Pharmacological Characterization of Novel Histamine H4 Receptor Ligands

Leurs, R. [Promotor]Vischer, H.F. [Copromotor

Collective Almost Synchronization in Complex Networks

This work introduces the phenomenon of Collective Almost Synchronization (CAS), which describes a universal way of how patterns can appear in complex networks even for small coupling strengths. The CAS phenomenon appears due to the existence of an approximately constant local mean field and is characterized by having nodes with trajectories evolving around periodic stable orbits. Common notion based on statistical knowledge would lead one to interpret the appearance of a local constant mean field as a consequence of the fact that the behavior of each node is not correlated to the behaviors of the others. Contrary to this common notion, we show that various well known weaker forms of synchronization (almost, time-lag, phase synchronization, and generalized synchronization) appear as a result of the onset of an almost constant local mean field. If the memory is formed in a brain by minimising the coupling strength among neurons and maximising the number of possible patterns, then the CAS phenomenon is a plausible explanation for it.Comment: 3 figure

Collision-free coordination of a group of unicycle mobile robots

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Onset of chaotic advection in open flows

Non peer reviewedPublisher PD

The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin

Bone Marrow Stromal Cell Antigen 2 (BST-2)/tetherin inhibits the release of numerous enveloped viruses by physically tethering nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency virus (HIV), and pandemic main (M) group HIV type 1s (HIV-1s) are thought to rely exclusively on their Vpu proteins to overcome tetherin-mediated restriction of virus release. However, at least one M group HIV-1 strain, the macrophage-tropic primary AD8 isolate, is unable to express Vpu due to a mutation in its translation initiation codon. Here, using primary monocyte-derived macrophages (MDMs), we show that AD8 Nef protein can compensate for the absence of Vpu and restore virus release to wild type levels. We demonstrate that HIV-1 AD8 Nef reduces endogenous cell surface tetherin levels, physically separating it from the site of viral budding, thus preventing HIV retention. Mechanistically, AD8 Nef enhances internalisation of the long isoform of human tetherin, leading to perinuclear accumulation of the restriction factor. Finally, we show that Nef proteins from other HIV strains also display varying degrees of tetherin antagonism. Overall, we show that M group HIV-1s can use an accessory protein other than Vpu to antagonise human tetherin

A data rate constrained observer for discrete nonlinear systems

In this paper, we develop a communication protocol for the observation of discrete time, possibly unstable, dynamical systems over communication channels with limited communication capacity. We develop an observer based on the upper box dimension for one-way communication channels that leads to a certain type of observability. This communication scheme preserves observability under communication losses which makes the communication scheme robust towards communication losses without feedback in the communication channel. Using Lyapunov-like techniques, we provide bounds on the minimum communication rate required to implement this observer. We also use the Lyapunov dimension to provide analytical upper bounds on the communication rate. We compute an analytical upper bound and an exact expression for the Lyapunov dimension of the smoothened Lozi map. This bound is then tested in simulations of the communication protocol for the observation problem of the smoothened Lozi map.</p

Collision-free coordination of a group of unicycle mobile robots

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The consistency of care for older patients with a hip fracture:are the results of the integrated orthogeriatric treatment model of the Centre of Geriatric Traumatology consistent 10 years after implementation?

Summary: In the past 10 years after implementation, the orthogeriatric treatment model led in general to consistent outcomes for 1555 older adults in terms of most of the complications and mortality. Surgery was more often delayed to 24–48 h after arrival at the hospital, while the length of hospital stay shortened. Introduction: Since 1 April 2008, patients aged ≥ 70 years presenting themselves with a hip fracture at Ziekenhuisgroep Twente (ZGT) have been treated according to the orthogeriatric treatment model. The aim of this study was to investigate if outcomes of the orthogeriatric treatment model are consistent over the first 10 years after implementation. Methods: Between 1 April 2008 and 31 December 2016, patients aged ≥ 70 years who were surgically treated at ZGT for a hip fracture were included and divided into three periods equally distributed in time. Patient characteristics, in-hospital logistics, complications, and mortality data were compared between the three periods. Results: A total of 1555 patients were included. There was a shift in the surgical treatment for the fractured neck of femur from dynamic hip screw/cannulated screws to hemiarthroplasty (p < 0.001). Surgery within 24 h after arrival to the hospital decreased (p < 0.001), while surgery within 48 h stayed the same (p = 0.085). Length of hospital stay significantly decreased over time (p < 0.001). Complication rates were consistent except for the number of postoperative anemia, delirium, and urinary tract infections. Mortality rates did not change over the years. Conclusions: The orthogeriatric treatment model leads in general to consistent outcomes concerning mortality and most of the complications, except for postoperative anemia, delirium, and urinary tract infections. Inconsistent complication rates were influenced by altered diagnosis and treatment protocols. Length of hospital stay reduced, while time to surgery was more often delayed to 24–48 h. Monitoring clinical outcomes of the orthogeriatric treatment model over time is recommended in order to optimize and maintain the quality of care for this frail patient population