TY - JOUR A1 - Salman Haider, Malik A1 - Schreiner, Jochen A1 - Kendl, Sabine A1 - Kroiss, Matthias A1 - Luxenhofer, Robert T1 - A Micellar Mitotane Formulation with High Drug-Loading and Solubility: Physico-Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models JF - Macromolecular Bioscience N2 - Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14–20 mg L\(^{-1}\)) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT‐loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI‐H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro. KW - adrenocortical carcinoma KW - amphiphilic block copolymer KW - NCI-H295R KW - poly(2-oxazoline) KW - solubility enhancement Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206224 VL - 20 IS - 1 ER - TY - JOUR A1 - Nazzal, Yousef A1 - Howari, Fares M. A1 - Yaslam, Aya A1 - Iqbal, Jibran A1 - Maloukh, Lina A1 - Ambika, Lakshmi Kesari A1 - Al-Taani, Ahmed A. A1 - Ali, Ijaz A1 - Othman, Eman M. A1 - Jamal, Arshad A1 - Naseem, Muhammad T1 - A methodological review of tools that assess dust microbiomes, metatranscriptomes and the particulate chemistry of indoor dust JF - Atmosphere N2 - Indoor house dust is a blend of organic and inorganic materials, upon which diverse microbial communities such as viruses, bacteria and fungi reside. Adequate moisture in the indoor environment helps microbial communities multiply fast. The outdoor air and materials that are brought into the buildings by airflow, sandstorms, animals pets and house occupants endow the indoor dust particles with extra features that impact human health. Assessment of the health effects of indoor dust particles, the type of indoor microbial inoculants and the secreted enzymes by indoor insects as allergens merit detailed investigation. Here, we discuss the applications of next generation sequencing (NGS) technology which is used to assess microbial diversity and abundance of the indoor dust environments. Likewise, the applications of NGS are discussed to monitor the gene expression profiles of indoor human occupants or their surrogate cellular models when exposed to aqueous solution of collected indoor dust samples. We also highlight the detection methods of dust allergens and analytical procedures that quantify the chemical nature of indoor particulate matter with a potential impact on human health. Our review is thus unique in advocating the applications of interdisciplinary approaches that comprehensively assess the health effects due to bad air quality in built environments. KW - indoor dust KW - allergens KW - metagenomics KW - particulate matter KW - microbiomes KW - transcriptomes KW - health effects Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285957 SN - 2073-4433 VL - 13 IS - 8 ER - TY - THES A1 - Reutelshöfer, Jochen T1 - A Meta-Engineering Approach for Document-Centered Knowledge Acquisition T1 - Ein Meta-Engineering Ansatz für dokumentenzentrierte Wissensakquisition N2 - Today knowledge base authoring for the engineering of intelligent systems is performed mainly by using tools with graphical user interfaces. An alternative human-computer interaction para- digm is the maintenance and manipulation of electronic documents, which provides several ad- vantages with respect to the social aspects of knowledge acquisition. Until today it hardly has found any attention as a method for knowledge engineering. This thesis provides a comprehensive discussion of document-centered knowledge acquisition with knowledge markup languages. There, electronic documents are edited by the knowledge authors and the executable knowledge base entities are captured by markup language expressions within the documents. The analysis of this approach reveals significant advantages as well as new challenges when compared to the use of traditional GUI-based tools. Some advantages of the approach are the low barriers for domain expert participation, the simple integration of informal descriptions, and the possibility of incremental knowledge for- malization. It therefore provides good conditions for building up a knowledge acquisition pro- cess based on the mixed-initiative strategy, being a flexible combination of direct and indirect knowledge acquisition. Further it turns out that document-centered knowledge acquisition with knowledge markup languages provides high potential for creating customized knowledge au- thoring environments, tailored to the needs of the current knowledge engineering project and its participants. The thesis derives a process model to optimally exploit this customization po- tential, evolving a project specific authoring environment by an agile process on the meta level. This meta-engineering process continuously refines the three aspects of the document space: The employed markup languages, the scope of the informal knowledge, and the structuring and organization of the documents. The evolution of the first aspect, the markup languages, plays a key role, implying the design of project specific markup languages that are easily understood by the knowledge authors and that are suitable to capture the required formal knowledge precisely. The goal of the meta-engineering process is to create a knowledge authoring environment, where structure and presentation of the domain knowledge comply well to the users’ mental model of the domain. In that way, the approach can help to ease major issues of knowledge-based system development, such as high initial development costs and long-term maintenance problems. In practice, the application of the meta-engineering approach for document-centered knowl- edge acquisition poses several technical challenges that need to be coped with by appropriate tool support. In this thesis KnowWE, an extensible document-centered knowledge acquisition environment is presented. The system is designed to support the technical tasks implied by the meta-engineering approach, as for instance design and implementation of new markup lan- guages, content refactoring, and authoring support. It is used to evaluate the approach in several real-world case-studies from different domains, such as medicine or engineering for instance. We end the thesis by a summary and point out further interesting research questions consid- ering the document-centered knowledge acquisition approach. N2 - Ein Meta-Engineering Ansatz für dokumentenzentrierte Wissensakquisition KW - Wissenstechnik KW - Knowledge engineering KW - knowledge acquisition KW - knowledge-based systems KW - documents KW - authoring environment Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-107523 ER - TY - JOUR A1 - Kunz, Philipp A1 - Azad Engel, Florian A1 - Holmberg, Hans-Christer A1 - Sperlich, Billy T1 - A meta-comparison of the effects of high-intensity interval training to those of small-sided games and other training protocols on parameters related to the physiology and performance of youth soccer players JF - Sports Medicine - Open N2 - Background High-intensity interval training (HIIT) is frequently employed to improve the endurance of various types of athletes. To determine whether youth soccer players may benefit from the intermittent load and time efficiency of HIIT, we performed a meta-analysis of the relevant scientific literature. Objectives Our primary objective was to compare changes in various physiological parameters related to the performance of youth soccer players in response to running-based HIIT to the effects of other common training protocols (i.e., small-sided games, technical training and soccer-specific training, or high-volume endurance training). A secondary objective was to compare specifically running-based HIIT to a soccer-specific form of HIIT known as small-sided games (SSG) in this same respect, since this latter type of training is being discussed extensively by coaches. Method A systematic search of the PubMed, SPORTDiscus, and Web of Science databases was performed in August of 2017 and updated during the review process in December of 2018. The criteria for inclusion of articles for analysis were as follows: (1) comparison of HIIT to SSG or some other training protocol employing a pre-post design, (2) involvement of healthy young athletes (≤ 18 years old), and (3) assessment of variables related to endurance or soccer performance. Hedges’ g effect size (dppc2) and associated 95% confidence intervals for the comparison of the responses to HIIT and other interventions were calculated. Results Nine studies, involving 232 young soccer players (mean age 16.2 ± 1.6 years), were examined. Endurance training in the form of HIIT or SSG produced similar positive effects on most parameters assessed, including peak oxygen uptake and maximal running performance during incremental running (expressed as Vmax or maximal aerobic speed (MAS)), shuttle runs (expressed as the distance covered or time to exhaustion), and time-trials, as well as submaximal variables such as running economy and running velocity at the lactate threshold. HIIT induced a moderate improvement in soccer-related tests involving technical exercises with the soccer ball and other game-specific parameters (i.e., total distance covered, number of sprints, and number of involvements with the ball). Neuromuscular parameters were largely unaffected by HIIT or SSG. Conclusion The present meta-analysis indicates that HIIT and SSG have equally beneficial impacts on variables related to the endurance and soccer-specific performance of youth soccer players, but little influence on neuromuscular performance. KW - adolescents KW - children KW - conditioning KW - endurance KW - repeated sprint Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200332 VL - 5 ER - TY - JOUR A1 - Planes, Maria D. A1 - Niñoles, Regina A1 - Rubio, Lourdes A1 - Bissoli, Gaetano A1 - Bueso, Eduardo A1 - García-Sánchez, María J. A1 - Alejandro, Santiago A1 - Gonzalez-Guzmán, Miguel A1 - Hedrich, Rainer A1 - Rodriguez, Pedro L. A1 - Fernández, José A. A1 - Serrano, Ramón T1 - A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane \(H^+\)-ATPase and decreased cytosolic pH, \(K^+\), and anions JF - Journal of Experimental Botany N2 - The stress hormone abscisic acid (ABA) induces expression of defence genes in many organs, modulates ion homeostasis and metabolism in guard cells, and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for \(H^+\) efflux (wat1-1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than the wild type. This suggested that ABA could inhibit \(H^+\) efflux (\(H^+\)-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA inhibited the root plasma-membrane H+-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and in vivo (\(H^+\) efflux from seedling roots). This inhibition involved the core ABA signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3). Electrophysiological measurements in root epidermal cells indicated that ABA, acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization (due to \(K^+\) efflux through the GORK channel) and cytosolic acidification. This acidification was not observed in the wat1-1D mutant. The mechanism of inhibition of the \(H^+\)-ATPase by ABA and its effects on cytosolic pH and membrane potential in roots were different from those in guard cells. ABA did not affect the in vivo phosphorylation level of the known activating site (penultimate threonine) of (\(H^+\)-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal regulatory domain of (\(H^+\)-ATPase while the guard-cell kinase SnRK2.6/OST1 did not. KW - ABA receptors KW - cytosolic pH KW - ion channels KW - microelectrodes KW - protein kinase KW - proton efflux Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121221 VL - 66 IS - 3 ER - TY - JOUR T1 - A measurement of the calorimeter response to single hadrons and determination of the jet energy scale uncertainty using LHC Run-1 \(pp\)-collision data with the ATLAS detector JF - European Physical Journal C N2 - A measurement of the calorimeter response to isolated charged hadrons in the ATLAS detector at the LHC is presented. This measurement is performed with 3.2 nb\(^{−1}\) of proton–proton collision data at \(\sqrt{s}\) = 7 TeV from 2010 and 0.1 nb\(^{−1}\) of data at \(\sqrt{s}\) = 8 TeV from 2012. A number of aspects of the calorimeter response to isolated hadrons are explored. After accounting for energy deposited by neutral particles, there is a 5% discrepancy in the modelling, using various sets of GEANT4 hadronic physics models, of the calorimeter response to isolated charged hadrons in the central calorimeter region. The description of the response to anti-protons at low momenta is found to be improved with respect to previous analyses. The electromagnetic and hadronic calorimeters are also examined separately, and the detector simulation is found to describe the response in the hadronic calorimeter well. The jet energy scale uncertainty and correlations in scale between jets of different momenta and pseudorapidity are derived based on these studies. The uncertainty is 2–5% for jets with transverse momenta above 2 TeV, where this method provides the jet energy scale uncertainty for ATLAS. KW - high energy physics KW - ATLAS detector KW - hadronic calorimeter KW - charged hadron response KW - identified particle response KW - hadronic physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173690 VL - 77 IS - 26 ER - TY - JOUR A1 - Ali, Quasim A1 - Montenegro, Sergio T1 - A Matlab Implementation of Differential GPS for Low-cost GPS Receivers N2 - A number of public codes exist for GPS positioning and baseline determination in off-line mode. However, no software code exists for DGPS exploiting correction factors at base stations, without relying on double difference information. In order to accomplish it, a methodology is introduced in MATLAB environment for DGPS using C/A pseudoranges on single frequency L1 only to make it feasible for low-cost GPS receivers. Our base station is at accurately surveyed reference point. Pseudoranges and geometric ranges are compared at base station to compute the correction factors. These correction factors are then handed over to rover for all valid satellites observed during an epoch. The rover takes it into account for its own true position determination for corresponding epoch. In order to validate the proposed algorithm, our rover is also placed at a pre-determined location. The proposed code is an appropriate and simple to use tool for post-processing of GPS raw data for accurate position determination of a rover e.g. Unmanned Aerial Vehicle during post-mission analysis. KW - marine navigation KW - Global Positioning System (GPS) KW - Matlab KW - Differential GPS (DGPS) KW - GPS Reciever KW - Unmanned Aerial Vehicle (UAV) KW - RINEX Format KW - Global Navigation Satellite System (GNSS) Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113618 ER - TY - THES A1 - Breitenbach, Tim T1 - A mathematical optimal control based approach to pharmacological modulation with regulatory networks and external stimuli T1 - Ein auf mathematischer Optimalkontrolle basierender Ansatz für pharmakologische Modulation mit regulatorischen Netzwerken und externen Stimuli N2 - In this work models for molecular networks consisting of ordinary differential equations are extended by terms that include the interaction of the corresponding molecular network with the environment that the molecular network is embedded in. These terms model the effects of the external stimuli on the molecular network. The usability of this extension is demonstrated with a model of a circadian clock that is extended with certain terms and reproduces data from several experiments at the same time. Once the model including external stimuli is set up, a framework is developed in order to calculate external stimuli that have a predefined desired effect on the molecular network. For this purpose the task of finding appropriate external stimuli is formulated as a mathematical optimal control problem for which in order to solve it a lot of mathematical methods are available. Several methods are discussed and worked out in order to calculate a solution for the corresponding optimal control problem. The application of the framework to find pharmacological intervention points or effective drug combinations is pointed out and discussed. Furthermore the framework is related to existing network analysis tools and their combination for network analysis in order to find dedicated external stimuli is discussed. The total framework is verified with biological examples by comparing the calculated results with data from literature. For this purpose platelet aggregation is investigated based on a corresponding gene regulatory network and associated receptors are detected. Furthermore a transition from one to another type of T-helper cell is analyzed in a tumor setting where missing agents are calculated to induce the corresponding switch in vitro. Next a gene regulatory network of a myocardiocyte is investigated where it is shown how the presented framework can be used to compare different treatment strategies with respect to their beneficial effects and side effects quantitatively. Moreover a constitutively activated signaling pathway, which thus causes maleficent effects, is modeled and intervention points with corresponding treatment strategies are determined that steer the gene regulatory network from a pathological expression pattern to physiological one again. N2 - In dieser Arbeit werden Modelle für molekulare Netzwerke bestehend aus gewöhnlichen Differentialgleichungen durch Terme erweitert, die die Wechselwirkung zwischen dem entsprechenden molekularen Netzwerk und der Umgebung berücksichtigen, in die das molekulare Netzwerk eingebettet ist. Diese Terme modellieren die Effekte von externen Stimuli auf das molekulare Netzwerk. Die Nutzbarkeit dieser Erweiterung wird mit einem Modell der circadianen Uhr demonstriert, das mit gewissen Termen erweitert wird und Daten von mehreren verschiedenen Experimenten zugleich reproduziert. Sobald das Modell einschließlich der externen Stimuli aufgestellt ist, wird eine Grundstruktur entwickelt um externe Stimuli zu berechnen, die einen gewünschten vordefinierte Effekt auf das molekulare Netzwerk haben. Zu diesem Zweck wird die Aufgabe, geeignete externe Stimuli zu finden, als ein mathematisches optimales Steuerungsproblem formuliert, für welches, um es zu lösen, viele mathematische Methoden zur Verfügung stehen. Verschiedene Methoden werden diskutiert und ausgearbeitet um eine Lösung für das entsprechende optimale Steuerungsproblem zu berechnen. Auf die Anwendung dieser Grundstruktur pharmakologische Interventionspunkte oder effektive Wirkstoffkombinationen zu finden, wird hingewiesen und diese diskutiert. Weiterhin wird diese Grundstruktur in Bezug zu existierenden Netzwerkanalysewerkzeugen gesetzt und ihre Kombination für die Netzwerkanalyse diskutiert um zweckbestimmte externe Stimuli zu finden. Die gesamte Grundstruktur wird mit biologischen Beispielen verifiziert, indem man die berechneten Ergebnisse mit Daten aus der Literatur vergleicht. Zu diesem Zweck wird die Blutplättchenaggregation untersucht basierend auf einem entsprechenden genregulatorischen Netzwerk und damit assoziierte Rezeptoren werden detektiert. Weiterhin wird ein Wechsel von einem T-Helfer Zelltyp in einen anderen in einer Tumorumgebung analysiert, wobei fehlende Agenzien berechnet werden um den entsprechenden Wechsel in vitro zu induzieren. Als nächstes wird ein genregulatorisches Netzwerk eines Myokardiozyten untersucht, wobei gezeigt wird wie die präsentierte Grundstruktur genutzt werden kann um verschiedene Behandlungsstrategien in Bezug auf ihre nutzbringenden Wirkungen und Nebenwirkungen quantitativ zu vergleichen. Darüber hinaus wird ein konstitutiv aktivierter Signalweg, der deshalb unerwünschte Effekte verursacht, modelliert und Interventionspunkte mit entsprechenden Behandlungsstrategien werden bestimmt, die das genregulatorische Netzwerk wieder von einem pathologischen Expressionsmuster zu einem physiologischen steuern. KW - Bioinformatik KW - systematic drug targeting KW - optimal drug combination KW - disease modelling KW - external stimuli KW - intervention point analyzing KW - Molekülsystem KW - Reiz Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174368 ER - TY - THES A1 - Mark, Stefan T1 - A Magnetic Semiconductor based Non-Volatile Memory and Logic Element T1 - Ein auf magnetischen Halbleiter basierendes nicht-flüchtiges Speicher- und Logik-Element N2 - For the realization of a programmable logic device, or indeed any nanoscale device, we need a reliable method to probe the magnetization direction of local domains. For this purpose we extend investigations on the previously discovered tunneling anisotropic magneto resistance effect (TAMR) by scaling the pillar size from 100 µm down to 260 nm. We start in chapter 4 with a theoretical description of the TAMR effect and show experimental data of miniaturized pillars in chapter 5. With such small TAMR probes we are able to locally sense the magnetization on the 100 nm scale. Sub-micron TAMR and anisotropic magneto resistance (AMR) measurements of sub-millimeter areas show that the behavior of macroscopic (Ga,Mn)As regions is not that of a true macrospin, but rather an ensemble average of the behavior of many nearly identical macrospins. This shows that the magnetic anisotropies of the local regions are consistent with the behavior extracted from macroscopic characterization. A fully electrically controllable read-write memory device out the ferromagnetic semiconductor (Ga,Mn)As is presented in chapter 6. The structure consists of four nanobars which are connected to a circular center region. The first part of the chapter describes the lithography realization of the device. We make use of the sub-micron TAMR probes to read-out the magnetization state of a 650 nm central disk. Four 200 nm wide nanobars are connected to the central disk and serve as source and drain of a spin-polarized current. With the spin-polarized current we are able to switch the magnetization of the central disk by means of current induced switching. Injecting polarized holes with a spin angular momentum into a magnetic region changes the magnetization direction of the region due to the p-d exchange interaction between localized Mn spins and itinerant holes. The magnetization of the central disk can be controlled fully electrically and it can serve as one bit memory element as part of a logic device. In chapter 7 we discuss the domain wall resistance in (Ga,Mn)As. At the transition from nanobars to central disk we are able to generate 90° and 180° domain walls and measure their resistance. The results presented from chapter 5 to 7 combined with the preexisting ultracompact (Ga,Mn)As-based memory cell of ref. [Papp 07c] are the building blocks needed to realize a fully functioning programmable logic device. The work of ref. [Papp 07c] makes use of lithographically engineered strain relaxation to produce a structure comprised of two nanobars with mutually orthogonal uniaxial easy axes, connected by a narrow constriction. Measurements showed that the resistance of the constriction depends on the relative orientation of the magnetization in the two bars. The programmable logic device consists of two central disks connected by a small constriction. The magnetization of the two central disks are used as the input bits and the constriction serves as the output during the logic operation. The concept is introduced in the end of chapter 6 and as an example for a logic operation an XOR gate is presented. The functionality of the programmable logic scheme presented here can be straightforwardly extended to produce multipurpose functional elements, where the given geometry can be used as various different computational elements depending on the number of input bits and the chosen electrical addressing. The realization of such a programmable logic device is shown in chapter 8, where we see that the constriction indeed can serve as a output of the logic operation because its resistance is dependent on the relative magnetization state of both disks. Contrary to ref. [Papp 07c], where the individual magnetic elements connected to the constriction only have two non-volatile magnetic states, each disk in our scheme connected to the constriction has four non-volatile magnetic states. Switching the magnetization of a central disk with an electrical current does not only change the TAMR read-out of the respective disk, it also changes the resistance of the constriction. The resistance polar plot of the constriction maps the relative magnetization states of the individual disks. The presented device design serves as an all-electrical, all-semiconductor logic element. It combines a memory cell and data processing in a single monolithic paradigm. N2 - Für die Realisierung eines programmierbaren Logikelements oder beliebiger nanometer großer Bauteile, brauchen wir eine verlässlige Methode, um die Magnetisierungsrichtung lokaler Domänen auzulesen. Dafür erweitern wir die Untersuchungen an TAMR (tunneling magneto resistance) Strukturen und skalieren die Fläche des Tunnelkontakts von 100 µm auf 260 nm. In Kapitel 4 geben wir zunächst eine theoretische Beschreibung des TAMR Effekts und zeigen darauf im folgenden Kapitel 5 experimentelle Daten der miniaturisierten Tunnelkontakte. Mit diesen TAMR-Kontakten ist es möglich die Magnetisierung lokal in einer Grössenordnung von 100 nm zu detektieren. Sub-micron TAMR-Messungen und anisotrope Magnetowiderstandmessungen (AMR) an sub-millimeter Gebieten zeigen, dass das Verhalten von makrokopischen (Ga,Mn)As nicht das eines Makrospins ist, sondern ein Ensembledurchschnitt von vielen fast identischen Makrospins. Dieses Ergebnis ist mit der makroskopischen Beschreibung der lokalen magnetischen Aniotropien konform.\\ Ein rein elektrisch kontrollierbares Read-Write Speicherelement aus dem ferromagnetischen Halbleiter (Ga,Mn)As wird in Kapitel 6 gezeigt. Das Element besteht aus vier 200 nm breiten Streifen, die mit einer kreisförmigen zentralen Disc verbunden sind. Der erste Teil des Kapitels beschreibt die einzelnen Lithographieschritte zur Herstellung des Elements. Zum Auslesen der Magnetisierungsrichtung der zentralen Disc mit einem Durchmesser von 650 nm verwenden wir einen miniaturisierten TAMR-Kontakt. Die 200 nm breiten Streifen dienen als Quelle eines spinpolarisierten Stromes in die zentrale Disc. Das Injezieren von polarisierten Löchern mit einem Spin-Drehimpuls in eine magnetische Region verändert die Magnetisierung der Region durch p-d Austauschwechselwirkung zwischen lokalisierten Mn-Spins und den Löchern. Die Magnetisierung der zentralen Disc kann rein elektrisch kontrolliert werden and als Bit eines Logikelementes verwendet werden. In Kapitel 7 untersuchen wir den Domänenwiderstand in (Ga,Mn)As. Am Übergang von den Streifen zur zentralen Disc ist es möglich 90°- und 180° Domänenwände zu erzeugen und deren Widerstand zu messen.\\ Die Ergebnisse von Kapitel 5 bis 7, kombiniert mit dem bereits existierenden Ergebnissen einer ultrakompakten (Ga,Mn)As-basierenden Speicherzelle von Ref. [Papp 07c], sind die Schlüsselelemente die man zur Realisierung eines programmierbaren Logikelements benötigt. Die Arbeit von Referenz [Papp 07c] nutzt Lithographie induzierte Deformationsrelaxation, um eine Struktur zu erzeugen, die aus zwei senkrechten Streifen besteht und durch eine Verengung verbunden sind. Der Widerstand dieser Verengung ist von der relativen Magnetisierungsorientierung der beiden Streifen abhängig. Das programmierbare Logikelement besteht aus zwei zentralen Discs, die mittels einer schmalen Verengung verbunden sind. Die Magnetisierung der beiden zentralen Discs dienen als Eingänge und die Verengung als Ausgang während der Logikoperation. Das Konzept wird am Ende des sechsten Kapitels eingeführt und als Beispiel für eine Logikoperation wird ein XOR-Gate präsentiert. Die Funktionalität des hier gezeigten programmierbaren Logikschemas kann Problemlos auf ein multifunktionales Element erweitert werden. Diese Geometrie kann abhängig von der Anzahl der Eingänge und der gewählten Adressierung für verschiedene Rechenelemente genutzt werden. \\ Die Realisierung eines programmierbaren Logikelements ist in Kapitel 8 gezeigt. Der Widerstand der Verengung hängt von der relativen Magnetisierungsrichtung der beiden zentralen Discs ab und wird als Ausgang während der Logikoperation verwendet. Im Gegensatz zu Referenz [Papp 07c], indem die einzelnen über die Verengung verbundenen magnetischen Elemente jeweils nur zwei nicht-flüchtige magnetische Zustände besitzen, hat jede zentrale Disc in unserem Schema vier nicht-flüchtige magnetische Zustände. Das Verändern der Magnetisierungsrichtung einer zentralen Disc durch einen elektrischen Strom kann durch den jeweiligen TAMR-Kontakt und durch die Widerstandänderung der Verengung gemessen werden. Der Widerstands-Fingerabdruck (resistance polar plot) der Verengung zeigt die verschiedenen relativen Magnetisierungszutände der zentralen Discs.\\ Das hier präsentierte Konzept dient als reines Halbleiter und rein-elektrisches Logikelement. Es kombiniert eine Speicherzelle und Datenverarbeitung in einem neuartigen monolithischen Bauelement. KW - Magnetischer Halbleiter KW - Magnetische Halbleiter KW - Magnetische Anisotropien KW - Spinelektronik KW - magnetic semiconductors KW - magnetic anisotropy KW - Magnetic properties of thin films interfaces KW - Spinelectronic KW - Magnetische Anisotropie KW - Spintronik Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71223 ER - TY - JOUR A1 - Schneider, Wolfgang A1 - Sodian, Beate T1 - A longitudinal study of young children's memory behavior and Performance in a sort-recall task N2 - No abstract available KW - Psychologie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62169 ER - TY - JOUR A1 - Dashkovskiy, Sergey A1 - Kapustyan, Oleksiy A1 - Schmid, Jochen T1 - A local input-to-state stability result w.r.t. attractors of nonlinear reaction–diffusion equations JF - Mathematics of Control, Signals, and Systems N2 - We establish the local input-to-state stability of a large class of disturbed nonlinear reaction–diffusion equations w.r.t. the global attractor of the respective undisturbed system. KW - local input-to-state stability KW - global attractor KW - lonlinear reaction-diffusion equations Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281099 VL - 32 IS - 3 ER - TY - JOUR A1 - Gerhard-Hartmann, Elena A1 - Wiegering, Verena A1 - Benoit, Clemens A1 - Meyer, Thomas A1 - Rosenwald, Andreas A1 - Maurus, Katja A1 - Ernestus, Karen T1 - A large retroperitoneal lipoblastoma as an incidental finding: a case report JF - BMC Pediatrics N2 - Background Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial. Case presentation A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far. Conclusion Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases. KW - retroperitoneal tumor KW - pediatric KW - lipoblastoma KW - PLAG1 rearrangement KW - case report Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260173 VL - 21 ER - TY - JOUR A1 - Semler, Elisa A1 - Anderl-Straub, Sarah A1 - Uttner, Ingo A1 - Diehl-Schmid, Janine A1 - Danek, Adrian A1 - Einsiedler, Beate A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Huppertz, Hans-Jürgen A1 - Jahn, Holger A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Muche, Rainer A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Schroeter, Matthias L. A1 - Ludolph, Albert C. A1 - Otto, Markus T1 - A language-based sum score for the course and therapeutic intervention in primary progressive aphasia JF - Alzheimer's Research & Therapy N2 - Background With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies. KW - frontotemporal dementia KW - cognitive neuropsychology in dementia KW - assessment of cognitive disorders/dementia KW - volumetric MRI KW - aphasia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236277 VL - 10 ER - TY - JOUR A1 - Karl, Veronika A1 - Neitzel, Ira A1 - Wachsmuth, Daniel T1 - A Lagrange multiplier method for semilinear elliptic state constrained optimal control problems JF - Computational Optimization and Applications N2 - In this paper we apply an augmented Lagrange method to a class of semilinear ellip-tic optimal control problems with pointwise state constraints. We show strong con-vergence of subsequences of the primal variables to a local solution of the original problem as well as weak convergence of the adjoint states and weak-* convergence of the multipliers associated to the state constraint. Moreover, we show existence of stationary points in arbitrary small neighborhoods of local solutions of the original problem. Additionally, various numerical results are presented. KW - optimal control KW - semilinear elliptic operators KW - state constraints KW - augmented Lagrange method Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232811 SN - 0926-6003 VL - 77 ER - TY - JOUR A1 - Latifi, Hooman A1 - Holzwarth, Stefanie A1 - Skidmore, Andrew A1 - Brůna, Josef A1 - Červenka, Jaroslav A1 - Darvishzadeh, Roshanak A1 - Hais, Martin A1 - Heiden, Uta A1 - Homolová, Lucie A1 - Krzystek, Peter A1 - Schneider, Thomas A1 - Starý, Martin A1 - Wang, Tiejun A1 - Müller, Jörg A1 - Heurich, Marco T1 - A laboratory for conceiving Essential Biodiversity Variables (EBVs)—The ‘Data pool initiative for the Bohemian Forest Ecosystem’ JF - Methods in Ecology and Evolution N2 - Effects of climate change‐induced events on forest ecosystem dynamics of composition, function and structure call for increased long‐term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non‐intervention zones. The long‐established concept of forest supersites generally relies on long‐term funds from national agencies and goes beyond the logistic and financial capabilities of state‐ or region‐wide protected area administrations, universities and research institutes. We introduce the concept of data pools as a smaller‐scale, user‐driven and reasonable alternative to co‐develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases. We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D‐based forest inventory. We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions. KW - bohemian forest ecosystem KW - data pool KW - forest ecosystem science KW - remote sensing KW - remote sensing‐enabled essential biodiversity variables Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262743 VL - 12 IS - 11 ER - TY - INPR A1 - Nassourou, Mohamadou T1 - A Knowledge-based Hybrid Statistical Classifier for Reconstructing the Chronology of the Quran N2 - Computationally categorizing Quran’s chapters has been mainly confined to the determination of chapters’ revelation places. However this broad classification is not sufficient to effectively and thoroughly understand and interpret the Quran. The chronology of revelation would not only improve comprehending the philosophy of Islam, but also the easiness of implementing and memorizing its laws and recommendations. This paper attempts estimating possible chapters’ dates of revelation through their lexical frequency profiles. A hybrid statistical classifier consisting of stemming and clustering algorithms for comparing lexical frequency profiles of chapters, and deriving dates of revelation has been developed. The classifier is trained using some chapters with known dates of revelation. Then it classifies chapters with uncertain dates of revelation by computing their proximity to the training ones. The results reported here indicate that the proposed methodology yields usable results in estimating dates of revelation of the Quran’s chapters based on their lexical contents. KW - Text Mining KW - Maschinelles Lernen KW - text categorization KW - Bayesian classifier KW - distance-based classifier KW - Quran Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-54712 ER - TY - JOUR A1 - Stange, Katja A1 - Désir, Julie A1 - Kakar, Naseebullah A1 - Mueller, Thomas D. A1 - Budde, Birgit S. A1 - Gordon, Christopher T. A1 - Horn, Denise A1 - Seemann, Petra A1 - Borck, Guntram T1 - A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia JF - Orphanet Journal of Rare Diseases N2 - Background: Grebe dysplasia, Hunter-Thompson dysplasia, and du Pan dysplasia constitute a spectrum of skeletal dysplasias inherited as an autosomal recessive trait characterized by short stature, severe acromesomelic shortening of the limbs, and normal axial skeleton. The majority of patients with these disorders have biallelic loss-of-function mutations of GDF5. In single instances, Grebe dysplasia and a Grebe dysplasia-like phenotype with genital anomalies have been shown to be caused by mutations in BMPR1B, encoding a GDF5 receptor. Methods: We clinically and radiologically characterised an acromesomelic chondrodysplasia in an adult woman born to consanguineous parents. We sequenced GDF5 and BMPR1B on DNA of the proposita. We performed 3D structural analysis and luciferase reporter assays to functionally investigate the identified BMPR1B mutation. Results: We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation. We show that the homozygous c.91C>T, p.(Arg31Cys) mutation causing du Pan dysplasia leads to a significant loss of BMPR1B function, but to a lesser extent than the previously reported p.Cys53Arg mutation that results in the more severe Grebe dysplasia. Conclusions: The phenotypic severity gradient of the clinically and radiologically related acromesomelic chondrodysplasia spectrum of skeletal disorders may be due to the extent of functional impairment of the ligand-receptor pair GDF5-BMPR1B. KW - linkage analysis KW - chondrodysplasia KW - specificity KW - Grebe dysplasia KW - BMPR1B KW - du Pan dysplasia KW - tool KW - missense KW - grebe KW - protein-1 CDMP1 gene KW - Acromesomelic dysplasias Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151650 VL - 10 IS - 84 ER - TY - JOUR A1 - Wilhelm, Gernot T1 - A Hurrian Letter from Tell Brak N2 - No abstract available. KW - Tell Brak Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85972 ER - TY - JOUR A1 - Koenig, Leopold A1 - Ramme, Anja Patricia A1 - Faust, Daniel A1 - Mayer, Manuela A1 - Flötke, Tobias A1 - Gerhartl, Anna A1 - Brachner, Andreas A1 - Neuhaus, Winfried A1 - Appelt-Menzel, Antje A1 - Metzger, Marco A1 - Marx, Uwe A1 - Dehne, Eva-Maria T1 - A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs JF - Cells N2 - Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood–brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier. KW - blood-brain barrier (BBB) model KW - human induced pluripotent stem cells (hiPSCs) KW - microphysiological systems (MPS) KW - multi-organ chip KW - brain–liver chip Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290375 SN - 2073-4409 VL - 11 IS - 20 ER - TY - JOUR A1 - Gattenloehner, Stefan A1 - Joerissen, H. A1 - Huhn, M. A1 - Vincent, A. A1 - Beeson, D. A1 - Tzartos, S. A1 - Mamalaki, A. A1 - Etschmann, B. A1 - Muller-Hermelink, H. K. A1 - Koscielniak, E. A1 - Barth, S. A1 - Marx, A. T1 - A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article] N2 - Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68200 ER -