@article{WaiderPoppLangeetal.2017, author = {Waider, J and Popp, S and Lange, MD and Kern, R and Kolter, JF and Kobler, J and Donner, NC and Lowe, KR and Malzbender, JH and Brazell, CJ and Arnold, MR and Aboagye, B and Schmitt-B{\"o}hrer, A and Lowry, CA and Pape, HC and Lesch, KP}, title = {Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice}, series = {Translational Psychiatry}, volume = {7}, journal = {Translational Psychiatry}, number = {e1246}, doi = {10.1038/tp.2017.209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170239}, year = {2017}, abstract = {Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2\(^{-/-}\)) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph\(^{+/-}\)) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.}, language = {en} } @article{WagnerWannerSchichetal.2017, author = {Wagner, Martin and Wanner, Christoph and Schich, Martin and Kotseva, Kornelia and Wood, David and Hartmann, Katrin and Fette, Georg and R{\"u}cker, Viktoria and Oezkur, Mehmet and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Patient's and physician's awareness of kidney disease in coronary heart disease patients - a cross-sectional analysis of the German subset of the EUROASPIRE IV survey}, series = {BMC Nephrology}, volume = {18}, journal = {BMC Nephrology}, number = {321}, doi = {10.1186/s12882-017-0730-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158387}, year = {2017}, abstract = {Background Chronic kidney disease (CKD) is a common comorbid condition in coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD patients and their treating physicians are lacking. In the current cross-sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the physician's awareness of kidney disease of patients hospitalized for CHD and also the patient's awareness of CKD in a study visit following hospital discharge. Methods All serum creatinine (SCr) values measured during the hospital stay were used to describe impaired kidney function (eGFR\(_{CKD-EPI}\) < 60 ml/min/1.73m2) at admission, discharge and episodes of AKI (KDIGO definition). Information extracted from hospital discharge letters and correct ICD coding for kidney disease was studied as a surrogate of physician's awareness of kidney disease. All patients were interrogated 0.5 to 3 years after hospital discharge, whether they had ever been told about kidney disease by a physician. Results Of the 536 patients, 32\% had evidence for acute or chronic kidney disease during the index hospital stay. Either condition was mentioned in the discharge letter in 22\%, and 72\% were correctly coded according to ICD-10. At the study visit in the outpatient setting 35\% had impaired kidney function. Of 158 patients with kidney disease, 54 (34\%) were aware of CKD. Determinants of patient's awareness were severity of CKD (OR\(_{eGFR}\) 0.94; 95\%CI 0.92-0.96), obesity (OR 1.97; 1.07-3.64), history of heart failure (OR 1.99; 1.00-3.97), and mentioning of kidney disease in the index event's hospital discharge letter (OR 5.51; 2.35-12.9). Conclusions Although CKD is frequent in CHD, only one third of patients is aware of this condition. Patient's awareness was associated with kidney disease being mentioned in the hospital discharge letter. Future studies should examine how raising physician's awareness for kidney dysfunction may improve patient's awareness of CKD.}, language = {en} } @article{WagenerLoiko2017, author = {Wagener, Johannes and Loiko, Veronika}, title = {Recent insights into the paradoxical effect of echinocandins}, series = {Journal of Fungi}, volume = {4}, journal = {Journal of Fungi}, number = {1}, issn = {2309-608X}, doi = {10.3390/jof4010005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197960}, pages = {5}, year = {2017}, abstract = {Echinocandin antifungals represent one of the most important drug classes for the treatment of invasive fungal infections. The mode of action of the echinocandins relies on inhibition of the β-1,3-glucan synthase, an enzyme essentially required for the synthesis of the major fungal cell wall carbohydrate β-1,3-glucan. Depending on the species, echinocandins may exert fungicidal or fungistatic activity. Apparently independent of this differential activity, a surprising in vitro phenomenon called the "paradoxical effect" can be observed. The paradoxical effect is characterized by the ability of certain fungal isolates to reconstitute growth in the presence of higher echinocandin concentrations, while being fully susceptible at lower concentrations. The nature of the paradoxical effect is not fully understood and has been the focus of multiple studies in the last two decades. Here we concisely review the current literature and propose an updated model for the paradoxical effect, taking into account recent advances in the field.}, language = {en} } @phdthesis{Wagemann2017, author = {Wagemann, Esther}, title = {Biopsiediagnostik von entz{\"u}ndlichen Polyneuropathien}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155031}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Polyneuropathien sind Erkrankungen des peripheren Nervensystems. Die Erkrankung kommt geh{\"a}uft als Zweiterkrankungen bei anderen Prim{\"a}rerkrankungen vor, daher ist es schwierig, epidemiologische Angaben zu machen. {\"A}tiologisch lassen sich Polyneuropathien in f{\"u}nf große Gruppen einteilen: Heredit{\"a}re Polyneuropathien, entz{\"u}ndliche Polyneuropathien, vaskul{\"a}r bedingte Polyneuropathien, exotoxische Polyneuropathien und endotoxisch-metabolische Polyneuropathien. Die Differentialdiagnose der Polyneuropathie richtet sich nach dem zeitlichen Verlauf der Krankheit, dem betroffenen System und danach, ob prim{\"a}r die Axone oder die Markscheiden betroffen sind. F{\"u}r die Diagnosestellung einer Polyneuropathie werden Anamnese und klinischer Befund, elektrophysiologische Untersuchungen, Laboruntersuchungen, genetische Untersuchungen und die histopathologische Untersuchung herangezogen. Entscheidend f{\"u}r die Therapie ist es, die behandelbaren Polyneuropathien zu erkennen, hierunter u.a. die entz{\"u}ndlichen Formen. Die hierf{\"u}r entnommene Suralisbiopsie ist wegen ihrer invasiven Natur erst dann indiziert, wenn die Differentialdiagnose mit nicht-invasiven Maßnahmen nicht gekl{\"a}rt werden kann, sich aber eine Behandlungskonsequenz erwarten l{\"a}sst. Die exakte Diagnose setzt bei einigen Polyneuropathien eine neuropathologische Diagnostik voraus. Die Nervenbiopsie muss optimal aufbereitet und ausgewertet werden. Hierf{\"u}r stehen verschiedene F{\"a}rbe- und Aufbereitungsmethoden zur Verf{\"u}gung. In dieser Arbeit wurde untersucht, ob anhand eines Schnellschnittes (d.h. Gefrier-Querschnitt des biopsierten Nerven mit H{\"a}matoxylin-Eosin gef{\"a}rbt) bereits Hinweise auf entz{\"u}ndliche Infiltrate als Zeichen einer Neuritis und damit einer therapiebed{\"u}rftigen und aber auch therapierbaren Neuropathie gefunden werden k{\"o}nnen. Anhand eines vordefinierten Schemas wurden die Biopsate in verblindeter Weise von einem Laien und einem erfahrenem Untersucher histologisch begutachtet und den entz{\"u}ndlichen/nicht entz{\"u}ndlichen Diagnosegruppen zugeordnet. Es wurde untersucht, ob die entz{\"u}ndlichen Ver{\"a}nderungen im H{\"a}matoxylin-Eosin-Gefrierschnitt so deutlich sind, dass auch ein Laienauswerter diese erkennen kann. Ebenso wurden die Untersuchungsergebnisse mittels H{\"a}matoxylin-Eosin- F{\"a}rbung an Gefrier- und Paraffinschnitten mit den Untersuchungsergebnissen mittels immunhistochemischer F{\"a}rbemethoden verglichen. Des weiteren wurde untersucht, ob bei histologisch gesicherter Entz{\"u}ndung klinische Einflussfaktoren ermittelt werden k{\"o}nnen, die auf die neuropathologische Diagnostik Auswirkung haben. Die Ergebnisse der Studie zeigen, dass sich die H{\"a}matoxylin-Eosin-F{\"a}rbung f{\"u}r eine erste und schnelle Diagnostik von entz{\"u}ndlichen Polyneuropathien als wertvoll erwies. Dies gilt f{\"u}r den erfahrenen und unerfahrenen Untersucher. Es zeigen sich keine klinischen Einflussfaktoren f{\"u}r die histopathologische Diagnosestellung. Die Ergebnisse der Studie zeigen, dass schon eine einfache F{\"a}rbemethode wie die H{\"a}matoxylin-Eosin-F{\"a}rbung an Gefrier-und Paraffinschnitten bei Polyneuropathie unklarer Genese hilfreich bei einer differenzierten Diagnosefindung sein kann.}, language = {de} } @phdthesis{WaagHiersch2017, author = {Waag-Hiersch, Luisa}, title = {„iClick"-Reaktionen von Ru- und Rh-Azid-Komplexen mit elektronenarmen Alkinen: Regioselektivit{\"a}t, Stabilit{\"a}t und Kinetik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146286}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Die regioselektive Funktionalisierung von Bio(makro)molek{\"u}len erfordert Reaktionen, die mit einem biologischen System weder interagieren noch interferieren. Bestimmte funktionelle Gruppen, wie Azide oder Alkine, sind unter physiologischen Bedingungen inert, kommen nicht in der Natur vor, lassen sich selektiv miteinander verkn{\"u}pfen und sind nicht-toxisch gegen{\"u}ber Zellen und Organismen. F{\"u}r die Einf{\"u}hrung metallbasierter Funktionalit{\"a}ten in solche Zielstrukturen stellen Click-Reaktionen daher einen schnellen Zugang dar, wobei Reaktionen, die ohne Zusatz von Katalysator und bei Raumtemperatur ablaufen von besonderem Interesse sind. Das Ziel der vorliegenden Arbeit war es daher die „iClick"-Reaktion von Ruthenium-Azid-Komplexen der allgemeinen Formel [Ru(N3)(aren)(N-N)]+ mit bidentaten Stickstoffliganden sowie Rhodium-Azid-Komplexen der allgemeinen Formel [Rh(Cp*)(N3)(bpyR,R)]+ mit unterschiedlich substituierten 2,2'-Bipyridin-Coliganden (R = OCH3, H, COOCH3) gegen{\"u}ber elektronenarmen Alkinen zu untersuchen. R{\"o}ntgenstrukturanalysen der resultierenden Triazolat-Komplexe sollten den Koordinationsmodus best{\"a}tigten, da die Produkte der Click-Reaktionen prinzipiell als zwei verschiedene Regioisomere auftreten k{\"o}nnen. Die [Rh(Cp*)(N3)(bpyR,R)]CF3SO3-Komplexe mit 2,2'-Bipyridin (bpy), dem elektronenziehenden Ligand 4,4'-Bis(methoxycarbonyl)-2,2′-bipyridin (bpyCOOCH3,COOCH3) sowie dem elektronenschiebenden Ligand 4,4'-Dimethoxy-2,2'-bipyridin (bpyOCH3,OCH3) wurden aus den entsprechenden Rhodium-Chlorido-Komplexen durch F{\"a}llung des Halogenids mit Silbertrifluormethansulfonat und anschließender Umsetzung mit Natriumazid hergestellt. In L{\"o}sung waren diese Verbindungen jedoch nur begrenzt stabil, wobei der Komplex mit bpyOCH3,OCH3 am wenigsten empfindlich war, w{\"a}hrend [Rh(Cp*)(N3)(bpyCOOCH3,COOCH3)]CF3SO3 aufgrund der sehr schnellen Zersetzung nicht isoliert werden konnte. Die „iClick"-Reaktion der Rhodium-Azid-Komplexe mit 4,4,4-Trifluorobut-2-ins{\"a}ureethylester ergab dann aber die stabilen Triazolat-Komplexe [Rh(Cp*)(triazolatCF3,COOEt)(bpyR,R)]CF3SO3 in sehr guter Ausbeute. Die Ruthenium-Azid-Komplexe [Ru(N3)(N-N)(p­cym)]PF6 mit N-N = bpy, bpyCOOCH3,COOCH3, bpyOCH3,OCH3, Bipyrimidin (bpym) sowie Dipyrido[3,2­a:2',3'­c]phenazin (dppz) wurden ausgehend von den jeweiligen Ruthenium-Chlorido-Komplexen durch F{\"a}llung des Halogenid-Liganden mit Silbertrifluormethansulfonat und anschließender Umsetzung mit Natriumazid in guter bis moderater Ausbeute hergestellt. Um den Einfluss des Aren-Liganden zu untersuchen wurde außerdem der entsprechende Hexamethylbenzol-Komplex [Ru(N3)(bpy)(hmb)]CF3SO3 in moderater Ausbeute hergestellt. Alle [Ru(N3)(aren)(N-N)]X-Komplexe mit X = PF6- oder CF3SO3- wurden mittels 1H, 13C NMR- und IR-Spektroskopie, CHN-Analyse sowie ESI-Massenspektrometrie charakterisiert. Die „iClick"-Reaktion dieser Komplexe erfolgte mit 4,4,4-Trifluorobut-2-ins{\"a}ureethylester und teilweise auch mit Dimethylacetylendicaboxylat (DMAD) in sehr guter bis guter Ausbeute. Außerdem konnten f{\"u}r die R{\"o}ntgenstrukturanalyse taugliche Einkristalle von [Ru(triazolatCF3,COOEt)(bpy)(hmb)]CF3SO3 und [Ru(triazolatCF3,COOEt)(bpyCOOCH3,COOCH3)(p­cym)]PF6 erhalten werden, die die N2-Koordination des Triazolat-Liganden an das Zentralatom best{\"a}tigten. Um diese als metallbasierte Marker einsetzen zu k{\"o}nnen, m{\"u}ssen die resultierenden Triazolat-Komplexe bei biologisch relevanten pH-Werten und gegen{\"u}ber Ligandenaustausch, zum Beispiel mit den Aminos{\"a}ureseitenketten von Proteinen, stabil sein. Durch HPLC-Untersuchungen an [Ru(triazolatCF3,COOEt)(bpy)(hmb)]CF3SO3 wurde gezeigt, dass dieser Komplex in w{\"a}ssriger L{\"o}sung {\"u}ber einen pH-Bereich von 1 bis 8 bei Raumtemperatur mindestens 24 h stabil ist. Außerdem konnte eine weitgehende Stabilit{\"a}t gegen{\"u}ber Ligandenaustausch mit den Seitenketten der Aminos{\"a}uren L­Cystein, L-Histidin, L­Methionin und L-Glutamins{\"a}ure bei 37 °C {\"u}ber mindestens 72 h festgestellt werden. Insbesondere die Geschwindigkeit der „iClick"-Reaktion ist in einem biologischen Kontext von Bedeutung, da die Konjugationsreaktionen schneller ablaufen m{\"u}ssen als interessierende biologische Prozesse. Mittels HPLC und IR-Spektroskopie wurde f{\"u}r die „iClick"-Reaktion der Rutheniumazid-Komplexe [Ru(N3)(bpyR,R)(p-cym)]PF6 mit R = OCH3, H oder COOCH3 sowie [Ru(N3)(bpy)(hmb)]CF3SO3 mit einem {\"U}berschuss an 4,4,4-Trifluorobut-2-ins{\"a}ureethylester Geschwindigkeitskonstanten pseudoerster Ordnung im Bereich von 1 ­ 3*10-3 s-1 bestimmt. Außerdem war es mittels IR-Spektroskopie in L{\"o}sung m{\"o}glich die Geschwindigkeits-konstante pseudoerster Ordnung f{\"u}r die „iClick"-Reaktion der Rhodiumazid-Verbindungen [Rh(Cp*)(N3)(bpyR,R)]CF3SO3 mit R = OCH3, H oder COOCH3 und 4,4,4-Trifluorobut-2-ins{\"a}ureethylester zu 2 ­ 4*10-3 s-1 zu ermitteln. Insgesamt zeigte sich, dass Komplexe mit elektronenreichen Coliganden schneller mit 4,4,4-Trifluorobut-2-ins{\"a}ureethylester reagieren als solche mit elektronen{\"a}rmeren Liganden. Auch war die Geschwindigkeitskonstante f{\"u}r die Reaktion der Rhodium-Komplexe h{\"o}her als f{\"u}r die Rutheniumverbindungen. Die Geschwindigkeitskonstanten zweiter Ordnung wurden aus der 19F NMR-spektroskopischen Untersuchung der Reaktion von 4,4,4-Trifluorobut-2-ins{\"a}ureethylester und [Ru(N3)(bpyR,R) (p-cym)]PF6 mit R = OCH3, H oder COOCH3 sowie [Ru(N3)(bpy)(hmb)]CF3SO3 bei 20 °C bestimmt. Bei ann{\"a}hernd gleichem Verh{\"a}ltnis von Alkin und Rutheniumazid-Komplexen wurden Geschwindigkeitskonstanten im Bereich von 1 - 2*10-2 L mol-1 s-1 erhalten. Diese sind gr{\"o}ßer als die der Staudinger-Ligation, aber kleiner als die der spannungsinduzierten Azid-Alkin Cycloaddition. Prinzipiell sollte damit also eine biologische Anwendung m{\"o}glich sein. Außerdem wurde die Aktivierungsenergie der Reaktion von [Ru(N3)(bpy)(p­cym)]PF6 mit 4,4,4-Trifluorobut-2-ins{\"a}ureethylester aus der Untersuchung der Temperaturabh{\"a}ngigkeit im Bereich von -20 °C bis +20 °C mit VT-NMR zu 46.1 kJ mol-1 bestimmt. In den 19F NMR-Spektren des Reaktionsgemisches zeigte sich bei -20 °C neben dem Signal des N2-koordinierten Triazolats außerdem ein weiteres, das dem N1-Isomer zuzuordnen ist, welches bei Erw{\"a}rmen jedoch wieder verschwand. In einer DFT-Rechnung wurde die Geometrie von [Ru(N3)(bpy)(hmb)]CF3SO3 optimiert. Dabei zeigte sich, dass nur etwa 25 - 30\% aller Trajektorien angreifender Alkinmolek{\"u}len einen Zugang zum Azid erm{\"o}glichen, sodass die Reaktionsgeschwindigkeit um etwa einen Faktor vier niedriger liegen sollte als f{\"u}r nicht oder nur wenig abgeschirmte Organoazid-Verbindungen. Die „iClick"-Reaktion der hier untersuchten Metall-Azid-Komplexe mit elektronenarmen Alkinen zeigt also bereits jetzt Reaktionsgeschwindigkeiten vergleichbar etablierter Biokonjugationsreaktionen. In Zukunft sollte daher das Potential anderer Metall-Azid-Bausteine untersucht und auch das Alkin variiert werden.}, subject = {Ruthenium}, language = {de} } @article{VonaNandaShehataDieleretal.2017, author = {Vona, Barbara and Nanda, Indrajit and Shehata-Dieler, Wafaa and Haaf, Thomas}, title = {Genetics of Tinnitus: Still in its Infancy}, series = {Frontiers in Neuroscience}, volume = {11}, journal = {Frontiers in Neuroscience}, number = {236}, doi = {10.3389/fnins.2017.00236}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170926}, year = {2017}, abstract = {Tinnitus is the perception of a phantom sound that affects between 10 and 15\% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade. Nine studies have examined genes in a case-control association approach. Recently, a genome-wide association study has highlighted several potentially significant pathways that are implicated in tinnitus. Two twin studies have calculated a moderate heritability for tinnitus and disclosed a greater concordance rate in monozygotic twins compared to dizygotic twins. Despite the more recent data alluding to genetic factors in tinnitus, a strong association with any specific genetic locus is lacking and a genetic study with sufficient statistical power has yet to be designed. Future research endeavors must overcome the many inherent limitations in previous study designs. This review summarizes the previously embarked upon tinnitus genetic investigations and summarizes the hurdles that have been encountered. The identification of candidate genes responsible for tinnitus may afford gene based diagnostic approaches, effective therapy development, and personalized therapeutic intervention.}, language = {en} } @article{vonMammenWagnerKnoteetal.2017, author = {von Mammen, Sebastian Albrecht and Wagner, Daniel and Knote, Andreas and Taskin, Umut}, title = {Interactive simulations of biohybrid systems}, series = {Frontiers in Robotics and AI}, volume = {4}, journal = {Frontiers in Robotics and AI}, issn = {2296-9144}, doi = {10.3389/frobt.2017.00050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195755}, year = {2017}, abstract = {In this article, we present approaches to interactive simulations of biohybrid systems. These simulations are comprised of two major computational components: (1) agent-based developmental models that retrace organismal growth and unfolding of technical scaffoldings and (2) interfaces to explore these models interactively. Simulations of biohybrid systems allow us to fast forward and experience their evolution over time based on our design decisions involving the choice, configuration and initial states of the deployed biological and robotic actors as well as their interplay with the environment. We briefly introduce the concept of swarm grammars, an agent-based extension of L-systems for retracing growth processes and structural artifacts. Next, we review an early augmented reality prototype for designing and projecting biohybrid system simulations into real space. In addition to models that retrace plant behaviors, we specify swarm grammar agents to braid structures in a self-organizing manner. Based on this model, both robotic and plant-driven braiding processes can be experienced and explored in virtual worlds. We present an according user interface for use in virtual reality. As we present interactive models concerning rather diverse description levels, we only ensured their principal capacity for interaction but did not consider efficiency analyzes beyond prototypic operation. We conclude this article with an outlook on future works on melding reality and virtuality to drive the design and deployment of biohybrid systems.}, language = {en} } @article{VeniaminovaCespuglioCheungetal.2017, author = {Veniaminova, Ekaterina and Cespuglio, Raymond and Cheung, Chi Wai and Umriukhin, Alexei and Markova, Nataliia and Shevtsova, Elena and Lesch, Klaus-Peter and Anthony, Daniel C. and Strekalova, Tatyana}, title = {Autism-like behaviours and memory deficits result from a Western Diet in mice}, series = {Neural Plasticity}, journal = {Neural Plasticity}, doi = {10.1155/2017/9498247}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158211}, pages = {9498247}, year = {2017}, abstract = {Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2\% of cholesterol and 21\% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in na{\"i}ve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.}, language = {en} } @article{VeldhoenBehzadiLenzetal.2017, author = {Veldhoen, Simon and Behzadi, Cyrus and Lenz, Alexander and Henes, Frank Oliver and Rybczynski, Meike and von Kodolitsch, Yskert and Bley, Thorsten Alexander and Adam, Gerhard and Bannas, Peter}, title = {Non-contrast MR angiography at 1.5 Tesla for aortic monitoring in Marfan patients after aortic root surgery}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {19}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {82}, doi = {10.1186/s12968-017-0394-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158693}, year = {2017}, abstract = {Background: Contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) is the established imaging modality for patients with Marfan syndrome requiring life-long annual aortic imaging before and after aortic root replacement. Contrast-free CMRA techniques avoiding side-effects of contrast media are highly desirable for serial imaging but have not been evaluated in the postoperative setup of Marfan patients. The purpose of this study was to assess the feasibility of non-contrast balanced steady-state free precession (bSSFP) magnetic resonance imaging for aortic monitoring of postoperative patients with Marfan syndrome. Methods: Sixty-four adult Marfan patients after aortic root replacement were prospectively included. Fourteen patients (22\%) had a residual aortic dissection after surgical treatment of type A dissection. bSSFP imaging and CE-CMRA were performed at 1.5 Tesla. Two radiologists evaluated the images regarding image quality (1 = poor, 4 = excellent), artifacts (1 = severe, 4 = none) and aortic pathologies. Readers measured the aortic diameters at defined levels in both techniques. Statistics included observer agreement for image scoring and diameter measurements and ROC analyses for comparison of the diagnostic performance of bSSFP and CE-CMRA. Results: Both readers observed no significant differences in image quality between bSSFP and CE-CMRA and found a median image quality score of 4 for both techniques (all p > .05). No significant differences were found regarding the frequency of image artifacts in both sequences (all p > .05). Sensitivity and specificity for detection of aortic dissections was 100\% for both readers and techniques. Compared to bSSFP imaging, CE-CMRA resulted in higher diameters (mean bias, 0.9 mm; p < .05). The inter-observer biases of diameter measurements were not significantly different (all p > .05), except for the distal graft anastomosis (p = .001). Using both techniques, the readers correctly identified a graft suture dehiscence with aneurysm formation requiring surgery. Conclusion: Unenhanced bSSFP CMR imaging allows for riskless aortic monitoring with high diagnostic accuracy in Marfan patients after aortic root surgery.}, language = {en} } @article{VargasCasanovaRodriguezGuerraUmanaPerezetal.2017, author = {Vargas Casanova, Yerly and Rodr{\´i}guez Guerra, Jorge Antonio and Uma{\~n}a P{\´e}rez, Yadi Adriana and Leal Castro, Aura Luc{\´i}a and Almanzar Reina, Giovanni and Garc{\´i}a Casta{\~n}eda, Javier Eduardo and Rivera Monroy, Zuly Jenny}, title = {Antibacterial synthetic peptides derived from bovine lactoferricin exhibit cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {10}, doi = {10.3390/molecules22101641}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173887}, year = {2017}, abstract = {Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)\(_2\)K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.}, language = {en} } @article{VangeelPishvaHompesetal.2017, author = {Vangeel, Elise Beau and Pishva, Ehsan and Hompes, Titia and van den Hove, Daniel and Lambrechts, Diether and Allegaert, Karel and Freson, Kathleen and Izzi, Benedetta and Claes, Stephan}, title = {Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\)}, series = {Clinical Epigenetics}, volume = {9}, journal = {Clinical Epigenetics}, doi = {10.1186/s13148-017-0408-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173825}, year = {2017}, abstract = {Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity. Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old. Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.}, language = {en} } @article{VanSteenbergenBalteauGinionetal.2017, author = {Van Steenbergen, Anne and Balteau, Magali and Ginion, Audrey and Fert{\´e}, Laura and Battault, Sylvain and de Meester de Ravenstein, Christophe and Balligand, Jean-Luc and Daskalopoulos, Evangelos-Panagiotis and Gilon, Patrick and Despa, Florin and Despa, Sanda and Vanoverschelde, Jean-Louis and Horman, Sandrine and Koepsell, Hermann and Berry, Gerard and Hue, Louis and Bertrand, Luc and Beauloye, Christophe}, title = {Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/srep41166}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180891}, pages = {14}, year = {2017}, abstract = {Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.}, language = {en} } @article{UriWernerLuehderetal.2017, author = {Uri, Anna and Werner, Sandra and L{\"u}hder, Fred and H{\"u}nig, Thomas and Kerkau, Thomas and Beyersdorf, Niklas}, title = {Protection of mice from acute graft-versus-host disease requires CD28 co-stimulation on donor CD4\(^{+}\) Foxp3\(^{+}\) regulatory T Cells}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {721}, doi = {10.3389/fimmu.2017.00721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158469}, year = {2017}, abstract = {Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT.}, language = {en} } @article{UllmannBanksSchmittetal.2017, author = {Ullmann, Tobias and Banks, Sarah N. and Schmitt, Andreas and Jagdhuber, Thomas}, title = {Scattering characteristics of X-, C- and L-Band PolSAR data examined for the tundra environment of the Tuktoyaktuk Peninsula, Canada}, series = {Applied Sciences}, volume = {7}, journal = {Applied Sciences}, number = {6}, doi = {10.3390/app7060595}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158362}, pages = {595}, year = {2017}, abstract = {In this study, polarimetric Synthetic Aperture Radar (PolSAR) data at X-, C- and L-Bands, acquired by the satellites: TerraSAR-X (2011), Radarsat-2 (2011), ALOS (2010) and ALOS-2 (2016), were used to characterize the tundra land cover of a test site located close to the town of Tuktoyaktuk, NWT, Canada. Using available in situ ground data collected in 2010 and 2012, we investigate PolSAR scattering characteristics of common tundra land cover classes at X-, C- and L-Bands. Several decomposition features of quad-, co-, and cross-polarized data were compared, the correlation between them was investigated, and the class separability offered by their different feature spaces was analyzed. Certain PolSAR features at each wavelength were sensitive to the land cover and exhibited distinct scattering characteristics. Use of shorter wavelength imagery (X and C) was beneficial for the characterization of wetland and tundra vegetation, while L-Band data highlighted differences of the bare ground classes better. The Kennaugh Matrix decomposition applied in this study provided a unified framework to store, process, and analyze all data consistently, and the matrix offered a favorable feature space for class separation. Of all elements of the quad-polarized Kennaugh Matrix, the intensity based elements K0, K1, K2, K3 and K4 were found to be most valuable for class discrimination. These elements contributed to better class separation as indicated by an increase of the separability metrics squared Jefferys Matusita Distance and Transformed Divergence. The increase in separability was up to 57\% for Radarsat-2 and up to 18\% for ALOS-2 data.}, language = {en} } @article{TymoshenkoOnykiienkoMuelleretal.2017, author = {Tymoshenko, Y. V. and Onykiienko, Y. A. and M{\"u}ller, T. and Thomale, R. and Rachel, S. and Cameron, A. S. and Portnichenko, P. Y. and Efremov, D. V. and Tsurkan, V. and Abernathy, D. L. and Ollivier, J. and Schneidewind, A. and Piovano, A. and Felea, V. and Loidl, A. and Inosov, D. S.}, title = {Pseudo-Goldstone magnons in the frustrated \(S=3/2\) Heisenberg helimagnet \(ZnCr_2Se_4\) with a pyrochlore magnetic sublattice}, series = {Physical Review X}, volume = {7}, journal = {Physical Review X}, number = {4}, doi = {10.1103/PhysRevX.7.041049}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172770}, year = {2017}, abstract = {Low-energy spin excitations in any long-range ordered magnetic system in the absence of magnetocrystalline anisotropy are gapless Goldstone modes emanating from the ordering wave vectors. In helimagnets, these modes hybridize into the so-called helimagnon excitations. Here we employ neutron spectroscopy supported by theoretical calculations to investigate the magnetic excitation spectrum of the isotropic Heisenberg helimagnet \({ZnCr_2Se_4}\) with a cubic spinel structure, in which spin\(-3/2\) magnetic \({Cr^{3+}}\) ions are arranged in a geometrically frustrated pyrochlore sublattice. Apart from the conventional Goldstone mode emanating from the \((0~ 0~ {q_h})\) ordering vector, low-energy magnetic excitations in the single-domain proper-screw spiral phase show soft helimagnon modes with a small energy gap of \({∼0.17~ meV}\), emerging from two orthogonal wave vectors \(({q_h}~ 0~ 0)\) and \({(0~ {q_h}~ 0)}\) where no magnetic Bragg peaks are present. We term them pseudo-Goldstone magnons, as they appear gapless within linear spinwave theory and only acquire a finite gap due to higher-order quantum-fluctuation corrections. Our results are likely universal for a broad class of symmetric helimagnets, opening up a new way of studying weak magnon-magnon interactions with accessible spectroscopic methods.}, language = {en} } @article{TuanScharfŽutičetal.2017, author = {Tuan, Dinh Van and Scharf, Benedikt and Žutič, Igor and Dery, Hanan}, title = {Marrying excitons and plasmons in monolayer transition-metal dichalcogenides}, series = {Physical Review X}, volume = {7}, journal = {Physical Review X}, number = {4}, doi = {10.1103/PhysRevX.7.041040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173030}, year = {2017}, abstract = {Just as photons are the quanta of light, plasmons are the quanta of orchestrated charge-density oscillations in conducting media. Plasmon phenomena in normal metals, superconductors, and doped semiconductors are often driven by long-wavelength Coulomb interactions. However, in crystals whose Fermi surface is comprised of disconnected pockets in the Brillouin zone, collective electron excitations can also attain a shortwave component when electrons transition between these pockets. In this work, we show that the band structure of monolayer transition-metal dichalcogenides gives rise to an intriguing mechanism through which shortwave plasmons are paired up with excitons. The coupling elucidates the origin for the optical sideband that is observed repeatedly in monolayers of WSe\(_2\) and WS\(_2\) but not understood. The theory makes it clear why exciton-plasmon coupling has the right conditions to manifest itself distinctly only in the optical spectra of electron-doped tungsten-based monolayers.}, language = {en} } @article{TsonevaMinevFrentzenetal.2017, author = {Tsoneva, Desislava and Minev, Boris and Frentzen, Alexa and Zhang, Qian and Wege, Anja K. and Szalay, Aladar A.}, title = {Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis}, series = {Molecular Therapy Oncolytics}, volume = {5}, journal = {Molecular Therapy Oncolytics}, doi = {10.1016/j.omto.2017.03.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170786}, pages = {41-61}, year = {2017}, abstract = {Oncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells was observed. We also demonstrated successful in vivo colonization of such tumors with systemically administered VACVs. Further, a new recombinant GLV-1h376 VACV encoding for a secreted human CTLA4-blocking single-chain antibody (CTLA4 scAb) was tested. Surprisingly, although proving CTLA4 scAb's in vitro binding ability and functionality in cell culture, beside the significant increase of CD56\(^{bright}\) NK cell subset, GLV-1h376 was not able to increase cytotoxic T or overall NK cell levels at the tumor site. Importantly, the virus-encoded β-glucuronidase as a measure of viral titer and CTLA4 scAb amount was demonstrated. Therefore, studies in our "patient-like" humanized tumor mouse model allow the exploration of newly designed therapy strategies considering the complex relationships between the developing tumor, the oncolytic virus, and the human immune system.}, language = {en} } @phdthesis{Tsoneva2017, author = {Tsoneva, Desislava}, title = {Humanized mouse model: a system to study the interactions of human immune system with vaccinia virus-infected human tumors in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118983}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Ein vielversprechender neuer Ansatz zur Behandlung von Krebs beim Menschen ist die Verwendung von onkolytischen Viren, die einen Tumor-spezifischen Tropismus aufweisen. Einer der Top-Kandidaten in diesem Bereich ist das onkolytische Vaccinia Virus (VACV), das bereits vielversprechende Ergebnisse in Tierversuchen und in klinischen Studien gezeigt hat. Aber die von den in vivo in tierischen Modellen erhaltenen Resultate k{\"o}nnten ungenaue Informationen wegen der anatomischen und physiologischen Unterschiede zwischen den Spezies liefern. Andererseits sind Studien in Menschen aufgrund ethischer Erw{\"a}gungen und potenzieller Toxizit{\"a}t nur limitiert m{\"o}glich. Die zahlreichen Einschr{\"a}nkungen und Risiken, die mit den Humanstudien verbunden sind, k{\"o}nnten mit der Verwendung eines humanisierten Mausmodells vermieden werden. Die LIVP-1.1.1, GLV-2b372, GLV-1h68, GLV-1h375, GLV-1h376 and GLV-1h377 VACV St{\"a}mmen wurden von der Genelux Corporation zur Verf{\"u}gung gestellt. GLV-2b372 wurde durch Einf{\"u}gen der TurboFP635 Expressionskassette in den J2R Genlocus des parentalen LIVP-1.1.1-Stammes konstruiert. GLV-1h375, -1h376 and -1h377 kodiert das Gen f{\"u}r den menschlichen CTLA4-blockierenden Einzelketten-Antik{\"o}rper (CTLA4 scAb). Befunde aus Replikations- and Zytotoxizit{\"a}tsstudien zeigten, dass alle sechs Viren Tumorzellen infizieren, sich in ihnen replizieren und sie in Zellkultur schließlich ebenso dosis- und zeitabh{\"a}ngig effizient abt{\"o}ten konnten. CTLA4 scAb und β-Glucuronidase (GusA) Expression sowie Virus Titer in GLV-1h376-infizierten A549-Zellen wurde anhand von ELISA-, β-Glucuronidase- and Standard Plaque-Assays bestimmt. Hierbei zeigte sich eine ausgezeichnete Korrelation mit Korrelationskoeffizienten R2>0.9806. Der durch das GLV-1h376 kodierte CTLA4 scAb wurde erfolgreich aus {\"U}berst{\"a}nden von infizierten CV-1-Zellen gereinigt. CTLA4 scAb hat eine hohe in-vitro-Affinit{\"a}t zu seinem menschlichen CTLA4-Zielmolek{\"u}l sowie abwesende Kreuzreaktivit{\"a}t gegen{\"u}ber murine CTLA4 gezeigt. CTLA4 scAb Funktionalit{\"a}t wurde in Jurkat-Zellen best{\"a}tigt. LIVP-1.1.1, GLV-2b372, GLV-1h68 und GLV-1h376 wurden auch in nicht-tumor{\"o}sen und/oder tumortragenden humanisierten M{\"a}usen getestet. Zun{\"a}chst wurde gezeigt, dass die Injektion von menschlichen CD34+ Stammzellen in die Leber von vorkonditionierten neugeborenen NSG M{\"a}usen zu einer erfolgreichen systemische Rekonstitution mit menschlichen Immunzellen gef{\"u}hrt hat. CD19+-B-Zellen, CD4+- und CD8+-CD3+-T-Zellen, NKp46+CD56- und NKp46+CD56+-NK-Zellen sowie CD33+-myeloischen Zellen wurden detektiert. Die Mehrheit der nachgewisenen humanen h{\"a}matopoetischen Zellen im M{\"a}useblut in den ersten Wochen nach der Humanisierung waren CD19+-B-Zellen, und nur ein kleiner Teil waren CD3+-T-Zellen. Mit der Zeit wurde eine signifikante Ver{\"a}nderung in CD19+/CD3+-Verh{\"a}ltnis beobachtet, die parallel zur Abnahme der B-Zellen und einem Anstieg der T-Zellen kam. Die Implantation von A549-Zellen unter die Haut dieser M{\"a}use f{\"u}hrte zu einem progressiven Tumorwachstum. Bildgebende Verfahren zur Detektion von Virus-vermittelter TurboFP635- und GFP-Expression, Standard Plaque Assays sowie immunohistochemische Analysen best{\"a}tigten die erfolgreiche Invasion der Viren in die subkutanen Tumoren. Die humane CD45+-Zellpopulation in Tumoren wurde haupts{\"a}chlich durch NKp46+CD56bright-NK-Zellen und einen hohen Anteil von aktivierten CD4+- und zytotoxische CD8+-T-Zellen dargestellt. Es wurden jedoch keine signifikanten Unterschiede zwischen den Kontroll- und LIVP-1.1.1-infizierten Tumoren beobachtet, was darauf hindeutete, dass die Rekrutierung von NK- und aktivierten T-Zellen, mehr Tumorgewebe-spezifisch als Virus-abh{\"a}ngig waren. Die GLV-1h376-vermittelten CTLA4 scAb-Expression in den infizierten Tumoren war ebenfalls nicht in der Lage, die Aktivierung von Tumor-infiltrierenden T-Zellen im Vergleich zur Kontrolle und GLV-1h68-behandelten M{\"a}usen, signifikant zu erh{\"o}hen. ELISA-, β-Glucuronidase- and Standard Plaque-Assays zeigten eine eindeutige Korrelation mit den Korrelationskoeffizienten R2>0,9454 zwischen CTLA4 scAb- und GusA-Konzentrationen und Virus Titer in Tumorproben von GLV-1h376-behandelten M{\"a}usen. T-Zellen, die aus der Milz dieser Tumor-tragenden M{\"a}use isoliert wurden, waren funktionell und konnten erfolgreich mit Beads aktiviert werden. Mehr CD25+ und IFN-ɣ+ T-Zellen wurden in der GLV-1h376-Gruppe gefunden, wahrscheinlich aufgrund der CTLA4-Blockade durch die Virus-vermittelte CTLA4 scAb-Expression in den M{\"a}usen. Außerdem wurde eine h{\"o}here Konzentration von IL-2 in dem Kultur{\"u}berstand von diesen Splenozyten im Vergleich zu Kontrollproben nachgewiesen. Im Gegensatz zu der Aktivierung mit Beads konnten T-Zellen von allen drei Maus-Gruppen nicht durch A549 Tumorzellen ex vivo aktiviert werden. Unser Mausmodell hat den besonderen Vorteil, dass sich Tumoren unter der Haut der humanisierten M{\"a}use entwickeln, was eine genaue {\"U}berwachung des Tumorwachstums und Auswertung der onkolytischen Virotherapie erm{\"o}glicht.}, subject = {Vaccinia virus}, language = {en} } @article{TshitengeFeineisMudogoetal.2017, author = {Tshitenge, Dieudonn{\´e} Tshitenge and Feineis, Doris and Mudogo, Virima and Kaiser, Marcel and Brun, Reto and Bringmann, Gerhard}, title = {Antiplasmodial Ealapasamines A-C,'Mixed' Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {5767}, doi = {10.1038/s41598-017-05719-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170645}, year = {2017}, abstract = {Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1-3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. L{\´e}onard. These 'mixed', constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1-3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range.}, language = {en} } @article{TsamadouFuerstVucinicetal.2017, author = {Tsamadou, Chrysanthi and F{\"u}rst, Daniel and Vucinic, Vladan and Bunjes, Donald and Neuchel, Christine and Mytilineos, Daphne and Gramatzki, Martin and Arnold, Renate and Wagner, Eva Maria and Einsele, Hermann and M{\"u}ller, Carlheinz and Schrezenmeier, Hubert and Mytilineos, Joannis}, title = {Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients}, series = {Haematologica}, volume = {102}, journal = {Haematologica}, number = {11}, doi = {10.3324/haematol.2017.169805}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173325}, pages = {1947-1955}, year = {2017}, abstract = {The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53\% vs. 38\%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95\%=0.48-0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50\% vs. 18\%, P=0.005; HR=0.40, CI 95\%=0.22-0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post-transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs.}, language = {en} } @article{TriphanJobstAnjorinetal.2017, author = {Triphan, Simon M. F. and Jobst, Bertram J. and Anjorin, Angela and Sedlaczek, Oliver and Wolf, Ursula and Terekhov, Maxim and Hoffmann, Christian and Ley, Sebastian and D{\"u}ber, Christoph and Biederer, J{\"u}rgen and Kauczor, Hans-Ulrich and Jakob, Peter M. and Wielp{\"u}tz, Mark O.}, title = {Reproducibility and comparison of oxygen-enhanced T\(_1\) quantification in COPD and asthma patients}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0172479}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171833}, year = {2017}, abstract = {T\(_1\) maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T\(_1\) and ΔT\(_1\), the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T\(_1\) mapping and to compare T\(_1\) found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T\(_1\) maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T\(_{1,RA}\) = 1206ms (room air) was reduced to T\(_{1,O2}\) = 1141ms under oxygen conditions (ΔT\(_1\) = 5.3\%, p < 5⋅10\(^{-4})\), while in COPD patients both native T\(_{1,RA}\) = 1125ms was significantly shorter (p < 10\(^{-3})\) and the relative reduction to T\(_{1,O2}\) = 1081ms on average ΔT\(_1\) = 4.2\%(p < 10\(^{-5}\)). On the second day, with T\(_{1,RA}\) = 1186ms in asthma and T\(_{1,RA}\) = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT\(_1\) reduction was the least repeatable parameter and varied from day to day by up to 23\% in individual asthma and 30\% in COPD patients. While for both patient groups T\(_1\) was below the values reported for healthy subjects, the T\(_1\) and ΔT\(_1\) found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T\(_1\) quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T\(_1\) on perfusion and thus current lung state.}, language = {en} } @misc{Tischer2017, author = {Tischer, Anuschka}, title = {Deutsche Reichstagsakten, Deutsche Reichstagsakten. Reichsversammlungen 1556-1662. Hrsg. v. der Historischen Kommission bei der Bayerischen Akademie der Wissenschaften durch Maximilian Lanzinner. Der Reichstag zu Regensburg 1556/57. 2 Teilbde. Bearb. v. Josef Leeb. M{\"u}nchen, Oldenbourg Wissenschaftsverlag 2013}, series = {Historische Zeitschrift}, volume = {304}, journal = {Historische Zeitschrift}, number = {1}, issn = {2196-680X}, doi = {10.1515/hzhz-2017-1034}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194256}, pages = {229 -- 231}, year = {2017}, abstract = {Rezension zu Deutsche Reichstagsakten, Deutsche Reichstagsakten. Reichsversammlungen 1556-1662. Hrsg. v. der Historischen Kommission bei der Bayerischen Akademie der Wissenschaften durch Maximilian Lanzinner. Der Reichstag zu Regensburg 1556/57. 2 Teilbde. Bearb. v. Josef Leeb. M{\"u}nchen, Oldenbourg Wissenschaftsverlag 2013}, language = {de} } @misc{Tischer2017, author = {Tischer, Anuschka}, title = {Stefano Andretta / St{\´e}phane P{\´e}quignot / Jean-Claude Waquet (Eds.), De l'ambassadeur. Les {\´e}crits relatifs {\`a} l'ambassadeur et {\`a} l'art de n{\´e}gocier du Moyen {\^A}ge au d{\´e}but du XIXe si{\`e}cle. Rome, {\´E}cole fran{\c{c}}aise de Rome 2015}, series = {Historische Zeitschrift}, volume = {305}, journal = {Historische Zeitschrift}, number = {1}, issn = {2196-680X}, doi = {10.1515/hzhz-2017-1273}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194970}, pages = {137 -- 138}, year = {2017}, abstract = {Rezension zu Stefano Andretta / St{\´e}phane P{\´e}quignot / Jean-Claude Waquet (Eds.), De l'ambassadeur. Les {\´e}crits relatifs {\`a} l'ambassadeur et {\`a} l'art de n{\´e}gocier du Moyen {\^A}ge au d{\´e}but du XIXe si{\`e}cle. Rome, {\´E}cole fran{\c{c}}aise de Rome 2015}, language = {de} } @article{TiffeWagnerRueckeretal.2017, author = {Tiffe, Theresa and Wagner, Martin and R{\"u}cker, Viktoria and Morbach, Caroline and Gelbrich, G{\"o}tz and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Control of cardiovascular risk factors and its determinants in the general population - findings from the STAAB cohort study}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {276}, doi = {10.1186/s12872-017-0708-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159391}, year = {2017}, abstract = {Background: While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD). Methods: Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed. Results: Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9\% were female; 30.8\% were physically inactive, 55.2\% overweight, 19.3\% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8\%, 57.6\%, and 3.9\%, respectively. Treatment goals were not reached despite medication in 52.7\% of hypertensive, in 37.3\% of hyperlipidemic and in 44.0\% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95\%CI 1.44-2.61), higher age (OR for 30-39 years vs. 70-79 years 4.01, 95\%CI 1.94-8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95\%CI 1.48-3.11). Conclusions: In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.}, language = {en} } @phdthesis{Then2017, author = {Then, Patrick}, title = {Waveguide-based single molecule detection in flow}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140548}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In this work fluorescence-based single molecule detection at low concetration is investigated, with an emphasis on the usage of active transport and waveguides. Active transport allows to overcome the limits of diffusion-based systems in terms of the lowest detectable threshold of concentration. The effect of flow in single molecule experiments is investigated and a theoretical model is derived for laminar flow. Waveguides on the other hand promise compact detection schemes and show great potential for their possible integration into lab-on-a-chip applications. Their properties in single molecule experiments are analyzed with help of a method based on the reciprocity theorem of electromagnetic theory.}, subject = {Optik}, language = {en} } @article{Thalhammer2017, author = {Thalhammer, Johanna}, title = {L'art de bien chanter und Von der Kunst zierlich zu singen und zu spielen - Eine kontrastive Analyse von Texten der musikalischen Fachsprache im 18. Jahrhundert anhand von Ausz{\"u}gen aus Code de musique pratique, Rameau (1760) und Der vollkommene Capellmeister, Mattheson (1739)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {3}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2510-2613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172958}, pages = {203-224}, year = {2017}, abstract = {This article is an analysis and a comparison of German and French special language of music in the 18th century, more precisely about the terms used to describe the activity of singing. The analysis is based on two treatises about music theory. The first writing, Der Vollkommene Capellmeister, was written by Johann Mattheson in 1739 and the second, Code de musique pratique by Jean-Philippe Rameau was published in 1760. Both texts contain a chapter which gives explanations how to sing. The treatises include different types of technical words: specific terms easy identified as special language terms like names of ornaments in the music, special verbs standing for singing, and words and anaphors to describe tonality and dynamics. By having a look on the terms of music language, the influence of Italian and French words on German vocabulary of music becomes obvious. The vocabulary is often similar in both languages, but not always defined as a part of the special language of music.}, language = {de} } @phdthesis{Terveer2017, author = {Terveer, Nils}, title = {Springs and Parachutes - Development and Characterization of Novel Formulations for Poorly Water-Soluble Drugs}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154311}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Successful formulation development of novel, particularly organic APIs of low molecular weight as candidates for ground-breaking pharmaceutical products is a major challenge for the pharmaceutical industry because of the poor aqueous solubility of most of these compounds. The hit identification strategies of drug development in use today apply high throughput screening techniques for the investigation of thousands of substances. This approach led to a systematical increase in molecular weight and lipophilicity and a decrease of water solubility of lead compounds reaching market access. The high lipophilicity causes an excellent permeability of the compounds which favours the absorption process from the small intestine, but it causes a decrease of water-solubility. It becomes evident that an adequate aqueous solubility is necessary for absorption of the API from the gastrointestinal fluids into the systemic circulation and hence for efficacy of the pharmaceutical product. Only an dissolved API is getting absorbed and becomes efficacious. The precipitated proportion is resigned directly. Therefore, the development of an individual formulation aligning the physicochemical characteristics is necessary for every API to produce supersaturated solutions in the small intestine and to reach an adequate bioavailability after absorption into the systemic circulation. In this thesis a specific formulation development was investigated for two exemplary poorly water-soluble APIs to replace the empirical approach often used today. The basic tyrosine-kinase inhibitor imatinib and six different acetylated amino acids were transferred into ILs. As compared to the free base and the mesylate salt, which is marketed by Novartis AG as Gleevec®, the dissolution rate as well as the supersaturation time was increased significantly. By changing the mesylate anion with its potential genotoxic risks, the total toxicity of the drug product could be decreased. The amorphous ILs proved adequate stability under forcing conditions and there was no recrystallization of the free base observed. The amorphous character of the ILs caused an increased amount of water vapour sorption which can be compensated by special packaging materials. Taken together, the presentation of imatinib as an IL is intended for oral administration as a tablet and can cause a reduction of dose because of the increased solubility. Therefore, the occurrence of side effects can be reduced as compared to Gleevec®. If there is actually an increased bioavailability to observe, has to be proved by the execution of animal trials. The novel NOX inhibitor VAS3947 is intended for the treatment of endothelial dysfunctions causing diseases like heart failure and stroke. The compounds poor aqueous solubility hindered further clinical development so far and make the drug candidate to remain in a very early stage of the drug development process. Therefore, different formulation concepts were evaluated in this study: An amorphous solid dispersion prepared from VAS3947 and Eudragit® L100 by means of spray drying was able to increase the dissolution rate and solubility of the compound significantly, but with the accomplished kinetic solubility being in the low µM range it is not possible to reach therapeutic plasma concentrations. In contrast, the incorporation into cyclodextrins resulted in an 760-fold increased solubility. Different cyclodextrins were evaluated. Especially the lipophilic derivatives of the β-cyclodextrin showed to be the most adequate excipients. The incorporation of the API into the cyclodextrin cavity was proved by means of NMR spectroscopy. Additionally, a formulation of VAS3947 and hydroxypropyl-β-cyclodextrin was prepared. This formulation is intended for the intravenous application during animal trials, which have to be conducted to get to know the pharmacokinetics of VAS3947. This formulation reached a concentration of 1 mg/mL spending striking protection of VAS3947 against degradation. Presentation of VAS3947 as a microemulsion system led also to increase the aqueous solubility of the compound, but not in the same extent as the cyclodextrin formulation. Beside the formulation development a physicochemical characterization was performed to get to know important parameters such as log P and pKa values of VAS3947. An HPLC method was developed and validated to analyse the extent of solubility improvement. A major issue of the compound VAS3947 and all related triazolopyrimidine derivatives, developed by Vasopharm GmbH, is the insufficient chemical stability because of presence of a hemiaminal moiety in the chemical structure. Stability investigations and an extensive biopharmaceutical characterization confirm the hindering of further clinical development by insufficient drug stability and high cytotoxicity. Poor aqueous solubility is an additional disadvantage which can be handled by a concerted formulation development.}, language = {en} } @article{TemmeFriebeSchmidtetal.2017, author = {Temme, Sebastian and Friebe, Daniela and Schmidt, Timo and Poschmann, Gereon and Hesse, Julia and Steckel, Bodo and St{\"u}hler, Kai and Kunz, Meik and Dandekar, Thomas and Ding, Zhaoping and Akhyari, Payam and Lichtenberg, Artur and Schrader, J{\"u}rgen}, title = {Genetic profiling and surface proteome analysis of human atrial stromal cells and rat ventricular epicardium-derived cells reveals novel insights into their cardiogenic potential}, series = {Stem Cell Research}, volume = {25}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2017.11.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172716}, pages = {183-190}, year = {2017}, abstract = {Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73,CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.}, language = {en} } @article{TemmeAdamAhnenetal.2017, author = {Temme, Fabian and Adam, Jan and Ahnen, Max L. and Baack, Dominik and Balbo, Matteo and Bergmann, Matthias and Biland, Adrian and Blank, Michael and Bretz, Thomas and Br{\"u}gge, Kai A. and Buss, Jens and Dmytriiev, Anton and Dorner, Daniela and Einecke, Sabrina and Hempfling, Christina and Hildebrand, Dorothee and Hughes, Gareth and Linhoff, Lena and Mannheim, Karl and M{\"u}ller, Sebastian and Neise, Dominik and Neronov, Andrii and N{\"o}the, Max and Paravac, Aleksander and Pauss, Felicitas and Rhode, Wolfgang and Shukla, Amit and Thaele, Julia and Walter, Roland}, title = {Long-Term monitoring of bright blazars in the multi-GeV to TeV range with FACT}, series = {Galaxies}, volume = {5}, journal = {Galaxies}, number = {1}, publisher = {MDPI}, issn = {2075-4434}, doi = {10.3390/galaxies5010018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198088}, pages = {18}, year = {2017}, abstract = {Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed.}, language = {en} } @article{Teichmann2017, author = {Teichmann, Christoph}, title = {Die GmbH im europ{\"a}ischen Wettbewerb der Rechtsformen}, series = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, volume = {46}, journal = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, number = {5}, issn = {1612-7048}, doi = {10.1515/zgr-2017-0024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194060}, pages = {543 -- 582}, year = {2017}, abstract = {In den 125 Jahren seit ihrer Einf{\"u}hrung im Jahre 1892 hat die deutsche GmbH einerseits einen Siegeszug um die ganze Welt angetreten und musste sich andererseits im eigenen Heimatland der scharfen Konkurrenz der englischen Limited erwehren. Dieser Wettbewerb setzte im Internationalen Gesellschaftsrecht einen Wechsel von der Sitz- zur Gr{\"u}ndungstheorie voraus. Seine negativen Auswirkungen lassen sich, wie die j{\"u}ngere EuGH-Rechtsprechung zeigt, durch eine am Sachproblem orientierte Anwendung inl{\"a}ndischer Drittschutzregeln zielgerichtet eingrenzen. Im europ{\"a}ischen Ideenwettbewerb ist das deutsche GmbH-Recht derweil deutlich zur{\"u}ckgefallen. Das liegt weniger an der vermeintlichen Dominanz des englischen Rechts als am Ideenreichtum der kleineren EU-Staaten, denen es mit gut durchdachten Reformprojekten gelingt, international Aufmerksamkeit auf sich zu ziehen.}, language = {de} } @article{Teichmann2017, author = {Teichmann, Christoph}, title = {Die grenz{\"u}berschreitende Unternehmensgruppe im Compliance-Zeitalter}, series = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, volume = {46}, journal = {Zeitschrift f{\"u}r Unternehmens- und Gesellschaftsrecht}, number = {4}, issn = {1612-7048}, doi = {10.1515/zgr-2017-0021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194940}, pages = {485 -- 508}, year = {2017}, abstract = {Die europ{\"a}ische Konzernorganisation und die „Europa GmbH" (SPE) bilden zwei wichtige Forschungsschwerpunkte im Werk von Peter Hommelhoff. Beide Projekte haben sich {\"u}ber die Jahre als außerordentlich dicke Bretter erwiesen. Doch davon l{\"a}sst sich der Jubilar nicht beirren. R{\"u}ckschl{\"a}ge und Umwege geh{\"o}ren in der Wissenschaft zum kollektiven Lernprozess, der neue Erkenntnisse bringt. Ganz in diesem Sinne m{\"u}nden die Erfahrungen aus der Diskussion um ein europ{\"a}isches Konzernrecht und um die SPE im vorliegenden Beitrag in die Konzeption eines supranationalen Konzernbausteins f{\"u}r europ{\"a}ische Unternehmensgruppen.}, language = {de} } @article{TawkSharanEulalioetal.2017, author = {Tawk, Caroline and Sharan, Malvika and Eulalio, Ana and Vogel, J{\"o}rg}, title = {A systematic analysis of the RNA-targeting potential of secreted bacterial effector proteins}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-09527-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158815}, pages = {9328}, year = {2017}, abstract = {Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins.}, language = {en} } @phdthesis{Tabisz2017, author = {Tabisz, Barbara}, title = {Site Directed Immobilization of BMP-2: Two Approaches for the Production of Osteoinductive Scaffolds}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153766}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Bone fractures typically heal without surgical intervention. However, pathological situations exist which impede the healing process resulting in so-called non-union fractures. Such fractures are nowadays treated with scaffold material being introduced into the defect area. These scaffolds can be doped with osteogenic factors, such as bone morphogenetic protein (BMP)2. BMP2 belongs to the most osteogenic growth factors known to date. Its medical use, efficiency and safety have been approved by FDA for certain applications. Currently, BMP2 is distributed with a stabilizing scaffold, which is simply soaked with the growth factor. Due to fast release kinetics supraphysiological high doses of BMP2 are required which are causally associated with severe side effects observed in certain applications being most harmful in the area of the cervical spine. These side-effects include inflammation, swelling and breathing problems, leading to disastrous consequences or secondary surgical interventions. Since it could be shown that a retardation of BMP2 release from the scaffold resulted in superior bone forming properties in vivo, it seems obvious to further reduce this release to a minimum. This can be achieved by covalent coupling which in the past was already elaborated using mainly classical EDC/NHS chemistry. Using this technique coupling of the protein occurs non-site-directedly leading mainly to an unpredictable product outcome with variable osteogenic activities. In order to improve the reproducibility of scaffold functionalization by BMP2 we created variants one of which contains a unique unnatural amino acid substitution within the mature polypeptide sequence (BMP2-K3Plk) and another, BMP2-A2C, in which an N-terminal alanine has been substituted by cysteine. These modifications enable site-specific and covalent immobilization of BMP2 e.g. onto polymeric beads. Both proteins were expressed in E. coli, renatured and purified by cation-exchange chromatography. Both variants were extensively analyzed in terms of purity and biological activity which was tested by in vitro interaction analyses as well as in cell based assays. Both proteins could be successfully coupled to polymeric beads. The different BMP2 functionalized beads were shown to interact with the ectodomain of the type I receptor BMPR-IA in vitro indicating that the biological activity of both BMP2 variants retained upon coupling. Both functionalized beads induced osteogenic differentiation C2C12 cells but only of those cells which have been in close contact to the particular beads. This strongly indicates that the BMP2 variant are indeed covalently coupled and not just adsorbed. We claim that we have developed a system for a site-specific and covalent immobilization of BMP-2 onto solid scaffolds, potentially eliminating the necessity of high-dose scaffold loading. Since immobilized proteins are protected from removal by extracellular fluids, their activities now rely mainly on the half-life of the used scaffold and the rate of proteolytic degradation. Assuming that due to prolonged times much lower loading capacities might be required we propose that the immobilization strategy employed in this work may be further refined and optimized to replace the currently used BMP2-containing medical products.}, subject = {Protein chemistry}, language = {en} } @article{SanchezThierschmannMolenkamp2017, author = {S{\´a}nchez, Rafael and Thierschmann, Holger and Molenkamp, Laurens W.}, title = {Single-electron thermal devices coupled to a mesoscopic gate}, series = {New Journal of Physics}, volume = {19}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/aa8b94}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172982}, year = {2017}, abstract = {We theoretically investigate the propagation of heat currents in a three-terminal quantum dot engine. Electron-electron interactions introduce state-dependent processes which can be resolved by energy-dependent tunneling rates. We identify the relevant transitions which define the operation of the system as a thermal transistor or a thermal diode. In the former case, thermal-induced charge fluctuations in the gate dot modify the thermal currents in the conductor with suppressed heat injection, resulting in huge amplification factors and the possible gating with arbitrarily low energy cost. In the latter case, enhanced correlations of the state-selective tunneling transitions redistribute heat flows giving high rectification coefficients and the unexpected cooling of one conductor terminal by heating the other one. We propose quantum dot arrays as a possible way to achieve the extreme tunneling asymmetries required for the different operations.}, language = {en} } @article{SyperekAndrzejewskiRudnoRudzińskietal.2017, author = {Syperek, M. and Andrzejewski, J. and Rudno-Rudziński, W. and Maryński, A. and Sȩk, G. and Misiewicz, J. and Reithmaier, J. P. and Somers, A. and H{\"o}fling, S.}, title = {The issue of 0D-like ground state isolation in GaAs- and InP-based coupled quantum dots-quantum well systems}, series = {Journal of Physics: Conference Series}, volume = {906}, journal = {Journal of Physics: Conference Series}, number = {1}, issn = {1742-6588}, doi = {10.1088/1742-6596/906/1/012019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262876}, year = {2017}, abstract = {The issue of quantum mechanical coupling between a semiconductor quantum dot and a quantum well is studied in two families of GaAs- and InP- based structures at cryogenic temperatures. It is shown that by tuning the quantum well parameters one can strongly disturb the 0D-character of the coupled system ground state, initially located in a dot. The out-coupling of either an electron or a hole state from the quantum dot confining potential is viewed by a significant elongation of the photoluminescence decay time constant. Band structure calculations show that in the GaAs-based coupled system at its ground state a hole remains isolated in the dot, whereas an electron gets delocalized towards the quantum well. The opposite picture is built for the ground state of a coupled system based on InP.}, language = {en} } @phdthesis{Swimm2017, author = {Swimm, Katrin}, title = {Experimentelle und theoretische Untersuchungen zur gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeit von por{\"o}sen Materialien}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153887}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Als W{\"a}rmed{\"a}mmstoffe werden {\"u}blicherweise makropor{\"o}se Stoffsysteme wie Sch{\"a}ume, Pul-versch{\"u}ttungen, Faservliese und - wolle eingesetzt. Zus{\"a}tzlich finden mikro- und mesopor{\"o}se D{\"a}mmstoffe wie Aerogele Anwendung. Um effiziente W{\"a}rmed{\"a}mmstoffe entwickeln zu k{\"o}nnen, muss der Gesamtw{\"a}rmetransport in por{\"o}sen Materialien verstanden werden. Die ein-zelnen W{\"a}rmetransport-Mechanismen Festk{\"o}rperw{\"a}rmeleitung, Gasw{\"a}rmeleitung und W{\"a}rme-strahlung k{\"o}nnen zuverl{\"a}ssig analytisch beschrieben werden. Bei manchen por{\"o}sen Materialien liefert jedoch auch eine Wechselwirkung zwischen den verschiedenen W{\"a}rmetransport-Mechanismen, d.h. die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung, einen hohen Beitrag zur Gesamtw{\"a}rmeleitf{\"a}higkeit. Wie hoch dieser Kopplungseffekt bei einer bestimmten Probe ausf{\"a}llt, kann bisher schwer abgesch{\"a}tzt werden. Um den Kopplungseffekt von Festk{\"o}rper- und Gasw{\"a}rmeleitung besser zu verstehen, sind sowohl experimentelle als auch theoretische Untersuchungen an verschiedenen por{\"o}sen Stoffsystemen erforderlich. Zus{\"a}tzlich kann ein zuverl{\"a}ssiges theoretisches Modell dazu beitragen, die mittlere Porengr{\"o}ße von por{\"o}sen Mate-rialien zerst{\"o}rungsfrei anhand von gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeitsmessungen zu bestimmen. Als Modellsystem f{\"u}r die experimentellen Untersuchungen wurde der hochpor{\"o}se Feststoff Aerogel verwendet, da seine strukturellen Eigenschaften wie Porengr{\"o}ße und Dichte w{\"a}hrend der Synthese gut eingestellt werden k{\"o}nnen. Es wurden Resorcin-Formaldehyd-Aerogele mit mittleren Porengr{\"o}ßen von etwa 600 nm, 1 µm und 8 µm sowie daraus mittels Pyrolyse abge-leitete Kohlenstoff-Aerogele synthetisiert und jeweils hinsichtlich ihrer Struktur und W{\"a}rme-leitf{\"a}higkeiten experimentell charakterisiert. Die Gesamtw{\"a}rmeleitf{\"a}higkeiten dieser Aerogele wurden f{\"u}r verschiedene Gasatmosph{\"a}ren (Kohlenstoffdioxid, Argon, Stickstoff und Helium) in Abh{\"a}ngigkeit vom Gasdruck durch das Hitzdraht-Verfahren bestimmt. Hierf{\"u}r wurde der Messbereich der Hitzdraht-Apparatur des ZAE Bayern mittels einer Druckzelle auf 10 MPa erweitert. Die Messergebnisse zeigen, dass bei allen Aerogel-Proben Festk{\"o}rper- und Gasw{\"a}r-meleitung einen deutlichen Kopplungsbeitrag liefern: Die gemessenen gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeiten sind um Faktor 1,3 bis 3,3 h{\"o}her als die entsprechenden reinen Gas-w{\"a}rmeleitf{\"a}higkeiten. Die jeweilige H{\"o}he h{\"a}ngt sowohl vom verwendeten Gas (Gasw{\"a}rmeleitf{\"a}higkeit) als auch vom Aerogeltyp (Festk{\"o}rperw{\"a}rmeleitf{\"a}higkeit und Festk{\"o}rperstruktur) ab. Ein stark vernetzter Festk{\"o}rper verursacht beispielsweise einen niedrigeren Kopplungsbei-trag als ein weniger stark vernetzter Festk{\"o}rper. Andererseits wurde die gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit von Melaminharzschaum - einem flexiblen, offenporigen und hochpor{\"o}sen Material - in einer evakuierbaren Zwei-Plattenapparatur unter Stickstoff-Atmosph{\"a}re bestimmt. Das Material zeichnet sich dadurch aus, dass die Addition der Einzelw{\"a}rmeleitf{\"a}higkeiten gut erf{\"u}llt ist, d.h. kein Kopplungsef-fekt auftritt. Allerdings konnte gezeigt werden, dass die gestauchte und damit unregelm{\"a}ßige Struktur von Melaminharzschaum die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung deut-lich beg{\"u}nstigt. Je st{\"a}rker die Melaminharzschaumprobe komprimiert wird, umso st{\"a}rker f{\"a}llt der Kopplungseffekt aus. Bei einer Kompression um 84 \% ist beispielsweise die gemessene gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit bei 0,1 MPa um ca. 17 \% gegen{\"u}ber der effektiven W{\"a}rmeleitf{\"a}higkeit von freiem Stickstoff erh{\"o}ht. Die experimentellen Untersuchungen wurden durch theoretische Betrachtungen erg{\"a}nzt. Zum einen wurde die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung anhand einer Serienschal-tung der thermischen Widerst{\"a}nde von Festk{\"o}rper- und Gasphase dargestellt, um die Abh{\"a}n-gigkeit von verschiedenen Parametern zu untersuchen. Dadurch konnte gezeigt werden, dass der Kopplungsterm stets von den Verh{\"a}ltnissen aus Festk{\"o}rper- und Gasw{\"a}rmeleitf{\"a}higkeit sowie aus den geometrischen Parametern beider Phasen abh{\"a}ngt. Des Weiteren wurden mit dem Computerprogramm HEAT2 Finite-Differenzen-Simulationen an Modellstrukturen durchgef{\"u}hrt, die f{\"u}r por{\"o}se Stoffsysteme, insbesondere Aerogel, charakteristisch sind (Stege, H{\"a}lse, Windungen und tote Enden). Die simulierten gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeiten zeigen deutlich, dass die Festk{\"o}rperstruktur mit der geringsten Vernetzung, d.h. das tote Ende, am meisten zur Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung beitr{\"a}gt. Dies korre-liert mit den experimentellen Ergebnissen. Dar{\"u}ber hinaus kann man erkennen, dass die Ge-samtw{\"a}rmeleitf{\"a}higkeit eines schlecht vernetzten por{\"o}sen Systems, wo also ein hoher Kopp-lungseffekt (Serienschaltung) auftritt, niemals gr{\"o}ßer wird als die eines gut vernetzten Sys-tems mit gleicher Porosit{\"a}t, wo haupts{\"a}chlich paralleler W{\"a}rmetransport durch beide Phasen stattfindet. Schließlich wurden drei Modelle entwickelt bzw. modifiziert, um die gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit von por{\"o}sen Stoffsystemen theoretisch beschreiben zu k{\"o}nnen. Zun{\"a}chst wurde ein f{\"u}r Kugelsch{\"u}ttungen entwickeltes Modell f{\"u}r Aerogel angepasst, d.h. Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung wurde nur in den L{\"u}cken zwischen zwei benachbarten Partikeln ber{\"u}cksichtigt. Ein Vergleich mit den Messkurven zeigt, dass der ermittelte Kopplungsterm zu gering ausf{\"a}llt. Daher wurde ein bereits existierendes Aerogelmodell mit kubischer Einheitszelle, welches zus{\"a}tzlich Kopplung zwischen den einzelnen Partikelstr{\"a}ngen beinhaltet, verbessert. Auch dieses Modell liefert keine zufriedenstellende {\"U}bereinstimmung mit den Messwerten, denn der Kopplungsbeitrag wird immer noch untersch{\"a}tzt. Das liegt daran, dass die gew{\"a}hlte regelm{\"a}ßige kubische Struktur f{\"u}r Aerogel zu ungenau ist. So geht bei der Berechnung des Kopplungsterms der bereits erw{\"a}hnte hohe Beitrag durch tote Enden (und auch Windungen) verloren. Erfahrungsgem{\"a}ß k{\"o}nnen jedoch alle f{\"u}r Aerogel erhaltenen gasdruckabh{\"a}ngigen Messkurven mit dem sogenannten Skalierungsmodell relativ gut beschrieben werden. Das entspricht dem Knudsen-Modell f{\"u}r reine Gasw{\"a}rmeleitung, welches mit einem konstanten Faktor skaliert wird. Die Anwendung dieses einfachen Modells auf die Messdaten hat gezeigt, dass die Akkommodationskoeffizienten von Helium in Aerogel deut-lich h{\"o}her sind als die Literaturwerte (ca. 0,3 auf Metalloberfl{\"a}chen): In den vermessenen RF- und Kohlenstoff-Aerogelen lassen sich Akkommodationskoeffizienten nahe 1 f{\"u}r Helium ab-leiten. Dar{\"u}ber hinaus ist das Skalierungsmodell gut geeignet, die mittleren Porengr{\"o}ßen por{\"o}ser Materialien zuverl{\"a}ssig aus gasdruckabh{\"a}ngig gemessenen W{\"a}rmeleitf{\"a}higkeitskurven zu bestimmen. Dies stellt somit eine unkomplizierte und zerst{\"o}rungsfreie Charakterisierungsmethode dar.}, subject = {W{\"a}rmeleitf{\"a}higkeit}, language = {de} } @phdthesis{Svistunov2017, author = {Svistunov, Andrey}, title = {Langzeitergebnisse der Erhaltungstherapie mit Gemcitabin nach Cisplatin-basierter adjuvanter Chemotherapie des operativ behandelten muskelinfiltrierenden Urothelkarzinoms}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154666}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Der Stellenwert der Erhaltungstherapie mit Gemcitabin (GEM), die im Anschluss an die Cisplatin-basierte Polychemotherapie (CBPC) bei den radikal operativ vorbehandelten Patienten mit fortgeschrittenem Urothelkarzinom (UC) erfolgt, bleibt bis dato unklar. In der vorliegenden Arbeit konnten die Ergebnisse der GEM-Erhaltungstherapie mittels retrospektiver Analyse evaluiert werden. Zwischen 1999 und 2013 erhielten 38 operativ vorbehandelte Patienten im Anschluss an die prim{\"a}re CBPC zus{\"a}tzlich im viertelj{\"a}hrlichen Intervall zwei konsekutive Infusionen von GEM (1 250 mg/m2) als Erhaltungstherapie. Dieses Kollektiv wurde durch ein ebenso operativ vorbehandeltes Kontrollkollektiv (n = 38), das lediglich eine prim{\"a}re CBPC erhielt, mittels eines `Propensity Score Matching`-Verfahrens gematched. Mittels Kaplan-Meier-Sch{\"a}tzungen mitsamt dem Log-rank-Test wurden die Gesamt{\"u}berlebens- und tumorspezifische {\"U}berlebensraten sowie das progressionsfreie {\"U}berleben in beiden Kollektiven beurteilt. Die Analyse der {\"U}berlebensdaten erfolgte durch die Regressionsmethode nach Cox (proportionales Hazard Modell). Die mediane Follow-Up Zeit betrug 37 Monate bei einem Interquartilsabstand von 9 bis 148 Monaten. Die Patienten, die die GEM-Erhaltungstherapie erhielten, zeigten signifikant bessere Ergebnisse bez{\"u}glich der Gesamt-5-Jahres-{\"U}berlebensrate (49,2 vs. 26,5 \%, p = 0,0314) sowie der tumorspezifischen 5-Jahres-{\"U}berlebensrate (61,3 vs. 33,4 \%, p = 0,0386). Dabei ergab sich in beiden Kollektiven kein statistisch signifikanter Unterschied bez{\"u}glich des progressionsfreien 5-Jahres-{\"U}berlebens (10,3 vs. 16,1 \%, p = 0,134). Es ist dargelegt, dass die zus{\"a}tzliche GEM-Erhaltungschemotherapie nach Abschluss der prim{\"a}ren CBPC bei operativ vorbehandelten Patienten mit fortgeschrittenem UC sowohl Gesamt- als auch tumorspezifisches {\"U}berleben (wenngleich an einem kleinen Patientenkollektiv) verbessern kann. Der Einfluss der GEM-Erhaltungstherapie auf das progressionsfreie {\"U}berleben sollte in prospektiven Studien mit großer Patientenanzahl k{\"u}nftig evaluiert werden.}, subject = {Gemcitabin}, language = {de} } @article{SunkavalliAguilarSilvaetal.2017, author = {Sunkavalli, Ushasree and Aguilar, Carmen and Silva, Ricardo Jorge and Sharan, Malvika and Cruz, Ana Rita and Tawk, Caroline and Maudet, Claire and Mano, Miguel and Eulalio, Ana}, title = {Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1006327}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158204}, pages = {e1006327}, year = {2017}, abstract = {MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells.}, language = {en} } @article{SuchomelBrodbeckLiewetal.2017, author = {Suchomel, H. and Brodbeck, S. and Liew, T. C. H. and Amthor, M. and Klaas, M. and Klembt, S. and Kamp, M. and H{\"o}fling, S. and Schneider, C.}, title = {Prototype of a bistable polariton field-effect transistor switch}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {5114}, doi = {10.1038/s41598-017-05277-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158323}, year = {2017}, abstract = {Microcavity exciton polaritons are promising candidates to build a new generation of highly nonlinear and integrated optoelectronic devices. Such devices range from novel coherent light emitters to reconfigurable potential landscapes for electro-optical polariton-lattice based quantum simulators as well as building blocks of optical logic architectures. Especially for the latter, the strongly interacting nature of the light-matter hybrid particles has been used to facilitate fast and efficient switching of light by light, something which is very hard to achieve with weakly interacting photons. We demonstrate here that polariton transistor switches can be fully integrated in electro-optical schemes by implementing a one-dimensional polariton channel which is operated by an electrical gate rather than by a control laser beam. The operation of the device, which is the polariton equivalent to a field-effect transistor, relies on combining electro-optical potential landscape engineering with local exciton ionization to control the scattering dynamics underneath the gate. We furthermore demonstrate that our device has a region of negative differential resistance and features a completely new way to create bistable behavior.}, language = {en} } @article{StrohmeierMontenegro2017, author = {Strohmeier, Michael and Montenegro, Sergio}, title = {Coupled GPS/MEMS IMU Attitude Determination of Small UAVs with COTS}, series = {Electronics}, volume = {6}, journal = {Electronics}, number = {1}, doi = {10.3390/electronics6010015}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171179}, pages = {15}, year = {2017}, abstract = {This paper proposes an attitude determination system for small Unmanned Aerial Vehicles (UAV) with a weight limit of 5 kg and a small footprint of 0.5m x 0.5 m. The system is realized by coupling single-frequency Global Positioning System (GPS) code and carrier-phase measurements with the data acquired from a Micro-Electro-Mechanical System (MEMS) Inertial Measurement Unit (IMU) using consumer-grade Components-Off-The-Shelf (COTS) only. The sensor fusion is accomplished using two Extended Kalman Filters (EKF) that are coupled by exchanging information about the currently estimated baseline. With a baseline of 48 cm, the static heading accuracy of the proposed system is comparable to the one of a commercial single-frequency GPS heading system with an accuracy of approximately 0.25°/m. Flight testing shows that the proposed system is able to obtain a reliable and stable GPS heading estimation without an aiding magnetometer.}, language = {en} } @phdthesis{Stritt2017, author = {Stritt, Simon}, title = {The role of the cytoskeleton in platelet production and the pathogenesis of platelet disorders in humans and mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122662}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Platelets are continuously produced from megakaryocytes (MK) in the bone marrow by a cytoskeleton-driven process of which the molecular regulation is not fully understood. As revealed in this thesis, MK/ platelet-specific Profilin1 (Pfn1) deficiency results in micro- thrombocytopenia, a hallmark of the Wiskott-Aldrich syndrome (WAS) in humans, due to accelerated platelet turnover and premature platelet release into the bone marrow. Both Pfn1-deficient mouse platelets and platelets isolated from WAS patients contained abnormally organized and hyper-stable microtubules. These results reveal an unexpected function of Pfn1 as a regulator of microtubule organization and point to a previously unrecognized mechanism underlying the platelet formation defect in WAS patients. In contrast, Twinfilin2a (Twf2a) was established as a central regulator of platelet reactivity and turnover. Twf2a-deficient mice revealed an age-dependent macrothrombocytopenia that could be explained by a markedly decreased platelet half-life, likely due to the pronounced hyper-reactivity of \(Twf2a^{-/-}\) platelets. The latter was characterized by sustained integrin acti- vation and thrombin generation in vitro that translated into accelerated thrombus formation in vivo. To further elucidate mechanisms of integrin activation, Rap1-GTP-interacting adaptor molecule (RIAM)-null mice were generated. Despite the proposed critical role of RIAM for platelet integrin activation, no alterations in this process could be found and it was concluded that RIAM is dispensable for the activation of β1 and β3 integrins, at least in platelets. These findings change the current mechanistic understanding of platelet integrin activation. Outside-in signaling by integrins and other surface receptors was supposed to regulate MK migration, but also the temporal and spatial formation of proplatelet protrusions. In this the- sis, phospholipase D (PLD) was revealed as critical regulator of actin dynamics and podo- some formation in MKs. Hence, the unaltered platelet counts and production in \(Pld1/2^{-/-}\) mice and the absence of a premature platelet release in the bone marrow of \(Itga2^{-/-}\) mice question the role of podosomes in platelet production and raise the need to reconsider the proposed inhibitory signaling by α2β1 integrins on proplatelet formation. Non-muscle myosin IIA (NMMIIA) has been implicated as a downstream effector of the in- hibitory signals transmitted via α2β1 integrins. Besides Rho-GTPase signaling, also \(Mg^{2+}\) and transient receptor potential melastatin-like 7 (TRPM7) channel α-kinase are known regulators of NMMIIA activity. In this thesis, TRPM7 was identified as major regulator of \(Mg^{2+}\) homeostasis in MKs and platelets. Furthermore, decreased \([Mg^{2+}]_i\) led to deregulated NMMIIA activity and altered cytoskeletal dynamics that impaired thrombopoiesis and resulted in macrothrombocytopenia in humans and mice.}, subject = {Thrombozytopoese}, language = {en} } @article{StrasserSchrauthDembskietal.2017, author = {Straßer, Marion and Schrauth, Joachim H. X. and Dembski, Sofia and Haddad, Daniel and Ahrens, Bernd and Schweizer, Stefan and Christ, Bastian and Cubukova, Alevtina and Metzger, Marco and Walles, Heike and Jakob, Peter M. and Sextl, Gerhard}, title = {Calcium fluoride based multifunctional nanoparticles for multimodal imaging}, series = {Beilstein Journal of Nanotechnology}, volume = {8}, journal = {Beilstein Journal of Nanotechnology}, doi = {10.3762/bjnano.8.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170657}, pages = {1484-1493}, year = {2017}, abstract = {New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5-10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd\(^{3+}\) ions on the surface, the NPs reduce the MR T\(_{1}\) relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg\(^{-1}\)·s\(^{-1}\). Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL\(^{-1}\) was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs are suitable for medical imaging.}, language = {en} } @article{StoevesandtHospKerstanetal.2017, author = {Stoevesandt, Johanna and Hosp, Christine and Kerstan, Andreas and Trautmann, Axel}, title = {Safety of 100 µg venom immunotherapy rush protocols in children compared to adults}, series = {Allergy, Asthma \& Clinical Immunology}, volume = {13}, journal = {Allergy, Asthma \& Clinical Immunology}, number = {32}, doi = {10.1186/s13223-017-0204-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157830}, year = {2017}, abstract = {Background: There is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls. Methods: 72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7-17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions. Results: Compared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9\% vs 2.5\%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04-4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25-5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg. Conclusions: The higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.}, language = {en} } @phdthesis{Stockinger2017, author = {Stockinger, Bastian}, title = {Causes and effects of worker mobility between firms: empirical studies for Germany}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153894}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {This dissertation investigates selected causes and effects of worker mobility between firms in three empirical studies for Germany. Chapter 2 investigates the productivity effects of worker inflows to manufacturing establishments, distinguishing inflows by their previous employers' wage level, as a proxy for productivity. The chapter is motivated by several empirical studies which find that worker inflows from more productive or higher-paying firms increase hiring firms' productivity. The analyses in chapter 2 are based on a unique linked employer-employee data set. The findings indicate that inflows from higher-paying establishments do not increase hiring establishments' productivity, but inflows from lower-paying establishments do. Further analyses suggest that this effect is due to a positive selectivity of such inflows from their sending establishments. These findings can be interpreted as evidence of a reallocation process by which the best employees of lower-paying establishments become hired by higher-paying establishments. This process reflects the assortative pattern of worker mobility in Germany documented by Card et al. (2013) for the past decades. The chapter thus contributes to the literature by linking establishment-level productivity analysis to the assortative pattern of inter-firm worker mobility, thereby providing a micro-foundation for the latter. Chapter 3 focuses on a positive selection of workers moving between firms from another, more specific perspective. The analysis focuses on the importance of regional labor market competition for establishments' apprentice training and poaching of apprenticeship completers. Previous studies have found that firms provide less training if they are located in regions with strong labor market competition. This finding is usually interpreted as evidence of a higher risk of poaching in these regions. Yet, there is no direct evidence that regional competition is positively correlated with poaching. Building on a recently established approach to ex-post identify poaching of apprenticeship completers, this chapter is the first to directly investigate the correlation between regional labor market competition and poaching. Using German administrative data, it is found that competition indeed increases training establishments' probability of becoming poaching victims. However, poaching victims do not change their apprenticeship training activity in reaction to poaching. Instead, the findings indicate that the lower training activity in competitive regions can be attributed to lower retention rates, as well as a less adverse selection and lower labor and hiring costs of apprenticeship completers hired from rivals. Chapter 4 investigates the effects of local broadband internet availability on establishment-level employment growth. The analysis uses data for Germany in the years 2005-2009, when broadband was introduced in rural regions of Western Germany and in large parts of Eastern Germany. Technical frictions in broadband rollout are exploited to obtain exogenous variation in local broadband availability. The results suggest that broadband expansion had a positive effect on employment growth in the Western German service sector and a negative effect in Western German manufacturing, suggesting that broadband expansion has accelerated the reallocation of workers from manufacturing to services. Furthermore, this pattern of results is driven by pronounced positive effects in knowledge- and computer-intensive industries, suggesting that it is the actual use of broadband in the production process that leads to complementary hiring, respectively a slowdown of employment growth, in the respective sectors. For Eastern Germany, no significant employment growth effects are found.}, subject = {Arbeitsmarkt}, language = {en} } @book{Stock2017, author = {Stock, Claudia}, title = {Wi man di ku fom ais kricht. Mit dem Grundschul-Wortschatz eine sichere Rechtschreibung erlernen}, edition = {1. Auflage}, publisher = {W{\"u}rzburg Univerity Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-054-2 (print)}, doi = {10.25972/WUP-978-3-95826-055-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154080}, publisher = {W{\"u}rzburg University Press}, pages = {300}, year = {2017}, abstract = {Die Grundschulw{\"o}rterliste ist eine Sammlung von ca. 6400 W{\"o}rtern bzw. Wortverbindungen auf knapp 280 Seiten, die es erleichtern sollen, {\"U}bungsdiktate f{\"u}r Grundschulkinder zu erstellen. Sie richtet sich damit vornehmlich an LehrerInnen, aber auch an LerntherapeutInnen und die Eltern der Kinder f{\"u}r das Lernen in der Schule, im Nachhilfeinstitut oder zu Hause. Die W{\"o}rterlisten basieren auf den Grundwortsch{\"a}tzen verschiedener Grundschullehrpl{\"a}ne und den W{\"o}rterlisten im Anhang von {\"u}ber 60 Schulb{\"u}chern. Damit decken sie repr{\"a}sentativ den in der Rechtschreibung zu erlernenden Wortschatz ab und erm{\"o}glichen es dar{\"u}ber hinaus, durch spezielle Themenlisten {\"U}bungstexte mit spezifischen orthographischen Schwerpunkten zusammenzustellen.}, subject = {Legasthenie}, language = {de} } @misc{Stickler2017, author = {Stickler, Matthias}, title = {Wolfram Siemann, Metternich. Stratege und Vision{\"a}r. Eine Biografie. M{\"u}nchen, Beck 2016}, series = {Historische Zeitschrift}, volume = {304}, journal = {Historische Zeitschrift}, number = {1}, issn = {2196-680X}, doi = {10.1515/hzhz-2017-1039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194240}, pages = {238 -- 240}, year = {2017}, abstract = {Rezension zu Wolfram Siemann, Metternich. Stratege und Vision{\"a}r. Eine Biografie. M{\"u}nchen, Beck 2016}, language = {de} } @misc{Stickler2017, author = {Stickler, Matthias}, title = {Dominik Feldmann, Von Journalisten und Diplomaten. Die Entdeckung der Presse f{\"u}r die Außenpolitik in Preußen und {\"O}sterreich 1849-1879. (Historische Forschungen, Bd. 110.) Berlin, Duncker \& Humblot 2016}, series = {Historische Zeitschrift}, volume = {304}, journal = {Historische Zeitschrift}, number = {3}, issn = {2196-680X}, doi = {10.1515/hzhz-2017-1225}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194075}, pages = {808 -- 810}, year = {2017}, abstract = {Rezension zu Dominik Feldmann, Von Journalisten und Diplomaten. Die Entdeckung der Presse f{\"u}r die Außenpolitik in Preußen und {\"O}sterreich 1849-1879. (Historische Forschungen, Bd. 110.) Berlin, Duncker \& Humblot 2016}, language = {de} } @phdthesis{Stengele2017, author = {Stengele, Anja}, title = {Systematische Analyse der Abbindereaktion von Magnesiumphosphat mit Polyacryls{\"a}ure im Vergleich zu klassischen w{\"a}ssrigen Zementsystemen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153871}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Gegenstand der vorliegenden Arbeit war eine systematische Analyse der Ver-arbeitbarkeit, Abbindedauer, pH Wert- und Temperatur-Verl{\"a}ufe w{\"a}hrend des Abbindens und der Eigenschaften der ausgeh{\"a}rteten Zementpaste, welche je-weils aus Farringtonit (Mg3(PO4)2) unterschiedlicher Reaktivit{\"a}t bestand und mit Diammoniumhydrogenphosphat und Polyacryls{\"a}ure zur Reaktion gebracht und konventionellen w{\"a}ssrigen Zementsystemen gegen{\"u}bergestellt wurde. Ein besonderer Fokus wurde hierbei auf die Beurteilbarkeit der Eignung dieser Zementsysteme als injizierbare Zementpasten in m{\"o}glicherweise lasttragenden Bereichen gelegt. Eine Reaktivierung von Farringtonit und anschließendes Ab-binden mit Wasser konnte durch Hochenergiemahlung f{\"u}r 2 h bis 24 h erzielt werden. Mechanisch aktiviertes Farringtonit mit Polyacryls{\"a}ure (100.000 g/mol) bzw. kurzzeitig gemahlenes Farringtonit mit h{\"o}her molekulargewichtiger Polyac-ryls{\"a}ure f{\"u}hrte auf Grund der zum Teil summierten Reaktivit{\"a}t in der sauren Umgebung der Polyacryls{\"a}ure zu einer schlechten Verarbeitbarkeit und unzu-reichenden Druckfestigkeiten. Um chelatisiertes Farringtonit mit angemessenen Festigkeiten zu erhalten, zeigte sich die Anwesenheit von Ammoniumionen als vielversprechende Strategie. Als hydratisierte Produkte wurden je nach Formu-lierung Struvit (MgNH4PO4·6H2O), Newberyit (MgHPO4·3H2O) oder Mag-nesiumphosphathydrat (Mg3(PO4)2·22H2O) gewonnen. Besonders die Kombina-tion von kurzzeitig gemahlenem Farringtonit mit 17,5 Gew.\%iger Poly-acryls{\"a}ure L{\"o}sung und 23,1 Gew.\%iger Diammoniumhydrogenphos-phat L{\"o}sung mit einem Pulver-zu-Fl{\"u}ssigkeitsverh{\"a}ltnis von 1,5 g/ml f{\"u}hrte zu Zementpasten, die hinsichtlich ihres Abbindeverhaltens und der mechanischen Eigenschaften denen der Einzelbestandteile {\"u}berlegen waren. Die entwickelten Zementsysteme zeigten 60 min nach Beginn des Abbindevor-gangs einen pH-Wert von 4,7 bis 6,4 und Temperaturmaxima von 28,5 °C bis 52 °C je nach Zusammensetzung. Der Mischzement, f{\"u}r welchen maximale Druckfestigkeiten von 15,0±4,1 MPa gemessen wurden, zeigte ein deutlich we-niger spr{\"o}des Bruchverhalten im Vergleich zu den reinen Verd{\"u}nnungen. Da der spr{\"o}de Charakter klassischer mineralische Knochenzemente einen limitie-renden Faktor f{\"u}r die Anwendung in lasttragenden Bereichen darstellt, kann dies als deutliche Verbesserung der mechanischen Eigenschaften beurteilt wer-den. Immerhin lagen die erzielten Festigkeitswerte in der Gr{\"o}ßenordnung der humanen Spongiosa. Besonders hervorzuheben ist außerdem der synergisti-sche Effekt, welcher bei Zementformulierungen aus kurzzeitig gemahlenem Farringtonit mit 17,5 Gew.\%iger Polyacryls{\"a}ure L{\"o}sung und 23,1 Gew.\%iger Diammoniumhydrogenphosphat L{\"o}sung mit einem Pulver-zu-Fl{\"u}ssigkeitsver-h{\"a}ltnis von 1,5 g/ml beobachtet werden konnte. Diese Formulierung wies bis zu vierfach h{\"o}here Festigkeitswerte als die Einzelbestandteile auf. Somit bildet das entwickelte Mischzement-System eine gute Basis f{\"u}r weitere Entwicklungen hin zu mechanisch lasttragenden Defekten.}, subject = {Magnesiumphosphate}, language = {de} } @phdthesis{Stender2017, author = {Stender, Benedikt}, title = {Einzelphotonenemitter und ihre Wechselwirkung mit Ladungstr{\"a}gern in organischen Leuchtdioden}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150913}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In dieser Arbeit wird die Photophysik von Einzelphotonenemittern unterschiedlicher Materialklassen, wie Fehlstellen in Diamant und Siliziumcarbid sowie organischer Molek{\"u}le bei Raumtemperatur untersucht. Zu diesem Zweck wurde ein hochaufl{\"o}sendes konfokales Mikroskop konzipiert und konstruiert, welches die optische Detektion einzelner Quantensysteme erm{\"o}glicht. Zus{\"a}tzlich werden verschiedene Methoden wie die Rotationsbeschichtung, das Inkjet-Printing und das Inkjet-Etching in Bezug auf die Reproduzierbarkeit und Strukturierbarkeit von organischen Leuchtdioden (OLEDs) verglichen. Im weiteren Verlauf werden die optoelektronischen Prozesse in dotierten OLEDs untersucht, ausgehend von hohen Dotierkonzentrationen bis hin zur Dotierung mit einzelnen Molek{\"u}len. Dadurch kann die Exzitonen-Ladungstr{\"a}ger Wechselwirkung auf und in der Umgebung von r{\"a}umlich isolierten Molek{\"u}len analysiert werden.}, subject = {Einzelphotonenemission}, language = {de} } @phdthesis{StelzergebNagel2017, author = {Stelzer [geb. Nagel], Corinna}, title = {Effekte der nicht-invasiven aurikul{\"a}ren Vagusnervstimulation auf Hirnaktivierungsmuster, kognitive Parameter und Befindlichkeit}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154717}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In der vorliegenden prospektiven Pilotstudie wurden die Hypothesen {\"u}berpr{\"u}ft, dass es durch die nicht-invasive aurikul{\"a}re Vagusnervstimulation, jedoch nicht durch eine Kontrollstimulation am Ohrl{\"a}ppchen (Innervationsgebiet des N. trigeminus) zu einer mittels NIRS messbaren Zunahme des regionalen zerebralen Blutflusses und damit der kortikalen Aktivit{\"a}t im Bereich des pr{\"a}frontalen Kortex, zu einer Steigerung der Befindlichkeit und zu einer Verbesserung der Kognition kommt. Die Ergebnisse zeigten eine Deaktivierung im Bereich des pr{\"a}frontalen Kortex, wobei keine signifikanten Unterschiede zwischen der Vagusnerv- und der Kontrollstimulation in allen drei Modulen (Hirnaktivierung, Kognition, Befindlichkeit) nachweisbar waren.}, subject = {Vagus}, language = {de} } @article{SteinbornHuestegge2017, author = {Steinborn, Michael B. and Huestegge, Lynn}, title = {Phone conversation while processing information: chronometric analysis of load effects in everyday-media multitasking}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {896}, doi = {10.3389/fpsyg.2017.00896}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158253}, year = {2017}, abstract = {This is a pilot study that examined the effect of cell-phone conversation on cognition using a continuous multitasking paradigm. Current theorizing argues that phone conversation affects behavior (e.g., driving) by interfering at a level of cognitive processes (not peripheral activity) and by implying an attentional-failure account. Within the framework of an intermittent spare-utilized capacity threading model, we examined the effect of aspects of (secondary-task) phone conversation on (primary-task) continuous arithmetic performance, asking whether phone use makes components of automatic and controlled information-processing (i.e., easy vs. hard mental arithmetic) run more slowly, or alternatively, makes processing run less reliably albeit with the same processing speed. The results can be summarized as follows: While neither expecting a text message nor expecting an impending phone call had any detrimental effects on performance, active phone conversation was clearly detrimental to primary-task performance. Crucially, the decrement imposed by secondary-task (conversation) was not due to a constant slowdown but is better be characterized by an occasional breakdown of information processing, which differentially affected automatic and controlled components of primary-task processing. In conclusion, these findings support the notion that phone conversation makes individuals not constantly slower but more vulnerable to commit attention failure, and in this way, hampers stability of (primary-task) information processing.}, language = {en} } @article{SteinCoulibalyStenchlyetal.2017, author = {Stein, Katharina and Coulibaly, Drissa and Stenchly, Kathrin and Goetze, Dethardt and Porembski, Stefan and Lindner, Andr{\´e} and Konat{\´e}, Souleymane and Linsenmair, Eduard K.}, title = {Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {17691}, doi = {10.1038/s41598-017-17970-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169914}, year = {2017}, abstract = {Mutualistic biotic interactions as among flowering plants and their animal pollinators are a key component of biodiversity. Pollination, especially by insects, is a key element in ecosystem functioning, and hence constitutes an ecosystem service of global importance. Not only sexual reproduction of plants is ensured, but also yields are stabilized and genetic variability of crops is maintained, counteracting inbreeding depression and facilitating system resilience. While experiencing rapid environmental change, there is an increased demand for food and income security, especially in sub-Saharan communities, which are highly dependent on small scale agriculture. By combining exclusion experiments, pollinator surveys and field manipulations, this study for the first time quantifies the contribution of bee pollinators to smallholders' production of the major cash crops, cotton and sesame, in Burkina Faso. Pollination by honeybees and wild bees significantly increased yield quantity and quality on average up to 62\%, while exclusion of pollinators caused an average yield gap of 37\% in cotton and 59\% in sesame. Self-pollination revealed inbreeding depression effects on fruit set and low germination rates in the F1-generation. Our results highlight potential negative consequences of any pollinator decline, provoking risks to agriculture and compromising crop yields in sub-Saharan West Africa.}, language = {en} } @article{SteijvenSpaetheSteffanDewenteretal.2017, author = {Steijven, Karin and Spaethe, Johannes and Steffan-Dewenter, Ingolf and H{\"a}rtel, Stephan}, title = {Learning performance and brain structure of artificially-reared honey bees fed with different quantities of food}, series = {PeerJ}, volume = {5}, journal = {PeerJ}, number = {e3858}, doi = {10.7717/peerj.3858}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170137}, year = {2017}, abstract = {Background Artificial rearing of honey bee larvae is an established method which enables to fully standardize the rearing environment and to manipulate the supplied diet to the brood. However, there are no studies which compare learning performance or neuroanatomic differences of artificially-reared (in-lab) bees in comparison with their in-hive reared counterparts. Methods Here we tested how different quantities of food during larval development affect body size, brain morphology and learning ability of adult honey bees. We used in-lab rearing to be able to manipulate the total quantity of food consumed during larval development. After hatching, a subset of the bees was taken for which we made 3D reconstructions of the brains using confocal laser-scanning microscopy. Learning ability and memory formation of the remaining bees was tested in a differential olfactory conditioning experiment. Finally, we evaluated how bees reared with different quantities of artificial diet compared to in-hive reared bees. Results Thorax and head size of in-lab reared honey bees, when fed the standard diet of 160 µl or less, were slightly smaller than hive bees. The brain structure analyses showed that artificially reared bees had smaller mushroom body (MB) lateral calyces than their in-hive counterparts, independently of the quantity of food they received. However, they showed the same total brain size and the same associative learning ability as in-hive reared bees. In terms of mid-term memory, but not early long-term memory, they performed even better than the in-hive control. Discussion We have demonstrated that bees that are reared artificially (according to the Aupinel protocol) and kept in lab-conditions perform the same or even better than their in-hive sisters in an olfactory conditioning experiment even though their lateral calyces were consistently smaller at emergence. The applied combination of experimental manipulation during the larval phase plus subsequent behavioral and neuro-anatomic analyses is a powerful tool for basic and applied honey bee research.}, language = {en} } @book{Steiger2017, author = {Steiger, Markus}, title = {Multiagentensysteme zur Simulation von Konsumentenverhalten - Untersuchung individuenbasierter Simulationsszenarien zur strategischen Standortplanung im Einzelhandel}, publisher = {Verlag MetaGIS Fachbuch}, address = {Mannheim}, isbn = {978-3-936438-93-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180782}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {xvii, 216 Seiten}, year = {2017}, abstract = {Im Rahmen der vorliegenden Untersuchung liegt der Fokus auf der {\"U}berpr{\"u}fung und Weiterentwicklung der Methode der Multiagentensysteme f{\"u}r die Prognosezwecke im Einzelhandel. Die konkrete Zielsetzung der Arbeit ist der Entwurf eines integrativen Systems zur Simulation m{\"o}glicher Zukunftsszenarien des (r{\"a}umlichen) Konsumentenverhaltens. Mit Hilfe einer agentenbasierten Modellierung ist es m{\"o}glich die bisher vorherrschenden Top-Down Ans{\"a}tze flexibel in ein Bottom-Up Modell zu integrieren. Die wichtigsten strukturpr{\"a}genden Impulse im Einzelhandelssystem und somit auch auf die Konsumenten gehen aktuell von der Digitalisierung des Verkaufsvorgangs aus. Hierbei wird der „Raum-Zeit-K{\"a}fig" der Kunden ausgeweitet und bestimmte Zw{\"a}nge der r{\"a}umlichen und zeitlichen Bindung innerhalb des Kaufprozesses entfallen. Die klassische zeitliche Abfolge des Einkaufsverhaltens wird aufgel{\"o}st; Information findet vermehrt digital statt. Vielmehr steht der Produktnutzen im Mittelpunkt, und zugeh{\"o}rige Dienstleistungen wie Information, Service und Logistik werden flexibel kombiniert. Vor diesem Hintergrund stellt die agentenbasierte Simulation einen dynamischen Ansatzpunkt dar, in dem eine Reihe der Defizite tradierter, statischer Methoden Ber{\"u}cksichtigung findet und sich vielf{\"a}ltige Einsatzm{\"o}glichkeiten f{\"u}r die Analyse der Wechselwirkungen zwischen Konsumentenverhalten und r{\"a}umlichen Einzelhandelsstrukturen ergeben. Aufgrund der zunehmenden Digitalisierung des Einkaufsprozesses und den daraus entstehenden Informationen zum Konsumentenverhalten in Kombination mit immer komplexeren Fragestellungen ist in den kommenden Jahren eine verst{\"a}rkte Dynamik bei der Anwendungsh{\"a}ufigkeit von Multiagentensimulationen in Einzelhandelsunternehmen zu erwarten.}, subject = {Einzelhandel}, language = {de} } @phdthesis{Steiger2017, author = {Steiger, Christoph}, title = {Drug delivery of therapeutic gases - strategies for controlled and local delivery of carbon monoxide}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141054}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The isoenzyme heme oxygenase 1 (HO-1) is a key element for maintaining cellular homeostasis. Upregulated in response to cellular stress, the HO-1 degrades heme into carbon monoxide (CO), biliverdin, and Fe2+. By means of a local cell-protective feedback loop the enzyme triggers numerous effects including anti-oxidative, anti-apoptotic, and anti-inflammatory events associated with complex signalling patterns which are largely orchestrated by CO. Various approaches to mimic this physiological HO-1 / CO system aiming for a treatment of medical conditions have been described [1]. These preclinical studies commonly applied CO systemically via (i) inhalation or (ii) using CO-Releasing Molecules (CORMs) [2]. The clinical use of these approaches, however, is challenged by a lack of practicability and substantial safety issues associated with the toxicity of high systemic doses of CO that are required for triggering therapeutic effects. Therefore, one rational of this thesis is to describe and evaluate strategies for the local delivery of CO aiming for safe and effective CO therapeutics of tomorrow.}, subject = {Targeted drug delivery}, language = {en} } @article{StegnervanEeuwijkAngayetal.2017, author = {Stegner, David and van Eeuwijk, Judith M.M. and Angay, Oğuzhan and Gorelashvili, Maximilian G. and Semeniak, Daniela and Pinnecker, J{\"u}rgen and Schmithausen, Patrick and Meyer, Imke and Friedrich, Mike and D{\"u}tting, Sebastian and Brede, Christian and Beilhack, Andreas and Schulze, Harald and Nieswandt, Bernhard and Heinze, Katrin G.}, title = {Thrombopoiesis is spatially regulated by the bone marrow vasculature}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, number = {127}, doi = {10.1038/s41467-017-00201-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170591}, year = {2017}, abstract = {In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Through imaging of MKs in the intact BM, here we show that MKs can be found within the entire BM, without a bias towards bone-distant regions. By combining in vivo two-photon microscopy and in situ light-sheet fluorescence microscopy with computational simulations, we reveal surprisingly slow MK migration, limited intervascular space, and a vessel-biased MK pool. These data challenge the current thrombopoiesis model of MK migration and support a modified model, where MKs at sinusoids are replenished by sinusoidal precursors rather than cells from a distant periostic niche. As MKs do not need to migrate to reach the vessel, therapies to increase MK numbers might be sufficient to raise platelet counts.}, language = {en} } @phdthesis{Sprengel2017, author = {Sprengel, Martin}, title = {A Theoretical and Numerical Analysis of a Kohn-Sham Equation and Related Control Problems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153545}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In this work, multi-particle quantum optimal control problems are studied in the framework of time-dependent density functional theory (TDDFT). Quantum control problems are of great importance in both fundamental research and application of atomic and molecular systems. Typical applications are laser induced chemical reactions, nuclear magnetic resonance experiments, and quantum computing. Theoretically, the problem of how to describe a non-relativistic system of multiple particles is solved by the Schr{\"o}dinger equation (SE). However, due to the exponential increase in numerical complexity with the number of particles, it is impossible to directly solve the Schr{\"o}dinger equation for large systems of interest. An efficient and successful approach to overcome this difficulty is the framework of TDDFT and the use of the time-dependent Kohn-Sham (TDKS) equations therein. This is done by replacing the multi-particle SE with a set of nonlinear single-particle Schr{\"o}dinger equations that are coupled through an additional potential. Despite the fact that TDDFT is widely used for physical and quantum chemical calculation and software packages for its use are readily available, its mathematical foundation is still under active development and even fundamental issues remain unproven today. The main purpose of this thesis is to provide a consistent and rigorous setting for the TDKS equations and of the related optimal control problems. In the first part of the thesis, the framework of density functional theory (DFT) and TDDFT are introduced. This includes a detailed presentation of the different functional sets forming DFT. Furthermore, the known equivalence of the TDKS system to the original SE problem is further discussed. To implement the TDDFT framework for multi-particle computations, the TDKS equations provide one of the most successful approaches nowadays. However, only few mathematical results concerning these equations are available and these results do not cover all issues that arise in the formulation of optimal control problems governed by the TDKS model. It is the purpose of the second part of this thesis to address these issues such as higher regularity of TDKS solutions and the case of weaker requirements on external (control) potentials that are instrumental for the formulation of well-posed TDKS control problems. For this purpose, in this work, existence and uniqueness of TDKS solutions are investigated in the Galerkin framework and using energy estimates for the nonlinear TDKS equations. In the third part of this thesis, optimal control problems governed by the TDKS model are formulated and investigated. For this purpose, relevant cost functionals that model the purpose of the control are discussed. Henceforth, TDKS control problems result from the requirement of optimising the given cost functionals subject to the differential constraint given by the TDKS equations. The analysis of these problems is novel and represents one of the main contributions of the present thesis. In particular, existence of minimizers is proved and their characterization by TDKS optimality systems is discussed in detail. To this end, Fr{\´e}chet differentiability of the TDKS model and of the cost functionals is addressed considering \(H^1\) cost of the control. This part is concluded by deriving the reduced gradient in the \(L^2\) and \(H^1\) inner product. While the \(L^2\) optimization is widespread in the literature, the choice of the \(H^1\) gradient is motivated in this work by theoretical consideration and by resulting numerical advantages. The last part of the thesis is devoted to the numerical approximation of the TDKS optimality systems and to their solution by gradient-based optimization techniques. For the former purpose, Strang time-splitting pseudo-spectral schemes are discussed including a review of some recent theoretical estimates for these schemes and a numerical validation of these estimates. For the latter purpose, nonlinear (projected) conjugate gradient methods are implemented and are used to validate the theoretical analysis of this thesis with results of numerical experiments with different cost functional settings.}, subject = {Optimale Kontrolle}, language = {en} } @phdthesis{Spitznagel2017, author = {Spitznagel, Niko}, title = {Energy transfer during molten fuel coolant interaction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142891}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The contact of hot melt with liquid water - called Molten Fuel Coolant Interaction (MFCI) - can result in vivid explosions. Such explosions can occur in different scenarios: in steel or powerplants but also in volcanoes. Because of the possible dramatic consequences of such explosions an investigation of the explosion process is necessary. Fundamental basics of this process are already discovered and explained, such as the frame conditions for these explosions. It has been shown that energy transfer during an MFCI-process can be very high because of the transfer of thermal energy caused by positive feedback mechanisms. Up to now the influence of several varying parameters on the energy transfer and the explosions is not yet investigated sufficiently. An important parameter is the melt temperature, because the amount of possibly transferable energy depends on it. The investigation of this influence is the main aim of this work. Therefor metallic tin melt was used, because of its nearly constant thermal material properties in a wide temperature range. With tin melt research in the temperature range from 400 °C up to 1000 °C are possible. One important result is the lower temperature limit for vapor film stability in the experiments. For low melt temperatures up to about 600 °C the vapor film is so unstable that it already can collapse before the mechanical trigger. As expected the transferred thermal energy all in all increases with higher temperatures. Although this effect sometimes is superposed by other influences such as the premix of melt and water, the result is confirmed after a consequent filtering of the remaining influences. This trend is not only recognizable in the amount of transferred energy, but also in the fragmentation of melt or the vaporizing water. But also the other influences on MFCI-explosions showed interesting results in the frame of this work. To perform the experiments the installation and preparation of the experimental Setup in the laboratory were necessary. In order to compare the results to volcanism and to get a better investigation of the brittle fragmentation of melt additional runs with magmatic melt were made. In the results the thermal power during energy transfer could be estimated. Furthermore the model of "cooling fragments " could be usefully applied.}, subject = {Vulkanologie}, language = {en} } @phdthesis{Spinner2017, author = {Spinner, Simon}, title = {Self-Aware Resource Management in Virtualized Data Centers}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153754}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Enterprise applications in virtualized data centers are often subject to time-varying workloads, i.e., the load intensity and request mix change over time, due to seasonal patterns and trends, or unpredictable bursts in user requests. Varying workloads result in frequently changing resource demands to the underlying hardware infrastructure. Virtualization technologies enable sharing and on-demand allocation of hardware resources between multiple applications. In this context, the resource allocations to virtualized applications should be continuously adapted in an elastic fashion, so that "at each point in time the available resources match the current demand as closely as possible" (Herbst el al., 2013). Autonomic approaches to resource management promise significant increases in resource efficiency while avoiding violations of performance and availability requirements during peak workloads. Traditional approaches for autonomic resource management use threshold-based rules (e.g., Amazon EC2) that execute pre-defined reconfiguration actions when a metric reaches a certain threshold (e.g., high resource utilization or load imbalance). However, many business-critical applications are subject to Service-Level-Objectives defined on an application performance metric (e.g., response time or throughput). To determine thresholds so that the end-to-end application SLO is fulfilled poses a major challenge due to the complex relationship between the resource allocation to an application and the application performance. Furthermore, threshold-based approaches are inherently prone to an oscillating behavior resulting in unnecessary reconfigurations. In order to overcome the deficiencies of threshold-based approaches and enable a fully automated approach to dynamically control the resource allocations of virtualized applications, model-based approaches are required that can predict the impact of a reconfiguration on the application performance in advance. However, existing model-based approaches are severely limited in their learning capabilities. They either require complete performance models of the application as input, or use a pre-identified model structure and only learn certain model parameters from empirical data at run-time. The former requires high manual efforts and deep system knowledge to create the performance models. The latter does not provide the flexibility to capture the specifics of complex and heterogeneous system architectures. This thesis presents a self-aware approach to the resource management in virtualized data centers. In this context, self-aware means that it automatically learns performance models of the application and the virtualized infrastructure and reasons based on these models to autonomically adapt the resource allocations in accordance with given application SLOs. Learning a performance model requires the extraction of the model structure representing the system architecture as well as the estimation of model parameters, such as resource demands. The estimation of resource demands is a key challenge as they cannot be observed directly in most systems. The major scientific contributions of this thesis are: - A reference architecture for online model learning in virtualized systems. Our reference architecture is based on a set of model extraction agents. Each agent focuses on specific tasks to automatically create and update model skeletons capturing its local knowledge of the system and collaborates with other agents to extract the structural parts of a global performance model of the system. We define different agent roles in the reference architecture and propose a model-based collaboration mechanism for the agents. The agents may be bundled within virtual appliances and may be tailored to include knowledge about the software stack deployed in a specific virtual appliance. - An online method for the statistical estimation of resource demands. For a given request processed by an application, the resource time consumed for a specified resource within the system (e.g., CPU or I/O device), referred to as resource demand, is the total average time the resource is busy processing the request. A request could be any unit of work (e.g., web page request, database transaction, batch job) processed by the system. We provide a systematization of existing statistical approaches to resource demand estimation and conduct an extensive experimental comparison to evaluate the accuracy of these approaches. We propose a novel method to automatically select estimation approaches and demonstrate that it increases the robustness and accuracy of the estimated resource demands significantly. - Model-based controllers for autonomic vertical scaling of virtualized applications. We design two controllers based on online model-based reasoning techniques in order to vertically scale applications at run-time in accordance with application SLOs. The controllers exploit the knowledge from the automatically extracted performance models when determining necessary reconfigurations. The first controller adds and removes virtual CPUs to an application depending on the current demand. It uses a layered performance model to also consider the physical resource contention when determining the required resources. The second controller adapts the resource allocations proactively to ensure the availability of the application during workload peaks and avoid reconfiguration during phases of high workload. We demonstrate the applicability of our approach in current virtualized environments and show its effectiveness leading to significant increases in resource efficiency and improvements of the application performance and availability under time-varying workloads. The evaluation of our approach is based on two case studies representative of widely used enterprise applications in virtualized data centers. In our case studies, we were able to reduce the amount of required CPU resources by up to 23\% and the number of reconfigurations by up to 95\% compared to a rule-based approach while ensuring full compliance with application SLO. Furthermore, using workload forecasting techniques we were able to schedule expensive reconfigurations (e.g., changes to the memory size) during phases of load load and thus were able to reduce their impact on application availability by over 80\% while significantly improving application performance compared to a reactive controller. The methods and techniques for resource demand estimation and vertical application scaling were developed and evaluated in close collaboration with VMware and Google.}, subject = {Cloud Computing}, language = {en} } @article{SperlichWallmannSperlichZinneretal.2017, author = {Sperlich, Billy and Wallmann-Sperlich, Birgit and Zinner, Christoph and Von Stauffenberg, Valerie and Losert, Helena and Holmberg, Hans-Christer}, title = {Functional High-intensity Circuit Training Improves Body Composition,Peak Oxygen Uptake, Strength, and Alters Certain Dimensions of Quality of Life in Overweight Women}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {172}, doi = {10.3389/fphys.2017.00172}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171015}, year = {2017}, abstract = {The effects of circuit-like functional high-intensity training (Circuit\(_{HIIT}\)) alone or in combination with high-volume low-intensity exercise (Circuit\(_{combined}\)) on selected cardio-respiratory and metabolic parameters, body composition, functional strength and the quality of life of overweight women were compared. In this single-center, two-armed randomized, controlled study, overweight women performed 9-weeks (3 sessions·wk\(^{-1}\)) of either Circuit\(_{HIIT}\) (n = 11), or Circuit\(_{combined}\) (n = 8). Peak oxygen uptake and perception of physical pain were increased to a greater extent (p < 0.05) by Circuit\(_{HIIT}\), whereas Circuit\(_{combined}\) improved perception of general health more (p < 0.05). Both interventions lowered body mass, body-mass-index, waist-to-hip ratio, fat mass, and enhanced fat-free mass; decreased ratings of perceived exertion during submaximal treadmill running; improved the numbers of push-ups, burpees, one-legged squats, and 30-s skipping performed, as well as the height of counter-movement jumps; and improved physical and social functioning, role of physical limitations, vitality, role of emotional limitations, and mental health to a similar extent (all p < 0.05). Either forms of these multi-stimulating, circuit-like, multiple-joint training can be employed to improve body composition, selected variables of functional strength, and certain dimensions of quality of life in overweight women. However, Circuit\(_{HIIT}\) improves peak oxygen uptake to a greater extent, but with more perception of pain, whereas Circuit\(_{Combined}\) results in better perception of general health.}, language = {en} } @article{SperlichHolmberg2017, author = {Sperlich, Billy and Holmberg, Hans-Christer}, title = {The responses of elite athletes to exercise: an all-day, 24-h integrative view is required!}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {564}, doi = {10.3389/fphys.2017.00564}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158655}, year = {2017}, abstract = {No abstract available.}, language = {en} } @article{SperlichDuekingHolmberg2017, author = {Sperlich, Billy and D{\"u}king, Peter and Holmberg, Hans-Christer}, title = {A SWOT analysis of the use and potential misuse of implantable monitoring devices by athletes}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {629}, doi = {10.3389/fphys.2017.00629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158742}, year = {2017}, abstract = {Kein Abstract vorhanden.}, language = {en} } @article{SperlichBeckerHothoetal.2017, author = {Sperlich, Billy and Becker, Martin and Hotho, Andreas and Wallmann-Sperlich, Birgit and Sareban, Mahdi and Winkert, Kay and Steinacker, J{\"u}rgen M. and Treff, Gunnar}, title = {Sedentary behavior among national elite rowers during off-training — a pilot study}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {655}, doi = {10.3389/fphys.2017.00655}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158753}, year = {2017}, abstract = {The aim of this pilot study was to analyze the off-training physical activity (PA) profile in national elite German U23 rowers during 31 days of their preparation period. The hours spent in each PA category (i.e., sedentary: <1.5 metabolic equivalents (MET); light physical activity: 1.5-3 MET; moderate physical activity: 3-6 MET and vigorous intense physical activity: >6 MET) were calculated for every valid day (i.e., >480 min of wear time). The off-training PA during 21 weekdays and 10 weekend days of the final 11-week preparation period was assessed by the wrist-worn multisensory device Microsoft Band II (MSBII). A total of 11 rowers provided valid data (i.e., >480 min/day) for 11.6 week days and 4.8 weekend days during the 31 days observation period. The average sedentary time was 11.63 ± 1.25 h per day during the week and 12.49 ± 1.10 h per day on the weekend, with a tendency to be higher on the weekend compared to weekdays (p = 0.06; d = 0.73). The average time in light, moderate and vigorous PA during the weekdays was 1.27 ± 1.15, 0.76 ± 0.37, 0.51 ± 0.44 h per day, and 0.67 ± 0.43, 0.59 ± 0.37, 0.53 ± 0.32 h per weekend day. Light physical activity was higher during weekdays compared to the weekend (p = 0.04; d = 0.69). Based on our pilot study of 11 national elite rowers we conclude that rowers display a considerable sedentary off-training behavior of more than 11.5 h/day.}, language = {en} } @phdthesis{Spenst2017, author = {Spenst, Peter}, title = {Xylylene Bridged Perylene Bisimide Cyclophanes and Macrocycles}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139015}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {This work is concerned with the syntheses and photophysical properties of para-xylylene bridged macrocycles nPBI with ring sizes from two to nine PBI units, as well as the complexation of polycyclic aromatic guest compounds. With a reduced but substantial fluorescence quantum yield of 21\% (in CHCl3) the free host 2PBI(4-tBu)4 can be used as a dual fluorescence probe. Upon encapsulation of rather electron-poor guests the fluorescence quenching interactions between the chromophores are prevented, leading to a significant fluorescence enhancement to > 90\% ("turn-on"). On the other hand, the addition of electron-rich guest molecules induces an electron transfer from the guest to the electron-poor PBI chromophores and thus quenches the fluorescence entirely ("turn-off"). The photophysical properties of the host-guest complexes were studied by transient absorption spectroscopy. These measurements revealed that the charge transfer between guest and 2PBI(4-tBu)4 occurs in the "normal region" of the Marcus-parabola with the fastest charge separation rate for perylene. In contrast, the charge recombination back to the PBI ground state lies far in the "inverted region" of the Marcus-parabola. Beside complexation of planar aromatic hydrocarbons into the cavity of the cyclophanes an encapsulation of fullerene into the cyclic trimer 3PBI(4-tBu)4 was observed. 3PBI(4-tBu)4 provides a tube-like structure in which the PBI subunits represent the walls of those tubes. The cavity has the optimal size for hosting fullerenes, with C70 fitting better than C60 and a binding constant that is higher by a factor of 10. TA spectroscopy in toluene that was performed on the C60@3PBI(4-tBu)4 complex revealed two energy transfer processes. The first one comes from the excited PBI to the fullerene, which subsequently populates the triplet state. From the fullerene triplet state a second energy transfer occurs back to the PBI to generate the PBI triplet state. In all cycles that were studied by TA spectroscopy, symmetry-breaking charge separation (SB-CS) was observed in dichloromethane. This process is fastest within the PBI cyclophane 2PBI(4-tBu)4 and slows down for larger cycles, suggesting that the charge separation takes place through space and not through bonds. The charges then recombine to the PBI triplet state via a radical pair intersystem crossing (RP-ISC) mechanism, which could be used to generate singlet oxygen in yields of ~20\%. By changing the solvent to toluene an intramolecular folding of the even-numbered larger cycles was observed that quenches the fluorescence and increases the 0-1 transition band in the absorption spectra. Force field calculations of 4PBI(4-tBu)4 suggested a folding into pairs of dimers, which explains the remarkable odd-even effect with respect to the number of connected PBI chromophores and the resulting alternation in the absorption and fluorescence properties. Thus, the even-numbered macrocycles can fold in a way that all chromophores are in a paired arrangement, while the odd-numbered cycles have open conformations (3PBI(4-tBu)4, 5PBI(4-tBu)4, 7PBI(4-tBu)4) or at least additional unpaired PBI unit (9PBI(4-tBu)4). With these experiments we could for the first time give insights in the interactions between cyclic PBI hosts and aromatic guest molecules. Associated with the encapsulation of guest molecules a variety of possible applications can be envisioned, like fluorescence sensing, chiral recognition and photodynamic therapy by singlet oxygen generation. Particularly, these macrocycles provide photophysical relaxation pathways of PBIs, like charge separation and recombination and triplet state formation that are hardly feasible in monomeric PBI dyes. Furthermore, diverse compound specific features were found, like the odd-even effect in the folding process or the transition of superficial nanostructures of the tetrameric cycle influenced by the AFM tip. The comprehensive properties of these macrocycles provide the basis for further oncoming studies and can serve as an inspiration for the synthesis of new macrocyclic compounds.}, subject = {Supramolekulare Chemie}, language = {en} } @phdthesis{Sonnenberg2017, author = {Sonnenberg, Christoph}, title = {Analyzing Technology-Enhanced Learning Processes: What Can Process Mining Techniques Contribute to the Evaluation of Instructional Support?}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152354}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The current dissertation addresses the analysis of technology-enhanced learning processes by using Process Mining techniques. For this purpose, students' coded think-aloud data served as the measurement of the learning process, in order to assess the potential of this analysis method for evaluating the impact of instructional support. The increasing use of digital media in higher education and further educational sectors enables new potentials. However, it also poses new challenges to students, especially regarding the self-regulation of their learning process. To help students with optimally making progress towards their learning goals, instructional support is provided during learning. Besides the use of questionnaires and tests for the assessment of learning, researchers make use increasingly of process data to evaluate the effects of provided support. The analysis of observed behavioral traces while learning (e.g., log files, eye movements, verbal reports) allows detailed insights into the student's activities as well as the impact of interventions on the learning process. However, new analytical challenges emerge, especially when going beyond the analysis of pure frequencies of observed events. For example, the question how to deal with temporal dynamics and sequences of learning activities arises. Against this background, the current dissertation concentrates on the application of Process Mining techniques for the detailed analysis of learning processes. In particular, the focus is on the additional value of this approach in comparison to a frequency-based analysis, and therefore on the potential of Process Mining for the evaluation of instructional support. An extensive laboratory study with 70 university students, which was conducted to investigate the impact of a support measure, served as the basis for pursuing the research agenda of this dissertation. Metacognitive prompts supported students in the experimental group (n = 35) during a 40-minute hypermedia learning session; whereas the control group (n = 35) received no support. Approximately three weeks later, all students participated in another learning session; however, this time all students learned without any help. The participants were instructed to verbalize their learning activities concurrently while learning. In the three analyses of this dissertation, the coded think aloud data were examined in detail by using frequency-based methods as well as Process Mining techniques. The first analysis addressed the comparison of the learning activities between the experimental and control groups during the first learning session. This study concentrated on the research questions whether metacognitive prompting increases the number of metacognitive learning activities, whether a higher number of these learning activities corresponds with learning outcome (mediation), and which differences regarding the sequential structure of learning activities can be revealed. The second analysis investigated the impact of the individual prompts as well as the conditions of their effectiveness on the micro level. In addition to Process Mining, we used a data mining approach to compare the findings of both analysis methods. More specifically, we classified the prompts by their effectiveness, and we examined the learning activities preceding and following the presentation of instructional support. Finally, the third analysis considered the long-term effects of metacognitive prompting on the learning process during another learning session without support. It was the key objective of this study to examine which fostered learning activities and process patterns remained stable during the second learning session. Overall, all three analyses indicated the additional value of Process Mining in comparison to a frequency-based analysis. Especially when conceptualizing the learning process as a dynamic sequence of multiple activities, Process Mining allows identifying regulatory loops and crucial routing points of the process. These findings might contribute to optimizing intervention strategies. However, before drawing conclusions for the design of instructional support based on the revealed process patterns, additional analyses need to investigate the generalizability of results. Moreover, the application of Process Mining remains challenging because guidelines for analytical decisions and parameter settings in technology-enhanced learning context are currently missing. Therefore, future studies need to examine further the potential of Process Mining as well as related analysis methods to provide researchers with concrete recommendations for use. Nevertheless, the application of Process Mining techniques can already contribute to advance the understanding of the impact of instructional support through the use of fine-grained process data.}, subject = {Selbstgesteuertes Lernen}, language = {en} } @phdthesis{Sommerlandt2017, author = {Sommerlandt, Frank M. J.}, title = {Mechanisms of visual memory formation in bees: About immediate early genes and synaptic plasticity}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136997}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Animals form perceptual associations through processes of learning, and retain that information through mechanisms of memory. Honeybees and bumblebees are classic models for insect perception and learning, and despite their small brains with about one million neurons, they are organized in highly social colonies and possess an astonishing rich behavioral repertoire including navigation, communication and cognition. Honeybees are able to harvest hundreds of morphologically divergent flower types in a quick and efficient manner to gain nutrition and, back in the hive, communicate discovered food sources to nest mates. To accomplish such complex tasks, bees must be equipped with diverse sensory organs receptive to stimuli of different modalities and must be able to associatively learn and memorize the acquired information. Particularly color vision plays a prominent role, e.g. in navigation along landmarks and when bees identify inflorescences by their color signals. Once acquired, bees are known to retain visual information for days or even months. Numerous studies on visual perception and color vision have been conducted in the past decades and largely revealed the information processing pathways in the brain. In contrast, there are no data available on how the brain may change in the course of color learning experience and whether pathways differ for coarse and fine color learning. Although long-term memory (LTM) storage is assumed to generally include reorganization of the neuronal network, to date it is unclear where in the bee brain such changes occur in the course of color learning and whether visual memories are stored in one particular site or decentrally distributed over different brain domains. The present dissertation research aimed to dissect the visual memory trace in bees that is beyond mere stimulus processing and therefore two different approaches were elaborated: first, the application of immediate early genes (IEG) as genetic markers for neuronal activation to localize early processes underlying the formation of a stable LTM. Second, the analysis of late consequences of memory formation, including synaptic reorganization in central brain areas and dependencies of color discrimination complexity. Immediate early genes (IEG) are a group of rapidly and transiently expressed genes that are induced by various types of cellular stimulation. A great number of different IEGs are routinely used as markers for the localization of neuronal activation in vertebrate brains. The present dissertation research was dedicated to establish this approach for application in bees, with focus on the candidate genes Amjra and Amegr, which are orthologous to the two common vertebrate IEGs c-jun and egr-1. First the general requirement of gene transcription for visual LTM formation was proved. Bumblebees were trained in associative proboscis extension response (PER) conditioning to monochromatic light and subsequently injected with an inhibitor of gene transcription. Memory retention tests at different intervals revealed that gene transcription is not required for the formation of a mid-term memory, but for stable LTM. Next, the appliance of the candidate genes was validated. Honeybees were exposed to stimulation with either alarm pheromone or a light pulse, followed by qPCR analysis of gene expression. Both genes differed in their expression response to sensory exposure: Amjra was upregulated in all analyzed brain parts (antennal lobes, optic lobes and mushroom bodies, MB), independent from stimulus modality, suggesting the gene as a genetic marker for unspecific general arousal. In contrast, Amegr was not significantly affected by mere sensory exposure. Therefore, the relevance of associative learning on Amegr expression was assessed. Honeybees were trained in visual PER conditioning followed by a qPCR-based analysis of the expression of all three Amegr isoforms at different intervals after conditioning. No learning-dependent alteration of gene expression was observed. However, the presence of AmEgr protein in virtually all cerebral cell nuclei was validated by immunofluorescence staining. The most prominent immune-reactivity was detected in MB calyx neurons. Analysis of task-dependent neuronal correlates underlying visual long-term memory was conducted in free-flying honeybees confronted with either absolute conditioning to one of two perceptually similar colors or differential conditioning with both colors. Subsequent presentation of the two colors in non-rewarded discrimination tests revealed that only bees trained with differential conditioning preferred the previously learned color. In contrast, bees of the absolute conditioning group chose randomly among color stimuli. To investigate whether the observed difference in memory acquisition is also reflected at the level of synaptic microcircuits, so called microglomeruli (MG), within the visual domains of the MB calyces, MG distribution was quantified by whole-mount immunostaining three days following conditioning. Although learning-dependent differences in neuroarchitecture were absent, a significant correlation between learning performance and MG density was observed. Taken together, this dissertation research provides fundamental work on the potential use of IEGs as markers for neuronal activation and promotes future research approaches combining behaviorally relevant color learning tests in bees with examination of the neuroarchitecture to pave the way for unraveling the visual memory trace.}, subject = {Biene}, language = {en} } @article{Soder2017, author = {Soder, Lisa}, title = {An den Grenzen der Pragmatik}, series = {Zeitschrift f{\"u}r germanistische Linguistik}, volume = {45}, journal = {Zeitschrift f{\"u}r germanistische Linguistik}, number = {3}, issn = {1613-0626}, doi = {10.1515/zgl-2017-0024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195413}, pages = {428-434}, year = {2017}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @phdthesis{Slaby2017, author = {Slaby, Beate Magdalena}, title = {Exploring the microbiome of the Mediterranean sponge \(Aplysina\) \(aerophoba\) by single-cell and metagenomics}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151869}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Sponges (phylum Porifera) are evolutionary ancient, sessile filter-feeders that harbor a largely diverse microbial community within their internal mesohyl matrix. Throughout this thesis project, I aimed at exploring the adaptations of these symbionts to life within their sponge host by sequencing and analyzing the genomes of a variety of bacteria from the microbiome of the Mediterranean sponge Aplysina aerophoba. Employed methods were fluorescence-activated cell sorting with subsequent multiple displacement amplification and single-cell / 'mini-metagenome' sequencing, and metagenomic sequencing followed by differential coverage binning. These two main approaches both aimed at obtaining genome sequences of bacterial symbionts of A. aerophoba, that were then compared to each other and to references from other environments, to gain information on adaptations to the host sponge environment and on possible interactions with the host and within the microbial community. Cyanobacteria are frequent members of the sponge microbial community. My 'mini-metagenome' sequencing project delivered three draft genomes of "Candidatus Synechococcus spongiarum," the cyanobacterial symbiont of A. aerophoba and many more sponges inhabiting the photic zone. The most complete of these genomes was compared to other clades of this symbiont and to closely related free-living cyanobacterial references in a collaborative project published in Burgsdorf I*, Slaby BM* et al. (2015; *shared first authorship). Although the four clades of "Ca. Synechococcus spongiarum" from the four sponge species A. aerophoba, Ircinia variabilis, Theonella swinhoei, and Carteriospongia foliascens were approximately 99\% identical on the level of 16S rRNA gene sequences, they greatly differed on the genomic level. Not only the genome sizes were different from clade to clade, but also the gene content and a number of features including proteins containing the eukaryotic-type domains leucine-rich repeats or tetratricopeptide repeats. On the other hand, the four clades shared a number of features such as ankyrin repeat domain-containing proteins that seemed to be conserved also among other microbial phyla in different sponge hosts and from different geographic locations. A possible novel mechanism for host phagocytosis evasion and phage resistance by means of an altered O antigen of the lipopolysaccharide was identified. To test previous hypotheses on adaptations of sponge-associated bacteria on a broader spectrum of the microbiome of A. aerophoba while also taking a step forward in methodology, I developed a bioinformatic pipeline to combine metagenomic Illumina short-read sequencing data with PacBio long-read data. At the beginning of this project, no pipelines to combine short-read and long-read data for metagenomics were published, and at time of writing, there are still no projects published with a comparable aim of un-targeted assembly, binning and analysis of a metagenome. I tried a variety of assembly programs and settings on a simulated test dataset reflecting the properties of the real metagenomic data. The developed assembly pipeline improved not only the overall assembly statistics, but also the quality of the binned genomes, which was evaluated by comparison to the originally published genome assemblies. The microbiome of A. aerophoba was studied from various angles in the recent years, but only genomes of the candidate phylum Poribacteria and the cyanobacterial sequences from my above-described project have been published to date. By applying my newly developed assembly pipeline to a metagenomic dataset of A. aerophoba consisting of a PacBio long-read dataset and six Illumina short-read datasets optimized for subsequent differential coverage binning, I aimed at sequencing a larger number and greater diversity of symbionts. The results of this project are currently in review by The ISME Journal. The complementation of Illumina short-read with PacBio long-read sequencing data for binning of this highly complex metagenome greatly improved the overall assembly statistics and improved the quality of the binned genomes. Thirty-seven genomes from 13 bacterial phyla and candidate phyla were binned representing the most prominent members of the microbiome of A. aerophoba. A statistical comparison revealed an enrichment of genes involved in restriction modification and toxin-antitoxin systems in most symbiont genomes over selected reference genomes. Both are defense features against incoming foreign DNA, which may be important for sponge symbionts due to the sponge's filtration and phagocytosis activity that exposes the symbionts to high levels of free DNA. Also host colonization and matrix utilization features were significantly enriched. Due to the diversity of the binned symbiont genomes, a within-symbionts genome comparison was possible, that revealed three guilds of symbionts characterized by i) nutritional specialization on the metabolization of carnitine, ii) specialization on sulfated polysaccharides, and iii) apparent nutritional generalism. Both carnitine and sulfated polysaccharides are abundant in the sponge extracellular matrix and therefore available to the sponge symbionts as substrates. In summary, the genomes of the diverse community of symbionts in A. aerophoba were united in their defense features, but specialized regarding their nutritional preferences.}, subject = {Metagenom}, language = {en} } @article{SkryabinKartashovEgorovetal.2017, author = {Skryabin, D.V. and Kartashov, Y.V. and Egorov, O.A. and Sich, M. and Chana, J.K. and Tapia Rodriguez, L.E. and Walker, P.M. and Clarke, E. and Royall, B. and Skolnick, M.S. and Krizhanovskii, D.N.}, title = {Backward Cherenkov radiation emitted by polariton solitons in a microcavity wire}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-01751-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173046}, year = {2017}, abstract = {Exciton-polaritons in semiconductor microcavities form a highly nonlinear platform to study a variety of effects interfacing optical, condensed matter, quantum and statistical physics. We show that the complex polariton patterns generated by picosecond pulses in microcavity wire waveguides can be understood as the Cherenkov radiation emitted by bright polariton solitons, which is enabled by the unique microcavity polariton dispersion, which has momentum intervals with positive and negative group velocities. Unlike in optical fibres and semiconductor waveguides, we observe that the microcavity wire Cherenkov radiation is predominantly emitted with negative group velocity and therefore propagates backwards relative to the propagation direction of the emitting soliton. We have developed a theory of the microcavity wire polariton solitons and of their Cherenkov radiation and conducted a series of experiments, where we have measured polariton-soliton pulse compression, pulse breaking and emission of the backward Cherenkov radiation.}, language = {en} } @phdthesis{Simin2017, author = {Simin, Dmitrij}, title = {Quantum Sensing with Highly Coherent Spin Centers in Silicon Carbide}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156199}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In the present work, the energetic structure and coherence properties of the silicon vacancy point defect in the technologically important material silicon carbide are extensively studied by the optically detected magnetic resonance (ODMR) technique in order to verify its high potential for various quantum applications. In the spin vacancy, unique attributes are arising from the C3v symmetry and the spin-3/2 state, which are not fully described by the standard Hamiltonian of the uniaxial model. Therefore, an advanced Hamiltonian, describing well the appearing phenomena is established and the relevant parameters are experimentally determined. Utilizing these new accomplishments, several quantum metrology techniques are proposed. First, a vector magnetometry scheme, utilizing the appearance of four ODMR lines, allows for simultaneous detection of the magnetic field strength and the tilting angle of the magnetic field from the symmetry axis of the crystal. The second magnetometry protocol utilizes the appearance of energetic level anticrossings (LAC) in the ground state (GS) energy levels. Relying only on the change in photoluminescence in the vicinity of this GSLACs, this all-optical method does not require any radio waves and hence provides a much easier operation with less error sources as for the common magnetometry schemes utilizing quantum points. A similar all-optical method is applied for temperature sensing, utilizing the thermal shift of the zero field splitting and consequently the anticrossing in the excited state (ES). Since the GSLACs show no dependence on temperature, the all-optical magnetometry and thermometry (utilizing the ESLACs) can be conducted subsequently on the same defect. In order to quantify the achievable sensitivity of quantum metrology, as well as to prove the potential of the Si-vacancy in SiC for quantum processing, the coherence properties are investigated by the pulsed ODMR technique. The spin-lattice relaxation time T1 and the spin-spin relaxation time T2 are thoroughly analyzed for their dependence on the external magnetic field and temperature. For actual sensing implementations, it is crucial to obtain the best signal-to-noise ratio without loss in coherence time. Therefore, the irradiation process, by which the defects are created in the crystal, plays a decisive role in the device performance. In the present work, samples irradiated with electrons or neutrons with different fluences and energies, producing different defect densities, are analyzed in regard to their T1 and T2 times at room temperature. Last but not least, a scheme to substantially prolong the T2 coherence time by locking the spin polarization with the dynamic decoupling Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence is applied.}, subject = {Siliciumcarbid}, language = {en} } @article{SilvaVilchesPletinckxLohnertetal.2017, author = {Silva-Vilches, Cinthia and Pletinckx, Katrien and Lohnert, Miriam and Pavlovic, Vladimir and Ashour, Diyaaeldin and John, Vini and Vendelova, Emilia and Kneitz, Susanne and Zhou, Jie and Chen, Rena and Reinheckel, Thomas and Mueller, Thomas D. and Bodem, Jochen and Lutz, Manfred B.}, title = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0178114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158244}, pages = {e0178114}, year = {2017}, abstract = {Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.}, language = {en} } @article{ShityakovRoewerFoersteretal.2017, author = {Shityakov, Sergey and Roewer, Norbert and F{\"o}rster, Carola and Broscheit, Jens-Albert}, title = {In silico modeling of indigo and Tyrian purple single-electron nano-transistors using density functional theory approach}, series = {Nanoscale Research Letters}, volume = {12}, journal = {Nanoscale Research Letters}, number = {439}, doi = {10.1186/s11671-017-2193-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158332}, year = {2017}, abstract = {The purpose of this study was to develop and implement an in silico model of indigoid-based single-electron transistor (SET) nanodevices, which consist of indigoid molecules from natural dye weakly coupled to gold electrodes that function in a Coulomb blockade regime. The electronic properties of the indigoid molecules were investigated using the optimized density-functional theory (DFT) with a continuum model. Higher electron transport characteristics were determined for Tyrian purple, consistent with experimentally derived data. Overall, these results can be used to correctly predict and emphasize the electron transport functions of organic SETs, demonstrating their potential for sustainable nanoelectronics comprising the biodegradable and biocompatible materials.}, language = {en} } @article{ShibanDiemerMuelleretal.2017, author = {Shiban, Youssef and Diemer, Julia and M{\"u}ller, Jana and Br{\"u}tting-Schick, Johanna and Pauli, Paul and M{\"u}hlberger, Andreas}, title = {Diaphragmatic breathing during virtual reality exposure therapy for aviophobia: functional coping strategy or avoidance behavior? A pilot study}, series = {BMC Psychiatry}, volume = {17}, journal = {BMC Psychiatry}, doi = {10.1186/s12888-016-1181-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181007}, pages = {10}, year = {2017}, abstract = {Background: Although there is solid evidence for the efficacy of in vivo and virtual reality (VR) exposure therapy for a specific phobia, there is a significant debate over whether techniques promoting distraction or relaxation have impairing or enhancing effects on treatment outcome. In the present pilot study, we investigated the effect of diaphragmatic breathing (DB) as a relaxation technique during VR exposure treatment. Method: Twenty-nine patients with aviophobia were randomly assigned to VR exposure treatment either with or without diaphragmatic breathing (six cycles per minute). Subjective fear ratings, heart rate and skin conductance were assessed as indicators of fear during both the exposure and the test session one week later. Results: The group that experienced VR exposure combined with diaphragmatic breathing showed a higher tendency to effectively overcome the fear of flying. Psychophysiological measures of fear decreased and self-efficacy increased in both groups with no significant difference between the groups. Conclusions: Our findings indicate that diaphragmatic breathing during VR exposure does not interfere with the treatment outcome and may even enhance treatment effects of VR exposure therapy for aviophobic patients.}, language = {en} } @article{Shehata2017, author = {Shehata, Dahlia}, title = {Eine mannshohe Leier im altbabylonischen Ištar-Ritual aus Mari (FM 3, no. 2)}, series = {Altorientalische Forschungen}, volume = {44}, journal = {Altorientalische Forschungen}, number = {1}, issn = {2196-6761}, doi = {10.1515/aofo-2017-0008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195422}, pages = {68-81}, year = {2017}, abstract = {The Old Babylonian Ištar ritual from Mari (FM 3, no. 2) has been the focus of much discussion since its primary edition in 1938 by G. Dossin. This article offers a new analysis of the passage mentioning the balaĝ-deity Ninigizibara, which leads to identifying this balaĝ as a huge upright lyre as tall as a human played by two persons from both sides. Similar musical instruments are known from Anatolia and Egypt. Especially the Egyptian examples, which are attested only for the time of Echnaton, show striking parallels to the musical performance described in the Old Babylonian Ištar ritual. After discussing the possible background of cultural exchange, this article closes with a revaluation and new interpretation of the term balaĝ.}, language = {de} } @article{SharanFoerstnerEulalioetal.2017, author = {Sharan, Malvika and F{\"o}rstner, Konrad U. and Eulalio, Ana and Vogel, J{\"o}rg}, title = {APRICOT: an integrated computational pipeline for the sequence-based identification and characterization of RNA-binding proteins}, series = {Nucleic Acids Research}, volume = {45}, journal = {Nucleic Acids Research}, number = {11}, doi = {10.1093/nar/gkx137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157963}, pages = {e96}, year = {2017}, abstract = {RNA-binding proteins (RBPs) have been established as core components of several post-transcriptional gene regulation mechanisms. Experimental techniques such as cross-linking and co-immunoprecipitation have enabled the identification of RBPs, RNA-binding domains (RBDs) and their regulatory roles in the eukaryotic species such as human and yeast in large-scale. In contrast, our knowledge of the number and potential diversity of RBPs in bacteria is poorer due to the technical challenges associated with the existing global screening approaches. We introduce APRICOT, a computational pipeline for the sequence-based identification and characterization of proteins using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences using position-specific scoring matrices and Hidden Markov Models of the functional domains and statistically scores them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them by several biological properties. Here we demonstrate the application and adaptability of the pipeline on large-scale protein sets, including the bacterial proteome of Escherichia coli. APRICOT showed better performance on various datasets compared to other existing tools for the sequence-based prediction of RBPs by achieving an average sensitivity and specificity of 0.90 and 0.91 respectively. The command-line tool and its documentation are available at https://pypi.python.org/pypi/bio-apricot.}, language = {en} } @phdthesis{Sharan2017, author = {Sharan, Malvika}, title = {Bio-computational identification and characterization of RNA-binding proteins in bacteria}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153573}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {RNA-binding proteins (RBPs) have been extensively studied in eukaryotes, where they post-transcriptionally regulate many cellular events including RNA transport, translation, and stability. Experimental techniques, such as cross-linking and co-purification followed by either mass spectrometry or RNA sequencing has enabled the identification and characterization of RBPs, their conserved RNA-binding domains (RBDs), and the regulatory roles of these proteins on a genome-wide scale. These developments in quantitative, high-resolution, and high-throughput screening techniques have greatly expanded our understanding of RBPs in human and yeast cells. In contrast, our knowledge of number and potential diversity of RBPs in bacteria is comparatively poor, in part due to the technical challenges associated with existing global screening approaches developed in eukaryotes. Genome- and proteome-wide screening approaches performed in silico may circumvent these technical issues to obtain a broad picture of the RNA interactome of bacteria and identify strong RBP candidates for more detailed experimental study. Here, I report APRICOT ("Analyzing Protein RNA Interaction by Combined Output Technique"), a computational pipeline for the sequence-based identification and characterization of candidate RNA-binding proteins encoded in the genomes of all domains of life using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences of an input proteome using position-specific scoring matrices and hidden Markov models of all conserved domains available in the databases and then statistically score them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them according to functionally relevant structural properties. APRICOT performed better than other existing tools for the sequence-based prediction on the known RBP data sets. The applications and adaptability of the software was demonstrated on several large bacterial RBP data sets including the complete proteome of Salmonella Typhimurium strain SL1344. APRICOT reported 1068 Salmonella proteins as RBP candidates, which were subsequently categorized using the RBDs that have been reported in both eukaryotic and bacterial proteins. A set of 131 strong RBP candidates was selected for experimental confirmation and characterization of RNA-binding activity using RNA co-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) experiments. Based on the relative abundance of transcripts across the RIP-Seq libraries, a catalogue of enriched genes was established for each candidate, which shows the RNA-binding potential of 90\% of these proteins. Furthermore, the direct targets of few of these putative RBPs were validated by means of cross-linking and co-immunoprecipitation (CLIP) experiments. This thesis presents the computational pipeline APRICOT for the global screening of protein primary sequences for potential RBPs in bacteria using RBD information from all kingdoms of life. Furthermore, it provides the first bio-computational resource of putative RBPs in Salmonella, which could now be further studied for their biological and regulatory roles. The command line tool and its documentation are available at https://malvikasharan.github.io/APRICOT/.}, language = {en} } @misc{Shane2017, type = {Master Thesis}, author = {Shane, Nadine}, title = {The Country-of-Origin Effect and its Potential Impact on How German Consumers Perceive Chinese Luxury Goods}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153047}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {This thesis investigates the impact of the country-of-origin effect on Chinese luxury brands which intend to enter the German luxury goods market. By means of a questionnaire and a quantitative analysis, possible threats to Chinese newcomers that derive from an unfavorable country image are illustrated. In fact, the Chinese origin of luxury goods has an impact on German consumers' perception.}, subject = {China}, language = {en} } @article{ShamimMahapatraScappuccietal.2017, author = {Shamim, Saquib and Mahapatra, S. and Scappucci, G. and Klesse, W. M. and Simmons, M. Y. and Ghosh, Arindam}, title = {Dephasing rates for weak localization and universal conductance fluctuations in two dimensional Si: P and Ge: P δ-layers}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {46670}, doi = {10.1038/srep46670}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170934}, year = {2017}, abstract = {We report quantum transport measurements on two dimensional (2D) Si:P and Ge:P δ-layers and compare the inelastic scattering rates relevant for weak localization (WL) and universal conductance fluctuations (UCF) for devices of various doping densities (0.3-2.5 × 10\(^{18}\)m\(^{-2}\)) at low temperatures (0.3-4.2 K). The phase breaking rate extracted experimentally from measurements of WL correction to conductivity and UCF agree well with each other within the entire temperature range. This establishes that WL and UCF, being the outcome of quantum interference phenomena, are governed by the same dephasing rate.}, language = {en} } @article{ShadyElHossaryFouadetal.2017, author = {Shady, Nourhan Hisham and El-Hossary, Ebaa M. and Fouad, Mostafa A. and Gulder, Tobias A. M. and Kamel, Mohamed Salah and Abdelmohsen, Usama Ramadan}, title = {Bioactive natural products of marine sponges from the Genus Hyrtios}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {5}, doi = {10.3390/molecules22050781}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158227}, pages = {781}, year = {2017}, abstract = {Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.}, language = {en} } @phdthesis{Seufert2017, author = {Seufert, Michael Thomas}, title = {Quality of Experience and Access Network Traffic Management of HTTP Adaptive Video Streaming}, issn = {1432-8801}, doi = {10.25972/OPUS-15413}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154131}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The thesis focuses on Quality of Experience (QoE) of HTTP adaptive video streaming (HAS) and traffic management in access networks to improve the QoE of HAS. First, the QoE impact of adaptation parameters and time on layer was investigated with subjective crowdsourcing studies. The results were used to compute a QoE-optimal adaptation strategy for given video and network conditions. This allows video service providers to develop and benchmark improved adaptation logics for HAS. Furthermore, the thesis investigated concepts to monitor video QoE on application and network layer, which can be used by network providers in the QoE-aware traffic management cycle. Moreover, an analytic and simulative performance evaluation of QoE-aware traffic management on a bottleneck link was conducted. Finally, the thesis investigated socially-aware traffic management for HAS via Wi-Fi offloading of mobile HAS flows. A model for the distribution of public Wi-Fi hotspots and a platform for socially-aware traffic management on private home routers was presented. A simulative performance evaluation investigated the impact of Wi-Fi offloading on the QoE and energy consumption of mobile HAS.}, subject = {Quality of Experience}, language = {en} } @article{SelchoMillanPalaciosMunozetal.2017, author = {Selcho, Mareike and Mill{\´a}n, Carola and Palacios-Mu{\~n}oz, Angelina and Ruf, Franziska and Ubillo, Lilian and Chen, Jiangtian and Bergmann, Gregor and Ito, Chihiro and Silva, Valeria and Wegener, Christian and Ewer, John}, title = {Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, number = {15563}, doi = {10.1038/ncomms15563}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170831}, year = {2017}, abstract = {Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals.}, language = {en} } @article{SeherLaglerStuehmeretal.2017, author = {Seher, Axel and Lagler, Charlotte and St{\"u}hmer, Thorsten and M{\"u}ller-Richter, Urs Dietmar Achim and K{\"u}bler, Alexander Christian and Sebald, Walter and M{\"u}ller, Thomas Dieter and Nickel, Joachim}, title = {Utilizing BMP-2 muteins for treatment of multiple myeloma}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0174884}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158144}, pages = {e0174884}, year = {2017}, abstract = {Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies.}, language = {en} } @article{SchoeneggeGallionPicardetal.2017, author = {Sch{\"o}negge, Anne-Marie and Gallion, Jonathan and Picard, Louis-Philippe and Wilkins, Angela D. and Le Gouill, Christian and Audet, Martin and Stallaert, Wayne and Lohse, Martin J. and Kimmel, Marek and Lichtarge, Olivier and Bouvier, Michel}, title = {Evolutionary action and structural basis of the allosteric switch controlling β\(_2\)AR functional selectivity}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-02257-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172268}, year = {2017}, abstract = {Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β\(_2\)-adrenergic receptor reveals three clearly distinct phenotypical clusters, showing selective impairments of either the Gi or βarrestin/endocytosis pathways with no effect on Gs activation. Robustness of the results is confirmed using simulation-based error propagation. The structural changes resulting from functionally biasing mutations centered around the DRY, NPxxY, and PIF motifs, selectively linking these micro-switches to unique signaling profiles. Our data identify different receptor regions that are important for the stabilization of distinct conformations underlying functional selectivity.}, language = {en} } @article{SchaeferBauerDonhauseretal.2017, author = {Sch{\"a}fer, Kristina and Bauer, Boris and Donhauser, Julian and Kerstan, Andreas and Hamm, Henning}, title = {Becker Naevus Syndrome of the Lower Body: A New Case and Review of the Literature}, series = {Acta Dermato-Venereologica}, volume = {97}, journal = {Acta Dermato-Venereologica}, number = {4}, doi = {10.2340/00015555-2589}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171057}, pages = {499-504}, year = {2017}, abstract = {Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co-occurrence of a Becker naevus with various cutaneous, muscular and skeletal anomalies. In the majority of cases, abnormalities exclusively consist of ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus reaching from the left buttock to the left calf verified on histological examination. In addition, there was marked hypoplasia of the fatty tissue of the left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of the fatty tissue of the left gluteal area. Underlying muscles and bones were not affected. There was no difference in leg lengths. In addition, we review and discuss the features of Becker naevus syndrome with emphasis on 10 reported cases with involvement of the lower body.}, language = {en} } @article{Schaefer2017, author = {Sch{\"a}fer, Elena}, title = {Veo veo. ?'Qu{\´e} ves? Durch H{\"o}r-Seh-Verstehen zu Mehrsprachigkeitskompetenz}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {3}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, issn = {2510-2613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172946}, pages = {183-201}, year = {2017}, abstract = {Multilingualism is part of our everyday lives and has recently entered the medium of film. Based on the linguistic diversity of Spanish-speaking countries, the present paper explores multilingualism as a key competence of foreign language learning. Since film provides students with audiovisual access to multilingual situations, a selection of educational videos that form parts of German textbooks will be critically explored concerning the presentation of multilingual phenomena. The results will be discussed in order to contribute to the systematic acquisition of multilingual skills in the sense of language and cultural awareness during classroom learning.}, language = {de} } @book{Schwemmer2017, author = {Schwemmer, Marius}, title = {Studien zu Genealogie, Biographie und Werk von Joseph Willibald Michl (1745-1816)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145271}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {„Joseph Willibald Michl - Ein Komponist von vielem Kopfe", so schrieb einst Christian Friedrich Daniel Schubart {\"u}ber den wohl bedeutendsten Spross einer Musikerfamilie, die {\"u}ber mindestens vier Generationen das Musikgeschehen der Oberpfalz, Bayerns und dar{\"u}ber hinaus mitgestaltete. Neben dem deutschen Dichter, Organisten, Komponisten und Journalisten Schubart, sprechen sich auch andere Zeitgenossen wie der englische Musikforscher Charles Burney oder der Historiker und Schriftsteller Lorenz von Westenrieder sprechen sich lobend {\"u}ber den „Churf{\"u}rstlichen Kammer-Compositeur" von Maximilian III. Joseph aus. Diese Studie untersucht die Genealogie, die Biographie und das Werk von Joseph Willibald Michl anhand neuer Quellen und schließt dar{\"u}ber hinaus L{\"u}cken in seinem Curriculum Vitae. Erstmals wird ein systematisch-thematisches Werkverzeichnis des Komponisten vorgelegt, um das heute noch greifbare musikalische Œuvre zu erfassen bzw. zur Kl{\"a}rung fraglicher oder offensichtlicher Falschzuweisungen beizutragen. In einer Analyse repr{\"a}sentativ ausgew{\"a}hlter Werke der von Michl verwenden musikalischen Gattungen wird die Kompositionsart und Musiksprache Michls n{\"a}her betrachtet}, subject = {Michl, Joseph Willibald}, language = {de} } @article{SchwabMeeuwsenEhlickeetal.2017, author = {Schwab, Andrea and Meeuwsen, Annick and Ehlicke, Franziska and Hansmann, Jan and Mulder, Lars and Smits, Anthal and Walles, Heike and Kock, Linda}, title = {Ex vivo culture platform for assessment of cartilage repair treatment strategies}, series = {ALTEX - Alternatives to animal experimentation}, volume = {34}, journal = {ALTEX - Alternatives to animal experimentation}, number = {2}, doi = {10.14573/altex.1607111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181665}, pages = {267-277}, year = {2017}, abstract = {There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors pecific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we valuated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, atrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivotesting.}, language = {en} } @phdthesis{Schwab2017, author = {Schwab, Andrea}, title = {Development of an osteochondral cartilage defect model}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155617}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The limited intrinsic self-healing capability of articular cartilage requires treatment of cartilage defects. Material assisted and cell based therapies are in clinical practice but tend to result in formation of mechanical inferior fibro-cartilage in long term follow up. If a lesion has not been properly restored degenerative diseases are diagnosed as late sequela causing pain and loss in morbidity. Complex three dimensional tissue models mimicking physiological situation allow investigation of cartilage metabolism and mechanisms involved in repair. A standardized and reproducible model cultured under controllable conditions ex vivo to maintain tissue properties is of relevance for comparable studies. Topic of this thesis was the establishment of an cartilage defect model that allows for testing novel biomaterials and investigate the effect of defined defect depths on formation of repair tissue. In part I an ex vivo osteochondral defect model was established based on isolation of porcine osteochondral explants (OCE) from medial condyles, 8 mm in diameter and 5 mm in height. Full thickness cartilage defects with 1 mm to 4 mm in diameter were created to define ex vivo cartilage critical size after 28 days culture with custom developed static culture device. In part II of this thesis hydrogel materials, namely collagen I isolated from rat tail, commercially available fibrin glue, matrix-metalloproteinase clevable poly(ethylene glycol) polymerized with heparin (starPEGh), methacrylated poly(N-(2-hydroxypropyl) methacrylamide mono-dilactate-poly(ethylene glycol) triblock copolymer/methacrylated hyaluronic acid (MP/HA), thiol functionalized HA/allyl functionalized poly(glycidol) (P(AGE/G)-HA-SH), were tested cell free and chondrocyte loaded (20 mio/ml) as implant in 4 mm cartilage defects to investigate cartilage regeneration. Reproducible chondral defects, 8 mm in diameter and 1 mm in height, were generated with an artificial tissue cutter (ARTcut®) to investigate effect of defect depth on defect regeneration in part III. In all approaches OCE were analyzed by Safranin-O staining to visualize proteoglycans in cartilage and/or hydrogels. Immuno-histological and -fluorescent stainings (aggrecan, collagen II, VI and X, proCollagen I, SOX9, RUNX2), gene expression analysis (aggrecan, collagen II and X, SOX9, RUNX2) of chondrocyte loaded hydrogels (part II) and proteoglycan and DNA content (Part I \& II) were performed for detailed analysis of cartilage regeneration. Part I: The development of custom made static culture device, consisting of inserts in which OCE is fixed and deep well plate, allowed tissue specific media supply without supplementation of TGF � . Critical size diameter was defined to be 4 mm. Part II: Biomaterials revealed differences in cartilage regeneration. Collagen I and fibrin glue showed presence of cells migrated from OCE into cell free hydrogels with indication of fibrous tissue formation by presence of proCollagen I. In chondrocyte loaded study cartilage matrix proteins aggrecan, collagen II and VI and transcription factor SOX9 were detected after ex vivo culture throughout the two natural hydrogels collagen I and fibrin glue whereas markers were localized in pericellular matrix in starPEGh. Weak stainings resulted for MP/HA and P(AGE/G)-HA-SH in some cell clusters. Gene expression data and proteoglycan quantification supported histological findings with tendency of hypertrophy indicated by upregulation of collagen X and RunX2 in MP/HA and P(AGE/G)-HA-SH. Part III: In life-dead stainings recruitment of cells from OCE into empty or cell free collagen I treated chondral defects was seen. Separated and tissue specific media supply is critical to maintain ECM composition in cartilage. Presence of OCE stimulates cartilage matrix synthesis in chondrocyte loaded collagen I hydrogel and reduces hypertrophy compared to free swelling conditions and pellet cultures. Differences in cartilage repair tissue formation resulted in preference of natural derived polymers compared to synthetic based materials. The ex vivo cartilage defect model represents a platform for testing novel hydrogels as cartilage materials, but also to investigate the effect of cell seeding densities, cell gradients, cell co-cultures on defect regeneration dependent on defect depth. The separated media compartments allow for systematic analysis of pharmaceutics, media components or inflammatory cytokines on bone and cartilage metabolism and matrix stability.}, subject = {Hyaliner Knorpel}, language = {en} } @article{SchusterKruegerSubotaetal.2017, author = {Schuster, Sarah and Kr{\"u}ger, Timothy and Subota, Ines and Thusek, Sina and Rotureau, Brice and Beilhack, Andreas and Engstler, Markus}, title = {Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system}, series = {eLife}, volume = {6}, journal = {eLife}, doi = {10.7554/eLife.27656}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158662}, pages = {e27656}, year = {2017}, abstract = {The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture. Multicolour light sheet fluorescence microscopy provided information about tsetse tissue topology with unprecedented resolution and allowed the first 3D analysis of the infection process. High-speed fluorescence microscopy illuminated the versatile behaviour of trypanosome developmental stages, ranging from solitary motion and near-wall swimming to collective motility in synchronised swarms and in confinement. We correlate the microenvironments and trypanosome morphologies to high-speed motility data, which paves the way for cross-disciplinary microswimmer research in a naturally evolved environment.}, language = {en} } @article{SchulzRuppertHermsetal.2017, author = {Schulz, Herbert and Ruppert, Ann-Kathrin and Herms, Stefan and Wolf, Christiane and Mirza-Schreiber, Nazanin and Stegle, Oliver and Czamara, Darina and Forstner, Andreas J. and Sivalingam, Sugirthan and Schoch, Susanne and Moebus, Susanne and P{\"u}tz, Benno and Hillmer, Axel and Fricker, Nadine and Vatter, Hartmut and M{\"u}ller-Myhsok, Bertram and N{\"o}then, Markus M. and Becker, Albert J. and Hoffmann, Per and Sander, Thomas and Cichon, Sven}, title = {Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-01818-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173168}, year = {2017}, abstract = {Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.}, language = {en} } @article{SchuhmannLanghauserKraftetal.2017, author = {Schuhmann, Michael K. and Langhauser, Friederike and Kraft, Peter and Kleinschnitz, Christoph}, title = {B cells do not have a major pathophysiologic role in acute ischemic stroke in mice}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {112}, doi = {10.1186/s12974-017-0890-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158155}, year = {2017}, abstract = {Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. Methods Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD\(^{-/-}\) mice and Rag1\(^{-/-}\) mice 24 h after adoptive B cell transfer. Stroke outcome was assessed at days 1 and 3. Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated. The local inflammatory response was determined by real-time PCR and immunohistochemistry. Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot. Results Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke. Additionally, lack of circulating B cells in JHD\(^{-/-}\) mice also failed to influence stroke outcome at days 1 and 3. Furthermore, reconstitution of Rag1\(^{-/-}\) mice with B cells had no influence on infarct volumes. Conclusion Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase. Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke.}, language = {en} } @article{SchuhmannGuthmannStolletal.2017, author = {Schuhmann, Michael K. and Guthmann, Josua and Stoll, Guido and Nieswandt, Bernhard and Kraft, Peter and Kleinschnitz, Christoph}, title = {Blocking of platelet glycoprotein receptor Ib reduces "thrombo-inflammation" in mice with acute ischemic stroke}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {18}, doi = {10.1186/s12974-017-0792-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157582}, year = {2017}, abstract = {Background: Ischemic stroke causes a strong inflammatory response that includes T cells, monocytes/macrophages, and neutrophils. Interaction of these immune cells with platelets and endothelial cells facilitates microvascular dysfunction and leads to secondary infarct growth. We recently showed that blocking of platelet glycoprotein (GP) receptor Ib improves stroke outcome without increasing the risk of intracerebral hemorrhage. Until now, it has been unclear whether GPIb only mediates thrombus formation or also contributes to the pathophysiology of local inflammation. Methods: Focal cerebral ischemia was induced in C57BL/6 mice by a 60-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab). Rat immunoglobulin G (IgG) Fab was used as control treatment. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 1 after tMCAO. Results: Blocking of GPIb reduced stroke size and improved functional outcome on day 1 after tMCAO without increasing the risk of intracerebral hemorrhage. As expected, disruption of GPIb-mediated pathways in platelets significantly reduced thrombus burden in the cerebral microvasculature. In addition, inhibition of GPIb limited the local inflammatory response in the ischemic brain as indicated by lower numbers of infiltrating T cells and macrophages and lower expression levels of inflammatory cytokines compared with rat IgG Fab-treated controls. Conclusion: In acute ischemic stroke, thrombus formation and inflammation are closely intertwined ("thrombo-inflammation"). Blocking of platelet GPIb can ameliorate thrombo-inflammation.}, language = {en} } @article{SchuhmannFluri2017, author = {Schuhmann, Michael K. and Fluri, Felix}, title = {Effects of fullerenols on mouse brain microvascular endothelial cells}, series = {International Journal of Molecular Sciences}, volume = {18}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms18081783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158072}, year = {2017}, abstract = {Fullerenols, water-soluble C60-fullerene derivatives, have been shown to exert neuroprotective effects in vitro and in vivo, most likely due to their capability to scavenge free radicals. However, little is known about the effects of fullerenols on the blood-brain barrier (BBB), especially on cerebral endothelial cells under inflammatory conditions. Here, we investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood-brain barrier (BBB) properties in vitro. While fullerenols (1, 10, and 100 µg/mL) did not change transendothelial electrical resistance under basal and inflammatory conditions, 100 µg/mL of fullerenol significantly reduced erk1/2 activation and resulted in an activation of NFκB in an inflammatory milieu. Our findings suggest that fullerenols might counteract oxidative stress via the erk1/2 and NFκB pathways, and thus are able to protect microvascular endothelial cells under inflammatory conditions.}, language = {en} } @article{SchubertKoernerLindauetal.2017, author = {Schubert, Lisa and K{\"o}rner, Anita and Lindau, Berit and Strack, Fritz and Topolinski, Sascha}, title = {Open-Minded Midwifes, Literate Butchers, and Greedy Hooligans - The Independent Contributions of Stereotype Valence and Consistency on Evaluative Judgments}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {1723}, doi = {10.3389/fpsyg.2017.01723}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170222}, year = {2017}, abstract = {Do people evaluate an open-minded midwife less positively than a caring midwife? Both open-minded and caring are generally seen as positive attributes. However, consistency varies—the attribute caring is consistent with the midwife stereotype while open-minded is not. In general, both stimulus valence and consistency can influence evaluations. Six experiments investigated the respective influence of valence and consistency on evaluative judgments in the domain of stereotyping. In an impression formation paradigm, valence and consistency of stereotypic information about target persons were manipulated orthogonally and spontaneous evaluations of these target persons were measured. Valence reliably influenced evaluations. However, for strongly valenced stereotypes, no effect of consistency was observed. Parameters possibly preventing the occurrence of consistency effects were ruled out, specifically, valence of inconsistent attributes, processing priority of category information, and impression formation instructions. However, consistency had subtle effects on evaluative judgments if the information about a target person was not strongly valenced and experimental conditions were optimal. Concluding, in principle, both stereotype valence and consistency can play a role in evaluative judgments of stereotypic target persons. However, the more subtle influence of consistency does not seem to substantially influence evaluations of stereotyped target persons. Implications for fluency research and stereotype disconfirmation are discussed.}, language = {en} } @phdthesis{Schubert2017, author = {Schubert, Anna-Lena}, title = {Untersuchung potenzieller Biomarker in Haut- und Nervenbiopsaten von Patienten mit schmerzhaften und schmerzlosen Polyneuropathien}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153254}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Polyneuropathien sind eine {\"a}tiologisch heterogene Erkrankung des peripheren Nervensystems. In bis zu 30\% der F{\"a}lle ist eine Zuordnung zu einem bestimmten PNP Subtyp auch nach aufw{\"a}ndiger und zum Teil invasiver Diagnostik nicht m{\"o}glich. Bislang fehlt ein diagnostischer Biomarker bei PNP, der z.B. bei der Unterscheidung zwischen einzelnen diagnostischen Subgruppen oder entz{\"u}ndlichen und nicht-entz{\"u}ndlichen Erkrankungsformen helfen k{\"o}nnte. In einer prospektiven Studie mit insgesamt 97 Patienten mit Neuropathien verschiedenster {\"A}tiologie und 17 gesunden Kontrollpersonen erstellten wir Genexpressionsprofile von inflammatorischen Markern und Markern der Regeneration peripherer Nerven in Haut- und N. suralis-Biopsaten. Es wurden Inflammationsmarker (TAC1, CRMP2, AIF1, IL-6) und Marker, die in die Regeneration peripherer Nerven involviert sind (SCD, Netrin-1, DCC, UNC5H2, NEO1, Netrin-G1, Netrin-G2), mittels qRT-PCR untersucht. Alle Patienten erhielten eine N. suralis-Biopsie und/oder eine Hautbiopsie von Ober- beziehungsweise Unterschenkel. Weder in den Haut- noch in den N. suralis-Biopsaten konnten Unterschiede in der Genexpression dieser Marker zwischen einzelnen diagnostischen Subgruppen gefunden werden. Der Inflammationsmarker AIF1 war jedoch in Patienten-Hautproben sowohl proximal als auch distal h{\"o}her exprimiert als bei gesunden Kontrollpersonen (p < 0,05 bzw. p < 0,01). Zudem fand sich in den Hautproben von PNP-Patienten eine deutlich reduzierte Genexpression von Regenerationsmarkern aus der Netrin-Familie verglichen mit den Hautproben gesunder Probanden (Netrin-1, DCC, UNC5H2, NEO1 sowie Netrin-G1 und G2; p < 0,05 bis p < 0,001). Ferner wies Netrin-1 in distalen Hautproben bei Patienten mit einer entz{\"u}ndlichen PNP eine niedrigere Genexpression auf, als bei Patienten mit einer nicht-entz{\"u}ndlichen Erkrankungsform (p < 0,05). Die Genexpression von NEO1 in distalen Hautproben war bei schmerzloser PNP und gesunden Kontrollpersonen h{\"o}her als bei schmerzhafter PNP (p < 0,05). Sowohl eine Erh{\"o}hung bestimmter Inflammationsmarker als auch eine Verminderung von Regenerationsmarkern peripherer Nerven k{\"o}nnen bei der Pathophysiologie von Polyneuropathien involviert sein. Insbesondere Mitglieder der Netrin-Familie scheinen eine komplexe Rolle f{\"u}r das Axonwachstum, jedoch auch f{\"u}r entz{\"u}ndliche Prozesse zu spielen.}, subject = {Biomarker}, language = {de} } @misc{Schroeder2017, author = {Schr{\"o}der, Lina}, title = {Christoph Bernhardt, Im Spiegel des Wassers. Eine transnationale Umweltgeschichte des Oberrheins (1800-2000). (Umwelthistorische Forschungen, Bd. 5.) K{\"o}ln/Weimar/Wien, B{\"o}hlau 2016}, series = {Historische Zeitschrift}, volume = {305}, journal = {Historische Zeitschrift}, number = {2}, issn = {2196-680X}, doi = {10.1515/hzhz-2017-1429}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195388}, pages = {565-567}, year = {2017}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{ScholzGuanNieberleretal.2017, author = {Scholz, Nicole and Guan, Chonglin and Nieberler, Matthias and Grotmeyer, Alexander and Maiellaro, Isabella and Gao, Shiqiang and Beck, Sebastian and Pawlak, Matthias and Sauer, Markus and Asan, Esther and Rothemund, Sven and Winkler, Jana and Pr{\"o}mel, Simone and Nagel, Georg and Langenhan, Tobias and Kittel, Robert J}, title = {Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons}, series = {eLife}, volume = {6}, journal = {eLife}, number = {e28360}, doi = {10.7554/eLife.28360}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170520}, year = {2017}, abstract = {Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.}, language = {en} } @phdthesis{Scholz2017, author = {Scholz, Nicole}, title = {Genetic analyses of sensory and motoneuron physiology in Drosophila melanogaster}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123249}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {During my PhD I studied two principal biological aspects employing Drosophila melanogaster. Therefore, this study is divided into Part I and II. Part I: Bruchpilot and Complexin interact to regulate synaptic vesicle tethering to the active zone cytomatrix At the presynaptic active zone (AZ) synaptic vesicles (SVs) are often physically linked to an electron-dense cytomatrix - a process referred to as "SV tethering". This process serves to concentrate SVs in close proximity to their release sites before contacting the SNARE complex for subsequent fusion (Hallermann and Silver, 2013). In Drosophila, the AZ protein Bruchpilot (BRP) is part of the proteinous cytomatrix at which SVs accumulate (Kittel et al., 2006b; Wagh et al., 2006; Fouquet et al., 2009). Intriguingly, truncation of only 1\% of the C-terminal region of BRP results in a severe defect in SV tethering to this AZ scaffold (hence named brpnude; Hallermann et al., 2010b). Consistent with these findings, cell-specific overexpression of a C-terminal BRP fragment, named mBRPC-tip (corresponds to 1\% absent in brpnude; m = mobile) phenocopied the brpnude mutant in behavioral and functional experiments. These data indicate that mBRPC-tip suffices to saturate putative SV binding sites, which induced a functional tethering deficit at motoneuronal AZs. However, the molecular identity of the BRP complement to tether SVs to the presynaptic AZ scaffold remains unknown. Moreover, within larval motoneurons membrane-attached C-terminal portions of BRP were sufficient to tether SVs to sites outside of the AZ. Based on this finding a genetic screen was designed to identify BRP interactors in vivo. This screen identified Complexin (CPX), which is known to inhibit spontaneous SV fusion and to enhance stimulus evoked SV release (Huntwork and Littleton, 2007; Cho et al., 2010; Martin et al., 2011). However, so far CPX has not been associated with a function upstream of priming/docking and release of SVs. This work provides morphological and functional evidence, which suggests that CPX promotes recruitment of SVs to the AZ and thereby curtails synaptic short-term depression. Together, the presented findings indicate a functional interaction between BRP and CPX at Drosophila AZs. Part II: The Adhesion-GPCR Latrophilin/CIRL shapes mechanosensation The calcium independent receptor of α-latrotoxin (CIRL), also named Latrophilin, represents a prototypic Adhesion class G-protein coupled-receptor (aGPCR). Initially, Latrophilin was identified based on its capacity to bind the α-component of latrotoxin (α-LTX; Davletov et al., 1996; Krasnoperov et al., 1996), which triggers massive exocytotic activity from neurons of the peripheral nervous system (Scheer et al., 1984; Umbach et al., 1998; Orlova et al., 2000). As a result Latrophilin is considered to play a role in synaptic transmission. Later on, Latrophilins have been associated with other biological processes including tissue polarity (Langenhan et al., 2009), fertility (Pr{\"o}mel et al., 2012) and synaptogenesis (Silva et al., 2011). However, thus far its subcellular localization and the identity of endogenous ligands, two aspects crucial for the comprehension of Latrophilin's in vivo function, remain enigmatic. Drosophila contains only one latrophilin homolog, named dCirl, whose function has not been investigated thus far. This study demonstrates abundant dCirl expression throughout the nervous system of Drosophila larvae. dCirlKO animals are viable and display no defects in development and neuronal differentiation. However, dCirl appears to influence the dimension of the postsynaptic sub-synaptic reticulum (SSR), which was accompanied by an increase in the postsynaptic Discs-large abundance (DLG). In contrast, morphological and functional properties of presynaptic motoneurons were not compromised by the removal of dCirl. Instead, dCirl is required for the perception of mechanical challenges (acoustic-, tactile- and proprioceptive stimuli) through specialized mechanosensory devices, chordotonal organs (Eberl, 1999). The data indicate that dCirl modulates the sensitivity of chordotonal neurons towards mechanical stimulation and thereby adjusts their input-output relation. Genetic interaction analyses suggest that adaption of the molecular mechanotransduction machinery by dCirl may underlie this process. Together, these results uncover an unexpected function of Latrophilin/dCIRL in mechanosensation and imply general modulatory roles of aGPCR in mechanoception.}, subject = {Drosophila}, language = {en} } @phdthesis{Scholz2017, author = {Scholz, Franca}, title = {Einfluss verschiedener Untersuchungsbedingugen auf die Messwerte der bioelektrischen Impedanzanalyse (EULE)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156032}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {HINTERGRUND. In zahlreichen epidemiologischen Studien, so auch in der bev{\"o}lkerungsbasierten W{\"u}rzburger Kohortenstudie STAAB (STAdien A und B der Herzinsuffizienz) mit prim{\"a}ren kardiologischen Fragestellungen, wird die K{\"o}rperzusammensetzung mittels bioelektrischer Impedanzanalyse (BIA) gemessen. In einer Pilotstudie wurden das Messprotokoll und die Reproduzierbarkeit der Messungen {\"u}berpr{\"u}ft. Außerdem wurde untersucht, wie sich die Verletzung bestimmter Protokollvorschriften (Messung am n{\"u}chternen Probanden im Ruhezustand) verzerrend auf die Messwerte auswirken. METHODEN. Die Probanden (16 M{\"a}nner, 18 Frauen) waren vollj{\"a}hrig, hatten keine mit dem Protokoll unvertr{\"a}glichen Erkrankungen oder Medikationen und erteilten ihre schriftliche informierte Einwilligung. In sechs konsekutiven BIA-Messungen wurden mittels Seca® mBCA 515 fettfreie Masse, Muskelmasse, Fettmasse, Fettanteil, Gesamtk{\"o}rperwasser und extrazellul{\"a}res Wasser unter verschiedenen Bedingungen bestimmt. Zun{\"a}chst wurden unter den vorgeschriebenen Standardbedingungen zwei direkt aufeinander folgende Messungen durchgef{\"u}hrt, zwischen denen die Probanden das Ger{\"a}t verließen. Die dritte Messung erfolgte unmittelbar nach dem Trinken von 500mL Mineralwasser, die vierte nach 20-30min Wartezeit. Anschließend unterzogen sich die Probanden unterzogen einer k{\"o}rperlichen Belastung (Laufen im Stand, Springen, Kniebeugen) bis zum Einsetzen einer deutlichen Schweißproduktion. Die f{\"u}nfte BIA-Messung erfolgte im unmittelbaren Anschluss an die Belastung, die sechste nach weiteren 5min Ruhepause. ERGEBNISSE. Die beiden unter Standardbedingungen durchgef{\"u}hrten Messungen lieferten bei den Probanden jeweils fast identische Werte. Die Wasseraufnahme wurde vom Ger{\"a}t bei M{\"a}nnern nur marginal (+100g), bei Frauen gar nicht als solche registriert. Vielmehr wurde eine signifikante Zunahme der Fettmasse angezeigt (M{\"a}nner +300g, Frauen +500g, siehe Abbildung). Die Fehlzuordnung des aufgenommenen Wassers verschob sich nach der Wartezeit nur geringf{\"u}gig. Nach der k{\"o}rperlichen Belastung wurde bei den M{\"a}nnern eine gestiegene Fettmasse gemessen (+400g, siehe Abbildung), die sich nach der kurzen Ruhepause wieder reduzierte (-300g), w{\"a}hrend sich die angezeigte K{\"o}rperwassermasse genau gegenl{\"a}ufig verhielt. Bei den Frauen waren die Ver{\"a}nderungen unter Belastung und nach der Ruhepause geringf{\"u}gig. Die Verlaufsprofile der Geschlechter unterschieden sich in allen Messvariablen signifikant (Interaktionstest). SCHLUSSFOLGERUNG. Die Messwerte des BIA-Ger{\"a}ts sind unter den definierten Standardbedingungen gut reproduzierbar. Die experimentellen Ver{\"a}nderungen der Protokollstandards simulierten allt{\"a}glich vorkommende Einflussfaktoren wie Wasserzufuhr oder k{\"o}rperliche Belastung kurz vor der Untersuchung. Die Ergebnisse zeigen, dass die Nichteinhaltung der Standards zu messbaren Verzerrungen f{\"u}hren. Dies ist umso gravierender, da die Verzerrungen in den vom Ger{\"a}t angezeigten Messwerten physikalisch nicht ihren kausalen Ursachen entsprechen und zudem bei den Geschlechtern verschieden ausgepr{\"a}gt sind. Vor dem Hintergrund dieser Ergebnisse sollten bei der epidemiologischen Interpretation statistischer Zusammenh{\"a}nge von BIA-Werten mit anderen Messgr{\"o}ßen auch immer die m{\"o}glichen Auswirkungen fehlerhafter Zuordnung von K{\"o}rperanteilen kritisch gepr{\"u}ft und er{\"o}rtert werden.}, subject = {Impedanzmessung}, language = {de} } @article{SchneiderNiklas2017, author = {Schneider, Wolfgang and Niklas, Frank}, title = {Intelligence and verbal short-term memory/working memory: their interrelationships from childhood to young adulthood and their impact on academic achievement}, series = {Journal of Intelligence}, volume = {5}, journal = {Journal of Intelligence}, number = {2}, issn = {2079-3200}, doi = {10.3390/jintelligence5020026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198004}, pages = {26}, year = {2017}, abstract = {Although recent developmental studies exploring the predictive power of intelligence and working memory (WM) for educational achievement in children have provided evidence for the importance of both variables, findings concerning the relative impact of IQ and WM on achievement have been inconsistent. Whereas IQ has been identified as the major predictor variable in a few studies, results from several other developmental investigations suggest that WM may be the stronger predictor of academic achievement. In the present study, data from the Munich Longitudinal Study on the Genesis of Individual Competencies (LOGIC) were used to explore this issue further. The secondary data analysis included data from about 200 participants whose IQ and WM was first assessed at the age of six and repeatedly measured until the ages of 18 and 23. Measures of reading, spelling, and math were also repeatedly assessed for this age range. Both regression analyses based on observed variables and latent variable structural equation modeling (SEM) were carried out to explore whether the predictive power of IQ and WM would differ as a function of time point of measurement (i.e., early vs. late assessment). As a main result of various regression analyses, IQ and WM turned out to be reliable predictors of academic achievement, both in early and later developmental stages, when previous domain knowledge was not included as additional predictor. The latter variable accounted for most of the variance in more comprehensive regression models, reducing the impact of both IQ and WM considerably. Findings from SEM analyses basically confirmed this outcome, indicating IQ impacts on educational achievement in the early phase, and illustrating the strong additional impact of previous domain knowledge on achievement at later stages of development.}, language = {en} }