Intelligent virtual agents as language trainers facilitate multilingualism

In this paper we introduce a new generation of language trainers: intelligent virtual agents (IVAs) with human appearance and the capability to teach foreign language vocabulary. We report results from studies that we have conducted with Billie, an IVA employed as a vocabulary trainer, as well as research findings on the acceptance of the agent as a trainer by adults and children. The results show that Billie can train humans as well as a human teacher can and that both adults and children accept the IVA as a trainer. The advantages of IVAs are multiple. First, their teaching methods can be based on neuropsychological research findings concerning memory and learning practice. Second, virtual teachers can provide individualized training. Third, they coach users during training, are always supportive, and motivate learners to train. Fourth, agents will reside in the user's mobile devices and thus be at the user's disposal everywhere and anytime. Agents in apps will make foreign language training accessible to anybody at low cost. This will enable people around the world, including physically, financially, and geographically disadvantaged persons, to learn a foreign language and help to facilitate multilingualism

Kontrolle des prä-mRNA Spleißens durch synthetische Riboswitche

RNA-Aptamere sind Moleküle, die über in vitro-Selektion aus einer randomisierten RNA-Bibliothek gewonnen werden und ihre Zielmoleküle mit hoher Affinität und Spezifität binden. In dieser Arbeit wurde die Möglichkeit untersucht, eine für Protein-Selektionen etablierte Methode auf niedermolekulare Substanzen zu übertragen. Zur Etablierung der Selektionsmethode, die auf Streptavidin-beschichteten, paramagnetischen beads beruhte, wurde das Fluorchinolon Ciprofloxacin als Zielmolekül verwendet. Das pharmakologisch gut untersuchte Ciprofloxacin wies eine niedrige Zytotoxizität und eine hohe Zellgängigkeit auf, was für die spätere in vivo-Applikation wichtige Eigenschaften darstellte. Die Selektion gegen Ciprofloxacin führte zu einer spezifischen Anreicherung von Aptameren. Der Großteil der angereicherten Sequenzen enthielt eine Stamm-Schleifenstruktur mit einem ausgebulgten Guanin benachbart zu einem G-U Wobble-Paar im Stamm und dem Sequenzmotiv GCAGGA in der terminalen Schleife. Die nähere Charakterisierung zeigte jedoch, dass die Aptamere nicht den freien Liganden alleine erkennen, sondern die Selektionsmatrix in die Bindung involviert ist. Eine Visualisierung des immobilisierten Ciprofloxacins an Streptavidin zeigte, dass sich der Ligand für eine erfolgreiche Selektion wahrscheinlich nicht genug von der Streptavidinmatrix abhebt und sich somit diese Selektionsmethode nicht für niedermolekulare Substanzen eignet. Im zweiten Teil dieser Arbeit wurde das TetR-bindende Aptamer verwendet, um Intronretention zu kontrollieren. Das TetR-Aptamer wurde in die Nähe der 5’-Spleißstelle eines chimären Introns platziert und durch Überexpression von TetR wurde die Zugänglichkeit des Spleißosoms zur Spleißstelle reduziert. Durch Zugabe von Doxycyclin konnte die TetR-TetR- Aptamer-Interaktion unterbrochen und so die 5’-Spleißstelle wieder zugänglich gemacht werden. Dies führte auf Reportergen-Ebene zu einem Regulationsfaktor von 12,6-fach. Durch die systematische Untersuchung von Intronposition, relative Aptamerposition sowie Stammlänge und -stabilität des Aptamers wurden Regeln für die Anwendbarkeit des Systems aufgestellt. Der Einfluss der Sequenzumgebung lies den Schluss zu, dass die 5’-Speißstelle 2 bzw. 4 nt einzelsträngig vorliegen muss, damit es zur Konkurrenzsituation zwischen Spleißosom und TetR kommen kann. Die mittlere Stammstabilität wurde auf -15,0 kcal/mol berechnet und die relative Aptamerposition sollte bei 6 bzw. 7 nt nach der 5’-Spleißstelle liegen. Im Kontext des verwendeten chimären Introns konnte der durch Doxycyclin erhaltene Phänotyp (AN-Schalter) durch Variation des Abstands zur 5’-Spleißstelle umgekehrt werden (AUS-schalter). Darüber hinaus wurde in dieser Studie das TetR-Protein durch Anfügen einer N-terminalen Kernlokalisationssequenz für die Spleißregulation optimiert. Die Übertragbarkeit dieses synthetischen Riboregulators wurde durch Anwendung auf die Gene CD20 und HSV- TK gezeigt. Durch Kontrolle dieser Gene konnte die Induktion der Apoptose kontrolliert und die Zellviabilität von Hek-293-Zellen um den Faktor 3,5x beeinflusst werden. Die hohe Modularität des Systems, die einfache Verwendung des Riboregulators in prinzipiell jedem Gen ohne weiteres Re-Design des Regulators selbst und die hohe Affinität und Reversibilität der Schaltung machen dieses System basierend auf der Kontrolle der Intronretention zum idealen Baustein, um synthetisch konstruierte Schaltkreise zu kontrollieren. Zudem kann dieses System genutzt werden, um die Grundlagen von Intronretention in Zukunft näher zu verstehen

Aspect-Orientation: from Design to Code

ABSTRACT The AO paradigm focuses mainly at the implementation phases of the software lifecycle and is missing standardized concepts for early stages of the development lifecycle. The term Early Aspects refers to crosscutting properties at the requirements and architecture level and this paper addresses the separation of crosscutting concerns at the architecture design phases by offering AML (Aspect Modeling Language), a notation for aspect-oriented architecture design modeling that is standard UML conform. Within the notation, crosscutting artifacts are clearly encapsulated and completely kept apart from the business logic to foster their reuse. A clear separation of the AO language dependent from AO independent parts simplifies the support of a number of different AO languages and concepts. To extend the support beyond the architecture phase a code generator is presented addressing lowlevel design support by offering an automated mapping from design models to programming models to prevent inconsistencies among design and implementation

Manifold learning for image-based gating of intravascular ultrasound(IVUS) pullback sequences

Intravascular Ultrasound(IVUS) is an imaging technology which provides cross-sectional images of internal coronary vessel struc- tures. The IVUS frames are acquired by pulling the catheter back with a motor running at a constant speed. However, during the pullback, some artifacts occur due to the beating heart. These artifacts cause inaccu- rate measurements for total vessel and lumen volume and limitation for further processing. Elimination of these artifacts are possible with an ECG (electrocardiogram) signal, which determines the time interval cor- responding to a particular phase of the cardiac cycle. However, using ECG signal requires a special gating unit, which causes loss of impor- tant information about the vessel, and furthermore, ECG gating function may not be available in all clinical systems. To address this problem, we propose an image-based gating technique based on manifold learning. Quantitative tests are performed on 3 different patients, 6 different pull- backs and 24 different vessel cuts. In order to validate our method, the results of our method are compared to those of ECG-Gating method

CASE Tool support for variability management in software product lines

Software product lines (SPL) aim at reducing time-to-market and increasing software quality through extensive, planned reuse of artifacts. An essential activity in SPL is variability management, i.e., defining and managing commonality and variability among member products. Due to the large scale and complexity of today’s software-intensive systems, variability management has become increasingly complex to conduct. Accordingly, tool support for variability management has been gathering increasing momentum over the last few years and can be considered a key success factor for developing and maintaining SPLs. While several studies have already been conducted on variability management, none of these analyzed the available tool support in detail. In this work, we report on a survey in which we analyzed 37 existing variability management tools identified using a systematic literature review to understand the tools’ characteristics, maturity, and the challenges in the field. We conclude that while most studies on variability management tools provide a good motivation and description of the research context and challenges, they often lack empirical data to support their claims and findings. It was also found that quality attributes important for the practical use of tools such as usability, integration, scalability, and performance were out of scope for most studies

Adapting integrity checking techniques for concurrent operation executions

One challenge for achieving executable models is preserving the integrity of the data. That is, given a structural model describing the constraints that the data should satisfy, and a behavioral model describing the operations that might change the data, the integrity checking problem consists in ensuring that, after executing the modeled operations, none of the specified constraints is violated. A multitude of techniques have been presented so far to solve the integrity checking problem. However, to the best of our knowledge, all of them assume that operations are not executed concurrently. As we are going to see, concurrent operation executions might lead to violations not detected by these techniques. In this paper, we present a technique for detecting and serializing those operations that can cause a constraint violation when executed concurrently , so that, previous incremental techniques, exploiting our approach, can be safely applied in systems with concurrent operation executions guaranteeing the integrity of the data.Peer ReviewedPostprint (author's final draft

Interventional tool tracking using discrete optimization.

This work presents a novel scheme for tracking of motion and deformation of interventional tools such as guide-wires and catheters in fluoroscopic X-ray sequences. Being able to track and thus to estimate the correct positions of these tools is crucial in order to offer guidance enhancement during interventions. The task of estimating the apparent motion is particularly challenging due to the low signal-to-noise ratio (SNR) of fluoroscopic images and due to combined motion components originating from patient breathing and tool interactions performed by the physician. The presented approach is based on modeling interventional tools with B-splines whose optimal configuration of control points is determined through efficient discrete optimization. Each control point corresponds to a discrete random variable in a Markov random field (MRF) formulation where a set of labels represents the deformation space. In this context, the optimal curve corresponds to the maximum a posteriori (MAP) estimate of the MRF energy. The main motivation for employing a discrete approach is the possibility to incorporate a multi-directional search space which is robust to local minima. This is of particular interest for curve tracking under large deformation. This work analyzes feasibility of employing efficient first-order MRFs for tracking. In particular it shows how to achieve a good compromise between energy approximations and computational efficiency. Experimental results suggest to define both the external and internal energy in terms of pairwise potential functions. The method was successfully applied to the tracking of guide-wires in fluoroscopic X-ray sequences of several hundred frames which requires extremely robust techniques. Comparisons with state-of-the-art guide-wire tracking algorithms confirm the effectiveness of the proposed method. © 1982-2012 IEEE