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See detailNew method to combine molecular and pedigree relationships
Bömcke, Elisabeth ULg; Soyeurt, Hélène ULg; Szydlowski, Maciej et al

in Journal of Animal Science (2011), 89

Relationship coefficients are traditionally based on pedigree data. Today, with the development of molecular techniques, they are often completely replaced by coefficients calculated from molecular data ... [more ▼]

Relationship coefficients are traditionally based on pedigree data. Today, with the development of molecular techniques, they are often completely replaced by coefficients calculated from molecular data. Examples are relationships from microsatellites for biodiversity studies but also genomic relationships from SNP as currently used in genomic prediction of breeding values. There are, however, many situations in which optimal combination of both sources would be the best solutions. Obviously, this is the case for incompletely genotyped populations, but also when pedigree information is sparse. Also, markers, even dense ones, do not reflect the whole genome and therefore give only an incomplete picture of relationships. The main objective of this study was therefore to develop a method to calculate a relationship matrix by the combination of molecular and pedigree data. It will be useful for all situations where pedigree and molecular data are available. In this study, based on simulations of pedigree and marker data, we used partial least squares regression and linear regression to combine total allelic relationship coefficients calculated for each marker with additive relationship coefficients calculated from incomplete pedigree. The results showed that the greatest advantage of this method, compared with the one that replaces a part of the pedigree-based relationship matrix by a genomic relationship matrix, is that adding the partial pedigree data allows for the correction of the molecular coefficient for the ungenotyped part of the genome. [less ▲]

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See detailNew Method to Combine Pedigree and Molecular Relationships applied to Brandrood Cattle
Bömcke, Elisabeth ULg; Windig, J. J.; Gengler, Nicolas ULg

in 9th World Congress of Genetics Applied to Livestock Production: Leipzig, Germany (2010)

Relationship coefficients are traditionally based on pedigree data. Today, they are often replaced by coefficients calculated from molecular data, for example, microsatellites-based relationships for bio ... [more ▼]

Relationship coefficients are traditionally based on pedigree data. Today, they are often replaced by coefficients calculated from molecular data, for example, microsatellites-based relationships for bio-diversity studies or genomic relationships for prediction of breeding values. However, in many situations, optimal combination of both sources would be the best solutions; i.e. when population is incompletely genotyped or when pedigree information is sparse. Also even dense markers do not reflect the whole genome. The objective of this study was to applied a new method to calculate a relationship matrix by the combination of molecular and pedigree data on Brandrood cattle. The results showed that combining marker and pedigree information produced more accurate A-matrices what will be useful for future management of the breed genetic variability. [less ▲]

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See detailA new method to detect long term trends of methane (CH4) and nitrous oxide (N2O) total columns measured within the NDACC ground-based high resolution solar FTIR network
Angelbratt, J.; Mellqvist, J.; Blumenstock, T. et al

in Atmospheric Chemistry and Physics (2011), 11(13), 6167--6183

Total columns measured with the ground-based solar FTIR technique are highly variable in time due to atmospheric chemistry and dynamics in the atmosphere above the measurement station. In this paper, a ... [more ▼]

Total columns measured with the ground-based solar FTIR technique are highly variable in time due to atmospheric chemistry and dynamics in the atmosphere above the measurement station. In this paper, a multiple regression model with anomalies of air pressure, total columns of hydrogen fluoride (HF) and carbon monoxide (CO) and tropopause height are used to reduce the variability in the methane (CH4) and nitrous oxide (N2O) total columns to estimate reliable linear trends with as small uncertainties as possible. The method is developed at the Harestua station (60 N, 11 E, 600m a.s.l.) and used on three other European FTIR stations, i.e. Jungfraujoch (47 N, 8 E, 3600m a.s.l.), Zugspitze (47 N, 11 E, 3000m a.s.l.), and Kiruna (68 N, 20 E, 400m a.s.l.). Linear CH4 trends between 0.13±0.01-0.25±0.02%yr-1 were estimated for all stations in the 1996-2009 period. A piecewise model with three separate linear trends, connected at change points, was used to estimate the short term fluctuations in the CH4 total columns. This model shows a growth in 1996–1999 followed by a period of steady state until 2007. From 2007 until 2009 the atmospheric CH4 amount increases between 0.57±0.22–1.15±0.17%yr-1. Linear N2O trends between 0.19±0.01–0.40±0.02%yr-1 were estimated for all stations in the 1996-2007 period, here with the strongest trend at Harestua and Kiruna and the lowest at the Alp stations. From the N2O total columns crude tropospheric and stratospheric partial columns were derived, indicating that the observed difference in the N2O trends between the FTIR sites is of stratospheric origin. This agrees well with the N2O measurements by the SMR instrument onboard the Odin satellite showing the highest trends at Harestua, 0.98±0.28%yr-1, and considerably smaller trends at lower latitudes, 0.27±0.25%yr-1. The multiple regression model was compared with two other trend methods, the ordinary linear regression and a Bootstrap algorithm. The multiple regression model estimated CH4 and N2O trends that differed up to 31% compared to the other two methods and had uncertainties that were up to 300% lower. Since the multiple regression method were carefully validated this stresses the importance to account for variability in the total columns when estimating trend from solar FTIR data. [less ▲]

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See detailA new method to determine tissue specific tissue factor thrombomodulin activities: endotoxin and particulate air pollution induced disbalance.
Frederix, Kim ULg; Kooter, Ingeborg M; van Oerle, Rene et al

in Thrombosis Journal (2008), 6(14), 14

ABSTRACT: BACKGROUND: Increase in tissue factor (TF) and loss in thrombomodulin (TM) antigen levels has been described in various inflammatory disorders. The functional consequences of such changes in ... [more ▼]

ABSTRACT: BACKGROUND: Increase in tissue factor (TF) and loss in thrombomodulin (TM) antigen levels has been described in various inflammatory disorders. The functional consequences of such changes in antigen concentrations in the coagulation balance are, however, not known. This study was designed to assess the consequences of inflammation-driven organ specific functional properties of the procoagulant response. METHODS: Tissue specific procoagulant activity was assessed by adding tissue homogenate to normal human pool plasma and recording of the thrombin generation curve. The new technique was subsequently applied on two inflammation driven animal models: 1) mouse lipopolysaccharide (LPS) induced endotoxemia and 2) spontaneously hypertensive rats exposed to environmental air pollution (particulate matter (PM). RESULTS: Addition of lung tissue from untreated animals to human plasma suppressed the endogenous thrombin potential (ETP) (175 +/- 61 vs. 1437 +/- 112 nM.min for control). This inhibitory effect was due to TM, because a) it was absent in protein C deficient plasma and b) lungs from TMpro/pro mice allowed full thrombin generation (ETP: 1686 +/- 209 nM.min). The inhibitory effect of TM was lost after LPS administration to mice, which induced TF activity in lungs of C57Bl/6 mice as well as increased the ETP (941 +/- 523 vs. 194 +/- 159 nM.min for control). Another pro-inflammatory stimulus, PM dose-dependently increased TF in the lungs of spontaneously hypertensive rats at 4 and 48 hours after PM exposure. The ETP increased up to 48 hours at the highest concentration of PM (1441 +/- 289 nM.min vs. saline: 164 +/- 64 nM.min, p < 0.0001), suggesting a concentration- and time dependent reduction in TM activity. CONCLUSION: Inflammation associated procoagulant effects in tissues are dependent on variations in activity of the TF-TM balance. The application of these novel organ specific functional assays is a useful tool to monitor inflammation-driven shifts in the coagulation balance within animal or human tissues. [less ▲]

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See detailA New Method to Evaluate Wave Impact Forces on Offshores Structures
Marchal, Jean ULg

in Proceedings of the Offshore Technology Conference (1984)

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See detailA new method to fuzzy modeling and its application in performance evaluation of tenants in incubators
Rezaei Sadrabadi, Mahmood ULg

in International Journal of Advanced Manufacturing Technology (2008), 37

As we know fuzzy modeling is one of the most powerful techniques to extract experts’ knowledge in the form of fuzzy if-then rules. In this research work, a new method to fuzzy modeling is proposed in ... [more ▼]

As we know fuzzy modeling is one of the most powerful techniques to extract experts’ knowledge in the form of fuzzy if-then rules. In this research work, a new method to fuzzy modeling is proposed in which the main goal is to construct a fuzzy rule-base of the type of Mamdani. In the proposed method, fuzzy c-means (FCM) clustering is used for structure identification and two optimization problems are used for parameter identification. The proposed method is used to simulate experts’ knowledge for performance evaluation of tenants in incubators. The authors have implemented their proposed method in a real numerical example successfully. [less ▲]

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See detailA new method to measure residual stresses in veneering ceramic
Mainjot, Amélie ULg; Van Heusden, Alain ULg; Sadoun, Michael

Conference (2010, July 16)

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See detailNew Methode for a Two-Step Hydrolysis and Chromatographic Analysis of Pectin Neutral Sugar Chains
Haikel, Garna; Mabon, Nicolas ULg; Wathelet, Bernard ULg et al

in Journal of Agricultural and Food Chemistry (2004), 52

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See detailA new methodological approach for error distributions selection in Finance
Hambuckers, julien ULg; Heuchenne, Cédric ULg

Conference (2014, April)

In this article, we propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the ... [more ▼]

In this article, we propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the traditional approach, we don't use any GARCH-type estimation of the conditional variance. Instead, we propose to use a recently developed nonparametric procedure (Mercurio and Spokoiny, 2004): the Local Adaptive Volatility Estimation (LAVE). The motivation for using this method is to avoid a possible model misspecification for the conditional variance. In a second step, we suggest a set of estimation and model selection procedures (Berk-Jones tests, kernel density-based selection, censored likelihood score, coverage probability) based on the so-obtained residuals. These methods enable to assess the global fit of a given distribution as well as to focus on its behavior in the tails. Finally, we illustrate our methodology on three time series (UBS stock returns, BOVESPA returns and EUR/USD exchange rates). [less ▲]

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See detailA new methodological approach for error distributions selection in Finance
Hambuckers, julien ULg; Heuchenne, Cédric ULg

E-print/Working paper (2014)

In this article, we propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the ... [more ▼]

In this article, we propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the traditional approach, we don't use any GARCH-type estimation of the conditional variance. Instead, we propose to use a recently developed nonparametric procedure (Mercurio and Spokoiny, 2004): the Local Adaptive Volatility Estimation (LAVE). The motivation for using this method is to avoid a possible model misspecification for the conditional variance. In a second step, we suggest a set of estimation and model selection procedures (Berk-Jones tests, kernel density-based selection, censored likelihood score, coverage probability) based on the so-obtained residuals. These methods enable to assess the global fit of a given distribution as well as to focus on its behavior in the tails. Finally, we illustrate our methodology on three time series (UBS stock returns, BOVESPA returns and EUR/USD exchange rates). [less ▲]

Detailed reference viewed: 21 (12 ULg)
See detailA new methodological approach for error distributions selection
Hambuckers, julien ULg; Heuchenne, Cédric ULg

Scientific conference (2013, November)

Since 2008 and its financial crisis, an increasing attention has been devoted to the selection of an adequate error distribution in risk models, in particular for Value-at-Risk (VaR) predictions. We ... [more ▼]

Since 2008 and its financial crisis, an increasing attention has been devoted to the selection of an adequate error distribution in risk models, in particular for Value-at-Risk (VaR) predictions. We propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the traditional approach, we do not use any GARCH-type estimation of the conditional variance. Instead, we propose to use a recently developed nonparametric procedure: the Local Adaptive Volatility Estimation (LAVE). The motivation for using this method is to avoid a possible model misspecification for the conditional variance. In a second step, we suggest a set of estimation and model selection procedures tests based on the so-obtained residuals. These methods enable to assess the global fit of a given distribution as well as to focus on its behaviour in the tails. Finally, we illustrate our methodology on three time series (UBS stock returns, BOVESPA returns and EUR/USD exchange rates). [less ▲]

Detailed reference viewed: 19 (4 ULg)
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See detailA new methodological approach for error distributions selection
Hambuckers, julien ULg; Heuchenne, Cédric ULg

Conference (2013, December 15)

Since 2008 and its financial crisis, an increasing attention has been devoted to the selection of an adequate error distribution in risk models, in particular for Value-at-Risk (VaR) predictions. We ... [more ▼]

Since 2008 and its financial crisis, an increasing attention has been devoted to the selection of an adequate error distribution in risk models, in particular for Value-at-Risk (VaR) predictions. We propose a robust methodology to select the most appropriate error distribution candidate, in a classical multiplicative heteroscedastic model. In a first step, unlike to the traditional approach, we do not use any GARCH-type estimation of the conditional variance. Instead, we propose to use a recently developed nonparametric procedure: the Local Adaptive Volatility Estimation (LAVE). The motivation for using this method is to avoid a possible model misspecification for the conditional variance. In a second step, we suggest a set of estimation and model selection procedures tests based on the so-obtained residuals. These methods enable to assess the global fit of a given distribution as well as to focus on its behaviour in the tails. Finally, we illustrate our methodology on three time series (UBS stock returns, BOVESPA returns and EUR/USD exchange rates). [less ▲]

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See detailA new methodological approach to try to link past disturbances and modern landscapes
Bourland, Nils ULg; Livingstone Smith, Alexandre; Doucet, Jean-Louis ULg

in Primate Tidings (2011, July), 24

Detailed reference viewed: 25 (10 ULg)
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See detailNew methodology for generating realistic data for evaluation of performance of radar STAP algorithms
Ries, Philippe; Tey, Shuwen; Verly, Jacques ULg et al

Conference (2007)

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See detailNew Methodology for the Development of Chromatographic Methods
Rozet, Eric ULg; Debrus, Benjamin ULg; Lebrun, Pierre ULg et al

Conference (2011, September 08)

As defined by ICH [1] and FDA, Quality by Design (QbD) stands for “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process ... [more ▼]

As defined by ICH [1] and FDA, Quality by Design (QbD) stands for “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management”. A risk–based QbD–compliant approach is proposed for the robust development of analytical methods. This methodology based on Design of Experiments (DoE) to study the experimental domain models the retention times at the beginning, the apex and the end of each peak corresponding to the compounds of a mixture and uses the separation criterion (S) rather than the resolution (RS) as a Critical Quality Attribute. Stepwise multiple linear regressions are used to create the models. The estimated error is propagated from the modelled responses to the separation criterion (S) using Monte Carlo simulations in order to estimate the predictive distribution of the separation criterion (S) over the whole experimental domain. This allows finding ranges of operating conditions that will guarantee a satisfactory quality of the method in its future use. These ranges define the Design Space (DS) of the method. In chromatographic terms, the chromatograms processed at operating conditions within the DS will assuredly show high quality, with well separated peaks and short run time, for instance. This Design Space can thus be defined as the subspace, necessarily encompassed in the experimental domain (i.e. the knowledge space), within which the probability for the criterion to be higher than an advisedly selected threshold is higher than a minimum quality level. Precisely, the DS is defined as “the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality” [1]. Therefore, this DS defines a region of operating conditions that provide prediction of assurance of quality rather than only quality as obtained with traditional mean response surface optimisation strategies. For instance, in the liquid chromatography there is a great difference in e.g. predicting a resolution (RS) higher than 1.5 vs. predicting that the probability for RS to be higher than 1.5 (i.e. P(RS> 1.5)) is high. The presentation of this global methodology will be illustrated for the robust optimisation and DS definition of several liquid chromatographic methods dedicated to the separation of different mixtures: pharmaceutical formulations, API and impurities/degradation products, plant extracts, separation of enantiomers, … References [1] International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, Topic Q8(R2): Pharmaceutical development, Geneva, 2009. Acknowledgements A research grant from the Belgium National Fund for Scientific Research (F.R.S-FNRS) to E. Rozet is gratefully acknowledged. [less ▲]

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See detailA new methodology to analyse monthly somatic cell counts
Detilleux, Johann ULg; Volckaert, D.; Leroy, Pascal ULg

(1998)

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See detailNew Methodology to detect toxin-GPCR binding by MALDI-TOF Mass Spectrometry
Echterbille, Julien ULg; De Pauw, Edwin ULg; Gilles, Nicolas et al

Poster (2011)

Introduction More than 50 thousands of venomous species are currently indexed in the world. Each of their venoms is composed of 200 to 1000 different toxins which potentially exhibit a high selectivity ... [more ▼]

Introduction More than 50 thousands of venomous species are currently indexed in the world. Each of their venoms is composed of 200 to 1000 different toxins which potentially exhibit a high selectivity for membrane receptors such as ionic channels or G-protein coupled receptors (GPCRs). GPCRs constitute the larger family of receptors since around 800 different kinds of them are knows. GPCRs are the target of around 30% of the current pharmacopeia drugs. Notable examples include Novartis’s Zelnorm, Eli Lilly’s Zyprexa and Schering-Plough’s Clarinex used to treat constipation, schizophrenia and allergies, respectively. Finding new GPCRs ligands appears of prime interest to design new pharmacological tools and potentially discover the drugs of our future. Interestingly, several toxins from venoms have already been described to bind to this particular family of receptor, opening the way to the discovery of new peptide drugs from animal venoms1-2. This work presents a pioneering MALDI-TOF/TOF based strategy to fish new GPCRs ligands from complex mixtures such as venom fractions. Methods The proof of concept of this methodology was built by studying the binding of [Arg8]-vasopressin (AVP) on type 2-vasopressin receptor (V2). Experimentally, fragments of cellular membranes over-expressing V2 receptors were incubated with cone snail’s venom fraction (~30 peptide toxins) doped by a small amount of AVP. After 2 hours incubation, free and bound fractions were carefully purified with a combination of centrifugation and micro column purifications. Samples were finally analyzed with a Bruker Ultraflex II MALDI-TOF/TOF mass spectrometer and the resulting spectra were interpreted with FlexAnalysis (v3.0), BioTools (v3.2) and SequenceEditor (v3.2) bioinformatics’ softwares from Bruker Daltonics. Preliminary data After the incubation of cellular membranes overexpressing V2 GPCR with a complex mixture of peptides doped by AVP, we clearly detect that the only V2 ligand present in the fraction was the AVP. Our result demonstrates the possibility to identify a ligand of GPCRs from a complex peptide mixture, such as venom fractions. Contrary to radiobinding, this approach allows detecting the direct binding of the toxin and does not imply to know a ligand of the studied GPCR before starting the experiments. This opens the way to the deorphanization of receptors (180 orphans GPCRs over 800). Moreover, since the new ligand is detected by mass spectrometry, it is directly identified from the mixture, without additional purification. Its structural characterization can be directly performed by de novo sequencing experiments. The drawback of our approach is the very long (but crucial!) sample preparation as each sample requires 2 purification steps (for both free and bound fraction). The next step of our work will be the automation of the procedure to allow a high-throughput screening of venom fractions on different GPCRs and the discovery of new ligands. Novel aspect GPCR’s ligands discovery by MALDI-TOF/TOF based techniques: a new pharmacological tool. 1 Quinton, L. et al. Isolation and pharmacological characterization of AdTx1, a natural peptide displaying specific insurmountable antagonism of the a1A-adrenoceptor. British Journal of Pharmacology 159, 316-325 (2010). 2 Rouget, C. et al. Identification of a novel snake peptide toxin displaying high affinity and antagonist behaviour for the α2-adrenoceptors. British Journal of Pharmacology 161, 1361-1374, doi:10.1111/j.1476-5381.2010.00966.x (2010). [less ▲]

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