MicroRNAs in kidney health and disease

This thesis describes a role for microRNAs in kidney (patho)physiology. First, it is shown that miR-155 negatively regulates RhoA signaling in TGF-induced endothelial-to-mesenchymal-transition (EndoMT). EndoMT associates with reorganization of the cytoskeleton and production of extracellular matrix, and is potentially involved in the loss of microvascular capillaries in renal fibrosis. Second, we focused on ischemia/reperfusion-injury (IRI), a central event in conditions such as acute kidney injury and organ transplantation, where the renal peritubular capillary network is considered the primary site of injury. Consequently, capillary integrity is a key determinant for preservation of renal function. Systemic silencing of miR-126 impairs ischemia-induced angiogenesis, and affects mobilization of vasculogenic progenitor cells, potentially by modulating SDF-1 expression. Furthermore, overexpression of miR-126 in the hematopoietic compartment protects against renal IRI by promoting vascular integrity. We identified miR-132 to be involved in renal fibrosis. Lineage analysis of kidney stroma showed that pericytes are the major source of myofibroblasts Silencing miR-132 results in decreased pericyte differentiation towards myofibroblasts. Subsequently we demonstrated that miR-132 regulates diuresis by altering Aquaporin-2 localization in collecting ducts, which is responsible for water-reabsorption, by modulating vasopressin- and prostaglandin-dependent pathways. This thesis illustrates the essential role that microRNAs play in kidney health and disease.LUMC / Geneeskund

Self-contained in-vacuum in situ thin film stress measurement tool

A fully self-contained in-vacuum device for measuring thin film stress in situ is presented. The stress was measured by measuring the curvature of a cantilever on which the thin film was deposited. For this, a dual beam laser deflectometer was used. All optics and electronics needed to perform the measurement are placed inside a vacuum-compatible vessel with the form factor of the substrate holders of the deposition system used. The stand-alone nature of the setup allows the vessel to be moved inside a deposition system independently of optical or electronic feedthroughs while measuring continuously. A Mo/Si multilayer structure was analyzed to evaluate the performance of the setup. A radius of curvature resolution of 270 km was achieved. This allows small details of the stress development to be resolved, such as the interlayer formation between the layers and the amorphous-to-crystalline transition of the molybdenum which occurs at around 2 nm. The setup communicates with an external computer via a Wi-Fi connection. This wireless connection allows remote control over the acquisition and the live feedback of the measured stress. In principle, the vessel can act as a general metrology platform and add measurement capabilities to deposition setups with no modification to the deposition system

Surface and sub-surface oxidation of thin films using Low Energy Ion Scattering

Ru and ZrN are candidate capping layers for applications such as catalysis, electronics and optical coatings: Ru exhibits a low resistivity, high thermal stability, excellent oxidation resistance and good diffusion capabilities. ZrN is thermally stable, and is known for its good mechanical properties. Although the oxidation process has been studied for both materials, the surface and especially the sub-surface oxidation is not properly understood and well addressed. We use the sub-monolayer surface sensitivity of the low energy ion scattering (LEIS) technique for in-situ monitoring of surface oxidation and determination of the oxygen sticking probabilities. From the LEIS in-depth signal, sub-nanometer sub-surface oxidation can be determined as a function of time and from these data oxygen diffusion constants can be extracted. These data support the applications for which adequate protecting surface films are required. i) Author to whom correspondence should be addressed. Electronic mail: [email protected]

Surface and sub-surface thermal oxidation of thin ruthenium films

A mixed 2D (film) and 3D (nano-column) growth of ruthenium oxide has been experimentally observed for thermally oxidized polycrystalline ruthenium thin films. Furthermore, in situ x-ray reflectivity upon annealing allowed the detection of 2D film growth as two separate layers consisting of low density and high density oxides. Nano-columns grow at the surface of the low density oxide layer, with the growth rate being limited by diffusion of ruthenium through the formed oxide film. Simultaneously, with the growth of the columns, sub-surface high density oxide continues to grow limited by diffusion of oxygen or ruthenium through the oxide fil

Imaging the renal microcirculation in cell therapy

Renal microvascular rarefaction plays a pivotal role in progressive kidney disease. Therefore, modalities to visualize the microcirculation of the kidney will increase our understanding of disease mechanisms and consequently may provide new approaches for evaluating cell-based therapy. At the moment, however, clinical practice is lacking non-invasive, safe, and efficient imaging modalities to monitor renal microvascular changes over time in patients suffering from renal disease. To emphasize the importance, we summarize current knowledge of the renal microcirculation and discussed the involvement in progressive kidney disease. Moreover, an overview of available imaging techniques to uncover renal microvascular morphology, function, and behavior is presented with the associated benefits and limitations. Ultimately, the necessity to assess and investigate renal disease based on in vivo readouts with a resolution up to capillary level may provide a paradigm shift for diagnosis and therapy in the field of nephrology.Nephrolog

Specular reflection intensity modulated by grazing-incidence diffraction in a wide angular range

Grazing-incidence X-ray diffraction (GID) is a well known technique for the characterization of crystal surfaces. A theoretical study has been performed of the sensitivity of GID to the structure of a crystal surface and distorted nanometre-thin surface layers. To simulate GID from crystals that have a complex subsurface structure, a matrix formalism of the dynamical diffraction theory has been applied. It has been found that the azimuthal rocking curves of a crystal that has a distorted subsurface, measured over a wide angular range, show asymmetric thickness oscillations with two distinguishable sets of frequencies: one corresponding to the diffraction in the single-crystal subsurface layer and the second corresponding to the diffraction in the single-crystal substrate. Therefore, azimuthal rocking curves allow characterization of the subsurface structure of a single crystal. Furthermore, thickness oscillations induced by evanescent diffraction modulate the specular reflection intensity, showing high-intensity modulations. This will potentially allow implementation of subsurface crystal characterization using, for instance, a laboratory-scale X-ray diffractometer.</p

Mo/Si multilayer-coated amplitude division beam splitters for XUV radiation sources

Amplitude-division beam splitters for XUV radiation sources have been developed and extensively characterized. Mo/Si multilayer coatings were deposited on 50 nm-thick SiN membranes. By changing the multilayer structure (periodicity, number of bilayers, etc.) the intensity of the reflected and transmitted beams were optimized for selected incident radiation parameters (wavelength, incident angle). The developed optical elements were characterized by means of XUV reflectometry and transmission measurements, atomic force microscopy and optical interferometry. Special attention was paid to the spatial homogeneity of the optical response and reflected beam wavefront distortions. Here the results of the characterization are presented and improvements required for advanced applications at XUV free-electron lasers are identified. A flatness as low as 4 nm r.m.s. on 3 × 3 mm beam splitters and 22 nm r.m.s. on 10 × 10 mm beam splitters has been obtained. The high-spatial-frequency surface roughness was about 0.7-1 nm r.m.s. The middle-spatial-frequency roughness was in the range 0.2-0.8 nm r.m.s. The reflection and transmission of the beam splitters were found to be very homogeneous, with a deviation of less than 2% across the full optical element

Self-healing in B12P2 through Mediated Defect Recombination

Citation: Self-healing in B12P2 through Mediated Defect Recombination. S. P. Huber, E. Gullikson, C. D. Frye, J. H. Edgar, R. W. E. van de Kruijs, F. Bijkerk, and D. Prendergast. Chemistry of Materials 28 8415--8428 (2016) 10.1021/acs.chemmater.6b04075The icosahedral boride B12P2 has been reported to exhibit “self-healing” properties, after transmission electron microscopy recordings of sample surfaces, which were exposed to highly energetic particle beams, revealed little to no damage. In this work, employing calculations from first-principles within the density functional theory (DFT) framework, the structural characteristics of boron interstitial and vacancy defects in B12P2 are investigated. Using nudged elastic band simulations, the diffusion properties of interstitial and vacancy defects and their combination, in the form of Frenkel defect pairs, are studied. We find that boron icosahedra maintain their structural integrity even when in a degraded state in the presence of a vacancy or interstitial defect and that the diffusion activation energy for the recombination of an interstitial vacany pair can be as low as 3 meV, in line with the previously reported observation of “self-healing”