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Bethune, France

Fenart L.,University of Artois
Current Alzheimer research | Year: 2013

Ever since amyloid-β (Aβ) peptides were first identified in cerebral plaques in patients with Alzheimer's disease (AD), much research work has focused on the complex mechanisms through which these peptides are synthesized, transported and degraded. Although new information emerges on a regular basis, we consider that the importance of the blood-brain barrier (BBB) in the pathogenesis of AD has been underestimated. In fact, there are a number of obstacles that make it difficult to convince specialists in AD that the BBB indeed plays a key role in this disease: these include the complex physiology of the BBB and the technical difficulty of studying the barrier in vivo and reproducing its main properties in vitro. With these considerations in mind, the present review sets out summarize our current knowledge about the physiology of the BBB and describe recent research findings on the barrier's role in Aβ peptide proteostasis and thus in the mechanism of AD. Source

Dombu C.Y.,University of Lille Nord de France | Betbeder D.,University of Lille Nord de France | Betbeder D.,Lille 2 University of Health and Law | Betbeder D.,University of Artois
Biomaterials | Year: 2013

Delivery of peptides and proteins via the airways is one of the most exciting potential applications of nanomedicine. These macromolecules could be used for many therapeutic applications, however due to their poor stability in physiological medium and difficulties in delivering them across biological barriers, they are very difficult to use in therapy. Nanoparticulate drug delivery systems have emerged as one of the most promising technologies to overcome these limitations, owing mainly to their proven capacity to cross biological barriers and to enter cells in high yields, thus improving delivery of macromolecules. In this review, we summarize the current advances in nanoparticle designed for transmucosal delivery of peptides and proteins. Challenges that must be overcome in order to derive clinical benefits are also discussed. © 2012 Elsevier Ltd. Source

Lang J.,University of Paris Dauphine | Marquis P.,University of Artois
Artificial Intelligence | Year: 2010

In this paper, a fairly general framework for reasoning from inconsistent propositional bases is defined. Variable forgetting is used as a basic operation for weakening pieces of information so as to restore consistency. The key notion is that of recoveries, which are sets of variables whose forgetting enables restoring consistency. Several criteria for defining preferred recoveries are proposed, depending on whether the focus is laid on the relative relevance of the atoms or the relative entrenchment of the pieces of information (or both). Our framework encompasses several previous approaches as specific cases, including reasoning from preferred consistent subsets, and some forms of information merging. Interestingly, the gain in flexibility and generality offered by our framework does not imply a complexity shift compared to these specific cases. © 2010 Elsevier B.V. All rights reserved. Source

Marquis P.,University of Artois
IJCAI International Joint Conference on Artificial Intelligence | Year: 2011

We study the existential closures of several propositional languages L considered recently as target languages for knowledge compilation (KC), namely the incomplete fragments KROM-C, HORN-C, K/H-C, renH-C, AFF, and the corresponding disjunction closures KROM-C[V], HORN-C[V], K/H-C[V], renH-C[V], and AFF[V]. We analyze the queries, transformations, expressiveness and succinctness of the resulting languages L[∃] in order to locate them in the KC map. As a by-product, we also address several issues concerning disjunction closures that were left open so far. From our investigation, the language HORN - C[V, ∃] (where disjunctions and existential quantifications can be applied to Horn CNF formulae) appears as an interesting target language for the KC purpose, challenging the influential DNNF languages. Source

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.07M | Year: 2015

The brain barriers function to protect the central nervous system (CNS) from neurotoxic compounds. By the same traits they unfortunately block delivery of drugs to the CNS thus hindering proper diagnosis and effective treatment of neurological disorders including Alzheimers disease and multiple sclerosis. The unusual complexity of the brain barriers has severely hampered progress in the market of CNS targeting therapeutics. BtRAIN bridges this gap by creating particular knowledge on vertebrate brain barrier signature genes and their specific roles in regulating brain barrier function in development, health, ageing and disease. Brain barrier signature genes will be identified by combining cross-species and cross-system brain barrier transcriptome analysis with dedicated bioinformatics. These data will be made available for brain barrier datamining in the userfriendly online platform BBBHub. Within BtRAIN, the side-by-side comparison of a unique and broad armamentarium of different vertebrate in vitro and in vivo brain barrier models will allow to develop and validate particular in vitro brain barrier models that are suited to reliably predict brain barrier function in vivo. Combined with an accompanying in depth analysis of the pathological alterations of the brain barriers during neurological disorders BtRAIN will create unique knowledge to overcome the unmet need for the development of diagnostic and therapeutic tools able to breach the brain barriers. In BtRAIN 12 academic, 6 non-academic partners and 1 European network will jointly train young researchers at unique interfaces of brain barrier research, bioinformatics, business development and science communication for an international research or entrepreneur career. To create this expert pool is the motivation for the involved partners as it will advance the Euopean capacity to bring innovative approaches to the untapped potential of the CNS therapeutic market.

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