Characterisation and processing of amorphous binary mixtures with low glass transition temperature

The number of drug substances in formulation development in the pharmaceutical industry is increasing. Some of these are amorphous drugs and have glass transition below ambient temperature, and thus they are usually difficult to formulate and handle. One reason for this is the reduced viscosity, related to the stickiness of the drug, that makes them complicated to handle in unit operations. Thus, the aim in this thesis was to develop a new processing method for a sticky amorphous model material. Furthermore, model materials were characterised before and after formulation, using several characterisation methods, to understand more precisely the prerequisites for physical stability of amorphous state against crystallisation. The model materials used were monoclinic paracetamol and citric acid anhydrate. Amorphous materials were prepared by melt quenching or by ethanol evaporation methods. The melt blends were found to have slightly higher viscosity than the ethanol evaporated materials. However, melt produced materials crystallised more easily upon consecutive shearing than ethanol evaporated materials. The only material that did not crystallise during shearing was a 50/50 (w/w, %) blend regardless of the preparation method and it was physically stable at least two years in dry conditions. Shearing at varying temperatures was established to measure the physical stability of amorphous materials in processing and storage conditions. The actual physical stability of the blends was better than the pure amorphous materials at ambient temperature. Molecular mobility was not related to the physical stability of the amorphous blends, observed as crystallisation. Molecular mobility of the 50/50 blend derived from a spectral linewidth as a function of temperature using solid state NMR correlated better with the molecular mobility derived from a rheometer than that of differential scanning calorimetry data. Based on the results obtained, the effect of molecular interactions, thermodynamic driving force and miscibility of the blends are discussed as the key factors to stabilise the blends. The stickiness was found to be affected glass transition and viscosity. Ultrasound extrusion and cutting were successfully tested to increase the processability of sticky material. Furthermore, it was found to be possible to process the physically stable 50/50 blend in a supercooled liquid state instead of a glassy state. The method was not found to accelerate the crystallisation. This may open up new possibilities to process amorphous materials that are otherwise impossible to manufacture into solid dosage forms.

Language and Letters of the Bluestocking Network : Sociolinguistic Issues in Eighteenth Century Epistolary English

This study deals with language change and variation in the correspondence of the eighteenth-century Bluestocking circle, a social network which provided learned men and women with an informal environment for the pursuit of scholarly entertainment. Elizabeth Montagu (1718 1800), a notable social hostess and a Shakespearean scholar, was one of their key figures. The study presents the reconstruction of Elizabeth Montagu s social networks from her youth to her later years with a special focus on the Bluestocking circle, and linguistic research on private correspondence between Montagu and her Bluestocking friends and family members between the years 1738 1778. The epistolary language use is investigated using the methods and frameworks of corpus linguistics, historical sociolinguistics, and social network analysis. The approach is diachronic and concerns real-time language change. The research is based on a selection of manuscript letters which I have edited and compiled into an electronic corpus (Bluestocking Corpus). I have also devised a network strength scale in order to quantify the strength of network ties and to compare the results of the linguistic research with the network analysis. The studies range from the reconstruction and analysis of Elizabeth Montagu s most prominent social networks to the analysis of changing morphosyntactic features and spelling variation in Montagu s and her network members correspondence. The linguistic studies look at the use of the progressive construction, preposition stranding and pied piping, and spelling variation in terms of preterite and past participle endings in the regular paradigm (-ed, - d, -d, - t, -t) and full / contracted spellings of auxiliary verbs. The results are analysed in terms of social network membership, sociolinguistic variables of the correspondents, and, when relevant, aspects of eighteenth-century linguistic prescriptivism. The studies showed a slight diachronic increase in the use of the progressive, a significant decrease of the stigmatised preposition stranding and increase of pied piping, and relatively informal but socially controlled epistolary spelling. Certain significant changes in Elizabeth Montagu s language use over the years could be attributed to her increasingly prominent social standing and the changes in her social networks, and the strength of ties correlated strongly with the use of the progressive in the Bluestocking Corpus. Gender, social rank, and register in terms of kinship/friendship had a significant influence in language use, and an effect of prescriptivism could also be detected. Elizabeth Montagu s network ties resulted in language variation in terms of network membership, her own position in a given network, and the social factors that controlled eighteenth-century interaction. When all the network ties are strong, linguistic variation seems to be essentially linked to the social variables of the informants.

Incarnate Subjectivity : The Constitutive Significance of Embodiment in Husserlian Phenomenology

This work offers a systematic phenomenological investigation of the constitutive significance of embodiment. It provides detailed analyses of subjectivity in relation to itself, to others, and to objective reality, and it argues that these basic structures cannot be made intelligible unless one takes into account how they are correlated with an embodied subject. The methodological and conceptual starting point of the treatise is the philosophy of Edmund Husserl. The investigation employs the phenomenological method and uses the descriptions and analyses provided by Husserl and his successors. The treatise is motivated and outlined systematically, and textual exegesis serves as a means for the systematic phenomenological investigation. The structure of the work conforms to the basic relations of subjectivity. The first part of the thesis explores the intimate relation between lived-body and selfhood, analyzes the phenomena of localization, and argues that self-awareness is necessarily and fundamentally embodied self-awareness. The second part examines the intersubjective dimensions of embodiment, investigates the corporal foundations of empathy, and unravels the bodily aspects of transcendental intersubjectivity. The third part scrutinizes the role of embodiment in the constitution of the surrounding objective reality: it focuses on the complex relationship between transcendental subjectivity and transcendental intersubjectivity, carefully examines the normative aspects of genetic and generative self-constitution, and argues eventually that what Husserl calls the paradox of subjectivity originates in a tension between primordial and intersubjective normativity. The work thus reinterprets the paradox of subjectivity in terms of a normative tension, and claims that the paradox is ultimately rooted in the structures of embodiment. In this manner, as a whole, the work discloses the constitutive significance of embodiment, and argues that transcendental subjectivity must be fundamentally embodied.

Factors related to seat belt use : A Turkish case

Seat belts are effective safety devices used to protect car occupants from severe injuries and fatalities during road vehicle accidents. Despite the proven effectiveness of seat belts, seat belt use rates are quite low, especially in developing countries, such as Turkey. The general aim of the present study was to investigate a large variety of factors related to seat belt use among Turkish car occupants using different perspectives and methods and therefore, to contribute to the design of effective seat belt use interventions for increasing seat belt use rates in Turkey. Five sub-studies were conducted within the present study. In the first sub-study, environmental (e.g., road type) and psycho-social factors (e.g., belt use by other car occupants) related to the seat belt use of front-seat occupants were investigated using observation techniques. Being male, of a young age, and traveling on city roads were the main factors negatively related to seat belt use. Furthermore, seat belt use by the drivers and front-seat passengers was highly correlated and a significant predictors of each other. In the second sub-study, the motivations of the car occupants for seat belt use and non-use were investigated using interview techniques. Situational conditions, such as traveling on city roads and for short distances, and not believing in the effectiveness and relevance of seat belt use for safety, were the most frequently reported reasons for not using a seat belt. Safety, habit and avoiding punishment were among the most frequently reported reasons for using a seat belt. In the third sub-study, the Theory of Planned Behavior (TPB) and the Health Belief Model (HBM) were applied to seat belt use using Structural Equation Modeling techniques. The TPB model showed a good fit to the data, whereas the HBM showed a poor fit to the data. Within the TPB model, attitude and subjective norm were significant predictors of intentions to use a seat belt on both urban and rural roads. In the fourth sub-study, seat belt use frequency and motivations for seat belt use among taxi drivers were investigated and compared between free-time and work-time driving using a survey. The results showed that taxi drivers used seat belts more when driving a private car in their free-times compared to when driving a taxi during their work-times. The lack of a legal obligation to use a seat belt in city traffic and fear of being attacked or robbed by the passengers were found as two specific reasons for not using a seat belt when driving a taxi. Lastly, in the fifth sub-study, the relationship of seat belt use to driver and health behaviors was investigated using a survey. Although seat belt use was related both to health and driver behaviors, factor analysis results showed that it grouped with driver behaviors. Based on the results of the sub-studies, a tentative empirical model showing different predictors of seat belt use was proposed. According to the model, safety and normative motivations and perceived physical barriers related to seat belt use are the three important predictors of seat belt use. Keywords: Seat belt use; environmental factors; psycho-social factors; safety and normative motivations; the Theory of Planned Behavior; the Health Belief Model; health behaviors; driver behaviors; front-seat occupants; taxi drivers; Turkey.

Visual search and eye movements: Studies of perceptual span

In visual search one tries to find the currently relevant item among other, irrelevant items. In the present study, visual search performance for complex objects (characters, faces, computer icons and words) was investigated, and the contribution of different stimulus properties, such as luminance contrast between characters and background, set size, stimulus size, colour contrast, spatial frequency, and stimulus layout were investigated. Subjects were required to search for a target object among distracter objects in two-dimensional stimulus arrays. The outcome measure was threshold search time, that is, the presentation duration of the stimulus array required by the subject to find the target with a certain probability. It reflects the time used for visual processing separated from the time used for decision making and manual reactions. The duration of stimulus presentation was controlled by an adaptive staircase method. The number and duration of eye fixations, saccade amplitude, and perceptual span, i.e., the number of items that can be processed during a single fixation, were measured. It was found that search performance was correlated with the number of fixations needed to find the target. Search time and the number of fixations increased with increasing stimulus set size. On the other hand, several complex objects could be processed during a single fixation, i.e., within the perceptual span. Search time and the number of fixations depended on object type as well as luminance contrast. The size of the perceptual span was smaller for more complex objects, and decreased with decreasing luminance contrast within object type, especially for very low contrasts. In addition, the size and shape of perceptual span explained the changes in search performance for different stimulus layouts in word search. Perceptual span was scale invariant for a 16-fold range of stimulus sizes, i.e., the number of items processed during a single fixation was independent of retinal stimulus size or viewing distance. It is suggested that saccadic visual search consists of both serial (eye movements) and parallel (processing within perceptual span) components, and that the size of the perceptual span may explain the effectiveness of saccadic search in different stimulus conditions. Further, low-level visual factors, such as the anatomical structure of the retina, peripheral stimulus visibility and resolution requirements for the identification of different object types are proposed to constrain the size of the perceptual span, and thus, limit visual search performance. Similar methods were used in a clinical study to characterise the visual search performance and eye movements of neurological patients with chronic solvent-induced encephalopathy (CSE). In addition, the data about the effects of different stimulus properties on visual search in normal subjects were presented as simple practical guidelines, so that the limits of human visual perception could be taken into account in the design of user interfaces.