Monogenic models of migraine : from clinical phenotypes to pathophysiological mechanisms

This thesis explores clinical phenotypes and the pathophysiology of rare monogenic models of migraine with the ultimate goal to identify novel treatment targets for these disorders, as well as for the common types of migraine. The research is divided in two parts: part one describes studies on hemiplegic migraine (HM), a monogenic form of migraine, part two describes studies on Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S), a monogenic vascular syndrome hypothesised to be associated with migraine.LUMC / Geneeskund

Towards a transportable aluminium ion quantum logic optical clock

With the advent of optical clocks featuring fractional frequency uncertainties on the order of 10-17 and below, new applications such as chronometric leveling with few-centimeter height resolution emerge. We are developing a transportable optical clock based on a single trapped aluminum ion, which is interrogated via quantum logic spectroscopy. We employ singly charged calcium as the logic ion for sympathetic cooling, state preparation, and readout. Here, we present a simple and compact physics and laser package for manipulation of 40Ca+. Important features are a segmented multilayer trap with separate loading and probing zones, a compact titanium vacuum chamber, a near-diffraction-limited imaging system with high numerical aperture based on a single biaspheric lens, and an all-in-fiber 40Ca+ repump laser system. We present preliminary estimates of the trap-induced frequency shifts on 27Al+, derived from measurements with a single calcium ion. The micromotion-induced second-order Doppler shift for 27Al+ has been determined to be δνEMMν=-0.4-0.3 +0.4×10-18 and the black-body radiation shift is δνBBR/ν = (-4.0 ± 0.4) × 10-18. Moreover, heating rates of 30 (7) quanta per second at trap frequencies of ωrad,Ca+ ≈ 2π × 2.5 MHz (ωax,Ca+ ≈ 2π × 1.5 MHz) in radial (axial) direction have been measured, enabling interrogation times of a few hundreds of milliseconds

Identifying a gene expression signature of cluster headache in blood.

Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach

Generalized 2d dilaton gravity with matter fields

We extend the classical integrability of the CGHS model of 2d dilaton gravity [1] to a larger class of models, allowing the gravitational part of the action to depend more generally on the dilaton field and, simultaneously, adding fermion- and U(1)-gauge-fields to the scalar matter. On the other hand we provide the complete solution of the most general dilaton-dependent 2d gravity action coupled to chiral fermions. The latter analysis is generalized to a chiral fermion multiplet with a non-abelian gauge symmetry as well as to the (anti-)self-dual sector df = *df (df = -*df) of a scalar field f.Comment: 37 pages, Latex; typos and Eqs. (44,45) corrected; paragraph on p. 26, referring to a work of S. Solodukhin, reformulated; references adde

Heterozygous TREX1 mutations in early-onset cerebrovascular disease

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Dynamical N-body Equlibrium in Circular Dilaton Gravity

We obtain a new exact equilibrium solution to the N-body problem in a one-dimensional relativistic self-gravitating system. It corresponds to an expanding/contracting spacetime of a circle with N bodies at equal proper separations from one another around the circle. Our methods are straightforwardly generalizable to other dilatonic theories of gravity, and provide a new class of solutions to further the study of (relativistic) one-dimensional self-gravitating systems.Comment: 4 pages, latex, reference added, minor changes in wordin

Online Monitoring of the Osiris Reactor with the Nucifer Neutrino Detector

Originally designed as a new nuclear reactor monitoring device, the Nucifer detector has successfully detected its first neutrinos. We provide the second shortest baseline measurement of the reactor neutrino flux. The detection of electron antineutrinos emitted in the decay chains of the fission products, combined with reactor core simulations, provides an new tool to assess both the thermal power and the fissile content of the whole nuclear core and could be used by the Inter- national Agency for Atomic Energy (IAEA) to enhance the Safeguards of civil nuclear reactors. Deployed at only 7.2m away from the compact Osiris research reactor core (70MW) operating at the Saclay research centre of the French Alternative Energies and Atomic Energy Commission (CEA), the experiment also exhibits a well-suited configuration to search for a new short baseline oscillation. We report the first results of the Nucifer experiment, describing the performances of the 0.85m3 detector remotely operating at a shallow depth equivalent to 12m of water and under intense background radiation conditions. Based on 145 (106) days of data with reactor ON (OFF), leading to the detection of an estimated 40760 electron antineutrinos, the mean number of detected antineutrinos is 281 +- 7(stat) +- 18(syst) electron antineutrinos/day, in agreement with the prediction 277(23) electron antineutrinos/day. Due the the large background no conclusive results on the existence of light sterile neutrinos could be derived, however. As a first societal application we quantify how antineutrinos could be used for the Plutonium Management and Disposition Agreement.Comment: 22 pages, 16 figures - Version

Migraine prevalence in patients with unruptured intracranial aneurysms: A case-control study

Paroxysmal Cerebral Disorder