Château-du-Loir, France
Château-du-Loir, France

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van Mastbergen J.,Eurodrug Laboratories | Jolas T.,CEREP | Allegra L.,IRCCS Policlinic Hospital | Page C.P.,King's College London
Pulmonary Pharmacology and Therapeutics | Year: 2012

Xanthines such as theophylline have been used in the treatment of lung diseases since the early 1900's, but have a major drawback of a very narrow therapeutic window and many drug/drug interactions. This means that plasma levels have to be measured regularly and can make the use of theophylline problematic. With the increasing availability of other classes of drugs for the treatment of respiratory diseases, this has limited the use of xanthines, despite their clear clinical benefit in the treatment of patients with asthma and COPD. Doxofylline is a xanthine molecule having both bronchodilator and anti-inflammatory activity with an improved therapeutic window over conventional xanthines such as theophylline. However, the mechanistic basis of this improved therapeutic window is not understood. The present study has investigated some pharmacological activities of doxofylline in comparison with theophylline. Doxofylline does not directly inhibit any of the known HDAC enzymes, and did not inhibit any PDE enzyme sub types or act as an antagonist at any of the known adenosine receptors, except for PDE2A 1, and adenosine A 2A and only at the highest tested concentration (10 -4M). These results may explain the improved tolerability profile of doxofylline compared with theophylline. © 2011 .


Sayadi M.,CEREP | Fnaiech F.,CEREP | Mathlouthi A.,CEREP | Chaari A.,CEREP | Najim M.,Equipe Signal Image
European Signal Processing Conference | Year: 2015

In this paper, we present a new fast algorithm for two-dimensional (2-D) linear adaptive filtering using the fast Chandrasekhar equations. Using the analogy between the multichannel linear model and the 2-D one, we transform an image into multichannel sequence and we extend the fast Chandrasekhar adaptive multichannel filtering algorithm to the 2-D case i.e. image filtering. The performance of the new 2-D adaptive filter is tested by using this filter to estimate the coefficients of a 2-D Moving Average (2-D MA) model of an unknown system. Furthermore, an application on adaptive noise cancellation of images is proposed throw a 2-D adaptive noise canceller based on the 2-D Chandrasekhar fast algorithm. Simulation results prove the superiority of the new 2-D Chandrasekhar filter comparing to similar approaches for image model identification. © 2002 EUSIPCO.


Souheil A.,CEREP | Sadok T.,University of Lorraine | Zied H.,University of Lorraine
IFAC Proceedings Volumes (IFAC-PapersOnline) | Year: 2015

This paper deals with a manufacturing system M1 which has to satisfy a random demand during a finite horizon given a required service level. To help meet this demand, subcontracting is used through another production system M2 which has a random service level β. The aim of this study is to determine the production plan of the manufacturing system M1 for each period of the horizon taking into account the machine M1 degradation according its production rate. Baring in mind that realistically the subcontractor is not always available to satisfy each demand variation, we assume that we can only order a minimum fixed quantity - defined a prioriduring the entire horizon. The optimal production plan then will correspond to the minimum sum of production (M1 and M2), inventory, lost sales cost and degradation cost. © 2015, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.


Mehdi R.,École de Technologie Supérieure of Montreal | Nidhal R.,French Institute for Research in Computer Science and Automation | Anis C.,CEREP
Computers and Industrial Engineering | Year: 2010

In this paper, we develop a joint quality control and preventive maintenance policy for a production system producing conforming and non-conforming units. The considered system consists of one machine which must supply another production line operating on a just-in-time basis. According to the proportion l of non-conforming units observed on each lot and compared to a threshold value lm, one decides to undertake or not maintenance actions on the system. In order to palliate perturbations caused by the stopping of the machine to undergo preventive maintenance or an overhaul, a buffer stock h is built up from the instant when the rejection rate reaches a threshold level lA in order to ensure the continuous supply of the subsequent production line. Our objective is to determine simultaneously the optimal rates lm* and lA*, and the optimal size h* which minimize the expected total cost per time unit including the average costs related to maintenance, quality and inventory. © 2009 Elsevier Ltd. All rights reserved.


Berge C.,Hoffmann-La Roche | Froloff N.,Cerep | Kalathur R.K.R.,LBGI IGBMC | Maumy M.,Institute Of Recherche Mathematique Avancee Irma | And 3 more authors.
Journal of Computational Biology | Year: 2010

Large multidimensional data matrices are frequent in biology. However, statistical methods often have difficulties dealing with such matrices because they contain very complex data sets. Consequently variable selection and dimensionality reduction methods are often used to reduce matrix complexity, although at the expense of information conservation. A new method derived from multidimensional scaling (MDS) is presented for the case where two matrices are available to describe the same population. The presented method transforms one of the matrices, called the target matrix, with some constraints to make it fit with the second matrix, referred to as the reference matrix. The fitting to the reference matrix is performed on the distances computed for the two matrices, and the transformation depends on the problem at hand. A special feature of this method is that a variable can be only partially modified. The method is applied on the exclusive-or (XOR) problem and then on a biological application with large-scale gene expression data. © Copyright 2010, Mary Ann Liebert, Inc.


Watterson S.H.,Bristol Myers Squibb | Xiao Z.,Bristol Myers Squibb | Dodd D.S.,Bristol Myers Squibb | Tortolani D.R.,Bristol Myers Squibb | And 26 more authors.
Journal of Medicinal Chemistry | Year: 2010

Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological target. This article will detail the Structure-activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clinical compound (1), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3- (3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl) nicotinic acid (2e) was selected to advance into clinical trials. © 2010 American Chemical Society.


Yedes Y.,CEREP LGIPM | Chelbi A.,CEREP | Rezg N.,French Institute for Research in Computer Science and Automation
Journal of Intelligent Manufacturing | Year: 2012

In this paper we deal with the integrated supply chain management problem in the context of a single vendor-single buyer system for which the production unit is assumed to randomly shift from an in-control to an out-of-control state. At the end of each production cycle, a corrective or preventive maintenance action is performed, depending on the state of the production unit, and a new setup is carried out. Two different integrated production, shipment and maintenance strategies are proposed to satisfy the buyer's demand at minimum total cost. The first one suggests that the buyer orders batches of size nQ and the vendor produces nQ and makes equal shipments of size Q. The second policy proposes that to satisfy the same ordered quantity, the vendor produces separately smaller batches of size Q, n times. The total integrated average cost per time unit corresponding to each strategy is considered as the performance criterion allowing choosing the best policy for any given situation. © 2010 Springer Science+Business Media, LLC.


Radhoui M.,CEREP | Rezg N.,LGIPM | Chelbi A.,CEREP
Journal of Intelligent Manufacturing | Year: 2010

In this paper, we develop a joint quality control and preventive maintenance policy for a production system producing conforming and nonconforming units. The considered system consists of one machine which must supply another production line operating on a just-in-time basis. Each lot produced by the machine is subject to a quality control. According to the proportion l of nonconforming units observed and compared to a threshold value l m, one decides to undertake or not maintenance actions on the system. In order to palliate perturbations caused by the stopping of the machine for preventive and corrective maintenance actions of random durations, a buffer stock h is built up to ensure the continuous supply of the subsequent production line. The proposed strategy is modelled using simulation and experimental design. This approach allows to generate a second order response surface allowing to easily determine the optimal rate, l m*, of nonconforming units on the basis of which preventive maintenance actions should be performed, and the optimal size, h*, of the buffer stock to be built. These values minimize the total cost per time unit which includes the costs related to maintenance, quality and inventory. © 2008 Springer Science+Business Media, LLC.


Daniel Stamer W.,University of Arizona | Piwnica D.,Cerep | Jolas T.,Cerep | Carling R.W.,Selcia Ltd | And 6 more authors.
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. Bimatoprost is a widely used ocular hypotensive agent to treat glaucoma. It lowers intraocular pressure in humans by increasing both pressure-independent (uveoscleral) and pressure-dependent (conventional) aqueous humor outflow. The present study specifically examines bimatoprost effects on the cells that populate human outflow tissues. METHODS. The authors tested for prostamide receptor activation in primary cultures of human trabecular meshwork (TM), Schlemm's canal (SC), and ciliary smooth muscle (CSM) cells using cellular dielectric spectroscopy (CDS). RESULTS. The authors observed that bimatoprost produced an immediate and concentration-dependent increase in cell monolayer impedance for TM, SC, and CSM cells with EC50 values of 4.3, 1.2, and 1.7 nM, respectively; corresponding to decreased cell contractility. Notably, in TM, SC, and CSM cells, bimatoprost was approximately equipotent to the selective FP receptor agonists fluprostenol and 17-phenyl PGF2α. Bimatoprost effects were insensitive to cholera toxin and pertussis toxin but were abolished by phorbol 12-myristate 13-acetate pretreatment, suggesting Gq-involvement in cell signaling. The effects of bimatoprost on TM and SC cells were inhibited by the prostamide receptor antagonist AGN211334, with IC50 values of 1.2 and 3.3 μM, respectively. Interestingly, AGN211334 behaved as an apparent inverse agonist in CDS assays involving TM cells but as a neutral prostamide antagonist with SC cells. CONCLUSIONS. Taken together, results suggest that bimatoprost specifically activates receptors in both cell types of the human conventional outflow pathway to modify intraocular pressure. However, only TM cell monolayers appear to have autocrine, or agonist-independent, receptor signaling that is sensitive to a prostamide receptor antagonist. © Association for Research in Vision and Ophthalmology.


Hassene S.,CEREP | Eddine M.N.,CEREP
2nd International Conference on Advanced Technologies for Signal and Image Processing, ATSIP 2016 | Year: 2016

This paper proposes a new hybrid technique for combined encryption text and image based on hyperchaos system. Since antiquity, man has continued looking for ways to send messages to his correspondents in order to communicate with them safely. It needed, through successive epochs, both physical and intellectual efforts in order to find an effective and appropriate communication technique. On another note, there is a behavior between the rigid regularity and randomness. This behavior is called chaos. In fact, it is a new field of investigation that is opened along with a new understanding of the frequently misunderstood long effects. The chaotic cryptography is thus born by inclusion of chaos in encryption algorithms. This article is in this particular context. Its objective is to create and implement an encryption algorithm based on a hyperchaotic system. This algorithm is composed of four methods: two for encrypting images and two for encrypting texts. The user chose the type of the input of the encryption (image or text) and as well as of the output. This new algorithm is considered a renovation in the science of cryptology, with the hybrid methods. This research opened a new features. © 2016 IEEE.

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