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Quantum chromodynamics predicts the existence of a phase transition from hadronic to quark-gluon matter when temperature and pressure are sufficiently high. Colliding heavy nuclei at ultra-relativistic speeds allows to deposit large amounts of energy in a small volume of space, and is the only available experimental mean to produce the extreme conditions necessary to obtain the deconfined state. Numerous models and ideas were developed in the last decades to study heavy ion physics and understand the properties of extremely heated and compressed nuclear matter. With the ever increasing energy available in the center of mass frame (and thus number of particles produced) and the development of large acceptance detectors, it has become possible to study the fluctuations of physical quantities on an event-by-event basis, and access thermodynamical properties not present in particle spectra. The characteristics of the highly excited matter produced, e.g. thermalization, effect of resonance decay. . . can be investigated by fluctuation analyses. In fact, fluctuations are good indicators for a phase transition and a plethora of fluctuation probes have been proposed to pin down the existence and the properties of the QGP. We study various fluctuation quantities within the Ultra-relativistic Quantum Molecular Dynamics UrQMD and the quantum Molecular Dynamics qMD models. UrQMD is based on hadron and string degrees of freedom and allows to disentangle purely hadronic effects. In contrast, the qMD model includes an explicit transition from quark to hadronic matter and can serve to test adequate probes of the initial QGP state. We show that the qMD model can reasonably reproduce various experimental particles rapidity distributions and transverse mass spectra in wide energy range. Within the frame of the dynamical recombination procedure used in qMD, we study the enhancement of protons over pions (p/π) ratio in the intermediate pt range (1.5 < pt < 2.5). We show that qMD can reproduce the large p/π ≈ 1 observed experimentally at RHIC energies at hadronization. However, the subsequent decay of resonances makes the ratio fall to values incompatible with experimental data. We thus conclude that resonance decay might have a drastic influence on this observable in the quark recombination picture. Charged particles multiplicity fluctuations measured at SPS by the NA49 collaboration are enhanced in midperipheral events for Pb+Pb collisions at Elab = 160 AGeV. This feature is not reproduce by hadron-string transport approaches, which show a flat centrality dependence, within the proper experimental acceptance and with the proper centrality selection procedure. However, we show that the behavior of multiplicity fluctuations in transport codes is similar to the experimental result in full 4π acceptance. We identify the centrality selection procedure as the reason for the enhanced particle multiplicity fluctuations in midperipheral reactions and argue that it can be used to distinguish between different scenarios of particle productions. We show that experimental data might indicate a strong mixing of projectile and target related production sources. Strangeness over entropy K/π and baryon number over entropy p/π ratio fluctuations have been measured by the NA49 experiment in the SPS energy range, from Elab = 20 AGeV up to Elab = 160 AGeV. We investigate the sensitivity of this observable to kinematical cuts and discuss the influence of resonance decay. We find the dynamical p/π ratio fluctuations to increase with beam energy, in agreement with the measured data points. On the contrary, the dynamical K/π ratio fluctuations are essential flat as a function of centrality and depend only weakly on the kinematical cuts applied. Our results are in line with the simulations performed earlier by the NA49 collaboration in their detector acceptance filter. Finally, we focus on the correlations and fluctuations of conserved charges. It was proposed that these fluctuations are sensitive to the fractional charge carried by the quarks in the initial QGP stage and survive the whole course of heavy ion reactions. A crucial point is the influence of hadronization that may relax the initial QGP fluctuation/correlation signals to their hadronic values. We use the quark Molecular Dynamics qMD model to disentangle the effect of recombination-hadronization on charged particles ratio fluctuations, charge transfer fluctuations, baryon number-strangeness correlation coefficient and various ratios of susceptibilities (i.e. correlations over fluctuations). We find that the dynamical recombination procedure implemented in the qMD model destroys all studied initial QGP fluctuations and correlations and might ex- plain why no signal of a phase transition based on event-by-event fluctuations was found in the experimental data until now.
The current thesis is devoted to a systematic study of fluctuations and correlations in heavy-ion collisions, which might be considered as probes for the phase transition and the critical point in the phase diagram, within the Hadron-String- Dynamics (HSD) microscopic transport approach. This is a powerful tool to study nucleus-nucleus collisions and allows to completely simulate experimental collisions on an event-by-event basis. Thus, the transport model has been used to study fluctuations and correlations including the influence of experimental acceptance as well as centrality, system size and collision energy. The comparison to experimental data can separate the effects induced by a phase transition since there is no phase transition in the HSD version used here. Firstly the centrality dependence of multiplicity fluctuations has been studied. Different centrality selections have been performed in the analysis in correspondence to the experimental situation. For the fixed target experiment NA49 events with fixed numbers of the projectile participants have been studied while in the collider experiment PHENIX centrality classes of events have been defined by the multiplicity in certain phase space region. A decrease of participant number fluctuations (and thus volume fluctuations) in more central collisions for both experiments has been obtained. Another area of this work addresses to transport model calculations of multiplicity fluctuations in nucleus-nucleus collisions as a function of colliding energy and system size. This study is in full correspondence to the experimental program of the NA61 Collaboration at the SPS. Central C+C, S+S, In+In, and Pb+Pb nuclear collisions at Elab = 10, 20, 30, 40, 80, 158 AGeV have been investigated. The expected enhanced fluctuations - attributed to the critical point and phase transition - can be observed experimentally on top of a monotonic and smooth ‘hadronic background’. These findings should be helpful for the optimal choice of collision systems and collision energies for the experimental search of the QCD critical point. Other observables are fluctuations of ratios of hadrons (e.g. pions, kaons, protons, etc.) which are not so much affected by volume fluctuations. In particular HSD results for the kaon-to-pion ratio fluctuations, which has been regarded as promising observable for a long time, are presented from low SPS energies up to high energies at RHIC. In addition to the HSD calculations statistical model is also used in terms of microcanonical, canonical and grand canonical ensembles. Further a study of the system size event-by-event fluctuations causing rapidity forward-backward correlations in relativistic heavy-ion collisions is presented. The HSD simulations reveal strong forward-backward correlations and reproduce the main qualitative features of the STAR data in A+A collisions at RHIC energies. It has been shown that strong forward-backward correlations arise due to an averaging over many different events that belong to one centrality bin. An optimization of the experimental selection of centrality classes is presented, which is relevant for the program of the NA61 collaboration at CERN, the low-energy program at RHIC, as well as future experiments at FAIR.
Die vorliegende Dissertation befasst sich mit Flow-Zuständen beim Lesen fiktiver Texte. Das 1975 von Mihaly Csikszentmihalyi vorgestellte Konzept des Flow bezieht sich auf das völlige Aufgehen in einer optimal herausfordernden Tätigkeit, das mit Absorption, Verarbeitungsflüssigkeit und intrinsische Freude einhergeht. Bislang wurde Flow zumeist im Kontext motorischer und leistungsorientierter Aktivitäten empirisch untersucht und in erster Linie theoretisch mit Lesefreude in Verbindung gebracht. Ziel der drei Studien, die diese Dissertation umfasst, war es daher einerseits, Flow beim Lesen erstmals anhand größerer Leser-Stichproben und mithilfe von psychometrischen Gütekriterien genügenden Messinstrumenten nachzuweisen. Andererseits sollte Flow im Rahmen eines Modells für positives Leseerleben mit anderen in der Leseforschung diskutierten Konzepten in Verbindung gebracht und im Hinblick auf potenzielle psychophysiologische Korrelate untersucht werden.
In der ersten Studie wurde eine in der allgemeinen Flow-Forschung verbreitete Kurz-Skala an den Lesekontext adaptiert und anhand einer 229 Leser umfassenden Stichprobe psychometrisch getestet. Hierzu wurden die Teilnehmer im Rahmen einer Online-Studie gebeten, nach 20-minütigem Lesen in einem selbstgewählten Roman Fragebögen zu ihrem Leseerleben auszufüllen. Zufriedenstellende Reliabilitätskoeffizienten, positive Korrelationen mit konvergenten Maßen, die faktoranalytische Unterscheidbarkeit zu diskriminanten Maßen und die erwartete Assoziation mit einem Flow-Kriterium bestätigten die Güte der Flow-Skala. Eine Explorative Faktorenanalyse ergab jedoch, dass fast alle Items auf dem Faktor Absorption luden. Zudem ließ die zweifakorielle Skalenstruktur keine abschließende Aussage zur Legitimierung eines globalen Flow-Scores zu. Daher wurde in der zweiten Studie auf Basis der ersten Skala und der aus der Theorie bekannten Flow-Komponenten ein umfassenderer lesespezifischer Flow-Fragebogen entwickelt. Dessen Reliabilität und Validität konnte anhand einer Online-Studie mit 373 Teilnehmern, in deren Rahmen ein Kapitel aus Homers Odyssee gelesen wurde, bestätigt werden. Neben Hinweisen zur konvergenten und diskriminanten Konstrukt- und zur Kriteriumsvalidität stützten die Ergebnisse einer Konfirmatorischen Faktorenanalyse eine theoretisch angemessene Skalenstruktur, mit den einzelnen Komponenten, mit Absorption, Verarbeitungsflüssigkeit und intrinsischer Freude als Subdimensionen und mit Flow als übergeordnetem Faktor. Mittels eines Strukturgleichungsmodells konnte zudem demonstriert werden, dass der auf Basis dieses Fragebogens gemessene Flow eine zentrale Rolle beim Leseerleben einnehmen kann. So wurde Flow als Mediator für andere, ebenfalls erhobene Erlebnisformen beim Lesen wie etwa Identifikation oder Spannung bestätigt. Von diesen Konzepten klärte Flow den größten Anteil an Varianz in Lesefreude und Textverständnis auf, die als Outcomes von positivem Leseerleben modelliert wurden. Da Flow gegenüber anderen Konzepten der Leseforschung den Vorteil hat, die Ableitung experimenteller Paradigmen und psychophysiologischer Hypothesen zu ermöglichen, wurden in der dritten Studie über die Manipulation des stilistischen Herausforderungsgrades eines weiteren Odyssee-Kapitels unterschiedliche Lese-Bedingungen hergestellt und kardiovaskuläre Daten gemessen. Es zeigten sich zwar keine signifikanten Gruppenunterschiede im Flow-Erleben, jedoch Interaktionen zwischen der Lesebedingung und kardiovaskulären Indikatoren bei der Vorhersage von Flow. So scheinen parasympathische Dominanz und ein entsprechender innerer Entspannungszustand, indiziert durch eine geringe Herzrate und hohe Herzratenvariabilität, Flow beim Lesen zu begünstigen, wenn der Text stilistisch anspruchsvoll ist. Es fanden sich hingegen keine Hinweise dafür, dass Flow-Erleben die Herzaktivität von Lesern verändert oder sich durch sie objektiv erfassen lässt.
Insgesamt sprechen die Ergebnisse dieses Forschungsprojektes somit für das Auf-treten von Flow beim Lesen sowie für dessen zentrale Rolle bei positiven Leseerlebnissen. Außerdem zeigen sie das Potenzial des Flow-Konzeptes für die Leseforschung auf, insbesondere hinsichtlich psychophysiologischer Experimentalstudien.
Multicellular organisms require that cells adhere to each other. This cell-cell adhesion is indispensable for the formation and the integrity of epithelial structures, tissues and organs. Mammals have developed four different cell-cell adhesion structures, the adhering junctions, which ensure the tight contact between cells but are also important platforms for communication and exchange in tissues. Two of these adhering junctions are cadherin based, the belt-like adherens junctions and the spot-like desmosomes. Both structures have in common that they are composed of single membrane spanning proteins, the cadherins, which accomplish adhesion in a calcium-dependent manner. The intracellular parts of classical as well as desmosomal cadherins bind to different adaptor proteins of the armadillo-protein family and others which build a protein plaque underneath the membrane and link the cadherins to the actin or intermediate filament cytoskeleton.
Desmosomes are of special importance for tissues that have to withstand mechanical stress. Although they are essential to stabilize tissues they have to be highly flexible and dynamic structures, as processes like wound healing or tissue remodeling require that adhesive interactions can be modulated. The molecular dynamics within desmosomes are not jet understood in detail, but it is assumed that two different membrane associated pools of desmosomal cadherins exist in cells. Cadherins that are incorporated in mature desmosomes are part of the junctional pool, whereas cadherins that are not associated with firm desmosomes and the intermediate filament cytoskeleton belong to the non-junctional pool. Lateral movements between the two pools results in a dynamic equilibrium and allows for example the exchange of old cadherins. Little is known about the breakdown of desmosomal cadherins. Several studies found that desmosome assembly or endocytosis are cholesterol dependent processes and claimed that membrane microdomains play a role in the regulation of desmosome dynamics. Moreover, membrane rafts may be involved in the pathomechanism of the desmosome associated disease pemphigus, were autoantibodies bind to the cadherin desmoglein-3 and trigger its internalization which results in a loss of adhesion in skin cells.
Membrane rafts are cholesterol dependent nanoscale structures of cellular membranes that are able to regulate the distribution of proteins within the plasma membrane and thus form platforms for cell signaling and membrane trafficking. Flotillins are proteins that are associated with membrane rafts and are reported to be involved in processes like endocytosis, endosomal sorting and a multitude of different signaling events. We could recently show that the membrane raft associated proteins flotillin-1 and flotillin-2 bind directly to the armadillo protein y-catenin which can be part of both, the adherens junction and the desmosome. The aim of this study was to eluciadate a possible role of flotillins in the regulation of desmosomes.
HaCaT keratinocytes were chosen as the main cell system for this study and at first the association of desmosomal components with flotillins was analyzed in detail. It was found that flotillins are clearly associated with desmosomal proteins. They colocalize with desmoglein-3 at cell borders and precipitate the other desmogleins. Further binding assays revealed that both flotillins bind to all desmogleins and the long isoforms of the second class of desmosomal cadherins, the desmocollins. The interaction is a direct one and was mapped to the ICS sequence within the cadherins. This close association rendered the question whether flotillins are functionally implicated in desmosome regulation. To address this issue, stable flotillin knockdown HaCaT cells were analyzed in detail. The molecular morphology of desmoglein-3, desmoglein-1 and two plaque proteins was clearly altered in the absence of flotillins. The membrane staining of all tested desmosomal proteins was derailed and disordered. Furthermoore, the loss of flotillins had an impact on the adhesive capacity of HaCaT keratinocytes. The cell-cell adhesion was weakened in the absence of flotillins, which was monitored by an increased fragmentation of knockdown cells in a cell dissociation assay.
In order to find out the mechanism by which flotillins influence the membrane morphology and the adhesiveness in keratinocytes, the association of desmosomal proteins with membrane microdomains was examined, at first. A predominant part of desmoglein-3 is associated with membrane rafts in HaCaT keratinocytes, whereas only a minor part of desmoglein-1 is found there. However, the raft-association of none of the examined proteins was altered in the absence of flotillins. Furthermore, flotillin depletion did not change the distribution of desmogleins with the two different cadherin pools. Less desmoglein-3 is found in the junctional pool of the flotillin depleted cells compared to the control cells, but this is due to an overall diminished desmoglein-3 protein level in these cells.
Flotillins are involved in endocytic processes but their exact role there is under debate. The endocytic uptake of desmosomal cadherins requires intact membrane rafts, but the precise mechanism is still unknown. A possible involvement of flotillins on the endocytosis of desmoglein-3 was addressed next. It is known that the internalization of desmoglein-2 is dependent on the GTPase dynamin, arguing for an involvement of dynamin in the endocytosis of desmoglein-3 as well. When dynamin and thus desmoglein-3 endocytosis was inhibited using chemical compounds, the mislocalization of desmoglein-3 that was observed in flotillin knockdown cells was restored. This suggest that inhibition of desmoglein-3 endocytosis enhances the amount and/or availability of desmoglein-3 at the plasma membrane, which then normalizes the morphological alterations caused by a knockdown of flotillins. Furthermore the morphological alterations in the flotillin knockdown HaCaT cells were found to be similar to the localization of desmoglein-3 that was observed upon treatment of keratinocytes with PV IgG These structures have been described before as linear arrays and are assumed to be sites of endocytic uptake. This strengthens the idea that enhanced desmoglein-3 internalization takes place in the absence of flotillins, which then results in a weakened adhesion.
Altogether this study revealed flotillins as novel players in desmosome mediated cell-cell adhesion processes. By binding to desmosomal cadherins and desmosomal plaque proteins, flotillins stabilize desmosomes at the plasma membrane and are required for a proper cell-cell adhesion.
Mit der vorliegenden Arbeit wird für den südöstlichen Taunus und sein Vorland erstmals eine umfassende monographische Bearbeitung von Flora und Vegetation des Grünlands auf Basis umfangreicher Geländeerhebungen und Literaturrecherchen vorgelegt. Die wesentlichen Ziele der Untersuchung sind: • Darstellung der aktuellen und historischen Vorkommen und räumlichen Verbreitung von Pflanzenarten, Pflanzengesellschaften und Nutzungsintensitäten des Grünlands. • Darstellung der historischen Entwicklung des Grünlands und der sozioökonomischen Situation der Landwirtschaft. • Gefärdungseinstufung der Pflanzenarten und -gesellschaften (Rote Liste). • Kritische Bewertung des derzeitigen Stands der floristisch-vegetationskundlichen Landesforschung. • Bereitstellung von fachlichen Grundlagen für den praktischen Naturschutz, für Naturschutzbehörden, Planungsbüros, regionale Naturschutzforschung und die interessierte Öffentlichkeit. Das 1105 km2 große Untersuchungsgebiet liegt in nordwestlichen Rhein-Main-Gebiet und erstreckt sich von Wiesbaden im Südwesten und Bad Nauheim im Nordosten bzw. Schmitten im Nordwesten und Frankfurt im Südosten. Es umfasst mit dem Hebungsgebiet des Taunus (größte Höhe 878,5 m ü. NN) und dem Senkungsgebiet des Rhein-Main-Tieflands (tiefster Punkt 84 m ü. NN) zwei sehr unterschiedliche geowissenschaftliche Landschaftstypen, die im einzelnen 33 verschiedene naturräumliche Teileinheiten umfassen...
Das Ziel der Untersuchung von ultra-relativistischen Schwerionenkollisionen ist die Suche nach dem Quark Gluon Plasma (QGP), einem Zustand hochdichter stark wechselwirkender Materie in dem der Einschluss von Quarks und Gluonen in Hadronen aufgehoben ist. Die bisher gewonnenen experimentellen Hinweise deuten daraufhin,daß in Schwerionenkollisionen bei den derzeit höchsten zur Verfügung stehenden Energien von 158 GeV/Nukleon in Pb+Pb Reaktionen am CERN-SPS die Rahmenbedingungen für einen Phasenübergang von hadronischer Materie zu einer partonischen Phaseerfüllt sind. Die exakte Phasenstruktur stark wechselwirkender Materie hingegen ist derzeit noch nicht vollständig verstanden. Da inklusive hadronische Observablen und "penetrierende Proben" nicht direkt sensitiv auf die Existenz und Natur des Phasenübergangs sind, wurde die Analyse von Einzelereignis-"event-by-event"-Fluktuationenvorgeschlagen. Das Fluktuationsverhalten von Einzelereignis-Observablen sollte direkt sensitiv auf die Natur des zu beobachtenden Phasenübergangssein. In dieser Arbeit wurden Fluktuationen in der "chemischen" Zusammensetzung der Teilchenquelle untersucht und erste Ergebnisse werden präsentiert.
Flat Panel CT Pooled Blood Volume-Mappen vor mechanischer Rekanalisation beim akuten Schlaganfall
(2020)
In der Akutdiagnostik des Schlaganfalles sind die Multislice Computertomographie (MSCT) sowie gegebenenfalls die Kernspintomographie die radiologischen Methoden der Wahl zunächst zur Differenzierung eines ischämischen oder hämorrhagischen Geschehens sowie im Falle einer Ischämie zur Darstellung des Gefäßverschlusses und der Perfusionssituation. Mit Hilfe von Flat Panel Detektoren (flat panel detector computed tomography (FDCT)) in Angiographie-Einheiten konnten zunächst Schnittbilder des Kopfes ähnlich denen einer konventionellen MSCT angefertigt werden, womit ein Blutungsausschluss möglich ist. Des Weiteren wurden sogenannte „Pooled Blood Volume“ (PBV)-Karten entwickelt, welche konzipiert wurden, um das Areal mit vermindertem zerebralem Blutvolumen (cerebral blood volume = CBV) und somit annäherungsweise den Infarktkern darzustellen.
Innerhalb der letzten 10 Jahre hat sich die mechanische Rekanalisation als Therapie des akuten Verschlusses proximaler zerebraler Arterien durchgesetzt. Häufig müssen Patienten für die Intervention aus peripheren Krankenhäusern in Schlaganfall-Zentren verlegt werden, sodass eine Aktualisierung der zerebralen Perfusionsparameter zur Darstellung der Progression der Ischämie und zur Prognose-Abschätzung erstrebenswert ist. Gäbe es die Möglichkeit einer solchen Bildgebung innerhalb der Angiographie- und Interventions-Einheit, so könnte wertvolle Zeit, welche sonst für den innerklinischen Transport, Umlagerung des Patienten etc. benötigt wird, eingespart werden. Auch bei schwer betroffenen Patienten, welche direkt in das jeweilige Schlaganfall-Zentrum eingeliefert werden, könnte somit die Zeit zwischen Ankunft in der Klinik bis zur Gefäß-Rekanalisation bedeutsam verkürzt werden.
In der vorliegenden Studie wurde die Zuverlässigkeit der PBV-Karten hinsichtlich der Abschätzung des späteren Infarktareales untersucht. Hierfür wurden bei 29 aufeinanderfolgenden Patienten mit akuten intrakraniellen Verschlüssen der Arteria carotis interna oder Arteria cerebri media das präinterventionelle Volumen der in den Quellbildern der PBV-Karten dargestellten Minderperfusion mit dem finalen Infarktvolumen, wie es sich in den postinterventionellen konventionellen MSCT-Kontrollen darstellte, verglichen. Außerdem wurde durch Bestimmung der Hounsfield-Einheiten die Stärke der Minderperfusion in dem Areal der PBV-Veränderung gemessen und mit der gesunden Gegenseite verglichen. Die mechanische Rekanalisation war bei 26 der Patienten erfolgreich.
Insgesamt war das mediane präinterventionelle PBV-Defizit 9-mal größer als das mediane finale Infarktvolumen (86,4 ml (10,3; 111,6) versus 9,6 ml (3,6; 36,8)). Dieses Ergebnis basierte insbesondere auf der Subgruppe der erfolgreich rekanalisierten Patienten (PBV Defizit: 87,5 ml (10,6; 115,1), finales Infarktvolumen: 8,7 ml (3,6; 29)). Im Falle einer frustranen Intervention wurde das finale Infarktvolumen eher unterschätzt (PBV Defizit: 86,4 ml (5,9; -), finales Infarktvolumen: 116,4 ml (3,5; -)). Es gab keinen signifikanten Unterschied zwischen der HU Ratio im Bereich des später infarzierten Gewebes (0,45 (0,29; 0,51)) und der umgebenden minderperfundierten „Penumbra“ (0,4 (0,33; 0,5)) (p=0,679). Die HU Ratio zeigte eine signifikante negative Korrelation mit dem Volumen der PBV-Läsion (r= -0,448, p= 0,008).
Zusammenfassend wurde aus den Ergebnissen dieser Studie geschlossen, dass die FDCT PBV-Karten nicht zuverlässig das finale Infarktvolumen prognostizieren und daher keinen Einfluss auf die akute Therapieentscheidung haben sollten. Ursächlich sind technische und methodische Limitationen sowie die Art des untersuchten Perfusionsparameters.
Regulatory required, classical toxicity studies for environmental hazard assessment are costly, time consuming, and often lack mechanistic insights about the toxic mode of action induced through a compound. In addition, classical toxicological non-human animal tests raise serious ethical concerns and are not well suited for high throughput screening approaches. Molecular biomarker-based screenings could be a suitable alternative for identifying particular hazardous effects (e.g. endocrine disruption, developmental neurotoxicity) in non-target organisms at the molecular level. This, however, requires a better mechanistic understanding of different toxic modes of action (MoA) to describe characteristic molecular key events and respective markers.
Ecotoxicgenomics, which uses modern day omic technologies and systems biology approaches to study toxicological responses at the molecular level, are a promising new way for elucidating
the processes through which chemicals cause adverse effects in environmental organisms. In this context, this PhD study was designated to investigate and describe MoA-characteristic
ecotoxicogenomic signatures in three ecotoxicologically important aquatic model organisms of different trophic levels (Danio rerio, Daphnia magna and Lemna minor).
Applying non-target transcriptomic and proteomic methodologies post chemical exposure, the aim was to identify robust functional profiles and reliable biomarker candidates with potential
predictive properties to allow for a differentiation among different MoA in these organisms. For the sublethal exposure studies in the zebrafish embryo model (96 hpf), the acute fish embryo toxicity test guideline (OECD 236) was used as conceptual framework. As different test compounds with known MoA, the thyroid hormone 3,3′,5-triiodothyronine (T3) and the thyrostatic 6-propyl-2-thiouracil (6-PTU), as well as six nerve- and muscle-targeting insecticides (abamectin, carbaryl, chlorpyrifos, fipronil, imidacloprid and methoxychlor) were evaluated. Furthermore, a novel sublethal immune challenge assay in early zebrafish embryos (48 hpf) was evaluated for its potential to assess immuno-suppressive effects at the gene expression level. Therefore, toxicogenomic profiles after an immune response inducing stimulus with and without prior clobetasol propionate (CP) treatment were compared. For the aquatic invertebrate D. magna, the study was performed with previously determined low effect concentrations (EC5 & EC20) of fipronil and imidacloprid according to the acute immobilization test in water flea (OECD 202). The aim was to compare toxicogenomic signatures of the GABA-gated chloride channel blocker (fipronil) and the nAChR agonist (imidacloprid). With similar low effect concentrations, a shortened 3 day version of the growth inhibition test with L. minor (OECD 221) was conducted to find molecular profiles differentiating between photosynthesis and HMG-CoA reductase inhibitory effects. Here, the biological interpretation of the molecular stress response profiles in L. minor due to the lack of functional annotation of the reference genome was particularly challenging. Therefore, an annotation workflow was developed based on protein sequence homology predicted from the genomic reference sequences.
With this PhD work, it was shown how transcriptomic, proteomic and computational systems biology approaches can be coupled with aquatic toxicological tests, to gain important mechanistic insights into adverse effects at the molecular level. In general, for the different investigated adverse effects for the different organisms, biomarker candidates were identified, which describe a potential functional link between impaired gene expressions and previously reported apical effects. For the assessed chemicals in the zebrafish embryo model, biomarker candidates for thyroid disruption as well as developmental toxicity targeting the heart and central nervous system were described. The biomarkers derived from nerve- and muscletargeting insecticides were associated with three major affected processes: (1) cardiac muscle cell development and functioning, (2) oxygen transport and hypoxic stress and (3) neuronal development and plasticity. To our knowledge, this is the first study linking neurotoxic insecticide exposure and affected expression of important regulatory genes for heart muscle (tcap, actc2) and forebrain (npas4a) development in a vertebrate model. The proposed immunosuppression assay found CP to affect innate immune induction by attenuating the response of genes involved in antigen processing, TLR signalling, NF-КB signalling, and complement activation ...
By combining two unique facilities at the Gesellschaft fuer Schwerionenforschung (GSI), the Fragment Separator (FRS) and the Experimental Storage Ring (ESR), the first direct measurement of a proton capture reaction of stored radioactive isotopes was accomplished. The combination of well-defined ion energy, an ultra-thin internal gas target, and the ability to adjust the beam energy in the storage ring enables precise, energy-differentiated measurements of the (p,gamma) cross sections. The new setup provides a sensitive method for measuring (p,gamma) reactions relevant for nucleosynthesis processes in supernovae, which are among the most violent explosions in the universe and are not yet well understood. The cross sections of the 118Te(p,gamma) and 124Xe(p,gamma) reactions were measured
at energies of astrophysical interest. The heavy ions were stored with energies of 6 MeV/nucleon and 7 MeV/nucleon and interacted with a hydrogen gas-jet target.
The produced proton-capture products were detected with a double-sided silicon strip detector. The radiative recombination process of the fully stripped ions and electrons from the hydrogen target was used as a luminosity monitor.
Additionally, post-processing nucleosynthesis simulations within the NuGrid [1] research platform have been performed. The impact of the new experimental results on the p-process nucleosynthesis around 124Xe and 118Te in a core-collapse supernova was investigated. The successful measurement of the proton capture cross sections of radioactive isotopes rises the motivation to proceed with experiments in lower energy regions.
[1] M. Pignatari and F. Herwig, “The nugrid research platform: A comprehensive simulation approach for nuclear astrophysics,” Nuclear Physics News, vol. 22, no. 4, pp. 18–23, 2012.