Mechanismen hochfrequenter synaptischer Übertragung an einer zentralen Synapse: Mechanismen hochfrequenter synaptischer Übertragungan einer zentralen Synapse

Die vorliegende Dissertation verfolgt das Ziel, die von Nervenzellen maximal erreichte Signalrate zu bestimmen. Außerdem werden die bislang weitgehend unbekannten Anpassungen einer Synapse an die Anforderungen hochfrequenter Signalübertragung untersucht. Die maximale Übertragungsrate spielt im zentralen Nervensystem eine wichtige Rolle für die Codierung und Verarbeitung von Informationen. Neben den Grundlagen der synaptischen Übertragung und der neuronalen Informationscodierung werden in der Einleitung die anatomischen Gegebenheiten der Kleinhirnrinde und der Moosfaser-Körnerzell-Synapse vorgestellt. Präsynaptische patch-clamp-Messungen von Moosfaserboutons und die erstmals durchgeführten Messungen von präsynaptischen Boutons und postsynaptischen Körnerzellen („Paarableitungen“) werden erläutert. Mit Hilfe dieser Methoden wird gezeigt, dass die Kommunikation zwischen Nervenzellen mit Raten von bis zu einem Kilohertz stattfinden kann. Hierbei ist die präsynaptische Freisetzung von Botenstoffen schneller und effizienter als bisher bekannt. Ein einzigartiges Repertoire präsynaptischer Mechanismen wird charakterisiert und bildet die Grundlage der nachgewiesenen, hochfrequenten Informationsübertragung.:Abbildungsverzeichnis .......................................................................................... III Abkürzungsverzeichnis ........................................................................................ IV 1 Bibliographische Zusammenfassung .......................................................... 1 2 Einführung ..................................................................................................... 2 2.1 Der cerebelläre Cortex und die Moosfaser-Körnerzell-Synapse ............... 2 2.2 Grundlagen der synaptischen Übertragung .............................................. 5 2.3 Informationscodierung im Nervensystem .................................................. 6 2.4 Etablierung von Ableitungen an der Moosfaser-Körnerzell- Synapse .................................................................................................... 9 2.5 Quellen der Einführung ........................................................................... 13 3 Ziele der Arbeit ............................................................................................ 16 4 Publikationsmanuskript .............................................................................. 16 5 Zusammenfassung ...................................................................................... 29 6 Anlagen ........................................................................................................ 34 6.1 Supplemental Material ............................................................................ 34 6.2 Erklärung über den wissenschaftlichen Beitrag des Promovenden zur Publikation ............................................................................................... 54 6.3 Selbstständigkeitserklärung .................................................................... 55 6.4 Lebenslauf ............................................................................................... 56 6.5 Publikationen ........................................................................................... 58 6.6 Danksagung ............................................................................................ 5

Multimodal Deep Learning for Robust RGB-D Object Recognition

Robust object recognition is a crucial ingredient of many, if not all, real-world robotics applications. This paper leverages recent progress on Convolutional Neural Networks (CNNs) and proposes a novel RGB-D architecture for object recognition. Our architecture is composed of two separate CNN processing streams - one for each modality - which are consecutively combined with a late fusion network. We focus on learning with imperfect sensor data, a typical problem in real-world robotics tasks. For accurate learning, we introduce a multi-stage training methodology and two crucial ingredients for handling depth data with CNNs. The first, an effective encoding of depth information for CNNs that enables learning without the need for large depth datasets. The second, a data augmentation scheme for robust learning with depth images by corrupting them with realistic noise patterns. We present state-of-the-art results on the RGB-D object dataset and show recognition in challenging RGB-D real-world noisy settings.Comment: Final version submitted to IROS'2015, results unchanged, reformulation of some text passages in abstract and introductio

The Many Roles of FAS Receptor Signaling in the Immune System

SummaryFAS belongs to the subgroup of the tumor necrosis factor receptor (TNF-R) family that contains an intracellular “death domain” and triggers apoptosis. Its physiological ligand FASL is a member of the TNF cytokine family. Studies with mutant mice and cells from human patients have shown that FAS plays critical roles in the immune system, including the killing of pathogen-infected cells and the death of obsolete and potentially dangerous lymphocytes. Fas thereby functions as a guardian against autoimmunity and tumor development. FAS triggers apoptosis through FADD-mediated recruitment and activation of caspase-8. In certain cells such as hepatocytes, albeit not lymphocytes, FAS-induced apoptosis requires amplification through proteolytic activation of the proapoptotic BCL-2 family member BID. Curiously, several components of the FAS signaling machinery have been implicated in nonapoptotic processes, including cellular activation, differentiation, and proliferation. This review describes current understanding of Fas-induced apoptosis signaling and proposes experimental strategies for future advances

Inzidenz und Risikofaktoren für hypotensive Episoden nach Anlage rückenmarksnaher Regionalanästhesien : Analysen mit einem Anästhesie-Informations-Management-System

Eine Hypotension zählt zu den häufigsten und wichtigsten Nebenwirkungen bei der Anlage einer rückenmarksnahen Anästhesie wie Spinalanästhesie (SpA) und kombinierter Spinal-Epiduralanästhesie (CSE). Mit Hilfe der im Anästhesie-Informations-Management-System (AIMS) dokumentierten Datensätze wurde ein Algorithmus zur automatischen Detektion dieser Komplikation entwickelt. Dieser wurde als Abfall des mittleren arteriellen Blutdrucks um mehr als 30 % innerhalb von maximal zehn Minuten (min) nach SpA-Punktion und therapeutischer Applikation zusätzlicher Infusionen oder Vasopressoren innerhalb von 20 min nach Beginn des Blutdruckabfalls definiert. Die Analyse von 3.315 Online-Datensätzen singulärer SpA, die von 1997 bis 2000 mit dem AIMS dokumentiert wurden, zeigte eine Inzidenz von 5,4 % für dieses als relevante Hypotension bezeichnete Ereignis. Bei der Anlage einer SpA im Rahmen einer CSE lag diese Inzidenz bei 10,9 %, wie wir in einer zweiten Studie an 1.023 Patienten belegen konnten. In dieser Vergleichsstudie wurden zudem 1.596 singuläre SpA mit einer Inzidenz der relevanten Hypotension von 5 % detektiert. Um unabhängige Prädiktoren für den Auftritt einer relevanten Hypotension zu erkennen, wurden mehr als 20 patientenspezifische, operative und anästhesiologische Variablen in Hinblick auf dieses Ereignis zunächst univariat und folgend multivariat, mit Hilfe der schrittweise vorwärtsgerichteten Regression, getestet. Die Diskrimination der erstellten Modelle wurde mit einer Receiver-Operating-Characteristic Kurve (ROC) überprüft. Die Hosmer-Lemeshow goodness-of- fit-Statistik zeigte in beiden erstellten Modellen jeweils eine gute Kalibration. Als unabhängige Risikoprädiktoren erwiesen sich für die singuläre SpA als patientenspezifische Variablen der chronische Alkoholkonsum (Odds Ratio (OR) = 3,05), eine vorbekannte Hypertonie (OR = 2,21), ein erhöhter Body-Mass- Index (OR = 1,08) und als anästhesiologische Variable die Höhe des sensorischen Blocks >= Th6 (OR = 2,32) und die Dringlichkeit des Eingriffs (OR = 2,84). Die vorbekannte Hypertonie (OR = 1,83) und eine Th6 übersteigende sensorische Blockade konnten auch in der multivariaten Analyse der CSE-Daten als unabhängige Prädiktoren für das Ereignis einer relevanten Hypotension ermittelt werden. Die aufgefundenen Risikoprädiktoren sollten in der klinischen Routine zu einer erhöhten Vigilanz beitragen, um das erhöhte Hypotonierisiko rechtzeitig erkennen und einschätzen zu können und frühzeitig Behandlungsalgorithmen zu entwickeln und auch anwenden zu können.Hypotension is one of the most frequent side effects of spinal anesthesia (SpA) or combined spinal-epidural anesthesia (CSE). By using the data sets collected with an anesthesia information management system (AIMS), an algorithm for automatic detection of this complication after induction has been developed. Relevant hypotension was defined as a decrease of mean arterial blood pressure (MAP) of more than 30 % within a maximum of ten minutes and a therapeutic intervention by the attending anesthesiologist defined as an administration of an additional bolus of crystalloid or colloid fluids or the administration of a vasoconstrictor within 20 minutes after onset of decrease in MAP. Data sets from 3,315 patients receiving singular SpA were analysed and the predefined criteria - relevant hypotension - occured in 166 (5.4 %) cases. Analysing data of 1,023 patients having received CSE, confirmed this incidence at 10.9 %. In this study, relevant hypotension was observed in 5 % of 1,596 singular SpA patients. In order to find independent predictors with regard to relevant hypotension, more than 20 patient-related, operative and anesthesia-related variables, first through univariate and later through multivariate analysis, were tested by using a forward stepwise regression algorithm. The discriminative power of the resulting model was tested with a receiver operating characteristic curve (ROC). The Hosmer-Lemeshow goodness-of-fit test showed a good calibration of the customized models. Independent factors with a significant association to SpA as patient-related variables are chronic alcohol consumption (odds ratio (OR) = 3.05), preoperative history of hypertension (OR = 2.21), an increased Body Mass Index (OR = 1.08) and as anesthesia-related variables a sensory block height >= Th6 (OR = 2.32) and the urgency of surgery (OR = 2.84). A preoperative history of hypertension (OR = 1.83) and higher sensory block levels (>= Th6) have also been detected by the multivariate analysis of the CSE-data as independent factors for relevant hypotension. The knowledge of these risk factors should be useful in clinical routine in increasing vigilance in those patients showing highest risk for hypotension, to prematurely recognize and assess an increased risk of hypotension and in prematurely developing and use therapeutic intervention

Temperature-driven transition from a semiconductor to a topological insulator

We report on a temperature-induced transition from a conventional semiconductor to a two-dimensional topological insulator investigated by means of magnetotransport experiments on HgTe/CdTe quantum well structures. At low temperatures, we are in the regime of the quantum spin Hall effect and observe an ambipolar quantized Hall resistance by tuning the Fermi energy through the bulk band gap. At room temperature, we find electron and hole conduction that can be described by a classical two-carrier model. Above the onset of quantized magnetotransport at low temperature, we observe a pronounced linear magnetoresistance that develops from a classical quadratic low-field magnetoresistance if electrons and holes coexist. Temperature-dependent bulk band structure calculations predict a transition from a conventional semiconductor to a topological insulator in the regime where the linear magnetoresistance occurs.Comment: 7 pages, 6 figure

The cultural embeddedness of professional service purchasing-A comparative study of German and Swedish companies

Research on professional service purchasing generally takes a culturally universalistic approach, implicitly assuming the generalizability of research findings and normative models to different cultural contexts. However, research in related disciplines points to the influence of national culture on managers' decisions, thereby questioning the culturally universalistic approach. The purpose of this paper is to explore differences in professional service purchasing in different cultural contexts. Based on a survey of large organizations, we analyze how the purchasing process for a specific type of professional services - management consulting services - is organized in two cultural contexts (i.e. Germany and Sweden). The results indicate that organizations in Germany and Sweden differ in the way they approach key aspects of the purchasing process. These differences are discussed in relation to two central cultural dimensions - uncertainty avoidance and masculinity-femininity - in which Germany and Sweden take very different positions. It is proposed that uncertainty avoidance mainly influences the first steps in the purchasing process (specify, select and contract) whereas masculinity-femininity mainly influences the remaining steps (order, expedite and evaluate). The paper contributes to the purchasing and supply management literature by empirically illustrating differences in purchasing practices in different cultural contexts and developing theory-driven propositions for the influence of national culture on the professional service purchasing process

Respiratory rate estimation from multi-channel signals using auto-regulated adaptive extended Kalman filter

Background: Respiration rate (RR) is a major cause for false alarms in intensive care units (ICU) and is primarily impaired by the artifact prone signals from skin-attached electrodes. Catheter-integrated esophageal electrodes are an alternative source for multi-channel physiological signals from multiple organs such as the heart and the diaphragm. Nonlinear estimation and sensor fusion are promising techniques for extracting the respiratory activity from such multi-component signals, however, pathologic breathing patterns with rapid RR changes typically observed in patient populations such as premature infants, pose significant challenges. Methods: We developed an auto-regulated adaptive extended Kalman filter (AA-EKF), which iteratively adapts the system model and the noise parameters based on the respiratory pattern. AA-EKF was tested on neonatal esophageal observations (NEO), and also on simulated multi-components signals created using waveforms in CapnoBase and ETNA databases. Results: AA-EKF derived RR (RRAA-EKF) from NEO had lower median (inter-quartile range) error of 0.1 (10.6) breaths per minute (bpm) compared to contemporary neonatal ICU monitors (RRNICU): −3.8 (15.7) bpm (p <0.001). RRAA-EKF error of −0.2 (3.2) bpm was achieved for ETNA wave forms and a bias (95% LOA) of 0.1 (−5.6, 5.9) in breath count. Mean absolute error (MAE) of RRAA-EKF with Capnobase waveforms, as median (inter-quartile range), at 0.3 (0.2) bpm was comparable to the literature reported values. Discussion: The auto-regulated approach allows RR estimation on a broad set of clinical data without requiring extensive patient specific adjustments. Causality and fast response times of EKF based algorithms makes the AA-EKF suitable for bedside monitoring in the ICU setting

Genotype networks in metabolic reaction spaces

Background: A metabolic genotype comprises all chemical reactions an organism can catalyze via enzymes encoded in its genome. A genotype is viable in a given environment if it is capable of producing all biomass components the organism needs to survive and reproduce. Previous work has focused on the properties of individual genotypes while little is known about how genome-scale metabolic networks with a given function can vary in their reaction content. Results: We here characterize spaces of such genotypes. Specifically, we study metabolic genotypes whose phenotype is viability in minimal chemical environments that differ in their sole carbon sources. We show that regardless of the number of reactions in a metabolic genotype, the genotypes of a given phenotype typically form vast, connected, and unstructured sets -- genotype networks -- that nearly span the whole of genotype space. The robustness of metabolic phenotypes to random reaction removal in such spaces has a narrow distribution with a high mean. Different carbon sources differ in the number of metabolic genotypes in their genotype network; this number decreases as a genotype is required to be viable on increasing numbers of carbon sources, but much less than if metabolic reactions were used independently across different chemical environments. Conclusions: Our work shows that phenotype-preserving genotype networks have generic organizational properties and that these properties are insensitive to the number of reactions in metabolic genotypes.Comment: 48 pages, 10 main figures, 14 supplementary figure