The Silicon Tracking System of the CBM experiment at FAIR : development of microstrip sensors and signal transmission lines for a low-mass, low-noise system
- In this thesis, different physical and electrical aspects of silicon microstrip sensors and low-mass multi-line readout cables have been investigated. These silicon microstrip sensors and readout cables will be used in the Silicon Tracking System (STS) of the fixed-target heavy-ion Compressed Baryonic Matter (CBM) experiment which is under development at the upcoming Facility for Antiproton and ion Research (FAIR) in Darmstadt, Germany. The highly segmented low-mass tracking system is a central CBM detector system to resolve the high tracking densities of charged particles originating from beam-target interactions. Considering the low material budget requirement the double-sided silicon microstrip detectors have been used in several planar tracking stations. The readout electronics is planned to be installed at the periphery of the tracking stations along with the cooling system. Low-mass multi-line readout cables shall bridge the distance between the microstrip sensors and the readout electronics. The CBM running operational scenario suggests that some parts of the tracking stations are expected to be exposed to a total integrated particle fluence of the order of 1e14 neq/cm2. After 1e14 neq/cm2 the damaged modules in the tracking stations will be replaced. Thus radiation hard sensor is an important requirement for the sensors. Moreover, to cope with the high reaction rates, free-streaming (triggerless) readout electronics with online event reconstruction must be used which require high signal-to-noise (SNR) ratio (i.e., high signal efficiency, low noise contributions). Therefore, reduction in noise is a major goal of the sensor and cable development.
For better insight into the different aspects of the silicon microstrip sensors and multi-line readout cables, the simulation study has been performed using SYNOPSYS TCAD tools. 3D models of the silicon microstrip sensors and the readout cables were implemented which is motivated by the stereoscopic construction of the silicon microstrip sensors. For the evaluation of the performance of the silicon microstrip sensors in the harsh radiation environment during experimental operation, a radiation damage model has been included. It reproduces the behavior of the irradiated CBM prototype sensors. In addition to the static characteristics, the interstrip parameters relevant to understand strip isolation and cross-talk issues have been extracted. The transient simulations have been performed to estimate the charge collection performance of the irradiated sensors. The signal transmission in the readout cables has been evaluated with the finite element simulation tool RAPHAEL. Based on the performance of the front-end electronics used for early prototyping in the CBM experiment, capacitive and resistive noise contributions from the silicon microstrip sensors and multi-line readout cables have been extracted.
To validate the aforementioned simulations, numerous tests have been performed both on the multi-line readout cables and silicon microstrip sensors. Characterizations of multi-line readout cables and silicon microstrip sensors in laboratory conditions have been found to agree reasonably well with the simulations. Considering the expected radiation environment the behavior of silicon microstrip sensors have been studied especially in terms of noise and charge collection efficiency. Source-scan of the silicon microstrip sensors using 241Am is presented. In order to test a first system of detector stations including the data acquisition system, slow control and online monitoring software and for track reconstruction, in-beam tests have been performed at the COSY synchrotron of the Research Center Juelich, Germany. Further, different design parameters have been suggested to improve the sensor and readout cable design on the basis of the simulations and the measurements. Many of these parameters have been implemented in the new prototypes under production. These new prototypes will be tested in-beam by the end of 2013.
Analysis of splicing sensitive microarrays
- Due to recent technical developments, it became evident that the mammalian transcriptome is much more complex than originally expected. Alternative splicing(AS) and the transcription of long non-coding RNAs (lncRNAs) are two phenomenas which have been greatly underestimated in their frequency. Nowadays it is accepted that almost every gene has at least one alternative isoform and the number of lncRNAs exceeds the one of protein-coding genes.
We built user-friendly web interfaces which can process Affymetrix GeneChip Exon 1.0 ST Arrays (exon arrays) and GeneChip Gene 1.0 ST Arrays (gene arrays)for the analysis of alternative splicing events. Results are presented with detailed annotation information and graphics to identify splice events and to facilitate biological validations. Based on two studies using exon arrays, we show how our tools were used to profile genome-wide splicing changes under silencing of Jmjd6 and under hypoxic conditions. Since gene arrays are not intended for AS analysis originally, we demonstrated their applicability by profiling alternative splicing events during embryonic heart development.
To measure lncRNAs expressions with exon arrays, we completely re-annotation all probes and built a lncRNA specific annotation. To demonstrate the applicability of exon arrays in combination with our annotation, we profiled the expression of tens of thousands of lncRNAs. Further, our custom annotation allows for a detailed inspection of lncRNAs and to distinguish between isoforms, as we validated by RTPCR.
To allow for a general usage to the research community, we integrated the annotation in an easy-to-use web interface, which provides various helpful features for the analysis of lncRNAs.
Learning sequences of actions : infant experiments and neural network models
- In our daily life, we carry out lots of tasks like typing, playing tennis, and playing the piano, without even noticing there is sequence learning involved. No matter how simple or complex they are, these tasks require the sequential planning and execution of a series of movements. As an ability of primary importance in one’s life, and an ability that everyone manages to learn, action-sequence learning has been studied by researchers from different fields: psychologists, neurophysiologists as well as roboticists. In the concept of sequence learning, perceptual learning and motor learning, implicit and explicit learning have been studied and discussed independently.
We are interested in infancy research, because infants, with underdeveloped brain functions and with limited motor ability, have little experience with the world and not yet built internal models as presumption of how to interpret the world. A series of infant experiments in the 1980s provided evidence that infants can rapidly develop anticipatory eye movements for visual events. Even when infants have no control of those spatial-temporal patterns, they can respond actually prior to the onset of the visual event, referred as "Anticipation".
In this work, we applied a gaze-contingent paradigm using real-time eye tracking to put 6- and 8-month-old infants in direct control of their visual surroundings. This paradigm allows the infant to change an image on a screen by looking at a peripheral red disc, which functions as a switch. We found that infants quickly learn to perform eye movements to trigger the appearance of new stimuli and that they anticipate the consequences of their actions in an early stage of the experiment.
Attention-shift from learning one stimulus to the next novel stimulus is important in sequence learning. In the test phase of infant visual habituation with two objects, we propose a new theory of explaining the familiarity-to-novelty shift. In our opinion an infant’s interest in a stimulus is related to its learning progress, the improvement of performance. As a consequence, infants prefer the stimulus which their current learning progress is maximal for, naturally giving rise to a familiarity-to-novelty shift in certain situations. Our network model predicts that the familiarity-to-novelty-shift only emerges for complex stimuli that produce bell-shaped learning curves after brief familiarization, but does not emerge for simple stimuli that produce exponentially decreasing learning curves or for long familiarization time, which is consistent with experimental results. This research suggests the infant's interest in a stimulus may be related to its current learning progress. This can give rise to a dynamic familiarity-to-novelty shift depending on both the infant's learning efficiency and the task complexity.
We know that for both infants and adults, the performance on certain motor-sequence tasks can be improved through practice. However, adults usually have to perform complex tasks in complicated environments; for example, learning multiple tasks is unavoidable in our daily life. In existing research, learning multiple tasks showed puzzling and seemingly contradictory results. On the one hand, a wide variety of proactive and retroactive interference effects have been observed when multiple tasks have to be learned. On the other hand, some studies have reported facilitation and transfer of learning between different tasks.
In order to find out the interaction between multiple-task learning, and to find an optimal training schedule, we use a recurrent neural network to model a series of experiments on movement sequence learning. The network model learns to carry out the correct movement sequences through training and reproduces differences between training schedules such as blocked training vs. random training in psychophysics experiments. The network model also shows striking similarity to human performance, and makes prediction for tasks similarity and different training schedules.
In conclusion, the thesis presents learning sequences of actions in infants and recurrent neural networks. We carried out a gaze-contingent experiment to study infants’ rapid anticipation of their own action outcomes, and we also constructed two recurrent neural network models, with one model explaining infant attention shift in visual habituation, and the other model directing to task similarity and training schedule in motor sequence control in adults.
Recombinant measles viruses : use as bivalent vaccine and modulation of their membrane fusion activity
- Life-attenuated measles virus (MV) vaccines have revealed their capacity to routinely induce life-long immunity against MV after just a single or two low-dose injections. Moreover, MV vaccines have been shown to be extensively safe and well tolerated, in general. Thus, MV is a prime candidate for a recombinant vaccine platform to protect also against other pathogens after vaccination. For this purpose, foreign genes can be inserted into additional transcription units (ATU) in recombinant MV genomes so that the encoded foreign proteins are co-expressed with MV proteins in infected cells. These so-called bivalent MV should protect against infection by MV or the pathogen, which the encoded foreign protein had been derived from. Bivalent MVs have already been shown to be effective vaccines against e.g. dengue virus or hepatitis B virus infections by inducing humoral and sometimes also cellular immune responses. In most of these studies, soluble or soluble versions of the pathogens' antigens were used for generation of bivalent MVs.
We hypothesized that the form of the antigen expressed by bivalent MVs is crucial for the potency and constitution of the induced immune responses. Therefore, three different forms of an antigen expressed by bivalent MVs were analyzed, here. The model antigen chosen for this purpose has been the envelope protein (Env) of SIVsmmPBj1.9. In its natural mature form, Env is composed of the surface unit gp120 and the transmembrane unit gp41, which stay non-covalently linked after proteolytic processing of the common precursor protein gp160. However, gp120 can be shed by infected cells or virus particles. Therefore, natural gp160 antigen was used as shedding form. Furthermore, stabilized covalently-linked gp160 variants and soluble gp140 variants were used in this thesis. These different antigen forms were inserted either behind the P or behind the H expression cassettes into the MV genome. The respective bivalent MVs were rescued and characterized. Expression of SIVsmmPBj1.9 Env variants by the bivalent MVs was confirmed by immuno blot and in situ immunoperoxidase assays. Replication curves of bivalent MV showed that growth of MVs expressing the different Env variants was slightly delayed by approximately 24 h compared to control viruses.
For immunization of transgenic, MV-susceptible IFNAR-/--CD46Ge mice, which are the current standard to analyze MV vaccines in a small animal model, an optimal dose of 1x105 TCID50 was determined. For the evaluation of humoral immune responses in transgenic mice, two ELISA systems for the detection of total α-MV and α-SIV antibodies and neutralization assays for detection of neutralizing antibodies against MV and SIV in sera of immunized mice were established. Mice immunized with any of the bivalent MVs showed significant humoral immune responses against MV comparable to those elicited by the parental MV vaccine strain without further genetic modifications. Mice immunized with MVvac2-gp140(P) expressing the soluble gp140 variant revealed highest α-SIV titers with a maximal OD of up to 0.4. Second highest levels of α-SIV antibodies were detected in mice that were immunized with the shedding variants or soluble Env in other positions. MVs expressing the stabilized variants induced only very low α-SIV antibody titers. Neutralizing antibodies directed against SIV could be detected in sera of mice immunized with MVs expressing the soluble or shedding variants, but not in sera of mice immunized with MVs expressing the stabilized variants. In sera of control mice immunized with PBS no antibodies could be detected, as expected. Thus, soluble and shedding antigens induced humoral immune responses, whereas stabilized antigens induced only weak humoral immune responses but no neutralizing antibodies. Analysis of cellular immune responses is still ongoing.
Besides Env, further SIV antigens could be tested for their potency to induce humoral as well as cellular immune responses.
Besides being used as a vaccine platform, recombinant MVs are evaluated as future agent for cancer therapy due to their significant inherent tumor-lytic, so-called oncolytic activity. Currently, the anti-tumoral activity of MV is analyzed in clinical phase I trials. MV strains with high fusion activity are used as oncolytic agents. The fusion protein F of MV strain NSe is highly fusogenic, in contrast to e.g. F of MVwt323, a clone of the pathogenic strain IC-B. Sequence analysis of these two proteins identified one coding nucleotide difference at aa 94 in the F2 domain: a valine (V) in FNSe and a methionine (M) in Fwt323. To evaluate impact of this difference, residues at aa 94 were exchanged. After transient-transfection of MV F and H expression plasmids in receptor-positive cells, V94 in the F2 subunit of FNSe or Fwt323 led to about 6-fold higher fusion activity compared to F proteins with M94. The co-expressed H protein (HNSe or Hwt323) did not influence fusion activity, indicating that the receptor (CD46 or SLAM) bound by H does not quantitatively affect the F proteins' activation. Analysis of F and H showed that formation and transport of MV glycoprotein complexes are not altered by substitution in aa 94 of FNSe or Fwt323.
Furthermore, recombinant MVNSe, MVNSe-F-M94, MVwt323, or MVwt323-F-V94 were rescued. Viral replication revealed slightly higher titers for recombinant MVs expressing M94 in F after 96 h of replication, compared to MVs expressing V94. MVs expressing V94 in F2 showed 2.5-fold higher fusion activity on CD46- and SLAM-positive Vero-hSLAM cells and 2-fold higher fusion activity on B95a cells expressing only SLAM compared to MVs expressing F with M94. Fusion activity of recombinant MVs can thus be modulated by substituting a single aa. V94 in the F protein results in highly fusion active MVs with possibly increased direct cytotoxicity in infected tumors, whereas M94 in F could be associated with decreased fusion activity for therapies, where higher virus titers are required.
The development of infants' action-related object knowledge : deferred imitation and eye tracking studies in 12- and 18-month-olds
- Imitation paradigms are used in various domains of developmental psychological research to assess various cognitive processes such as memory (deferred imitation), action perception and action understanding (mainly direct imitation), as well as categorization and learning about objects (deferred imitation with a change in target objects and generalized imitation). Although these processes are most likely not independent from each other, their relations are still largely unclear. On the one hand, deferred imitation studies have shown that infants' performance improves with increasing age, resulting in the reproduction of more target actions after longer delay intervals. On the other hand, imitation studies focusing on infants' action understanding have found that infants do not necessarily imitate the model's exact actions – actions or action steps that seem to be irrational or irrelevant are omitted by infants under certain circumstances (selective imitation). Additionally, findings of imitation studies that require a transfer of the target actions to novel objects have demonstrated that infants do not only learn about actions, but also about objects, when they engage in imitation.
The present dissertation aims at integrating different perspectives of imitation research by testing 12- and 18-month-old infants in deferred imitation tests consisting of functional vs. arbitrary target actions, and by combining deferred imitation with eye tracking in half of the experiments. A deferred imitation paradigm was chosen to assess memory performance. Systematic variation of target action characteristics enabled the assessment of infants' imitation pattern, i.e., if they would imitate one kind of target actions more frequently than the other. Functionality was chosen as the action characteristic in focus because function is an object's most important property, thus this variation might shed some light on infants' learning about objects in the context of an imitation test. The main goal of the eye tracking experiments was to tackle the relations between infants' visual attention to, and deferred imitation of, different kinds of target actions.
The behavioral experiments revealed that both 12- and 18-month-olds imitated significantly more functional than arbitrary target actions after a delay of 30 minutes. In addition, while 12-month-olds showed a memory effect only for functional actions, 18-month-olds showed a memory effect for both kinds of actions. Thus, 12-month-olds imitated strictly selectively, and 18-month-olds imitated more exactly. This shows that the well established memory effect is modulated by target action functionality, which affects 12- and 18-month-olds' imitation differently. Furthermore, when retested after a two weeks delay, 18-month-olds' performance rates of functional and arbitrary target actions decreased parallel. This suggests that selective imitation is not affected by the duration of the retention interval, and that selection of target actions takes place at an earlier stage of action perception and memory processes.
In the eye tracking experiments, both 12- and 18-month-olds' imitation patterns replicated the findings of the behavioral experiments, showing consistently higher imitation rates of functional than arbitrary target actions. Contrary to this, infants' fixation times to the target actions were not affected by target action functionality. This contrast was supported by statistical analyses that found no clear correspondence between visual attention to and deferred imitation of target actions. This suggests that selective imitation cannot be explained by selective visual attention. Nevertheless, finer-grained analyses of gaze and imitation data in the 18 months old group suggested that infants' increased attention to the social-communicative context of the imitation task was related to more exact imitation, i.e. imitation of not only functional, but also arbitrary target actions.
The findings are discussed against the background of imitation theories, with regard to the relations between different cognitive processes underlying infants' imitation, such as memory, action perception and learning about objects.
Coalescent trees and their lengths
- The work presented in this thesis is devoted to two classes of mathematical population genetics models, namely the Kingman-coalescent and the Beta-coalescents. Chapters 2, 3 and 4 of the thesis include results concerned with the first model, whereas Chapter 5 presents contributions to the second class of models.
Learning strategies and oral proficiency: an investigation of the language learning strategies associated with the achievement of higher levels of oral proficiency in German
- This study identifies the language learning strategies associated with the achievement of higher levels o f oral proficiency in German for one hundred Irish third level students. It is one of the first studies of this kind to be conducted in Ireland and one of the very few, if any, conducted on third level learners of German. Furthermore, as well as identifying the strategies associated with higher levels of proficiency, the study also investigates how these strategies are used by learners displaying higher and lower levels of proficiency. It then explores the question of how the strategies associated with higher levels of proficiency contribute to the process of proficiency development, and how students perceive them as contributing to this process. Finally, the relationships between learner specific characteristics, strategic behaviour and proficiency levels are assessed. The experimental design combines a quantitative survey with in-depth interviews. The results indicate that orally more proficient students use more strategies more frequently. In particular, they use more cognitive, metacognitive and social strategies. Furthermore, they have a repertoire of approximately ten key strategies which they employ in a structured, purposeful manner and apply to a range of language learning situations. They are convinced that these strategies contribute to the development of proficiency, a view which is borne out by the quantitative findings. Finally, higher levels of motivation and more positive perceptions of personal proficiency levels are strongly associated with higher levels of both strategic behaviour and oral proficiency. These findings have significant theoretical and practical implications. Firstly, they demonstrate the importance of expanding the research framework in studies of this kind beyond the mere identification of the strategies associated with higher proficiency levels. Instead, as in this study, future research should incorporate questions relating to the process of strategy implementation by more and less successful learners and to relationships between the use of particular strategies and the process of foreign language acquisition. Secondly, the findings contribute to our understanding of the strategic behaviour of the orally more proficient student, and in particular the orally more proficient learner of German in an Irish third level context. This understanding relates primarily to the strategies these learners use, the way in which they use them and their attitudes towards their use. Such an understanding forms the basis of successful strategies based instruction in the language classroom.
The translators' tale: a translator-centred history of seven English translations (1823-1944) of the Grimms' fairy tale, Sneewittchen
- This thesis explores the backgrounds, motivations and translation practices of the translators of seven English translations of the fairy tale Sneewittchen. It attempts to identify the ‘imprint’ of each of the translators on their translations by highlighting the unique features of each text and formulating explanations for translation practices on the basis of bio-bibliographical research and analysis of translators’ prefaces. It thereby proposes a translator-centred model for research in translation history. It also represents a contribution to the largely unwritten translation history of the Grimms’ tales. The thesis addresses the problems involved in undertaking bio-bibliographical research on translators, the question of the value and reliability of translators’ prefaces, and issues involved in selecting an appropriate research corpus and constructing a corpus-specific translation analysis model. It also provides some insights into the why and how people retranslate texts and contributes to the debate on translation universals. The study demonstrates the complexities involved in seeking to account for translation practices. It nonetheless confirms the hypothesis that translators are ‘active efficient causes’ in the histoiy of translation (Pvm 1998: 160). Individual translators can play an important role in causing translations to be produced and leave a unique ‘imprint’ on their translations The study demonstrates that background information on translators and statements in their prefaces can help to locate this imprint. It also highlights the diversity of the translators’ backgrounds, reasons for translating the text, approach to translation, and attitudes towards the source text, source culture, and target audience. The translators in the study can be compared to storytellers, who shape their text according to time, place, occasion and their own subjectivity. The study shows above all the importance of taking this subjectivity into account, and suggests that the approach adopted here could be used to unite translators, texts, and contexts in translation history.
Treebank-based grammar acquisition for German
- Manual development of deep linguistic resources is time-consuming and costly and therefore often described as a bottleneck for traditional rule-based NLP. In my PhD thesis I present a treebank-based method for the automatic acquisition of LFG resources for German. The method automatically creates deep and rich linguistic presentations from labelled data (treebanks) and can be applied to large data sets. My research is based on and substantially extends previous work on automatically acquiring wide-coverage, deep, constraint-based grammatical resources from the English Penn-II treebank (Cahill et al.,2002; Burke et al., 2004; Cahill, 2004). Best results for English show a dependency f-score of 82.73% (Cahill et al., 2008) against the PARC 700 dependency bank, outperforming the best hand-crafted grammar of Kaplan et al. (2004). Preliminary work has been carried out to test the approach on languages other than English, providing proof of concept for the applicability of the method (Cahill et al., 2003; Cahill, 2004; Cahill et al., 2005). While first results have been promising, a number of important research questions have been raised. The original approach presented first in Cahill et al. (2002) is strongly tailored to English and the datastructures provided by the Penn-II treebank (Marcus et al., 1993). English is configurational and rather poor in inflectional forms. German, by contrast, features semi-free word order and a much richer morphology. Furthermore, treebanks for German differ considerably from the Penn-II treebank as regards data structures and encoding schemes underlying the grammar acquisition task. In my thesis I examine the impact of language-specific properties of German as well as linguistically motivated treebank design decisions on PCFG parsing and LFG grammar acquisition. I present experiments investigating the influence of treebank design on PCFG parsing and show which type of representations are useful for the PCFG and LFG grammar acquisition tasks. Furthermore, I present a novel approach to cross-treebank comparison, measuring the effect of controlled error insertion on treebank trees and parser output from different treebanks. I complement the cross-treebank comparison by providing a human evaluation using TePaCoC, a new testsuite for testing parser performance on complex grammatical constructions. Manual evaluation on TePaCoC data provides new insights on the impact of flat vs. hierarchical annotation schemes on data-driven parsing. I present treebank-based LFG acquisition methodologies for two German treebanks. An extensive evaluation along different dimensions complements the investigation and provides valuable insights for the future development of treebanks.
The representation of work in German grammar books
- This dissertation explores the language of three German grammar books and accompanying exercise books which are produced in Germany for international students of German. It examines how the examples and exercises presented in these books constitute ‘colony texts’ which convey different representations of human activity to the reader. Analysis of the language used in the German grammar books centres on the Linguistics of Representation and borrows techniques used normally in Corpus Linguistics. By using WordSmith Tools this study shows how particular terms (nouns, verbs, adverbs and adjectives) occur with greater frequency than others in the books under analysis thereby representing certain human activities more strongly than others. The activity of ‘work*, in particular, emerges in the grammar books as a key human activity and consequently provides the main focus for analysis in this study. Concordances relating to ‘work’ are grouped and analysed in terms of what they reveal about popular professions, workplace hierarchy and attitudes and approaches to work. Findings are considered from three perspectives: what they reveal to the researcher and learners of German about the representation of ‘work’ in the chosen context, how they compare to findings from comparative analyses of German textbooks and how they can contribute to our overall understanding of ‘text*. Grammar book examples and exercises emerge as ‘texts’ which have significant potential to reflect cultural norms and attitudes despite being considered generally as a source of innocuous and unremarkable language.