Shape Space Methods for Quantum Cosmological Triangleland

With toy modelling of conceptual aspects of quantum cosmology and the problem of time in quantum gravity in mind, I study the classical and quantum dynamics of the pure-shape (i.e. scale-free) triangle formed by 3 particles in 2-d. I do so by importing techniques to the triangle model from the corresponding 4 particles in 1-d model, using the fact that both have 2-spheres for shape spaces, though the latter has a trivial realization whilst the former has a more involved Hopf (or Dragt) type realization. I furthermore interpret the ensuing Dragt-type coordinates as shape quantities: a measure of anisoscelesness, the ellipticity of the base and apex's moments of inertia, and a quantity proportional to the area of the triangle. I promote these quantities at the quantum level to operators whose expectation and spread are then useful in understanding the quantum states of the system. Additionally, I tessellate the 2-sphere by its physical interpretation as the shape space of triangles, and then use this as a back-cloth from which to read off the interpretation of dynamical trajectories, potentials and wavefunctions. I include applications to timeless approaches to the problem of time and to the role of uniform states in quantum cosmological modelling.Comment: A shorter version, as per the first stage in the refereeing process, and containing some new reference

Unraveling von Willebrand factor extracellular traps

Endothelial cells (ECs) provide a barrier between blood and the underlying tissue. Upon stimulation, specific storage organelles, designated Weibel-Palade bodies (WPBs), fuse with the plasmamembrane and release various components into the bloodstream. The main component of WPBs is von Willebrand factor (VWF), a multimeric glycoprotein which upon its release by endothelial cells is converted into ultra large VWF strings that capture blood platelets. In this thesis we aim to further unravel the biogenesis and functional significance of VWF strings

Proteomic Screen Identifies IGFBP7 as a Novel Component of Endothelial Cell-Specific Weibel-Palade Bodies

Vascular endothelial cells contain unique storage organelles, designated Weibel-Palade bodies (WPBs), that deliver inflammatory and hemostatic mediators to the vascular lumen in response to agonists like thrombin and vasopressin. The main component of WPBs is von Willebrand factor (VWF), a multimeric glycoprotein crucial for platelet plug formation. In addition to VWF, several other components are known to be stored in WPBs, like osteoprotegerin, monocyte chemoattractant protein-1 and angiopoetin-2 (Ang-2). Here, we used an unbiased proteomics approach to identify additional residents of WPBs. Mass spectrometry analysis of purified WPBs revealed the presence of several known components such as VWF, Ang-2, and P-selectin. Thirty-five novel candidate WPB residents were identified that included insulin-like growth factor binding protein-7 (IGFBP7), which has been proposed to regulate angiogenesis. Immunocytochemistry revealed that IGFBP7 is a bona fide WPB component. Cotransfection studies showed that IGFBP7 trafficked to pseudo-WPB in HEK293 cells. Using a series of deletion variants of VWF, we showed that targeting of IGFBP7 to pseudo-WPBs was dependent on the carboxy-terminal D4-C1-C2-C3-CK domains of VWF. IGFBP7 remained attached to ultralarge VWF strings released upon exocytosis of WPBs under flow. The presence of IGFBP7 in WPBs highlights the role of this subcellular compartment in regulation of angiogenesi