4,874 research outputs found

    Image Classification with Limited Training Data and Class Ambiguity

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    Modern image classification methods are based on supervised learning algorithms that require labeled training data. However, only a limited amount of annotated data may be available in certain applications due to scarcity of the data itself or high costs associated with human annotation. Introduction of additional information and structural constraints can help improve the performance of a learning algorithm. In this thesis, we study the framework of learning using privileged information and demonstrate its relation to learning with instance weights. We also consider multitask feature learning and develop an efficient dual optimization scheme that is particularly well suited to problems with high dimensional image descriptors. Scaling annotation to a large number of image categories leads to the problem of class ambiguity where clear distinction between the classes is no longer possible. Many real world images are naturally multilabel yet the existing annotation might only contain a single label. In this thesis, we propose and analyze a number of loss functions that allow for a certain tolerance in top k predictions of a learner. Our results indicate consistent improvements over the standard loss functions that put more penalty on the first incorrect prediction compared to the proposed losses. All proposed learning methods are complemented with efficient optimization schemes that are based on stochastic dual coordinate ascent for convex problems and on gradient descent for nonconvex formulations

    Autologous coculture of primary human alveolar epithelial cells and macrophages for evaluating the safety and efficacy of novel inhalation pharmaceuticals

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    Animal experiments are general practice to study safety and to estimate the efficacy of orally inhaled drugs in preclinical trials. The relevance of these data for humans is questionable. The aim of this thesis is the development of a relevant in vitro model of the air-blood barrier that can better predict the human in vivo situation. The first chapter describes how particle uptake by alveolar macrophages can be visualized in vitro by correlative light and electron microscopy (CLEM). The second chapter focuses on the development of a cellular in vitro model addressing the alveolar space. The human alveolar autologous coculture consists of primary alveolar type I-like pneumocytes cocultured with primary alveolar macrophages from the same human donor. The model demonstrated its use to investigate cell-particle inreractions at the air-liquid interface. Only macrophages engulfed foreign particles in the in vitro model visualized by CLEM. The ability of the autologous coculture to mimic inflammatory processes in the lung is the focus of the third chapter. The in vitro model showed a typical interleukin release of inflammatory markers after stimulation with lipopolysaccharides. A subsequent treatment with IL-10 loaded particles counterregulated the inflammation.Tierversuche sind gängige Praxis um Unbedenklichkeit oder Wirksamkeit von Inhalanda in präklinischen Studien zu untersuchen. Die Relevanz der durch Tierversuche generierten Daten für den Menschen wird zunehmend in Frage gestellt. Das Ziel dieser Arbeit ist deshalb die Entwicklung eines für den Menschen relevanten in vitro Modells der Blut-Luft-Schranke zur genaueren Vorhersage der humanen in vivo Situation. Im ersten Kapitel wird beschrieben, wie die Aufnahme von Partikeln in Alveolarmakrophagen mit Korrelativer Licht- und Elektronenmikroskopie (CLEM) in vitro visualisiert werden kann. Das zweite Kapitel legt den Fokus auf die Entwicklung eines zellulären alveolaren in vitro Modells. Die humane autologe Kokultur besteht aus primären alveolaren Typ-I ähnlichen Pneumozyten, welche mit primären Alveolarmakrophagen des gleichen Spenders kokultiviert werden. Das Modell erwies sich als geeignet, um Zell-Partikel-Interaktionen zu untersuchen, wobei die Partikel direkt aus der Luft auf die Zelloberfläche abgeschieden wurden. Mittels CLEM konnte gezeigt werden, dass es lediglich die Makrophagen sind, die die Fremdpartikel aufnehmen. Der Fokus des dritten Kapitels liegt auf der Fähigkeit der autologen Kokultur entzündliche Prozesse nachzuahmen. Das in vitro Modell zeigte eine typische Freisetzung entzündlicher Marker nach Stimulation mit Lipopolysacchariden. Eine anschließende Behandlung mit IL-10 beladenen Partikeln führte zu einer anti-inflammatorischen Wirkung

    Studies to the total synthesis of polycyclic, polyprenylated acylphloroglucinols at the example of Hyperforin.

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    Polycyclische, polyprenylierte Acylphloroglucine (PPAPs), wie z.B. Hyperforin, stellen eine interessante Klasse von Naturstoffen dar, die bereits seit Jahrhunderten für ihre antiseptischen, antidepressiven und antibiotischen Eigenschaften bekannt sind. Aufgrund dieser, für pharmazeutische Anwendungen nützlichen Eigenschaften steigerte sich das Interesse an diesen biologisch aktiven Pflanzeninhaltsstoffen in den letzten Jahren. Diese Dissertation beschreibt die Entwicklung einer neuartigen Synthesestrategie, die zum Aufbau des bicyclischen Grundgerüstes von PPAPs führt. Als Schlüsselschritt diente hierzu eine transannulare Acylierung von Cycloocten-Derivaten, die zur Herstellung mehrerer Modellverbindungen für PPAPs genutzt wurde. Die entwickelte Methode zeichnet sich dabei durch große Flexibilität aus, da durch geringfügige Variationen eine Vielzahl an unterschiedlichen PPAPs aufgebaut werden können. Zusätzlich wurden im Rahmen dieser Arbeit viele Erkenntnisse zur Chemie von 8-gliedrigen Carbocyclen gewonnen, die für zukünftige Untersuchungen auf diesem Gebiet nützlich sein werden.Polycyclic polyprenylated acylphloroglucinols (PPAPs), e.g. hyperforin, are a very interesting class of natural products whose antiseptic, antidepressant and antibiotic properties have been known for centuries. In recent years the interest in these biological active plant-ingredients has increased, because of their beneficial properties for medicinal technology and pharmaceutical applications. This PhD-thesis describes the development of a novel strategy for the synthesis of the bicyclic framework of PPAPs. As key step serves a transannular acylation of cyclooctene derivatives, which was successfully applied to the preparation of several model compounds for PPAPs. The developed method shows high flexibility. With only a few variations numerous different PPAPs can be build that way. Furthermore, there were lots of scientific findings about the chemistry of 8-ring compounds, that will be useful for further investigations in this area

    Comparative Analyses of Murine and Human Formyl Peptide Receptor 3

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    Two become one: 19F magnetic resonance imaging and fluorescence imaging combined in BODIPY dyes

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    „Das Nicht-Wahrnehmen von etwas beweist nicht dessen Nicht-Existenz.“ Dalai Lama Im Gegensatz zum obigen Zitat beweist das Wahrnehmen von etwas dessen Existenz. Dieses Prinzip ist ein von Wissenschaftlern häufig angewendetes Prinzip und weist auf die Wichtigkeit von bildgebenden Verfahren für Medizin und life science hin. Bildgebende Verfahren, wie z.B. Fluorescence Imaging oder Magnetic Resonance Imaging, ermöglichen es Objekte oder Wechselwirkungen zwischen Objekten zu visualisieren, die im Interesse des Betrachters liegen. Allerdings kann eine bildgebende Technik nicht alle Daten eines Objektes vollständig liefern. Aufgrund dessen besteht die Möglichkeit zwei oder mehrere bildgebenden Techniken synergistisch zu kombinieren, um die Limitierung der einzelnen Methoden zu überschreiten. Im Fokus dieser Arbeit steht die Entwicklung von Molekülen, die gleichzeitig sowohl für das Fluorescence Imaging als auch für das Magnetic Resonanz Imaging geeignet sind. Als Fluoreszenzfarbstoffsystem dient hierbei die Farbstoffklasse der Boron-dipyrromethene (BODIPYs). Verschiedenste mono- bzw. difluorierte und trifluormethylierte BODIPY-Farbstoff wurden synthetisiert, um mit den erhaltenen Molekülen das erst seit einigen Jahrzehnten bekannte 19F-Magnetic Resonance Imaging durchzuführen. Zusätzlich wurde die Fragmentierung dieser BODIPYs mittels Massenspektroskopie untersucht. Die synthetisierten dualen Reporter zeigten gute Fluoreszenzeigenschaften, jedoch nur geringe 19F-Magnet-Resonanzaktivität. Aufgrund dessen wurden BODIPY-Farbstoffe mit 18 bzw. 27 magnetisch äquivalenten 19F-Atomen hergestellt. Diese hochfluorierten BODIPYs erwiesen sich als vielversprechende Kandidaten für das duale Fluorescence/ Magnetic Resonanz Imaging.“The non-perception of something does not prove its non-existence.” Dalai Lama Contrary to the quotation, the perception of something means its existence. This principle is often used by scientists and shows the importance of imaging modalities in medicine and life science. Imaging modalities, e.g. Fluorescence Imaging or Magnetic Resonance Imaging, allow visualizing objects of interest or interactions between different objects. However, a single imaging technique cannot provide all data of an object of interest. Hence, there exists the possibility to combine two or more imaging techniques to overcome the limitations of each single method. The focus of this work is the development of molecules which are suited for Fluorescence Imaging as well as Magnetic Resonance Imaging. The used chromophore scaffold for this project is the Boron-dipyrromethene (BODIPY). Several different mono- and difluororinated and trifluororinated BODIPY-dyes were synthesized to perform 19F-Magnetic Resonance Imaging, which is known for only a few decades. Additionally, the fragmentation of these BODIPYs was analyzed with mass spectroscopy. The synthesized dual reporters showed good fluorescence properties, but lacked 19F-magnetic resonance activity. As a result, BODIPY-dyes with 18 respectively 27 magnetic equivalent 19F-atoms were synthesized. These high fluorinated BODIPYs turned out to be promising candidates for dual fluorescence/ magnetic resonance imaging

    Sozialwissenschaften

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    This text was published as a book chapter in the publication "Praxishandbuch Open Access" ("Open Access Handbook") edited by Konstanze Söllner and Bernhard Mittermaier. It reflects the current state of Open Access to text publications, data and software in the Social Sciences

    Many{DSL} One Host for All Language Need

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    Languages shape thoughts. This is true for human spoken languages as much as for programming languages. As computers continue to expand their dominance in almost every aspect of our lives, the need to more adequately express new concepts and domains in computer languages arise. However, to evolve our thoughts we need to evolve the languages we speek in. But what tools are there to create and upgrade the computer languages? How can we encourage developers to define their own languages quickly to best match the domains they work in? Nowadays two main approaches exists. Dedicated language tools and parser generators allows to define new standalone languages from scratch. Alternatively, one can “abuse” sufficiently flexible host languages to embed small domain- specific languages within them. Both approaches have their own respective limitations. Creating standalone languages is a major endeavor. Such languages cannot be combined easily with other languages. Embedding, on the other hand, is limited by the syntax of the host language. Embedded languages, once defined, are always present without clear distinction between them and the host language. When used extensively, it leads to one humungous conglomerate of languages, with confusing syntax and unexpected interactions. In this work we present an alternative: ManyDSL. It is a unique interpreter and compiler taking strength from both approaches, while avoiding the above weaknesses. ManyDSL features its own LL1 parser generator, breaking the limits of the syntax of the host language. The grammar description is given in the same host language as the rest of the program. Portions of the grammar can be parametrized and abstracted into functions, in order to be used in other language definitions. Languages are created on the fly during the interpretation process and may be used to parse selected fragments of the subsequent source files. Similarly to embedded languages, ManyDSL translates all custom languages to the same host language before execution. The host language uses a continuation- passing style approach with a novel, dynamic approach to staging. The staging allows for arbitrary partial evaluation, and executing code at different phases of the compilation process. This can be used to define domain-specific optimiza- tions and auxiliary computation (e.g. for verification) — all within an entirely functional approach, without any explicit use of abstract syntax trees and code transformations. With the help of ManyDSL a user is able to create new languages with distinct, easily recognizable syntax. Moreover, he is able to define and use many of such languages within a single project. Languages can be switched with a well-defined boundary, enabling their interaction in a clear and controlled way. ManyDSL is meant to be the first step towards a broader language pluralism. With it we want to encourage developers to design and use languages that best suit their needs. We believe that over time, with the help of grammar libraries, creating new languages will become accessible to every programmer

    Probabilistic Graphical Models for Credibility Analysis in Evolving Online Communities

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    One of the major hurdles preventing the full exploitation of information from online communities is the widespread concern regarding the quality and credibility of user-contributed content. Prior works in this domain operate on a static snapshot of the community, making strong assumptions about the structure of the data (e.g., relational tables), or consider only shallow features for text classification. To address the above limitations, we propose probabilistic graphical models that can leverage the joint interplay between multiple factors in online communities --- like user interactions, community dynamics, and textual content --- to automatically assess the credibility of user-contributed online content, and the expertise of users and their evolution with user-interpretable explanation. To this end, we devise new models based on Conditional Random Fields for different settings like incorporating partial expert knowledge for semi-supervised learning, and handling discrete labels as well as numeric ratings for fine-grained analysis. This enables applications such as extracting reliable side-effects of drugs from user-contributed posts in healthforums, and identifying credible content in news communities. Online communities are dynamic, as users join and leave, adapt to evolving trends, and mature over time. To capture this dynamics, we propose generative models based on Hidden Markov Model, Latent Dirichlet Allocation, and Brownian Motion to trace the continuous evolution of user expertise and their language model over time. This allows us to identify expert users and credible content jointly over time, improving state-of-the-art recommender systems by explicitly considering the maturity of users. This also enables applications such as identifying helpful product reviews, and detecting fake and anomalous reviews with limited information.Comment: PhD thesis, Mar 201

    Development of an in vitro test system for characterization of transport processes at the peritoneum

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    Peritonealdialyse ist eine Behandlungsform des chronischen Nierenversagens. Hierbei wird dem Patienten eine Dialyselösung mit einem osmotischen Agens in den Bauchraum gefüllt und das Bauchfell des Patienten als semipermeable Membran genutzt, um Giftstoffe und überschüssiges Körperwasser zu entziehen. Die Druckdifferenz zwischen Dialyselösung und Blutplasma sowie die Porenstruktur der Blutgefäße ist verantwortlich für die Dialyseeffizienz. Die Poren der Blutgefäße werden in kleine, große Poren sowie Aquaporine unterteilt. Im Rahmen dieser Arbeit wurden verschiedene in vitro Testsysteme entwickelt, um die Transportvorgänge am Peritoneum hinsichtlich Wasser- und Stofftransport zu charakterisieren. Diese wurden parallel genutzt, um den Effekt verschiedener Substanzen zu analysieren. Testsystem A erwies sich als geeignete Methode, um die Ultrafiltrationsleistung an den kleinen Poren des Peritoneums unter Verwendung verschiedener osmotischer Agenzien zu testen. Hierbei zeigten zwei neue Stärkepolymere als osmotische Agenzien eine hohe Ultrafiltrationsleistung. Testsystem B wurde als Zwischenstufe verwendet, um den Wassertransport an einer Aquaporinmembran zu analysieren. Ziel der Arbeit war die Etablierung des Testsystems C, um den Transport über alle Poren parallel zu erfassen. Im Rahmen dieser Arbeit wurde eine Auswahl geeigneter Membranen getroffen und Versuche mit den osmotischen Agenzien Glucose und Icodextrin sowie einem Antagonisten an einer Aquaporinmembran durchgeführt.Peritoneal dialysis is a treatment option for chronic kidney failure. The dialysis solution with an osmotic agent is filled into the abdomen of the patient and the peritoneum the semipermeable membrane is used to remove toxins and water. The difference in pressure between dialysis solution and blood plasma as well as the pore structure of the blood vessels is responsible for the treatment effectiveness. In the course of this work different in vitro test systems have been developed to characterize the transport processes of water and substances at the peritoneum. In parallel these test systems have been used to analyze the effect of different test substances. Test setup A proved to be an appropriate method to test the ultrafiltration performance of different osmotic agents at the small pores of the peritoneum. Two new starch derivatives have shown a high ultrafiltration performance in this evaluation. Test setup B was used as an intermediate stage to analyze the water transport through an aquaporin membrane. The main objective of this work was the establishment of test setup C to perform ultrafiltration experiments with all types of pores in parallel. In the context of this work a selection of suitable membranes has been made and experiments with glucose and Icodextrin as osmotic candidates as well as with an antagonist of aquaporins have been performed

    Entwicklung und Realisierung einer hochauflösenden echtzeitfähigen 3D Sonar Kamera zum Einsatz in der Tiefsee

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    Die fortschreitende Erkundung und Nutzung der Tiefsee machen Visualisierungswerkzeuge notwendig, welche für einen Betrieb unter den extremen Umgebungsbedingungen geeignet sind. Optische Kamerasysteme sind durch die Beeinträchtigungen aufgrund hoher Schwebstoffkonzentrationen besonders im Bereich des Meeresbodens stark eingeschränkt. Als Alternative kommen akustische Bildgebungssysteme in Betracht, die von diesen Beeinträchtigungen deutlich weniger stark betroffen sind. Um eine optische Bildgebung ersetzen zu können, müssen diese akustischen Systeme eine hochaufgelöste volumetrische Abbildung der Umgebung in Echtzeit erlauben. Im Rahmen dieser Arbeit wurde ein Konzept für eine hochauflösende echtzeitfähige 3D Sonar Kamera für den Einsatz in der Tiefsee erarbeitet und in einen Demonstrator überführt. Anhand von Phantommessungen konnte die Leistungsfähigkeit des Kamerakonzeptes validiert werden.The ongoing exploration and utilization of the deep sea necessitate visualization tools which are suitable for an operation under the extreme environmental conditions. Optical camera systems are very restricted for this purpose due to a high concentration of suspended matter in the sea floor area. Acoustic imaging systems can be an appropriate alternative since they do suffer much less from this limitation. In order to substitute optical imaging systems, the acoustic systems have to provide high-resolution volumetric images of the environment in real-time. Within this work, a concept for a high-resolution real-time capable 3D sonar camera has been developed and transferred into a demonstrator. On the basis of measurements on various phantom structures, the system performance could be validated
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