Sleep-dependent consolidation in multiple memory systems

Before newly formed memories can last for the long-term, they must undergo a period of consolidation. It has been shown that sleep facilitates this process. One hypothesis about how this may occur is that learning-related neuronal activity is replayed during following sleep periods. Such a reactivation of neural activity patterns has been repeatedly shown in the hippocampal formation in animals. Hippocampally-induced reactivation can also be observed in other brain areas like the neocortex and basal ganglia. On the behavioral level, sleep has been found to benefit performance on a broad range of memory tasks that rely on different neural systems. Up to now, however, it is unclear whether the same mechanisms mediate effects of sleep on consolidation in different memory systems. In this thesis, we investigated both the effects and the mechanisms of sleep-dependent consolidation in multiple memory systems. We find that sleep benefits performance on a broad range of procedural and declarative memory tasks (studies 1 and 2). These beneficial effects of sleep go beyond a reduction of retroactive interference as effected by quiet wakeful meditation (study 1). In study 2, we demonstrate that the processes underlying these beneficial effects of sleep are different for different memory systems. We assessed performance on typical declarative and procedural memory tasks during one week after participants slept or were sleep deprived for one night after learning. Sleep-dependent consolidation of hippocampal and non-hippocampal memory follows different time-courses. Hippocampal memory shows a benefit of sleep only one day after learning. Performance after sleep deprivation recovers following the next night of sleep, so that no enduring effect of sleep can be observed. However, sleep deprivation before recall does not impair performance. For non-hippocampal memory, on the other hand, long-term benefits of sleep after learning can be observed even after four days. Here, delayed sleep cannot rescue performance. This indicates a dissociation between two sleep-related consolidation mechanisms, which rely on distinct neuronal processes. We studied the neuronal processes underlying sleep effects on declarative memory in study 3, where we investigate learning-related electrophysiological activity in the sleeping brain. With the help of multivariate pattern classification algorithms, we show that brain activity during sleep contains information about the kind of visual stimuli that were learned earlier. We thus find that learned material is actively reprocessed during sleep. In a next step, we examined whether procedural memory can also benefit from reactivation during sleep. We find that a procedural memory task that has been found to activate the hippocampus can be strengthened by externally cueing the reactivation process during sleep. Similar to study 2, this indicates that it is not the traditional distinction between declarative and procedural memory that determines how memories are consolidated during sleep. Rather, memory systems, and in particular hippocampal contribution, decide the sleep-dependent consolidation process. In the first four studies, we examined how sleep affects memory in different memory systems. In our last study, we went one step further and investigated whether multiple memory systems can also interact during consolidation in sleep. We devised a task during which both implicit and explicit memory develop during learning. Results show that sleep not only strengthens implicit and explicit memory individually, it also integrates these formerly separate representations of the learning task. Implicit and explicit memory are negatively correlated immediately after training. Sleep renders this association positive and allows cooperation between the two memory traces. We observe this change both in behavior, using structural equation modeling, and on the level of brain activity, measured by fMRI. After sleep, the hippocampus is more strongly activated during recall of implicit memory, whereas the caudate nucleus shows stronger activity during explicit memory recall. Moreover, both regions show correlated stimulus-induced responses in a task that allows memory systems cooperation. These results provide conclusive evidence that sleep not only strengthens memory, but also reorganizes the contributing neural circuits. In this way, sleep actually changes the quality of the memory representation

Characterisation of the gene regulatory network for posterior segmentation in Parasteatoda tepidariorum

My PhD project focused on the identification of components and the architecture of the gene regulatory network that controls the formation of the segment addition zone (SAZ) and posterior segments in the spider Parasteatoda tepidariorum. Analysis of the formation and function of the SAZ among arthropods suggests that Wnt and Delta-Notch signaling regulated this process ancestrally in an analogous mechanism to that regulating somitogenesis in vertebrates. However, it remained unknown how the two major signaling pathways interact during the formation of the SAZ and regulate other putatively downstream segmentation genes, such as evenskipped (Pt-eve) and runt (Pt-run-1). Therefore, I studied the interactions between Delta (Pt-Dl) and its receptor Notch (Pt-N) and the Wnt ligand gene Wnt8 (Pt-Wnt8). I showed that Pt-Dl initially activates Pt-Wnt8 in the posterior SAZ, but conversely inhibits Pt-Wnt8 expression in the anterior SAZ. Furthermore, I observed the dynamic expression of Pt-eve and Pt-run-1 in the SAZ and the forming segments, suggesting an important role in posterior development. Moreover my results show that the expression of Pt-eve and Ptrun-1 is regulated by the read out of Delta-Notch and Wnt signaling via caudal (Pt-cad), which might be a mechanism ancestral to all arthropods. To investigate the function of Wnt signaling in more detail in spiders, I also studied the evolution and expression of Frizzled receptors (Fz) during spider embryogenesis. Four Fz genes (Pt-fz1, Pt-fz2, Pt-fz4a, Pt-fz4b) have been identified in Parasteatoda and analysis of the expression of the frizzled receptor genes throughout embryonic development suggests an involvement in neuroectoderm development, segmentation and development of anterior 5 structures. Moreover, the early ubiquitous and later segmental expression of Pt-fz1 shows that this gene is a good candidate receptor for Wnt8 in Parasteatoda

Hä? Das geht doch gar nicht! Forschungsergebnisse zum Monitoring des Sprachverstehens (MSV) im Vorschulalter

Monitoring des Sprachverstehens (MSV) umfasst einerseits das Erkennen von nicht- oder missverständlichen Äußerungen sowie Inkonsistenzen und Erwartungsverletzungen in Texten, andererseits die entsprechende Reaktion darauf, z.B. fragender Blick oder Nachfragen. Im Rahmen eines mehrjährigen Forschungsprojekts (2006-2012) an der Ludwig-Maximilians-Universität fanden zahlreiche kleine Forschungsstudien zum MSV statt. Die Ergebnisse zur Entwicklung von MSV, zu MSV-Fähigkeiten bei Sprachentwicklungsstörungen sowie zu Diagnostik und Intervention von MSV im Kindergarten- und Vorschulalter werden im Folgen-den erläutert

Efficient Similarity Search in Structured Data

Modern database applications are characterized by two major aspects: the use of complex data types with internal structure and the need for new data analysis methods. The focus of database users has shifted from simple queries to complex analyses of the data, known as knowledge discovery in databases. Important tasks in this area are the grouping of data objects (clustering), the classification of new data objects or the detection of exceptional data objects (outlier detection). Most algorithms for solving those problems are based on similarity search in databases. This makes efficient similarity search in large databases of structured objects an important basic operation for modern database applications. In this thesis we develop efficient methods for similarity search in large databases of structured data and improve the efficiency of existing query processing techniques. For the data objects, only a tree or graph structure is assumed which can be extended with arbitrary attribute information. Starting with an analysis of the demands from two example applications, several important requirements for similarity measures are identified. One aspect is the adaptability of the similarity search method to the requirements of the user and the application domain. This can even imply a change of the similarity measure between two successive queries of the same user. An explanation component which makes clear why objects are considered similar by the system is a necessary precondition for a purposeful adaption of the measure. Consequently, the edit distance, well-known from string processing, is a common similarity measure for graph structured objects. Its feature to allow a visualization of corresponding substructures and the possibility to weight single operations are the reason for this popularity. But it turns out that the edit distance and similar measures for tree structures are computationally extremely complex which makes them unsuitable for today's large and even growing databases. Therefore, we develop a multi-step query processing architecture which reduces the number of necessary distance calculations significantly. This is achieved by employing suitable filter methods. Furthermore, we show that by easing certain restrictions on the similarity measure, a significant performance gain can be obtained without reducing the quality of the measure. To achieve this, matchings of substructures (vertices or edges) of the data objects are determined. An additional cost function for those matchings allows to derive a similarity measure for structured data, called the edge matching distance, from the cost optimal matching of the substructures. But even for this new similarity measure, efficiency can be improved significantly by using a multi-step query processing approach. This allows the use of the edge matching distance for knowledge discovery applications in large databases. Within the thesis, the properties of our new similarity search methods are proved both theoretically and through experiments.Moderne Datenbankanwendungen werden vor allem durch zwei wesentliche Aspekte charakterisiert. Dies ist zum einen die Verwendung komplexer Datentypen mit interner Struktur und zum anderen die Notwendigkeit neuer Recherchemöglichkeiten. Der Fokus bei der Datenbankbenutzung hat sich von einfachen Anfragen hin zu komplexen Analysen des Datenbestandes, dem sogenannten Knowledge-Discovery in Datenbanken, entwickelt. Wichtige Analysetechniken in diesem Bereich sind unter anderem die Gruppierung der Daten in Teilmengen (Clustering), die Klassifikation neuer Datenobjekte im Bezug auf den vorhandenen Datenbestand und das Erkennen von Ausreißern in den Daten (Outlier-Identifikation). Die Basis für die meisten Verfahren zur Lösung dieser Aufgaben bildet dabei die Bestimmung der Ähnlichkeit von Datenbankobjekten. Die effiziente Ähnlichkeitssuche in großen Datenbanken strukturierter Objekte ist daher eine wichtige Basisoperation für moderne Datenbankanwendungen. In dieser Doktorarbeit werden daher effiziente Verfahren für die Ähnlichkeitssuche in großen Mengen strukturierter Objekte entwickelt, bzw. die Effizienz vorhandener Verfahren deutlich zu verbessert. Dabei wird lediglich eine baum- oder allgemein graphartige innere Struktur der Datenobjekte vorausgesetzt, die durch beliebige Attribute erweitert wird. Ausgehend von einer Analyse der Anforderungen an Ähnlichkeitssuchverfahren in zwei Beispielsanwendungen aus dem Bereich der Bildsuche und des Proteindockings, wurden mehrere wichtige Aspekte der Ähnlichkeitssuche identifiziert. Ein erster Aspekt ist, das Maß für die Ähnlichkeit für den Benutzer anpassbar zu gestalten, da der zugrundeliegende Ähnlichkeitsbegriff sowohl benutzer- als auch situationsabhängig ist, was bis hin zur Änderung des Ähnlichkeitsbegriffs zwischen zwei aufeinanderfolgenden Anfragen gehen kann. Voraussetzung für eine zielgerichtete Anpassung des Ähnlichkeitsbegriffs ist dabei eine Erklärungskomponente, welche dem Benutzer das Zustandekommen eines Ähnlichkeitswertes verdeutlicht. Die aus der Stringverarbeitung bekannte Edit-Distanz ist deshalb ein weit verbreitetes Maß für die Ähnlichkeit von graphstrukturierten Objekten, da sie eine Gewichtung einzelner Operationen erlaubt und durch eine Zuordnung von Teilobjekten aus den zu vergleichenden Strukturen eine Erklärungskomponente liefert. Es zeigt sich jedoch, dass die Bestimmung der Edit-Distanz und vergleichbarer Ähnlichkeitsmaße für Baum- oder Graphstrukturen extrem zeitaufwendig ist. Es wird daher zunächst ein mehrstufiges Anfragebearbeitungsmodell entwickelt, welches durch geeignete Filterschritte die Anzahl der notwendigen Distanzberechnungen massiv reduziert und so die Geschwindigkeit der Anfragebearbeitung deutlich steigert bzw. erst für große Datenmengen akzeptabel macht. Im nächsten Schritt wird aufgezeigt, wie sich durch Lockerung einiger Bedingungen für das Ähnlichkeitsmaß deutliche Geschwindigkeitssteigerungen erreichen lassen, ohne Einbußen bezüglich der Qualität der Anfrageergebnisse hinnehmen zu müssen. Dazu werden Paarungen von Teilstrukturen (Knoten oder Kanten) der zu vergleichenden Objekte bestimmt, die zusätzlich mittels einer Kostenfunktion gewichtet werden. Eine bezüglich dieser Kostenfunktion optimale Paarung aller Teilstrukturen stellt dann ein Maß für die Ähnlichkeit der Vergleichsobjekte dar, die sogenannte "edge matching distance". Es zeigt sich jedoch, dass auch für dieses neue Ähnlichkeitsmaß eine mehrstufige Anfragebearbeitung zusammen mit entsprechenden, neuartigen Filtermethoden eine erhebliche Performanzsteigerung erlaubt. Diese stellt die Voraussetzung für die Anwendung der Verfahren im Rahmen des Knowledge-Discovery in großen Datenbanken dar. Dabei werden die genannten Eigenschaften der neu entwickelten Verfahren sowohl theoretisch als auch mittels praktischer Experimente belegt

Ionisation cooling in FFAG's

Japan's unique scenario for a neutrino factory is at present the only one that does not rely on ionisation cooling of the muon beam. This is made possible by the large intrinsic acceptances of the FFAG accelerators replacing the linacs and recirculators of the other scenarios. Nevertheless, it is shown, using basic cooling theory, that moderate cooling in the first FFAG could be beneficial for the overall muon yield. Moreover, a solution using Be windows in the radio-frequency accelerating cavities would improve their performance. Simulation results obtained with the ACCSIM code essentially corroborate the theoretical cooling predictions, although showing a yet unexplained emittance exchange mechanism between the transverse phase spaces

Self-dual instanton and nonself-dual instanton-antiinstanton solutions in d=4d=4 Yang-Mills theory

Subjecting the SU(2) Yang--Mills system to azimuthal symmetries in both the $x-y$ and the $z-t$ planes results in a residual subsystem described by a U(1) Higgs like model with two complex scalar fields on the quarter plane. The resulting instantons are labeled by integers $(m,n_1,n_2)$ with topological charges $q=\frac12 [1-(-1)^m]n_1n_2$. Solutions are constructed numerically for $m=1,2,3$ and a range of $n_1=n_2=n$. It is found that only the $m=1$ instantons are self-dual, the $m>1$ configurations describing composite instanton-antiinstanton lumps.Comment: 12 pages, 5 Figure