transnational University of Limburg
Diepenbeek, Belgium
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Geusens P.,Maastricht University | Geusens P.,transnational University of Limburg
RMD Open | Year: 2015

For the prevention of fractures, antiresorptive drugs (bisphosphonates and denosumab) that decrease high bone resorption and, secondarily, also bone formation, are the mainstream of therapy. Osteoanabolic drugs, such as teriparatide, increase bone formation more than bone resorption, and are used in severe osteoporosis, including patients treated with antiresorptive drugs who still lose bone and have recurrent fractures. New potential drugs for fracture prevention that uncouple bone resorption from bone formation include odanacatib, a specific inhibitor of cathepsin-K, the enzyme that degrades bone collagen type I, that inhibits bone resorption and only temporarily bone formation, and monoclonal antibodies against sclerostin (romosozumab, blosozumab), that stimulate bone formation and decrease bone resorption.

Ameloot T.J.,transnational University of Limburg
ACM Transactions on Database Systems | Year: 2015

A distributed database system often operates in an asynchronous communication model where messages can be arbitrarily delayed. This communication model causes nondeterministic effects like unpredictable arrival orders of messages. Nonetheless, in general we want the distributed system to be deterministic; the system should produce the same output despite the nondeterministic effects on messages. Previously, two interpretations of determinism have been proposed. The first says that all infinite fair computation traces produce the same output. The second interpretation is a confluence notion, saying that all finite computation traces can still be extended to produce the same output. A decidability result for the confluence notion was previously obtained for so-called simple transducer networks, a model from the field of declarative networking. In the current article, we also present a decidability result for simple transducer networks, but this time for the first interpretation of determinism, with infinite fair computation traces. We also compare the expressivity of simple transducer networks under both interpretations. © 2015 ACM.

Neven F.,transnational University of Limburg
Proceedings of the ACM SIGACT-SIGMOD-SIGART Symposium on Principles of Database Systems | Year: 2016

Database research has witnessed a renewed interest for data processing in distributed and parallel settings. While distributed and parallel data management systems have been around for quite some time, it is the rise of cloud computing and the advent of Big Data that presents the community with new challenges. This paper highlights recent research concerning the logical foundations of massively parallel and distributed systems. The first part of the paper concerns massively parallel systems where computation proceeds in a number of synchronized rounds. Here, the focus is on evaluation algorithms for conjunctive queries as well as on reasoning about correctness and optimization of such algorithms. The second part of the paper addresses a distributed asynchronous setting where eventual consistency comes into play. Here, the focus is on coordination-free computation and its relationship to logical monotonicity and Datalog programs.

Fraussen J.,transnational University of Limburg | Claes N.,transnational University of Limburg | de Bock L.,transnational University of Limburg | Somers V.,transnational University of Limburg
Autoimmunity Reviews | Year: 2014

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS) with heterogeneous clinical, genetic and pathophysiological characteristics. The establishment of reliable biomarkers for diagnosis, prognosis and treatment of MS has therefore proven to be very difficult. During the last decades, mounting evidence has been collected for the involvement of B cells and antibodies in MS pathogenesis. A wide variety of autoantibodies has been described in MS and these autoantibodies could be useful biomarkers for MS.Since demyelination is a key component of MS pathogenesis, myelin antigens were first investigated as primary targets of autoantibodies in MS. More recently, it became evident that the humoral autoimmune response is not restricted to myelin but is much more widespread throughout the brain. Autoantibodies are formed against different CNS cell types, including neurons, oligodendrocytes and astrocytes, and even immune cells, indicating the complex heterogeneity of the disease. In this review, we give an extensive overview of the known autoantibody targets in MS, not according to the traditional subdivision of myelin and non-myelin components but according to each of the affected cell types, including the most recently described target antigens. © 2014 Elsevier B.V.

Broux B.,transnational University of Limburg | Markovic-Plese S.,University of North Carolina at Chapel Hill | Stinissen P.,transnational University of Limburg | Hellings N.,transnational University of Limburg
Trends in Molecular Medicine | Year: 2012

Aging of the immune system contributes to the increased morbidity and mortality of the elderly population and may occur prematurely in patients with immune disorders. One of the main characteristics of immunosenescence is the expansion of CD4+CD28- T cells in the blood. These cells are effector memory T cells with cytotoxic capacity, and have been recently described to have pathogenic potential in a variety of immune disorders. Interestingly, CD4+CD28- T cells have now been found to infiltrate target tissues of patients with multiple sclerosis, rheumatoid arthritis, myopathies, acute coronary syndromes, and other immune-related diseases. In this review, we discuss potential factors and mechanisms that may induce the expansion of these cells, as well as their putative pathogenic mechanisms in immune disorders. © 2012 Elsevier Ltd.

Ameloot T.J.,transnational University of Limburg | Neven F.,transnational University of Limburg | Van Den Bussche J.,transnational University of Limburg
Journal of the ACM | Year: 2013

Motivated by a recent conjecture concerning the expressiveness of declarative networking, we propose a formal computation model for "eventually consistent" distributed querying, based on relational transducers. A tight link has been conjectured between coordination-freeness of computations, and monotonicity of the queries expressed by such computations. Indeed, we propose a formal definition of coordination-freeness and confirm that the class of monotone queries is captured by coordination-free transducer networks. Coordination-freeness is a semantic property, but the syntactic class of "oblivious" transducers we define also captures the same class of monotone queries. Transducer networks that are not coordination-free are much more powerful. © 2013 ACM.

Gelade W.,transnational University of Limburg
Theoretical Computer Science | Year: 2010

In this paper, we study the succinctness of regular expressions (REs) extended with interleaving, intersection and counting operators. We show that in a translation from REs with interleaving to standard regular expressions a double exponential size increase cannot be avoided. We also consider the complexity of translations to finite automata. We give a tight exponential lower bound on the translation of REs with intersection to NFAs, and, for each of the three classes of REs, we show that in a translation to a DFA a double exponential size increase cannot be avoided. Together with known results, this gives a complete picture of the complexity of translating REs extended with interleaving, intersection or counting into (standard) regular expressions, NFAs, and DFAs. © 2010 Elsevier B.V. All rights reserved.

Hellings J.,transnational University of Limburg | Fletcher G.H.L.,TU Eindhoven | Haverkort H.,TU Eindhoven
Proceedings of the ACM SIGMOD International Conference on Management of Data | Year: 2012

In this paper we introduce the first efficient external-memory algorithm to compute the bisimilarity equivalence classes of a directed acyclic graph (DAG). DAGs are commonly used to model data in a wide variety of practical applications, ranging from XML documents and data provenance models, to web taxonomies and scientific workflows. In the study of efficient reasoning over massive graphs, the notion of node bisimilarity plays a central role. For example, grouping together bisimilar nodes in an XML data set is the first step in many sophisticated approaches to building indexing data structures for efficient XPath query evaluation. To date, however, only internal-memory bisimulation algorithms have been investigated. As the size of real-world DAG data sets often exceeds available main memory, storage in external memory becomes necessary. Hence, there is a practical need for an efficient approach to computing bisimulation in external memory. Our general algorithm has a worst-case IO-complexity of O(Sort(|N| + |E|)), where |N| and |E| are the numbers of nodes and edges, resp., in the data graph and Sort(n) is the number of accesses to external memory needed to sort an input of size n. We also study specializations of this algorithm to common variations of bisimulation for tree-structured XML data sets. We empirically verify efficient performance of the algorithms on graphs and XML documents having billions of nodes and edges, and find that the algorithms can process such graphs efficiently even when very limited internal memory is available. The proposed algorithms are simple enough for practical implementation and use, and open the door for further study of external-memory bisimulation algorithms. To this end, the full open-source C++ implementation has been made freely available. © 2012 ACM.

Bogie J.F.J.,transnational University of Limburg | Stinissen P.,transnational University of Limburg | Hendriks J.J.A.,transnational University of Limburg
Acta Neuropathologica | Year: 2014

Along with microglia and monocyte-derived macrophages, macrophages in the perivascular space, choroid plexus, and meninges are the principal effector cells in neuroinflammatory and neurodegenerative disorders. These phagocytes are highly heterogeneous cells displaying spatial- and temporal-dependent identities in the healthy, injured, and inflamed CNS. In the last decade, researchers have debated on whether phagocytes subtypes and phenotypes are pathogenic or protective in CNS pathologies. In the context of this dichotomy, we summarize and discuss the current knowledge on the spatiotemporal physiology of macrophage subsets and microglia in the healthy and diseased CNS, and elaborate on factors regulating their behavior. In addition, the impact of macrophages present in lymphoid organs on CNS pathologies is defined. The prime focus of this review is on multiple sclerosis (MS), which is characterized by inflammation, demyelination, neurodegeneration, and CNS repair, and in which microglia and macrophages have been extensively scrutinized. On one hand, microglia and macrophages promote neuroinflammatory and neurodegenerative events in MS by releasing inflammatory mediators and stimulating leukocyte activity and infiltration into the CNS. On the other hand, microglia and macrophages assist in CNS repair through the production of neurotrophic factors and clearance of inhibitory myelin debris. Finally, we define how microglia and macrophage physiology can be harnessed for new therapeutics aimed at suppressing neuroinflammatory and cytodegenerative events, as well as promoting CNS repair. We conclude that microglia and macrophages are highly dynamic cells displaying disease stage and location-specific fates in neurological disorders. Changing the physiology of divergent phagocyte subsets at particular disease stages holds promise for future therapeutics for CNS pathologies. © 2014 Springer-Verlag.

Venken K.,transnational University of Limburg | Venken K.,Ghent University | Hellings N.,transnational University of Limburg | Liblau R.,Toulouse University Hospital Center | Stinissen P.,transnational University of Limburg
Trends in Molecular Medicine | Year: 2010

The pathological features of multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system, support an autoimmune etiology. Strong evidence has been provided for a potential functional defect of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in patients with relapsing-remitting MS. More recently, alterations in homeostatic parameters related to the development and function of naive and memory-like Tregs were discovered in MS patients. In this review, we evaluate the evidence for disturbed Treg homeostasis in MS and discuss the role of potential compensatory mechanisms in the chronic disease phase. Better insights into the processes underlying the compromised immune regulation in MS patients will be important to understand the potential of Treg-based therapies. © 2010 Elsevier Ltd. All rights reserved.

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