References of "Luxen, André"
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See detailBiased binomial assessment of cross-validated estimation of classification accuracies illustrated in diagnosis predictions
Noirhomme, Quentin ULg; Lesenfants, Damien ULg; Gomez, Francisco et al

in NeuroImage: Clinical (2014), 4

Multivariate classification is used in neuroimaging studies to infer brain activation or in medical applications to infer diagnosis. Their results are often assessed through either a binomial or a ... [more ▼]

Multivariate classification is used in neuroimaging studies to infer brain activation or in medical applications to infer diagnosis. Their results are often assessed through either a binomial or a permutation test. Here, we simulated classification results of generated random data to assess the influence of the cross-validation scheme on the significance of results. Distributions built from classification of random data with crossvalidation did not follow the binomial distribution. The binomial test is therefore not adapted. On the contrary, the permutation test was unaffected by the cross-validation scheme. The influence of the crossvalidation was further illustrated on real-data from a brain–computer interface experiment in patients with disorders of consciousness and from an fMRI study on patients with Parkinson disease. Three out of 16 patients with disorders of consciousness had significant accuracy on binomial testing, but only one showed significant accuracy using permutation testing. In the fMRI experiment, the mental imagery of gait could discriminate significantly between idiopathic Parkinson’s disease patients and healthy subjects according to the permutation test but not according to the binomial test. Hence, binomial testing could lead to biased estimation of significance and false positive or negative results. In our view, permutation testing is thus recommended for clinical application of classification with cross-validation. [less ▲]

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See detailAutomated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest
Noirhomme, Quentin ULg; Lehembre, Rémy; Lugo, Zulay et al

in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between ... [more ▼]

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between reviewers. Automated EEG analysis may help quantify the brain damage. Forty-six comatose patients in therapeutic hypothermia, after cardiac arrest, were included in the study. EEG background was quantified with burst-suppression ratio (BSR) and approximate entropy, both used to monitor anesthesia. Reactivity was detected through change in the power spectrum of signal before and after stimulation. Automatic results obtained almost perfect agreement (discontinuity) to substantial agreement (background reactivity) with a visual score from EEG-certified neurologists. Burst-suppression ratio was more suited to distinguish continuous EEG background from burst-suppression than approximate entropy in this specific population. Automatic EEG background and reactivity measures were significantly related to good and poor outcome. We conclude that quantitative EEG measurements can provide promising information regarding current state of the patient and clinical outcome, but further work is needed before routine application in a clinical setting. [less ▲]

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See detailSeasonal variation in human executive brain responses
Meyer, Christelle ULg; Jaspar, Mathieu ULg; Muto, Vincenzo ULg et al

Poster (2014)

It is well established that cognition shows daily fluctuations with changes in circadian phase and sleep pressure. The physiological impact of season changes, which is well characterized in animals ... [more ▼]

It is well established that cognition shows daily fluctuations with changes in circadian phase and sleep pressure. The physiological impact of season changes, which is well characterized in animals, remains largely unexplored in human. Here we investigated the impact of seasonal variation on human cognitive brain function. This cross-sectional study,conducted in Liège (Belgium),spanned from May 2010 to October 2011. Following 8h in-lab baseline night of sleep, 30 volunteers (age 20.9+1.5; 15F)spent 42h awake under constant routine conditions(<5lux, semi-recumbent position, no time-cues). After12h recovery night, they underwent15minfMRI recording while performing a working memory 3-back task (3b) and a letter detection 0-back task (0b). Thus, fMRI data were acquired when volunteers had been in isolation under controlled conditionsfor 63h. Executive brain responses were isolated by subtracting 0b activity from 3b responses (3b>0b).Analysis tested seasonal influence on executive brain responses at the random effects level, using a phasoranalysis across the year.Inferences were conducted at p<0.05, after correction for multiple comparisons over a priori small volume of interest. Significanteffects of season on executive responses were detected inmiddle frontal and frontopolarregions, insula, and thalamus, with a maximum response at the end of summer and a minimum response at the end of winter.These brain areas are key regions for executive control and alertness. These results constitute the first demonstration that seasonality directly impacts on human cognitive brain functions. [less ▲]

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See detailEnantioselective synthesis of [small alpha]-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan
Denoel, Thibaut; Zervosen, Astrid ULg; Lemaire, Christian ULg et al

in Organic & Biomolecular Chemistry (2014)

The synthesis of modified tripeptides (S)-Ala-[gamma]-(R)-Glu-X, where X = (R,S) or (R,R) diastereomers of [small alpha]-benzyl or [small alpha]-(4-azidobenzyl)lanthionine, was carried out. The chemical ... [more ▼]

The synthesis of modified tripeptides (S)-Ala-[gamma]-(R)-Glu-X, where X = (R,S) or (R,R) diastereomers of [small alpha]-benzyl or [small alpha]-(4-azidobenzyl)lanthionine, was carried out. The chemical strategy involved the enantioselective alkylation of a 4-MeO-phenyloxazoline. The reductive opening of the alkylated oxazolines, followed by cyclization and oxidation, led to four PMB-protected sulfamidates. Subsequent PMB removal, Boc protection and regioselective opening with cysteine methyl ester led to protected lanthionines. These compounds were further converted in a one pot process to the corresponding protected tripeptides. After ester and Boc deprotection, the four tripeptides were evaluated as potential analogues of the natural tripeptide (S)-Ala-[gamma]-(R)-Glu-meso-A2pm. These compounds were evaluated for introduction, by means of the biosynthetic recycling pathway, into the peptidoglycan of Escherichia coli. A successful in vitro biosynthesis of UDP-MurNAc-tripeptides from the tripeptides containing [small alpha]-benzyl lanthionine was achieved using purified murein peptide ligase (Mpl). Bioincorporation into E. coli W7 did not occur under different tested conditions probably due to the bulky benzyl group at the C[small alpha] carbon of the C-terminal amino acid. [less ▲]

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See detailStereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli.
Denoel, Thibaut; Zervosen, Astrid ULg; Gerards, Thomas ULg et al

in Bioorganic & medicinal chemistry (2014), 22(17), 4621-8

The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected ... [more ▼]

The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected sulfamidates were opened by nucleophilic attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the free lanthionines. Using the same chemistry, an alpha-benzyl lanthionine was also prepared. The proposed method, which avoids the need of enrichment by recrystallization, opens the way to the labelling of these compounds with (35)S. Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No incorporation of alpha-benzyl lanthionine was observed. In contrast, meso-lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in the presence of (R,R)-lanthionine the initial increase of bacterial growth was followed by cell lysis. In the future, meso-[(35)S]lanthionine could be used to study the biosynthesis of peptidoglycan and its turnover in relation to cell growth and division. [less ▲]

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See detailPrior light history impacts on cognitive brain function
Chellappa, Sarah Laxhmi ULg; Ly, Julien; Meyer, Christelle ULg et al

Conference (2014)

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See detailPrior light history impacts on higher order cognitive brain function
Chellappa, Sarah Laxhmi ULg; Ly, Julien; Meyer, Christelle ULg et al

Conference (2014)

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See detailSynthesis of protected α-alkyl lanthionine derivatives
Denoël, Thibaut; Zervosen, Astrid ULg; Lemaire, Christian ULg et al

in Tetrahedron (2014), 70(30), 4526-4533

Abstract Protected α-alkyl lanthionine derivatives were synthesized in five steps starting from a known phenyloxazoline precursor. This approach involved the synthesis of a family of substituted cyclic ... [more ▼]

Abstract Protected α-alkyl lanthionine derivatives were synthesized in five steps starting from a known phenyloxazoline precursor. This approach involved the synthesis of a family of substituted cyclic sulfamidates and their regioselective opening by nucleophilic attack with a protected cysteine. This efficient multistep strategy affords various α-alkylated lanthionine derivatives in high yields. [less ▲]

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See detailMemory Reactivation During Rapid Eye Movement (REM) Sleep Promotes Its Generalization and Integration in Cortical Stores
Sterpenich, Virginie; Schmidt, Christina ULg; Albouy, Genevièvre et al

in Sleep (2014), 37(6), 1061-1075

Memory reactivation appears to be a fundamental process in memory consolidation. Here, we tested the influence of memory reactivation during REM sleep on memory performance and brain responses at ... [more ▼]

Memory reactivation appears to be a fundamental process in memory consolidation. Here, we tested the influence of memory reactivation during REM sleep on memory performance and brain responses at retrieval in healthy human participants. Auditory cues were associated with pictures of faces during their encoding. These memory cues delivered during REM sleep enhanced subsequent accurate recollections but also false recognitions. These results suggest that reactivated memories interacted with semantically-related representations, and induced new creative associations, which subsequently reduced the distinction between new and previously encoded exemplars. Cues had no effect if presented during stage 2 sleep, or if they were not associated with faces during encoding. Functional MRI revealed that following exposure to conditioned cues during REM sleep, responses to faces during retrieval were enhanced both in a visual area and in a cortical region of multisensory (auditory-visual) convergence. These results show that reactivating memories during REM sleep enhances cortical responses during retrieval, suggesting the integration of recent memories within cortical circuits, favoring the generalization and schematization of the information. [less ▲]

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See detailPhotic memory for executive brain responses
Chellappa*, Sarah Laxhmi ULg; Ly*, Julien ULg; Meyer, Christelle ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2014), Epub ahead of print

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See detailOn the statistical assessment of small sample classification
Noirhomme, Quentin ULg; Lesenfants, Damien ULg; Gomez, Francisco et al

Conference (2013, December)

Classifiers start to be used in medical application to infer diagnosis. Their results are assessed through either a binomial or a permutation test. Distributions built from classification of random data ... [more ▼]

Classifiers start to be used in medical application to infer diagnosis. Their results are assessed through either a binomial or a permutation test. Distributions built from classification of random data with cross-validation, did not follow the theoretical binomial distribution, showing that binomial test was not conservative enough. A permutation test is thus recommended. [less ▲]

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See detailDer p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus
Herman, Julie ULg; Thelen, Nicolas ULg; Smargiasso, Nicolas ULg et al

in Biochimica et Biophysica Acta - General Subjects (2013), 1840

Background: The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation ... [more ▼]

Background: The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation cascade of their corresponding precursor forms and particularly to highlight the interconnection between proteases during this cascade. Methods: The cleavage of the four peptides corresponding to the mite zymogen activation sites was studied on the basis of the Förster Resonance Energy Transfermethod. The proDer p 6 zymogen was then produced in Pichia pastoris to elucidate its activation mechanismbymite proteases, especially Der p 1. The role of the propeptide in the inhibition of the enzymatic activity of Der p 6 was also examined. Finally, the Der p 1 and Der p 6 proteases were localised via immunolocalisation in D. pteronyssinus. Results: All peptides were specifically cleaved by Der p 1, such as proDer p 6. The propeptide of proDer p 6 inhibited the proteolytic activity of Der p 6, but once cleaved, it was degraded by the protease. The Der p 1 and Der p 6 proteases were both localised to the midgut of the mite. Conclusions: Der p 1 in either its recombinant formor in the natural context of house dustmite extracts specifically cleaves all zymogens, thus establishing its role as a major activator of both mite cysteine and serine proteases. General significance: This finding suggests that Der p 1 may be valuable target against mites. [less ▲]

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See detailFully Automated Production of 68Ga-DOTA-NOC with a Trasis miniAIO® Synthesizer
Léonard, Marc ULg; Aerts, Joël ULg; Voccia, Samuel et al

Poster (2013, October 22)

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See detailSynthesis of [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione: an agent for specific radiolabelling of tyrosine
Flagothier, Jessica ULg; Warnier, Corentin ULg; Dammicco, Sylvestre ULg et al

in RSC Advances (2013), 3

We developed a new [18F] prosthetic group, the [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione ([18F]FPTAD), used for its specific ligation with tyrosine-containing peptides or protein in order to ... [more ▼]

We developed a new [18F] prosthetic group, the [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione ([18F]FPTAD), used for its specific ligation with tyrosine-containing peptides or protein in order to develop a new and versatile radiolabelling technique that could provide a useful tool for new developments in PET imaging. [less ▲]

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See detailPerformance evaluation and X-ray dose quantification for various scanning protocols of the GE eXplore 120 micro-CT
Bretin, Florian ULg; Warnock, Geoffrey; Luxen, André ULg et al

in IEEE Transactions on Nuclear Science (2013), 60(5), 3235-3241

The aim of this study was to evaluate the performance of the General Electric eXplore 120 micro-CT regarding image quality and delivered dose of several protocols. Image quality (resolution, linearity ... [more ▼]

The aim of this study was to evaluate the performance of the General Electric eXplore 120 micro-CT regarding image quality and delivered dose of several protocols. Image quality (resolution, linearity, uniformity and geometric accuracy) was assessed using the vmCT phantom developed for the GE eXplore Ultra, the QRM low contrast and the QRM Bar Pattern Phantom. All dose measurements were performed using a mobileMOSFET dose verification system and the CTDI100 and the MSAD were determined with a custom built PMMA phantom. Additionally, in vivo scans in sacrificed rats with different weights were acquired to assess dose, contrast and resolution variation due to X-ray absorption in surrounding tissue. The spatial resolution was determined as between 95 and 138 μm with a geometric accuracy of 0.1%. The system has a highly linear response to the iodine concentrations (0.937 to 30 mg/ml) for all protocols. The calculated CTDI100 ranged from 20.15 to 56.79 mGy and the MSAD from 27.98 to 77.45 mGy. The results were confirmed by in vivo scans in rats with different weights and no impact of body weight on delivered dose could be observed. However, body weight had a slight impact on image contrast and resolution. [less ▲]

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See detailSynthesis and biological evaluation of potential threonine synthase inhibitors: Rhizocticin A and Plumbemycin A
Gahungu; Arguelles Arias, Anthony ULg; Fickers, Patrick ULg et al

in Bioorganic & Medicinal Chemistry (2013), 21

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See detailIn vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: A new tool for oncology and radiotracer development.
Warnock, Geoffrey; Turtoi, Andrei ULg; Blomme, Arnaud ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2013), 54(10), 1782-1788

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken ... [more ▼]

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost and ethically sustainable alternative. For the first time, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken chorioallantoic membrane (CAM), with the aim of applying this model for screening of novel PET tracers. Methods: U87 glioblastoma cells were implanted on the CAM at day 11 post-fertilization and imaged at day 18. A small animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium [18F]fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using [18F]fluorodeoxyglucose and tumor protein synthesis was imaged using 2-[18F]fluoro-L-tyrosine. Anatomical images were obtained by contrast enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo and accurate volume measurements. Results: PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with [18F]fluorodeoxyglucose and demonstrated the ability to study PET tracer uptake over time in individual tumors, while CT imaging improved the accuracy of tumor volume measurements. Conclusion: In summary, we describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers. [less ▲]

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See detailProduction at the Curie Level of No-Carrier-Added 6-18F-Fluoro-L-Dopa
Libert, Lionel ULg; Franci, Xavier; Plenevaux, Alain ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2013), 54(7), 1154-1161

6-18F-fluoro-L-dopa (18F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier ... [more ▼]

6-18F-fluoro-L-dopa (18F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier-added (NCA) nucleophilic method has several advantages. These include much higher available activity and specific activity. Recently, we have described an NCA enantioselective synthesis using a chiral phase-transfer catalyst. However, some chemicals were difficult to implement into a commercially available synthesizer, restricting access to this radiopharmaceutical to only a few PET centers. Methods: In this paper, 2 important chemical improvements are proposed to simplify production of 18F-FDOPA, resulting in straightforward automation of the synthesis in a commercially available module. Results: First, a fast, simple, and reliable synthesis of 2-18F-fluoro-4,5-dimethoxybenzyl iodide on a solid phase support was developed. Second, a phase-transfer catalyst alkylation of a glycine derivative at room temperature was used to enable enantioselective carbon–carbon bond formation. After hydrolysis and high-performance liquid chromatography purification, a high enantiomeric excess of 18F-FDOPA (~97%) was obtained using a chiral catalyst available from a biphenyl 3 substrate. The total synthesis time was 63 min, and the decay-corrected radiochemical yield was 36% +/- 3% (n = 8). Conclusion: By exploiting the advantages of this NCA approach, using a starting activity of 185 GBq of NCA 18F-fluoride, high activities of 18F-FDOPA (> 45 GBq) with high specific activity (>753 GBq/mmol) are now available at the end of synthesis for use in clinical investigations. [less ▲]

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See detailEnantioselective synthesis of thioesters as substrates for high-through put screening assays of Penicillin Binding Proteins
Simon, Justine ULg; Zervosen, Astrid ULg; Bouillez, André ULg et al

Poster (2013, June 19)

Excessive utilization of beta-lactam antibiotics like penicillin has created drug-resistant strains in bacteria. One of the main mechanisms of resistance is the production of drug resistant Penicillin ... [more ▼]

Excessive utilization of beta-lactam antibiotics like penicillin has created drug-resistant strains in bacteria. One of the main mechanisms of resistance is the production of drug resistant Penicillin Binding Proteins (PBPs) and the over expression of these proteins. The transglycosidase and transpeptidase activities of PBPs catalyze the last two steps of peptidoglycan biosynthesis, which is unique to bacteria, and lies outside the cytoplasmic membrane. PBPs are interesting targets and efforts are still done to find new inhibitors. <br />A thioesterase activity has been described for various PBPs. For example, the thioester S2d is a substrate of PBP R39 of Actinomadura and of PBP2x of Streptococcus pneumoniae. The utilization of thioesters allows a rapid screening of active compounds in high-through put screening assays. Furthermore detailed kinetic studies using thioesters as reporter substrates are also possible. <br />Here we will present the enantioselective synthesis of the thioesters and their application as substrates in high through put screening assays. [less ▲]

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