokal) Protagonistenziel assoziiert sind. Insgesamt zeigte sich, dass Sch{\"u}ler bis zu einem Alter von 11 Jahren nicht nur die Textoberfl{\"a}che besser erinnern, sondern auch besser in der Lage sind ein Situationsmodell zu konstruieren, wenn einem Text Bilder beigef{\"u}gt sind. Dies zeigte sich sowohl im Vergleich mit auditiver als auch mit schriftlicher Darbietung. Bei Erwachsenen zeigte sich kein Effekt der Darbietungsform. Sowohl 9- als auch 11-J{\"a}hrigen gelingt außerdem die Herstellung globaler Koh{\"a}renz bei audiovisueller Darbietung besser als bei auditiver. Die schriftliche Darbietung zeigte sich im Vergleich zur auditiven sowohl im Hinblick auf lokale als auch auf globale Koh{\"a}renz {\"u}berlegen.},
  subject      = {Textverstehen},
  language  = {en}
}
@phdthesis{Wandtner2018,
  author    = {Wandtner, Bernhard},
  title     = {Non-driving related tasks in highly automated driving - Effects of task characteristics and drivers' self-regulation on take-over performance},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173956},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The rise of automated driving will fundamentally change our mobility in the near future. This thesis specifically considers the stage of so called highly automated driving (Level 3, SAE International, 2014). At this level, a system carries out vehicle guidance in specific application areas, e.g. on highway roads. The driver can temporarily suspend from monitoring the driving task and might use the time by engaging in so called non-driving related tasks (NDR-tasks). However, the driver is still in charge to resume vehicle control when prompted by the system. This new role of the driver has to be critically examined from a human factors perspective. The main aim of this thesis was to systematically investigate the impact of different NDR-tasks on driver behavior and take-over performance. Wickens' (2008) architecture of multiple resource theory was chosen as theoretical framework, with the building blocks of multiplicity (task interference due to resource overlap), mental workload (task demands), and aspects of executive control or self-regulation. Specific adaptations and extensions of the theory were discussed to account for the context of NDR-task interactions in highly automated driving. Overall four driving simulator studies were carried out to investigate the role of these theoretical components. Study 1 showed that drivers focused NDR-task engagement on sections of highly automated compared to manual driving. In addition, drivers avoided task engagement prior to predictable take-over situations. These results indicate that self-regulatory behavior, as reported for manual driving, also takes place in the context of highly automated driving. Study 2 specifically addressed the impact of NDR-tasks' stimulus and response modalities on take-over performance. Results showed that particularly visual-manual tasks with high motoric load (including the need to get rid of a handheld object) had detrimental effects. However, drivers seemed to be aware of task specific distraction in take-over situations and strictly canceled visual-manual tasks compared to a low impairing auditory-vocal task. Study 3 revealed that also the mental demand of NDR-tasks should be considered for drivers' take-over performance. Finally, different human-machine-interfaces were developed and evaluated in Simulator Study 4. Concepts including an explicit pre-alert ("notification") clearly supported drivers' self-regulation and achieved high usability and acceptance ratings. Overall, this thesis indicates that the architecture of multiple resource theory provides a useful framework for research in this field. Practical implications arise regarding the potential legal regulation of NDR-tasks as well as the design of elaborated human-machine-interfaces.},
  subject      = {Autonomes Fahrzeug},
  language  = {en}
}
@article{VoelkerWeigelStrehletal.2018,
  author    = {V{\"o}lker, Hans-Ullrich and Weigel, Michael and Strehl, Annette and Frey, Lea},
  title     = {Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array},
  series = {Diagnostic Pathology},
  volume    = {13},
  journal   = {Diagnostic Pathology},
  number    = {67},
  doi       = {10.1186/s13000-018-0737-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176960},
  year      = {2018},
  abstract  = {Background: Conventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX\(^{®}\), a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction. The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test. Methods: The results of Ki67, uPA/PAI-1 and OncotypeDX\(^{®}\) were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed. Results: With a proliferation index Ki67 of < 14\%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14\%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5\%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9\%); p = 0.054, Student's t-test. When Ki67 was > 14\% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14\% with non-raised uPA/PAI-1 (p < 0.03, Student's t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values. Conclusion: A combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).},
  language  = {en}
}
@article{VonaMaroofianBellacchioetal.2018,
  author    = {Vona, Barbara and Maroofian, Reza and Bellacchio, Emanuele and Najafi, Maryam and Thompson, Kyle and Alahmad, Ahmad and He, Langping and Ahangari, Najmeh and Rad, Abolfazl and Shahrokhzadeh, Sima and Bahena, Paulina and Mittag, Falk and Traub, Frank and Movaffagh, Jebrail and Amiri, Nafise and Doosti, Mohammad and Boostani, Reza and Shirzadeh, Ebrahim and Haaf, Thomas and Diodato, Daria and Schmidts, Miriam and Taylor, Robert W. and Karimiani, Ehsan Ghayoor},
  title     = {Expanding the clinical phenotype of IARS2-related mitochondrial disease},
  series = {BMC Medical Genetics},
  volume    = {19},
  journal   = {BMC Medical Genetics},
  number    = {196},
  doi       = {10.1186/s12881-018-0709-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176620},
  year      = {2018},
  abstract  = {Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. Methods: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. Results: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. Conclusions: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.},
  language  = {en}
}
@article{VonaHofrichterSchroederetal.2018,
  author    = {Vona, Barbara and Hofrichter, Michaela A. H. and Schr{\"o}der, J{\"o}rg and Shehata-Dieler, Wafaa and Nanda, Indrajit and Haaf, Thomas},
  title     = {Hereditary hearing loss SNP-microarray pilot study},
  series = {BMC Research Notes},
  volume    = {11},
  journal   = {BMC Research Notes},
  number    = {391},
  doi       = {10.1186/s13104-018-3466-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176239},
  year      = {2018},
  abstract  = {Objectives: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis. Data description: Our data originate from the Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss. These anonymized SNP-microarray data have been uploaded to the NCBI Gene Expression Omnibus and are intended to benefit other investigators interested in aggregating platform-matched array patient datasets or as part of a supporting reference tool for other laboratories to better understand recurring copy number variations in other genetic disorders.},
  language  = {en}
}
@phdthesis{vonderMuehlen2018,
  author    = {von der M{\"u}hlen, Sarah},
  title     = {Fostering Students' Epistemic Competences when Dealing with Scientific Literature},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167343},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The abilities to comprehend and critically evaluate scientific texts and the various arguments stated in these texts are an important aspect of scientific literacy, but these competences are usually not formally taught to students. Previous research indicates that, although undergraduate students evaluate the claims and evidence they find in scientific documents to some extent, these evaluations usually fail to meet normative standards. In addition, students' use of source information for evaluation is often insufficient. The rise of the internet and the increased accessibility of information have yielded some additional challenges that highlight the importance of adequate training and instruction.The aim of the present work was to further examine introductory students' competences to systematically and heuristically evaluate scientific information, to identify relevant strategies that are involved in a successful evaluation, and to use this knowledge to design appropriate interventions for fostering epistemic competences in university students.To this end, a number of computer-based studies, including both quantitative and qualitative data as well as experimental designs, were developed. The first two studies were designed to specify educational needs and to reveal helpful processing strategies that are required in different tasks and situations. Two expert-novice comparisons were developed, whereby the performance of German students of psychology (novices) was compared to the performance of scientists from the domain of psychology (experts) in a number of different tasks, such as systematic plausibility evaluations of informal arguments (Study 1) or heuristic evaluations of the credibility of multiple scientific documents (Study 2). A think-aloud procedure was used to identify specific strategies that were applied in both groups during task completion, and that possibly mediated performance differences between students and scientists. In addition, relationships between different strategies and between strategy use and relevant conceptual knowledge was examined. Based on the results of the expert-novice comparisons, an intervention study, consisting of two training experiments, was constructed to foster some competences that proved to be particularly deficient in the comparisons (Study 3). Study 1 examined introductory students' abilities to accurately judge the plausibility of informal arguments according to normative standards, to recognise common argumentation fallacies, and to identify different structural components of arguments. The results from Study 1 indicate that many students, compared to scientists, lack relevant knowledge about the structure of arguments, and that normatively accurate evaluations of their plausibility seem to be challenging in this group. Often, common argumentation fallacies were not identified correctly. Importantly, these deficits were partly mediated by differences in strategy use: It was especially difficult for students to pay sufficient attention to the relationship between argument components when forming their judgements. Moreover, they frequently relied on their intuition or opinion as a criterion for evaluation, whereas scientists predominantly determined quality of arguments based on their internal consistency. In addition to students' evaluation of the plausibility of informal arguments, Study 2 examined introductory students' competences to evaluate the credibility of multiple scientific texts, and to use source characteristics for evaluation. The results show that students struggled not only to judge the plausibility of arguments correctly, but also to heuristically judge the credibility of science texts, and these deficits were fully mediated by their insufficient use of source information. In contrast, scientists were able to apply different strategies in a flexible manner. When the conditions for evaluation did not allow systematic processing (i.e. time limit), they primarily used source characteristics for their evaluations. However, when systematic evaluations were possible (i.e. no time limit), they used more sophisticated normative criteria for their evaluations, such as paying attention to the internal consistency of arguments (cf. Study 1). Results also showed that students, in contrast to experts, lacked relevant knowledge about different publication types, and this was related to their ability to correctly determine document credibility. The results from the expert-novice comparisons also suggest that the competences assessed in both tasks might develop as a result of a more fundamental form of scientific literacy and discipline expertise. Performances in all tasks were positively related. On the basis of these results, two training experiments were developed that aimed at fostering university students' competences to understand and evaluate informal arguments (Study 3). Experiment 1 describes an intervention approach in which students were familiarised with the formal structure of arguments based on Toulmin's (1958) argumentation model. The performance of the experimental group to identify the structural components of this model was compared to the performance of a control group in which speed reading skills were practiced, using a pre-post-follow-up design. Results show that the training was successful for improving the comprehension of more complex arguments and relational aspects between key components in the posttest, compared to the control group. Moreover, an interaction effect was found with study performance. High achieving students with above average grades profited the most from the training intervention. Experiment 2 showed that training in plausibility, normative criteria of argument evaluation, and argumentation fallacies improved students' abilities to evaluate the plausibility of arguments and, in addition, their competences to recognise structural components of arguments, compared to a speed-reading control group. These results have important implications for education and practice, which will be discussed in detail in this dissertation.},
  subject      = {Textverstehen},
  language  = {en}
}