University of Antwerp

About: University of Antwerp is a education organization based out in Antwerp, Belgium. It is known for research contribution in the topics: Population & Context (language use). The organization has 16682 authors who have published 48837 publications receiving 1689748 citations. The organization is also known as: Universiteit Antwerpen & UAntwerp.

Ram pressure stripping the hot gaseous haloes of galaxies in groups and clusters

Abstract: We use a large suite of carefully controlled full hydrodynamic simulations to study the ram pressure stripping of the hot gaseous haloes of galaxies as they fall into massive groups and clusters. The sensitivity of the results to the orbit, total galaxy mass, and galaxy structural properties is explored. For typical structural and orbital parameters, we find that ∼30 per cent of the initial hot galactic halo gas can remain in place after 10 Gyr. We propose a physically simple analytic model that describes the stripping seen in the simulations remarkably well. The model is analogous to the original formulation of Gunn & Gott, except that it is appropriate for the case of a spherical (hot) gas distribution (as opposed to a face-on cold disc) and takes into account that stripping is not instantaneous but occurs on a characteristic time-scale. The model reproduces the results of the simulations to within ≈10 per cent at almost all times for all the orbits, mass ratios, and galaxy structural properties we have explored. The one exception involves unlikely systems where the orbit of the galaxy is highly non-radial and its mass exceeds about 10 per cent of the group or cluster into which it is falling (in which case the model underpredicts the stripping following pericentric passage). The proposed model has several interesting applications, including modelling the ram pressure stripping of both observed and cosmologically simulated galaxies and as a way to improve present semi-analytic models of galaxy formation. One immediate consequence is that the colours and morphologies of satellite galaxies in groups and clusters will differ significantly from those predicted with the standard assumption of complete stripping of the hot coronae.

Phase retrieval through focus variation for ultra-resolution in field-emission transmission electron microscopy.

Abstract: The use of a coherent field-emission electron source in transmission electron microscopy is combined with phase retrieval by digital processing of a focal image series. For the first time, a dramatic improvement of the high-resolution performance of the electron microscope beyond the usual ``point-to-point'' resolution has been realized: Experiments on a 200-kV microscope with a point resolution of 0.24 nm reveal reconstructed information down to 0.14 nm. Examples are shown in the field of high-${\mathit{T}}_{\mathit{c}}$ superconductors and ferroelectric oxides. The oxygen sublattice in these structures is revealed.

Probabilistic fiber tracking using the residual bootstrap with constrained spherical deconvolution

Abstract: Constrained spherical deconvolution (CSD) is a new technique that, based on high-angular resolution diffusion imaging (HARDI) MR data, estimates the orientation of multiple intravoxel fiber populations within regions of complex white matter architecture, thereby overcoming the limitations of the widely used diffusion tensor imaging (DTI) technique One of its main applications is fiber tractography The noisy nature of diffusion-weighted (DW) images, however, affects the estimated orientations and the resulting fiber trajectories will be subject to uncertainty The impact of noise can be large, especially for HARDI measurements, which employ relatively high b-values To quantify the effects of noise on fiber trajectories, probabilistic tractography was introduced, which considers multiple possible pathways emanating from one seed point, taking into account the uncertainty of local fiber orientations In this work, a probabilistic tractography algorithm is presented based on CSD and the residual bootstrap CSD, which provides accurate and precise estimates of multiple fiber orientations, is used to extract the local fiber orientations The residual bootstrap is used to estimate fiber tract probability within a clinical time frame, without prior assumptions about the form of uncertainty in the data By means of Monte Carlo simulations, the performance of the CSD fiber pathway uncertainty estimator is measured in terms of accuracy and precision In addition, the performance of the proposed method is compared to state-of-the-art DTI residual bootstrap tractography and to an existing probabilistic CSD tractography algorithm using clinical DW data

Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

Abstract: A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

Abstract: Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells—together with data from the literature—suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.