828 research outputs found
Towards a better understanding of Vanishing White Matter disease
No full textKnaap, M.S. van der [Promotor]Scheper, G.C. [Copromotor]Thomas, A.A.M. [Copromotor
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation: Molecular mechanisms, clinical aspects and opening for treatment
No full textKnaap, M.S. van der [Promotor]Scheper, G.C. [Copromotor
Vanishing white matter: A study of phenotypic variation and the relationship between genotype and phenotype
No full textKnaap, M.S. van der [Promotor]Scheper, G.C. [Copromotor]Abbink, G.E.M. [Copromotor
Defective translation initiation causes vanishing of cerebral white matter
No full textLeukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited white-matter disorders, especially in Caucasian populations. VWM is unusual because of its sensitivity to febrile infections and minor head trauma. The basic defect of this enigmatic brain disease resides in the regulation of initiation of protein synthesis. Recently, undue activation of the unfolded-protein response has emerged as an important factor in the pathophysiology of VWM. Here, we discuss the mechanisms that might be responsible for the selective involvement of the brain white matter in VWM. At present, VWM research is in need of an animal model to study disease mechanisms and therapeutic interventions
The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization
No full textThe cap-binding eukaryotic initiation factor eIF4E is phosphorylated by the mitogen-activated protein
(MAP) kinase-interacting kinases (Mnk’s). Three forms of the Mnk’s exist in human cells: Mnk1, Mnk2a, and
Mnk2b. These last two are derived from the same gene by alternative splicing and differ only at their C termini.
While Mnk2a contains a MAP kinase-binding site in this region, Mnk2b lacks such a sequence and is much
less readily activated by MAP kinases in vitro. Expression of Mnk2b in mammalian cells leads to increased
phosphorylation of eIF4E, showing that it acts as an eIF4E kinase in vivo. While Mnk2a is cytoplasmic, a
substantial amount of Mnk2b is found in the nucleus. Both enzymes contain a stretch of basic residues in their
N termini that plays a role in binding to eIF4G and functions as a nuclear localization signal. Binding of eIF4G
or nuclear import appears to be regulated by the C terminus of Mnk2a. Furthermore, the MAP kinase-binding
site of Mnk2a regulates nuclear entry. Within the nucleus, Mnk2b and certain variants of Mnk2a that are
present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E
Translation matters: protein synthesis defects in inherited disease
No full textThe list of genetic diseases caused by mutations that affect mRNA translation is rapidly growing. Although protein synthesis is a fundamental process in all cells, the disease phenotypes show a surprising degree of heterogeneity. Studies of some of these diseases have provided intriguing new insights into the functions of proteins involved in the process of translation; for example, evidence suggests that several have other functions in addition to their roles in translation. Given the numerous proteins involved in mRNA translation, it is likely that further inherited diseases will turn out to be caused by mutations in genes that are involved in this complex process.<br/
Unearthing the Real Process Behind the Event Data The Case for Increased Process Realism
No full textThis book is a revised version of the PhD dissertation written by the author at Hasselt University in Belgium.This dissertation introduces the concept of process realism. Process realism is approached from two perspectives in this dissertation. First, quality dimensions and measures for process discovery are analyzed on a large scale and compared with each other on the basis of empirical experiments. It is shown that there are important differences between the different quality measures in terms of feasibility, validity and sensitivity. Moreover, the role and meaning of the generalization dimension is unclear. Second, process realism is also tackled from a data point of view. By developing a transparent and extensible tool-set, a framework is offered to analyze process data from different perspectives. From both perspectives, recommendations are made for future research, and a call is made to give the process realism mindset a central place within process mining analyses.
In 2020, the PhD dissertation won the “BPM Dissertation Award”, granted to outstanding PhD theses in the field of Business Process Management
Authorship as cultural performance: new perspectives in authorship studies
No full textThis article proposes a performative model of authorship, based on the historical alternation between predominantly 'weak' and 'strong' author concepts and related practices of writing, publication and reading. Based on this model, we give a brief overview of the historical development of such author concepts in English literature from the Middle Ages to the twentieth century. We argue for a more holistic approach to authorship within a cultural topography, comprising social contexts, technological and media factors, and other cultural developments, such as the distinction between privacy and the public sphere
A resilience assessment framework for complex engineered systems using graphical evaluation and review technique (GERT)
No full textSystem resilience characterizes the capability of maintaining the required functionality under disruptions, which is of great significance in evaluating the productivity and safety of complex engineered systems. Although most studies conduct resilience assessment from qualitative and quantitative perspectives, system functionality that reflects functional requirements for complex engineered systems needs to be elaborated. In addition, given that complex engineered systems achieve dynamic performance during disruptions, measuring the actual performance under uncertainty is imperative. To this end, this paper develops a quantitative framework to assess the resilience of complex engineered systems. The developed framework comprises three phases, functionality analysis, performance evaluation, and resilience assessment. Firstly, system functionality is analyzed using a functional tree illustrating the relationship between functions. The overall objective, primary functions, and sub-functions are identified according to task requirements. Secondly, system performance is quantified considering uncertain factors through Graphical Evaluation and Review Technique (GERT). Probabilistic branches and network logic are employed to represent the implementation of various functions. Finally, resilience assessment is carried out from the perspectives of anticipation, absorption, adaptation, and restoration abilities. A case study on the satellite network shows the effectiveness of the developed framework. The developed framework determines system functionality based on task requirements, evaluates system performance with limited information, and accurately assesses system resilience.Safety and Security Scienc
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