In this chapter, Gijsbert Rutten, Iris Van de Voorde and Rik Vosters, refine the Labovian distinction based primarily on the type of language learning involved by bringing in the contact-based... Show moreIn this chapter, Gijsbert Rutten, Iris Van de Voorde and Rik Vosters, refine the Labovian distinction based primarily on the type of language learning involved by bringing in the contact-based insights of Milroy (2007) on this issue. Exploring the extent to which the transmission-diffusion distinction can also apply to orthographic, rather than phonological or morphosyntactic, changes, the authors discuss a range of different examples of both transmission and – various subtypes of – diffusion, mostly from Dutch, German and English. Their central argument is that diffusion must be seen as the dominant driver of orthographic change, but transmission-type changes are also possible in specific historical contexts, for instance in relation to explicit instruction in schools or in closely-knit social networks. Building on different examples and cases, the chapter also explains the link between diffusion and supralocalization, as local and regional spelling practices in medieval times give way to more supraregional writing traditions in postmedieval times. As such, these processes of geographical diffusion of innovations across communities often lay the ground work for later standardization efforts. However, by discussing a slightly more elaborate case study on spelling change and pluricentricity in Dutch language history, the authors show how the development of such supraregional writing traditions often leads not only to linguistic standardization, but also results in a linguistic landscape which can best be described as pluricentric, consisting of different national and regional normative centers from which innovations spread Show less
Single-Molecule Microscopy (SMM) techniques constitute a group of powerful imaging tools that enable researchers to study the dynamic behavior of individual molecules.In the research described in... Show moreSingle-Molecule Microscopy (SMM) techniques constitute a group of powerful imaging tools that enable researchers to study the dynamic behavior of individual molecules.In the research described in this doctoral thesis, SMM techniques have been developed to image individual proteins inside cells of a living zebrafish embryo model and to study patterns of their mobility.The results of the mobility pattern analyses offer new insights into the dynamics of single molecules diffusing inside cells within the context of an intact vertebrate organism. Show less
Background and Purpose Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given... Show moreBackground and Purpose Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given previous evidence for CAA-related loss of cortical thickness and white matter volume, we hypothesized that CAA might also cause tissue loss in the basal ganglia. Methods We compared basal ganglia volumes expressed as a percentage of total intracranial volume (pBGV) of non-demented patients with sporadic and hereditary CAA to age-matched healthy control (HC) and Alzheimer's disease (AD) cohorts.Results Patients with sporadic CAA had lower pBGV (n=80, 1.16%+/- 0.14%) compared to HC (n=80, 1.30%+/- 0.13%, P<0.0001) and AD patients (n=80, 1.23%+/- 0.11%, P=0.001). Similarly, patients with hereditary CAA demonstrated lower pBGV (n=25, 1.26%+/- 0.17%) compared to their matched HC (n=25, 1.36%+/- 0.15%, P=0.036). Using a measurement of normalized basal ganglia width developed for analysis of clinical-grade magnetic resonance images, we found smaller basal ganglia width in patients with CAA-related lobar intracerebral hemorrhage (ICH; n=93, 12.35 +/- 1.47) compared to age-matched patients with hypertension-related deep ICH (n=93, 13.46 +/- 1.51, P<0.0001) or HC (n=93, 15.45 +/- 1.22, P<0.0001). Within the sporadic CAA research cohort, decreased basal ganglia volume was independently correlated with greater cortical gray matter atrophy (r=0.45, P<0.0001), increased basal ganglia fractional anisotropy (r=-0.36, P=0.001), and worse performance on language processing (r=0.35, P=0.003), but not with cognitive tests of executive function or processing speed.Conclusions These findings suggest an independent effect of CAA on basal ganglia tissue loss, indicating a novel mechanism for CAA-related brain injury and neurologic dysfunction. Show less
Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur... Show moreDiffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur within neurons can be reflected as changes in the diffusivity of tNAA, whereas the changes in glial cells can cause pronounced changes in the diffusivities of tCr and tCho. This information combined with that obtained from diffusion tensor imaging (DTI) and other MRI tools can help elucidate various disease processes in the future. The main purposes of this thesis are (i) to investigate neuroanatomy in vivo with DW-MRS, (ii) to develop methodology to enable future clinical applications of the technique in human brain in vivo, and (iii) to characterize the microstructural deficit in neuropsychiatric systemic lupus erythematous (NPSLE) with DW-MRS and other microstructural tools such as DTI and magnetization transfer imaging. The studies presented in this thesis show the robustness and clinical relevance of microstructural information obtained via DW-MRS. The contributions of this thesis such as the optimized acquisition protocols for single volume DW-MRS, the robust DW-CSI and DW-MRS post-processing pipelines that comprise information from DTI, will all facilitate the applications of DW-MRS both for basic neuroscience research and clinical research studies. Show less
The cell membrane acts as a barrier that controls the passage of substances from the outside to the inside of a cell. It is composed of various lipids organized in a bilayer with proteins embedded.... Show moreThe cell membrane acts as a barrier that controls the passage of substances from the outside to the inside of a cell. It is composed of various lipids organized in a bilayer with proteins embedded. Experimental data suggested that lipids are organized in nanometer-sized structures called membrane domains. I study the existence and the role of domains in living cells through single-molecule fluorescence microscopy. This technique allows pinpointing the position of each molecule with high spatial accuracy. I apply it to study the distribution of a membrane-anchored protein, HRas, in the inner leaflet of the membrane. From the single-molecule positions a map of protein distribution is reconstructed. Statistical analysis revealed dynamic partitioning in membrane domains. A different approach relies on tracking single proteins diffusion in the membrane. With this method I studied the influence of domains in the assembly of a two-component receptor, type I interferon receptor. I observed confinements of the components in small domains, which makes assembly faster and more efficient. Further, I present an advanced technique, to track proteins at microsecond time scale. After validating the technique on DNA, I applied it to GPI-anchor protein diffusion. These data confirmed the existence of theoretically proposed, complex diffusive modes. Show less
Brain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an... Show moreBrain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an in vivo visualization of the human brain became available. This thesis describes the development of two unique techniques, imaging of diffusion of water protons and manganese enhanced imaging, that both allow for the depiction of white matter tracts. The reported studies show, that these techniques can be used for a three-dimensional depiction of fiber bundles and that quantitative measures reflecting fiber integrity and neuronal function can be extracted from such data. In clinical applications, the potential use of the developed methods is illustrated in human gliomas, as measure for fiber infiltration, and in spinal cord injury, to monitor potential neuroprotective and __regenerative medication. Show less
Chemotaxis, the process in which cells detect a concentration gradient of a specific substance, interpret that information, and subsequently initiate movement towards the source is an essential... Show moreChemotaxis, the process in which cells detect a concentration gradient of a specific substance, interpret that information, and subsequently initiate movement towards the source is an essential part of many biological phenomena. It___s central to the processes in wound healing, in immune defense and in the formation of a viable embryo. In this thesis I used the well characterized social amoeba Dictyostelium discoideum to investigate, in depth, the dynamics that govern the first steps in the detection of a chemical gradient. D. discoideum detects cyclic adenosine mono-phosphate (cAMP) by a special receptor protein, cAMP receptor 1 (cAR1). Inside the cell this receptor activates a G protein which subsequently initiates a complex signaling cascade. Using fluorescence single-molecule microscopy I investigated the movements of both cAR1 and its associated G protein. During chemotaxis both proteins show striking differences in mobility between the leading and trailing edge of the cell. Those differences are presumably key to our understanding of gradient sensing by cells that have been ignored in models so far. Show less
A human consists of billions of cells. All these cells need to know in which organ they are located and what their position inside the organ is. One way to obtain this information is via morphogens... Show moreA human consists of billions of cells. All these cells need to know in which organ they are located and what their position inside the organ is. One way to obtain this information is via morphogens, small particles providing positional information. We quantitatively studied the transport of the morphogen Decapentaplegic (Dpp) in the __wing imaginal disc__ (the precursor of the wing) of fruit fly larvae. Certain cells in this disc produce Dpp, while others receive it and determine their position according to the Dpp concentration. To study Dpp transport we first developed a microscope able to follow single molecules in three dimensions in living tissue with high spatial and temporal accuracy. With this microscope we then studied the subcellular processes governing intracellular Dpp transport. We determined how long Dpp resides in different types of endosomes (a cellular compartment involved in transport). We also found that the movement of endosomes is too small to facilitate Dpp transport. Furthermore we found differences in the in- and outflow of Dpp in endosomes. This work is one of the first to quantitatively study intracellular morphogen transport. It provides new insights into growth and development of organisms. Show less
This thesis describes an STM study of the creation, diffusion and annihilation of missing atoms, so-called surface vacancies, in the Cu(100) surface. Because of the extremely high mobility of... Show moreThis thesis describes an STM study of the creation, diffusion and annihilation of missing atoms, so-called surface vacancies, in the Cu(100) surface. Because of the extremely high mobility of surface vacancies in combination with their extremely low density, we have been forced to use tracer particles, in form of indium atoms incorporated in the topmost copper layer, in order to investigate the behavior of the surface vacancies. In this study we have employed tailor-made geometries in the copper surface, in which indium atoms were surrounded exclusively by upward or by downward terrace ledges. Our STM movies show a striking difference between these two cases, with differences in jump frequencies and average jump lengths of more than one order of magnitude. This allowed us to determine that surface vacancies are primarily created and annihilated at the upper side of terrace ledges, which can be formulated, in analogy with the energetics of ad-atoms, in terms of an Ehrlich-Schwoebel barrier for surface vacancies. Dedicated low-temperature measurements, where surface vacancies have been artificially created, have directly revealed the diffusion characteristics of individual surface vacancies. These measurements allow us to construct the complete energy landscape for the birth, life and death of surface vacancies in Cu(100). Show less
