Skeletal muscle is defined to be atrophic in osteoporosis models and therefore is a potential target tissue for osteoporosis research. The aim of this longitudinal randomized controlled interdisciplinary study was to analyze the functional, histological, ultra-structral and molecular changes and the role of cachectic muscle atrophy inducer TNF-alpha in the skeletal muscles of the ovariectomized (OVX) rat model which mimics postmenopausal osteoporosis. Female Sprague-Dawley rats were randomly assigned to the control, the OVX and the OVX+10&amp / #956 / g/g/week TNF-alpha antagonist (Remicade) treated OVX-TNF groups. Maximum isometric and tetanic-twitch amplitudes were lower than the control group in the OVX group. Maximum isometric twitch amplitudes recovered in the fast-twitch extensor digitorum longus (EDL) muscles but not in the slow-twitch soleus muscles in the OVX-TNF group. The decrease in tetanic-twitch amplitudes recovered in the OVX-TNF group in both muscle types. Splitting and size variations of fibers, central nuclei and well-preserved overall ultrastructure were noted in the OVX and the OVX-TNF groups. Slow-twitch Type I fiber percentage, areas and diameters increased in EDL muscles of the OVX and the OVX-TNF group comparing to the control group. p65 and MyoD immune-labeling increased in OVX group whereas MyoD and C-Rel increased and p50 decreased in OVX-TNF group. Expressions of 61 genes and 42 unidentified transcripts were significantly different between the control, the OVX and the OVX-TNF groups. To sum up TNF-alpha has a role in skeletal muscle dysfunction in OVX rats and TNF-alpha antagonist administration recovered it. But this modulation was not sufficient for total structural recovery.

This thesis is about coalgebraic methods in software specification and verification. It extends known techniques of coalgebraic specification to a more general level to pave the way for real world applications of software verification. There are two main contributions of the present thesis: 1. Chapter 3 proposes a generalisation of the familiar notion of coalgebra such that classes containing methods with arbitrary types (including binary methods) can be modelled with these generalised coalgebras. 2. Chapter 4 presents the specification language CCSL (short for Coalgebraic Class Specification Language), its syntax, its semantics, and a prototype compiler that translates CCSL into higher-order logic. / Die Dissertation beschreibt coalgebraische Mittel und Methoden zur Softwarespezifikation und -verifikation. Die Ergebnisse dieser Dissertation vereinfachen die Anwendung coalgebraischer Spezifikations- und Verifikationstechniken und erweitern deren Anwendbarkeit. Damit werden Softwareverifikation im Allgemeinen und im Besonderen coalgebraische Methoden zur Softwareverifikation der praktischen Anwendbarkeit ein Stück nähergebracht. Diese Dissertation enthält zwei wesentliche Beiträge: 1. Im Kapitel 3 wird eine Erweiterung des klassischen Begriffs der Coalgebra vorgestellt. Diese Erweiterung erlaubt die coalgebraische Modellierung von Klassenschnittstellen mit beliebigen Methodentypen (insbesondere mit binären Methoden). 2. Im Kapitel 4 wird die coalgebraische Spezifikationssprache CCSL (Coalgebraic Class Specification Language) vorgestellt. Die Bescheibung umfasst Syntax, Semantik und einen Prototypcompiler, der CCSL Spezifikationen in Logik höherer Ordnung (passend für die Theorembeweiser PVS und Isabelle/HOL) übersetzt.

This thesis is concerned with the relationships between physiological changes and subjective and behavioural responses to stress. The effects of noise stress were examined under laboratory conditions, and retrospective studies of stress induced by life events were also carried out. Changes in blood glucose levels were of particular significance under stressful conditions and interesting relationships were found between changes in blood glucose levels and performance at experimental tasks under stressful conditions. Performance and the experience of stress were shown to be affected by the experimental manipulations of blood glucose levels. The effects of stressful conditions on diabetic subjects with impaired control of blood glucose levels were of particular interest. The poor control of blood glucose levels in the 'high glucose diabetics' was exaggerated when working under noise stress. Studies of life events demonstrated that diabetic subjects' experience of life events was associated with physiological disturbance of diabetic control. Diabetics' subjective experiences of stressful conditions were also examined and compared with the experiences of control subjects. Previous research showed considerable evidence to suggest that stress was a promoting factor in ischaemic heart disease (IHD). Subjects with IHD and controls were included in the present research. Experiments similar to those with diabetic subjects were carried out. The IHD subjects had enhanced physiological responses to noise stress which were associated with significantly low levels of reported stress. Subjective experiences of stress were further examined with investigations of the degree of stress associated with life events by Myocardial infarction patients. Differences in subjective experience of stress by patient groups and their controls were discussed in relation to the concept of alexithymia. Experiments with healthy subjects were carried out in order to examine the mechanisms involved in the relationships found between glucose, performance and the perception and experience of stress. The effects of glucose preloading were shown to be primarily of physiological rather than of psychological origin, and a vagal-insulin model was proposed to account for the relationship between glucose preloading and performance efficiency. Experimenter effects were examined in the studies of healthy subjects and the implications of such effects discussed in relation to the results of the experiments with hospital subjects in this work and with reference to other psychophysiological research. The experimental findings were evaluated and suggestions made for further research. In particular research directed towards the possibility of developing a more flexible, individual approach to diabetic management, taking account of unavoidable sources of stress, was outlined.

The aim of this thesis was to examine linguistic and social processing in autism and Asperger syndrome (AS), through computer-mediated communication. The first investigation used conversational analysis, on a corpus of computer-mediated dialogue, generated by two adults with AS. The results revealed that one of the two individuals had problems asking questions. Hence, an inability to ask questions may be one aspect of AS communication, though it may be not universal in this population. The second study used a computer program called Bubble Dialogue (Gray, Creighton, McMahon & Cunningham, 1991) to investigate the working understanding of nonliteral language and responses to inappropriate requests in individuals with AS and high-functioning autism (HFA). The AS/HFA group showed poorer understanding of a figure of speech and were more likely to consent to socially inappropriate requests compared to their typically developing peers. In contrast, understanding of sarcasm was predicted neither by verbal ability, executive ability nor clinical diagnosis. The results suggest that having AS/HFA does not, a priori, dispose someone to having problems with communication and socialisation, and that verbal ability protects the individual to a certain extent. Additionally, executive ability also seems important in mediating socialisation and communication ability. The third experiment tested the hypothesis that an autistic preference for internet-based communication may be due to the absence of verbal and non verbal cues, physical distance, and slower rate of information exchange through that medium. To test this, participants worked out predetermined map routes by asking the experimenter closed questions either via text chat, or through telephone conversations. An initial examination of the results suggested that AS performance may in fact have been better via the telephone. However, a detailed look at the strategies employed by some individuals with AS suggests that their executive problems may have resulted in their use of a less than systematic way to solve the task in both media. The results of this study also indicate a relation between executive and mentalising ability because both are required to solve the task. Interestingly, many of the participants with AS could generate novel closed questions to successfully solve the map task in both media, though they were slower than controls. Using computer mediated communication has therefore given us greater detail into the nature of, and the factors that influence, communication in autism.

The purpose of this study was to examine how different feedback conditions effect the skill learning in basketball. Two task were selected and participants were randomly grouped and assigned to the verbal, visual + verbal, and visual feedback groups. In task one, a continuos skill of basketball, dribbling and in task two a discrete skill of basketball lay up skill were used. Two experts evaluated performances of the participants. In the study first a pre test applied to the subjects to form the groups than a day later subjects performed both task 15 times (5 trails in 3 sets) and get relevant feedback after every 5 trails for three consequent days. 72 hours later a retention test was applied to the subjects to test learning. A 3 &acute / 2 (Group &acute / Condition) ANOVA was used to calculate the differences between the groups in the pre test and post test conditions. The results indicated no significant difference between the groups for the two skills in the pre test but the post-test results indicated significant difference among the verbal to visual + verbal group, visual to visual + verbal group and verbal and visual group. The total difference scores of the groups were also significant where visual + verbal condition indicated the highest improvement whereas the visual condition indicated the least improvement in the two selected basketball skills. The study indicated that the verbal feedback for novice group caused better improvement and retention of the dribbling and lay-up basketball skills compared to the visual feedback group. This watermark does not appear in the registered version -

Die Arbeit behandelt die Entwicklung der sächsischen FDP seit 1990. SIe geht der Frage nach, wie und ob es den Liberalen gelang, nach den desaströsen Wahlergebnissen in den 1990er Jahren im politischen System Sachsen eine Etablierung zu erzielen.

Establishing how cognitive abnormalities result in the signs and symptoms that define schizophrenia and anxiety disorders (and their co-morbidity) has become a prominent question in clinically, and sub-clinically, applied research. Abnormal performance in schizophrenia, schizotypy and anxiety has been observed in comparison to healthy individuals on a range of cognitive and behavioural tasks. For example, abnormal attention to irrelevant information has long been recognised by clinicians, which has since encouraged researchers to elucidate the nature of the relationship between schizophrenia, and anxiety more recently, with allocation of attention to stimuli in laboratory studies providing empirical evidence for an attentional view of these disorders. The pre-exposure effect (slower learning to a stimulus that has been rendered familiar by preexposure, relative to a novel cue), hereafter refered to as latent inhibition, has been shown to be inversely correlated with schizotypy, and abnormal in people with schizophrenia, but findings are inconsistent. One potential contributing factor to this inconsistency is that many tasks that purport to measure latent inhibition are confounded by alternative effects that also retard learning and co-vary with schizotypy, such as learned irrelevance (experience of a cue as irrelevant to the occurrence of an outcome due to inconsistent/uncorrelated presentations of a cue and a target). The general aim of this thesis is to address, or begin to address, some of the key questions and limitations with existing research that evaluate latent inhibition and learned irrelevance as potentially useful cognitive endophenotypes for schizophrenia and anxiety disorders. The current experiments separate out the effects of latent inhibition and learned irrelevance to assess the independent effects of these phenomena on schizotypy (and by extension schizophrenia) and anxiety. By teasing apart, the effects of latent inhibition and learned irrelevance the attempt is to disentangle, and improve understanding of attentional abnormalities observed in these sub-clinical traits and by extension, their related pathologies. Across Experiments 1-4, the purpose was two-fold. The first was to address the limitations of existing latent inhibition tasks by designing a paradigm that examines a purer effect of latent inhibition, by minimising the contribution of learned irrelevance, and assessing how this latent inhibition task co-varies with schizotypy and anxiety (Chapter 2: Experiments 1 and 2). The second was to examine the alternative, potentially less equivocal, learned attentional paradigm (learned irrelevance) and assess the relationship between this task with both schizotypy and anxiety (Chapter 3: Experiments 3 and 4). Based on the assumption that latent inhibition and learned irrelevance share similar psychological underpinnings (in this case, attentional), we anticipated the effect of schizotypy and anxiety to be comparable in the two types of attention tasks here. The results however indicate a double dissociation; an abnormally persistent latent inhibition effect in high positive schizotypy individuals (Experiments 1 and 2) and a reduced learned irrelevance effect in high state anxious individuals (Experiments 3 and 4). The possibility that latent inhibition is non-attentional and the implications of these findings for associative models of attention and learning are explored. The aim of Experiments 5 and 6 were to explore the causal relationship between induced variations in anxiety (stress, relaxation or neutral mood) and learned variations in attention, using a less ambiguous measure of attention (compared to latent inhibition): learned irrelevance. Based on the findings from Experiments 3 and 4, a reduced attentional bias towards previously established predictive cues was expected in individuals induced with an acute state of anxiousness, relative to individuals induced with either a relaxed or neutral mood state. This pattern of results was observed but to a weaker extent than the previous experiments, suggesting that induced variations in anxiety do not have the same relationship with learning as naturally occurring variations in anxiety, as observed in Experiments 3 and 4. Further analyses revealed that the relationship between reduced learned irrelevance and anxiety was mediated by individuals who were also characterised by high levels of schizotypy, and by extension vulnerability to schizophrenia. Given the potential common underlying cognitive processes to both anxiety and schizophrenia, it seems likely that therapies which target the symptoms of anxiety (e.g., Attentional Bias Modification Treatment; ABMT) would be beneficial to individuals who have also been diagnosed with a psychotic disorder. This work represents the first attempt to investigate the independent effects of latent inhibition and learned irrelevance on schizotypy and anxiety, using refined tasks that minimised the contribution of either learning phenomenon on each other. How these learning tasks co-vary in patients with schizophrenia and clinically diagnosed anxiety however remains for future research to determine . At this juncture, the current findings lend support to the potential cognitive endophenotype status of learned irrelevance (considering its status as a less ambiguous measure of attention) and its continued use to provide a base for the development of relevant attentional bias modification treatments.

Epidermal growth factor receptor (EGFR) is a key modulator of a number of cellular processes such as cell fate, proliferation, migration, and apoptosis. The EGFR gene is commonly amplified in a number of cancers and EGFR has been implicated in Alzheimer’s disease, but its role in this context is uncertain. An internal ribosome entry site (IRES) within the EGFR 5’untranslated region (UTR) has been previously discovered which maintains EGFR expression under hypoxic conditions and has a high requirement for the eukaryotic initiation factor (eIF) 4A helicase. Requirement for eIF4A suggests that the structure of the IRES is important in its regulation. Identifying the structure of the IRES and the conditions in which the IRES is active could lead to the development of therapeutics targeting the IRES. The IRES was investigated using bicistronic luciferase vectors. The IRES was found to be active in serum starvation stress but this activation appeared to be cell type specific, suggesting the IRES may depend upon tissue specific trans-acting factors for function. The EGFR IRES appears to not be modular, drawing similarities to the L-myc IRES. Structural data was used to improve prediction models for the IRES, which identified a structural switch that may be regulated by trans-acting factors. Targeting the IRES with anti-sense oligonucleotides proved moderately successful in inhibiting cap-independent translation. To study translational control in an environment closer to those found in Alzheimer’s disease, a 3-dimensional model was developed. Although the model was not spherical and could not be used as intended, it may be useful as a model for studying stress gradients. The effects that EGF stimulation has on translational regulation is poorly understood, yet may be a significant mediator in disease. RNA-seq allows for the quantification of the entire transcriptome for a given condition, whilst polysome profiling fractions mRNA based on ribosomal association. Through polysome profiling, RNA-seq and ontological clustering, it was revealed that EGF increased the translational efficiency of genes associated with Alzheimer’s disease aetiology. Some of these genes were found to be directly connected to the production and oligomerisation of the amyloid beta protein.

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