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See detailClinical settings in knee osteoarthritis: Pathophysiology guides treatment
Herrero-Beaumont, Gabriel; Roman-Blas, Jorge A; Bruyère, Olivier ULg et al

in Maturitas (2017), 96

Osteoarthritis (OA) is the most common chronic joint disorder and its prevalence increases rapidly during midlife. Complex interactions of genetic alterations, sex hormone deficit, and aging with ... [more ▼]

Osteoarthritis (OA) is the most common chronic joint disorder and its prevalence increases rapidly during midlife. Complex interactions of genetic alterations, sex hormone deficit, and aging with mechanical factors and systemic inflammation-associated metabolic syndrome lead to joint damage. Thus, the expression of a clinical phenotype in the early stages of OA relies on the main underlying pathway and predominant joint tissue involved at a given time. Moreover, OA often coexists with other morbidities in the same patient, which in turn condition the OA process. In this scenario, an appropriate identification of clinical phenotypes, especially in the early stages of the disease, may optimize the design of individualized treatments in OA. An ESCEO-EUGMS (European Union Geriatric Medicine Society) working group has recently suggested possible patient profiles in OA. Hereby, we propose the existence of 4 clinical phenotypes – biomechanical, osteoporotic, metabolic and inflammatory – whose characterization would help to properly stratify patients with OA in clinical trials or studies. Further research in this field is warranted. [less ▲]

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See detailQuantitative determination of salbutamol sulfate impurities using achiral supercritical fluid chromatography
Dispas, Amandine ULg; Desfontaine, Vincent; Andri, Bertyl ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2017), 134

In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of ... [more ▼]

In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of SFC for the quality control of pharmaceuticals, especially in the case of the determination of the active pharmaceutical ingredient (API).Nevertheless, quality control requires also the determination of impurities. The objectives of the present work were to i) demonstrate the interest of SFC as a reference technique for the determination of impurities in salbutamol sulfate API and ii) to propose an alternative to a reference HPLC method from the European Pharmacopeia (EP) involving ionpairing reagent. Firstly, a screening was carried out to select the most adequate and selective stationary phase. Secondly, in the context of robust optimization strategy, the method was developed using design space methodology. The separation of salbutamol sulfate and related impurities was achieved in 7 minutes, which is seven times faster than the LC-UV method proposed by European Pharmacopeia (total run time of 50 minutes). Finally, full validation using accuracy profile approach was successfully achieved for the determination of impurities B, D, F and G in salbutamol sulfate raw material. The validated dosing range covered 50 to 150 % of the targeted concentration (corresponding to 0.3 % concentration level), LODs close to 0.5 μg/mL were estimated. The SFC method proposed in this study could be presented as a suitable fast alternative to EP LC method for the quantitative determination of salbutamol impurities. [less ▲]

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See detailLes acteurs: introduction
Dubois, Christophe ULg

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Les mots de la justice (2017)

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See detailVictime
Dubois, Christophe ULg; Martin, Daniel

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Les mots de la justice (2017)

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See detailJustice restauratrice
Dubois, Christophe ULg

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Les mots de la justice (2017)

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See detailDe Actoren: inleiding
Dubois, Christophe ULg

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Het verhaal van justitie (2017)

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See detailSlachtoffer
Dubois, Christophe ULg; Martin, Daniel

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Het verhaal van justitie (2017)

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See detailHerstelgerichte Justitie
Dubois, Christophe ULg

in Hendrick, Aude; Musin, Aude; Rousseaux, Xavier (Eds.) et al Het verhaal van justitie (2017)

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See detailLearning from blind tests: Determining the function of experimental grinding stones through use-wear and residue analysis
Hayes, Elspeth H.; Cnuts, Dries ULg; Lepers, Christian et al

in Journal of Archaeological Science: Reports (2017), 11

Abstract Blind tests provide an objective means to evaluate the accuracy of functional interpretations based on the presence of use-wear and residue traces on stone tools. Previous blind tests have ... [more ▼]

Abstract Blind tests provide an objective means to evaluate the accuracy of functional interpretations based on the presence of use-wear and residue traces on stone tools. Previous blind tests have highlighted interpretive errors commonly associated with use-wear and residue analyses leading to significant methodological developments in each of the respective fields. While a number of blind tests have been performed on flaked stone tools, only a single blind test has been published for use-wear on grinding tools. We present the results of a two-part blind test performed on 15 experimental grinding implements that were used in a controlled setting, designed to evaluate the relative importance of residue analysis for determining the worked material (1) when contextual information is available and (2) when contextual information is absent. We argue that use-wear and residue analyses are successful procedures to identify the use of grinding stones, and that residue analysis may be a particularly valuable means for determining the worked material on tools that have insufficient use-wear development. We suggest that residues should be sufficiently abundant to infer use, if we are to avoid the potential confusion caused by contamination. [less ▲]

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See detailThe importance of open data and software: Is energy research lagging behind?
Pfenninger, Stefan; DeCariolis, Joseph; Hirth, Lion et al

in Energy Policy (2017)

Energy policy often builds on insights gained from quantitative energy models and their underlying data. As climate change mitigation and economic concerns drive a sustained transformation of the energy ... [more ▼]

Energy policy often builds on insights gained from quantitative energy models and their underlying data. As climate change mitigation and economic concerns drive a sustained transformation of the energy sector, transparent and well-founded analyses are more important than ever. We assert that models and their associated data must be openly available to facilitate higher quality science, greater productivity through less duplicated effort, and a more effective science-policy boundary. There are also valid reasons why data and code are not open: ethical and security concerns, unwanted exposure, additional workload, and institutional or personal inertia. Overall, energy policy research ostensibly lags behind other fields in promoting more open and reproducible science. We take stock of the status quo and propose actionable steps forward for the energy research community to ensure that it can better engage with decision-makers and continues to deliver robust policy advice in a transparent and reproducible way. [less ▲]

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See detailApproximate Bayes Optimal Policy Search using Neural Networks
Castronovo, Michaël ULg; François-Lavet, Vincent ULg; Fonteneau, Raphaël ULg et al

in Proceedings of the 9th International Conference on Agents and Artificial Intelligence (ICAART 2017) (2017, February)

Bayesian Reinforcement Learning (BRL) agents aim to maximise the expected collected rewards obtained when interacting with an unknown Markov Decision Process (MDP) while using some prior knowledge. State ... [more ▼]

Bayesian Reinforcement Learning (BRL) agents aim to maximise the expected collected rewards obtained when interacting with an unknown Markov Decision Process (MDP) while using some prior knowledge. State-of-the-art BRL agents rely on frequent updates of the belief on the MDP, as new observations of the environment are made. This offers theoretical guarantees to converge to an optimum, but is computationally intractable, even on small-scale problems. In this paper, we present a method that circumvents this issue by training a parametric policy able to recommend an action directly from raw observations. Artificial Neural Networks (ANNs) are used to represent this policy, and are trained on the trajectories sampled from the prior. The trained model is then used online, and is able to act on the real MDP at a very low computational cost. Our new algorithm shows strong empirical performance, on a wide range of test problems, and is robust to inaccuracies of the prior distribution. [less ▲]

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See detailLa notion d’attention virtuelle dans la philosophie médiévale
Dubouclez, Olivier ULg

Scientific conference (2017, February)

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See detailAn App-based Algorithmic Approach for Harvesting Local and Renewable Energy Using Electric Vehicles
Dubois, Antoine; Wehenkel, Antoine; Fonteneau, Raphaël ULg et al

in Proceedings of the 9th International Conference on Agents and Artificial Intelligence (ICAART 2017) (2017, February)

The emergence of electric vehicles (EVs), combined with the rise of renewable energy production capacities, will strongly impact the way electricity is produced, distributed and consumed in the very near ... [more ▼]

The emergence of electric vehicles (EVs), combined with the rise of renewable energy production capacities, will strongly impact the way electricity is produced, distributed and consumed in the very near future. This position paper focuses on the problem of optimizing charging strategies for a fleet of EVs in the context where a significant amount of electricity is generated by (distributed) renewable energy. It exposes how a mobile application may offer an efficient solution for addressing this problem. This app can play two main roles. Firstly, it would incite and help people to play a more active role in the energy sector by allowing photovoltaic (PV) panel owners to sell their electrical production directly to consumers, here the EVs’ agents. Secondly, it would help distribution system operators (DSOs) or transmission system operators (TSOs) to modulate more efficiently the load by allowing them to influence EV charging behaviour in real time. Finally, the present paper advocates for the introduction of a two-sided market-type model between EV drivers and electricity producers. [less ▲]

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See detailResidential heat pump as flexible load for direct control service with parametrized duration and rebound effect
Georges, Emeline ULg; Cornélusse, Bertrand ULg; Ernst, Damien ULg et al

in Applied Energy (2017), 187

This paper addresses the problem of an aggregator controlling residential heat pumps to offer a direct control flexibility service. The service consists of a power modulation, upward or downward, that is ... [more ▼]

This paper addresses the problem of an aggregator controlling residential heat pumps to offer a direct control flexibility service. The service consists of a power modulation, upward or downward, that is activated at a given time period over a fixed number of periods. The service modulation is relative to an optimized baseline that minimizes the energy costs. The load modulation is directly followed by a constrained rebound effect, consisting of a delay time with no deviations from the baseline consumption and a payback time to return to the baseline state. The potential amount of modulation and the constrained rebound effect are computed by solving mixed integer linear problems. Within these problems, the thermal behavior of the building is modeled by an equivalent thermal network made of resistances and lumped capacitances. Simulations are performed for different sets of buildings typical of the Belgian residential building stock and are presented in terms of achievable modulation amplitude, deviations from the baseline and associated costs. A cluster of one hundred ideal buildings, corresponding to retrofitted freestanding houses, is then chosen to investigate the influence of each parameter defined within the service. Results show that with a set of one hundred heat pumps, a load aggregator could expect to harvest mean modulation amplitudes of up to 138 kW for an upward modulation and up to 51 kW for a downward modulation. The obtained values strongly depend on the proposed flexibility service. For example, they can decrease down to 2.6 kW and 0.4 kW, respectively, if no rebound effect is allowed. [less ▲]

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See detailNew data on the Mesozoic radiation of chelonioids
Scavezzoni, Isaure ULg; Fischer, Valentin ULg

Poster (2017, February)

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See detailMegaloolithid dinosaur eggs: scrambled parataxonomy and nesting strategies
Jentgen, Benjamin ULg; Stein, Koen; Fischer, Valentin ULg

Poster (2017, February)

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See detailVoyage[s] à travers le thymus
Geenen, Vincent ULg

in Science et Culture (2017), (465), 14-15

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See detailChez Froidmont au Nord : lectures polyphoniques d’une quête identitaire
Baiwir, Esther ULg; Adams, Juliette; Demonchaux, Chloé et al

in Tortue verte. Revue en ligne des littératures francophones (2017)

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See detailDe Barcelone à Amsterdam : l'émergence de la conservation intégrée à travers les colloques internationaux du Conseil de l'Europe et de l'ICOMOS
Houbart, Claudine ULg

Conference (2017, January 31)

En 1975, la notion de conservation intégrée est consacrée par la Charte européenne du Patrimoine architectural, adoptée par le Comité des Ministres du Conseil de l’Europe avant d’être solennellement ... [more ▼]

En 1975, la notion de conservation intégrée est consacrée par la Charte européenne du Patrimoine architectural, adoptée par le Comité des Ministres du Conseil de l’Europe avant d’être solennellement proclamée et développée au Congrès d’Amsterdam (21-25 octobre 1975). Renouvelant fondamentalement les pratiques de rénovation des centres anciens avec l’ambition de créer un dialogue entre aménageurs et conservateurs, cette approche résulte de dix années de réflexions nourries par des échanges entre experts principalement européens, initiés non seulement par le Conseil de l’Europe (Confrontations de Barcelone (1965), Bath (1966), La Haye (1967) et Avignon (1968)), mais également par l’ICOMOS, dès sa fondation en 1965 (Colloques de Cacérès (1965), Tunis (1966), Leningrad et Graz (1969), Lausanne (1973), Rothenburg et Bruges (1975)). Si un regard macroscopique révèle le rôle central joué par Piero Gazzola et Raymond Lemaire, respectivement président et secrétaire général de l’ICOMOS et auteurs, avec François Sorlin, d’une étude de synthèse préalable à la Charte européenne, cette contribution se propose d’augmenter la focale afin de révéler, à travers l’étude des actes des colloques, le rôle des réseaux d’acteurs en présence dans l’élaboration de la nouvelle politique. [less ▲]

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See detailDEVELOPMENT OF FUNCTIONAL MICELLES FROM BIODEGRADABLE AMPHIPHILIC BLOCK COPOLYMERS FOR DRUG DELIVERY AND TUMOUR THERAPY
Gulfam, Muhammad ULg

Doctoral thesis (2017)

Drug delivery systems in the size range of ~ 10-250 nm are enabling tools for the site-specific targeting and controlled release applications. To take advantage of these capabilities, various nanocarriers ... [more ▼]

Drug delivery systems in the size range of ~ 10-250 nm are enabling tools for the site-specific targeting and controlled release applications. To take advantage of these capabilities, various nanocarriers e.g., micelles, dendrimers, liposomes, nanoparticles, nanocapsules, nanotubes, and nanogels have been designed for drug delivery. Specifically, micelle-based drug carrier systems have emerged as promising tools for site-specific delivery and controlled release applications. Despite several advantages over conventional drugs, some limitations of micelle-based drug delivery have also been reported. These drawbacks include low stability in vivo, poor penetration, modest accumulation in tumor tissues, and inadequate control over drug release. To overcome these limitations, stimuli-responsive or smart polymeric nanocarriers have been developed for drug delivery and tumour therapy, previously. The most well-known internal stimuli in cancerous regions include higher acidity associated with dysregulated metabolism in tumour tissues, elevated levels of glutathione in the cytosol and nucleus of cancer cells, and altered degradative enzymes in the lysosomes, and reactive oxygen species in the mitochondria. These intrinsic microenvironments can be exploited as internal stimuli to attain active drug release in the tumor tissues or cancer cells. Particularly, the reducing potential inside the cancer cells is considerably higher than found in the extracellular environment and bloodstream. Therefore, such varying redox potential can be exploited for tumor specific drug delivery and controlled release applications. Various types of redox-responsive micelles have been developed previously. Generally, redox responsive micelles have disulfide linkages that undergo rapid cleavage in the presence of reducing agents in the intracellular components, however, are stable at oxidizing extracellular environment. The redox-responsive disulfide bridges can be incorporated into nanocarriers by placing multiple disulfide bonds in the hydrophobic backbone or by conjugating therapeutic agents to the side chain of the polymer via a disulfide linker. Another strategy to construct redox-responsive linkages is to crosslink the polymeric nanocarriers with a disulfide crosslinker. It has been studied that polymeric micelles can dissociate, especially upon administration when they are diluted below their critical micelle concentration. The stability of polymeric micelles can be enhanced by chemical crosslinking. Various types of crosslinked micelles can be prepared subjected to the localisation of the crosslinking, e.g. shell crosslinked micelles, and core crosslinked micelles. Introducing redox-responsive bridges by disulfide crosslinker may not only provide stability to nanocarriers against dilutions during circulation, but also render them responsive to reduction conditions. Specifically, redox-responsive core-crosslinked micelles have demonstrated good stability and better ‘stealth’ properties, however, the hydrophobic cores of most of the existing core-crosslinked micelles have been based on non-degradable polymers such as polyacrylamide or polyacrylate. The non-degradable constituent of the block copolymer may cause complications in clinical applications. Therefore, reduction-responsive core-crosslinked micelles comprising entirely of biologically inert or biocompatible and biodegradable polymers would be better candidates for drug delivery and controlled release application. To overcome these limitations, micelles based on polyesters (a class of aliphatic biodegradable polymers) can used for drug delivery application. In the last few decades, various FDA approved aliphatic polyesters e.g. poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone), and poly(lactic acid), have been intensively studied to exploit their potential in drug, gene and protein delivery and controlled release applications. However, most of these polyesters lack functional groups which make it difficult to incorporate redox-responsive linkages to core-crosslink their micelles. To address these issues, we have synthesized functional biodegradable and biocompatible block copolymers based on mPEG-b-poly(εCL-co-αClεCL). The pendent chloro groups of the block copolymer were converted into azides using nucleophilic substitution reaction to produce mPEG-b-poly(εCL-co-αN3CL) block copolymer as a precursor of reactive polymeric micelles. The synthesized polymers were characterized by NMR, FT-IR and size exclusion chromatography (SEC). Micelles were prepared using dialysis method and methotrexate (an anticancer drug) was loaded into the hydrophobic core of the reactive micelles. Micelles were subsequently crosslinked by a redox-responsive bis-alkyne ethyl disulfide crosslinker. The size distributions and morphology of core-crosslinked micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy. The drug release studies were performed under simulated non-reducing and reducing conditions. Cellular uptake studies in human breast cancer cells (MCF7 cells) were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their cytotoxicity in human breast cancer cells by MTT assays. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/PI assays and was further probed by annexin-V/PI assays. The data from these studies indicate that drug release from these cross-linked micelles can be controlled and that the redox-responsive micelles are more effective carriers for MTX than non-cross-linked analogues in the cell-lines tested. In another strategy, a multifunctional amphiphilic block copolymer based on α-amine-PEG-b-poly(εCL-co-αN3εCL) was synthesized and subsequently was used to conjugate methotrexate on the hydrophilic block for receptor mediated targeting of breast cancer cells. Cellular uptake studies revealed 2.3-fold higher uptake of MTX-conjugated micelles as compared with un-conjugated micelles. The blank micelles showed low cytotoxicities in breast cancer cells, however, MTX-conjugated micelles exhibited greater antitumor activities in contrast to free-MTX. We hypothesize that these functional micelles could be potentially powerful nanocarriers for stimuli-responsive controlled release, active tumour targeting and therapy. [less ▲]

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