Therapeutic proteins have become very successful in the treatment of various chronic and life-threatening diseases. However, besides their benefits, therapeutic proteins seem to have a common... Show moreTherapeutic proteins have become very successful in the treatment of various chronic and life-threatening diseases. However, besides their benefits, therapeutic proteins seem to have a common problem - the response of a patient’s immune system against the protein. This means that the immune system of the patient actively removes the drug from the body, thereby potentially decreasing or reversing the effect of the therapy. By now there is strong consensus that damaged and aggregated proteins are important risk factors. Protein aggregates are, due to their heterogeneity and often low quantity, challanging to characterize. Further, there is a large academic interest in understanding the mechanisms of aggregation and the role of non-proteinaceous particles in the process of protein aggregation and unwanted immunogenicity in order to design more effective and safe protein-based medicines. This PhD thesis supported that research effort by developing and improving analytical methodologies to detect the size, quantity and other properties of protein aggregates and particles, especially in the relevant nano- and micrometer size range. These techniques were then applied to study a so far unknown nanoparticulate impurity in pharmaceutical-grade sugars. Further, the results shown in this thesis revealed that these nanoparticulate impurities pose a threat to protein stability. Show less
My research addresses the function of the much-debated particle -nā in Biblical Hebrew, often translated with “please”, from the point of view of the most important ancient Bible translations ... Show moreMy research addresses the function of the much-debated particle -nā in Biblical Hebrew, often translated with “please”, from the point of view of the most important ancient Bible translations (Greek, Syriac, Latin). It combines textual criticism, translation technique, discourse pragmatics, and the study of politeness in language. The bewildering amount of variation in the rendering of this particle in the ancient versions can be explained as the result of a conscious choice by the translator or as a reflex of a different Hebrew original. After a survey of previous research, a systematic and comprehensive investigation of the evidence shows that the pragmatic function of this particle is strongly conditioned by the context and cannot be explained by a unified denominator. Its primary function appears to be emphasis, hence it sensitizes the addressee/reader. Cases of schematic translation can indicate with relative certainty where -nā was present or not in the Hebrew original of a given translation. By and large, the following tendencies can be observed: the Greek often has dē as the most obvious translation equivalent, the Syriac only translates it occasionally, and the Latin connects it most directly with politeness by a Latin expression for request (generally obsecro or quaeso). Show less
The aim of this research was to establish if the semiotactic theory of C.L. Ebeling could be applied to Modern Japanese and mathematical descriptions of Japanese sentences could be made that are... Show moreThe aim of this research was to establish if the semiotactic theory of C.L. Ebeling could be applied to Modern Japanese and mathematical descriptions of Japanese sentences could be made that are consistent, clear and easy to understand. For this purpose example sentences from various sources, containing the most frequently used structures and expressions of Modern Japanese, were analyzed and described. In doing so, new light has been shed on various aspects of the Japanese language. Firstly, the general assumption that particles, also called postpositions, are similar in meaning and function to the prepositions in English proved to be true only for a number of the particles. Furthermore it was found that the traditional definitions for transitivity do not apply for Japanese, and the commonly assumed classification of noun phrases marked by the particle ga as direct objects has been rejected, in favor of the view that all noun phrases marked by nominative ga are subjects. That this method yields a better insight into the structure of the Japanese language is also demonstrated by the fact that, contrary to the classification commonly assumed until now, it was concluded that there are no indirect objects in Japanese. Show less
