Publications by authors named "Philippe André"

32 Publications

Ventricular Arrhythmia in Septal and Apical Hypertrophic Cardiomyopathy: The French-Canadian Experience.

Front Cardiovasc Med 2020 22;7:548564. Epub 2020 Oct 22.

Division of Cardiology, Multidisciplinary Cardiovascular Department, Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ-UL), Université Laval, Québec City, QC, Canada.

Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients ( = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.
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http://dx.doi.org/10.3389/fcvm.2020.548564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642600PMC
October 2020

Evaluation of Antiviral, Antibacterial and Antiproliferative Activities of the Endophytic Fungus , and Isolation of a New Polyhydroxyacid.

Microorganisms 2020 Sep 4;8(9). Epub 2020 Sep 4.

Université de Lorraine, CNRS, L2CM, F-54000 Nancy, France.

An endophytic fungus isolated from a medicinal plant from Sudan, was taxonomically characterized as Ethyl acetate crude extract of revealed an important antiviral effect against two viral pathogens, the human coronavirus HCoV 229E and a norovirus surrogate, the feline coronavirus FCV F9. For the last one, 40% of the reduction of the virus-induced cytopathogenic effect at lower multiplicity of infection (MOI) 0.0001 was observed. Selective antibacterial activity was obtained against sp. (312 µg/mL), and interesting antiproliferative activity with half maximal inhibitory concentration (IC) value of 21.5 ± 5.9 µg/mL was observed against human breast carcinoma MCF7 cell line. Therefore, crude extract was further investigated and fractionated. Twenty-two metabolites were identified by gas chromatography coupled to mass spectrometry (GC-MS), and two pure compounds, mannitol and a new polyhydroxyacid, called kheiric acid, were characterized. A combination of spectroscopic methods was used to elucidate the structure of the new aliphatic carboxylic acid: kheiric acid (3,7,11,15-tetrahydroxy-18-hydroxymethyl-14,16,20,22,24-pentamethyl-hexacosa-4E,8E,12E,16,18-pentaenoic acid). Kheiric acid showed an interesting result with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL against meticillin-resistant (MRSA). Hence, endophytes associated with medicinal plants from Sudan merit more attention, as they could be a treasure of new bioactive compounds.
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http://dx.doi.org/10.3390/microorganisms8091353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564059PMC
September 2020

Validation of a novel single lead ambulatory ECG monitor - Cardiostat™ - Compared to a standard ECG Holter monitoring.

J Electrocardiol 2019 Mar - Apr;53:57-63. Epub 2018 Dec 19.

IUCPQ - Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada.

Background: Cardiostat™ is a single lead ambulatory ECG monitor. Recording is made through 2 electrodes positioned in a lead 1-like configuration. We first validated its accuracy for atrial fibrillation detection compared to a 12-lead ECG. In the second phase of the study, arrhythmia detection accuracy was compared between Cardiostat™ ambulatory ECG and a standard 24 h Holter ECG monitoring.

Method/results: Phase one of the study included patients undergoing cardioversion for atrial fibrillation (AF) or atrial flutter. Cardiostat™ tracings were compared with standard 12-lead ECG. In the second phase, patients undergoing 24 h ambulatory Holter ECG monitoring for control or suspicion of atrial fibrillation (AF) were included. Simultaneous Holter monitoring and Cardiostat™ ECG recordings were performed. Tracings were analysed and compared. Two hundred twelve monitoring were compared. AF was diagnosed in 73 patients. Agreement between Cardiostat™ ECG and standard Holter monitoring was 99% for AF detection with kappa = 0.99. Kappa correlation for atrial flutter detection was only moderate at 0.51. AF burden was similar in both recordings. Noise hindered analysis in a greater proportion with Cardiostat™ compared to Holter ambulatory ECG (8.5 vs 3.8%).

Conclusion: Cardiostat™ ambulatory ECG device showed excellent correlation with the standard Holter ECG monitoring for AF detection. Holter monitoring was however superior to discriminate premature atrial and ventricular beats and to qualify the morphology of PVCs since it has more vectors for analysis. Added value of Cardiostat™ includes longer monitoring duration, less cumbersome installation and water resistance.
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http://dx.doi.org/10.1016/j.jelectrocard.2018.12.011DOI Listing
July 2020

Clinical performance of different DF-4 implantable cardioverter defibrillator leads.

Pacing Clin Electrophysiol 2018 Jun 1. Epub 2018 Jun 1.

Department of Cardiology, Institut universitaire de cardiologie et pneumologie de Québec, Quebec, QC, Canada.

Introduction: Implantable cardioverter-defibrillator (ICD) DF-4 connectors have been introduced to facilitate defibrillator lead connection and to reduce the size of device header. There are limited data regarding the overall performance of those leads and no comparison between different ICD DF-4 leads.

Methods: This is a cohort study of consecutive patients implanted with ICD DF-4 lead system at one University Centre between October 2010 and February 2015. A historical control group of patients with ICD DF-1 lead implantation was used for comparison. The following ICD DF-4 leads were evaluated: St. Jude Medical Durata 7122Q (St. Jude Medical, St. Paul, MN, USA), Medtronic Sprint Quattro Secure 6935 M (Medtronic Inc., Minneapolis, MN, USA), Boston Scientific Endotak Reliance 4-Site 0293 (Boston Scientific, Marlborough, MA, USA), and Boston Scientific Reliance 4-Front 0693. This study evaluated the acute and mid-term performances of those leads as well as complications.

Results: A total of 812 patients (age 63 ± 12 years, 80% male, left ventricular ejection fraction 31 ± 12%) underwent implantation of an ICD DF-4 lead. Acute and follow-up R-wave sensing and threshold were excellent. Compared to implantation, intrinsic R waves were higher at follow-up for Boston Scientific and Medtronic leads, and pacing lead impedances were lower for all leads at first follow-up (P < 0.001). The number of lead dislodgement or failure was similar between all leads. The estimated lead survival rates at 3 years were 95.6% for Boston Scientific Endotak 4-Site, 97.1% for Boston Scientific 4-Front, 97.7% for Medtronic Sprint Quattro, and 97.5% for St. Jude Durata (P  =  0.553).

Conclusion: All ICD DF-4 leads had excellent acute and mid-term electrical performances. Longer follow-up will be necessary to confirm their sustained performance.
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http://dx.doi.org/10.1111/pace.13400DOI Listing
June 2018

Efficient and rapid generation of large genomic variants in rats and mice using CRISMERE.

Sci Rep 2017 03 7;7:43331. Epub 2017 Mar 7.

PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.

Modelling Down syndrome (DS) in mouse has been crucial for the understanding of the disease and the evaluation of therapeutic targets. Nevertheless, the modelling so far has been limited to the mouse and, even in this model, generating duplication of genomic regions has been labour intensive and time consuming. We developed the CRISpr MEdiated REarrangement (CRISMERE) strategy, which takes advantage of the CRISPR/Cas9 system, to generate most of the desired rearrangements from a single experiment at much lower expenses and in less than 9 months. Deletions, duplications, and inversions of genomic regions as large as 24.4 Mb in rat and mouse founders were observed and germ line transmission was confirmed for fragment as large as 3.6 Mb. Interestingly we have been able to recover duplicated regions from founders in which we only detected deletions. CRISMERE is even more powerful than anticipated it allows the scientific community to manipulate the rodent and probably other genomes in a fast and efficient manner which was not possible before.
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http://dx.doi.org/10.1038/srep43331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339700PMC
March 2017

Comparative Epidemiologic Characteristics of Pertussis in 10 Central and Eastern European Countries, 2000-2013.

PLoS One 2016 3;11(6):e0155949. Epub 2016 Jun 3.

Department of Paediatrics, Riga Stradins University, Riga, Latvia.

We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (<1 year) in Bulgaria, Hungary, Latvia, Romania, and Serbia, but not in the other participating countries where the burden may have shifted to older children, though surveillance of adults may be inappropriate. There was no consistent pattern associated with the switch from wP to aP vaccines on reported pertussis incidence rates. The heterogeneity in reported data may be related to a number of factors including surveillance system characteristics or capabilities, different case definitions, type of pertussis confirmation tests used, public awareness of the disease, as well as real differences in the magnitude of the disease, or a combination of these factors. Our study highlights the need to standardize pertussis detection and confirmation in surveillance programs across Europe, complemented with carefully-designed seroprevalence studies using the same protocols and methodologies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155949PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892528PMC
July 2017

Endophytic fungi associated with Sudanese medicinal plants show cytotoxic and antibiotic potential.

FEMS Microbiol Lett 2016 06 18;363(11). Epub 2016 Apr 18.

Université de Lorraine, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France CNRS, SRSMC, UMR 7565, BP 70239, F-54506 Vandœuvre-lès-Nancy, France

In this study, we isolated 15 endophytic fungi from five Sudanese medicinal plants. Each fungal endophytic strain was identified by sequencing of internal transcribed spacer (ITS) regions of rDNA. Ethyl acetate extracts were prepared from each endophyte cultivated in vitro and tested for their respective antibacterial activities and antiproliferative activities against human cancer cells. Antibacterial screening was carried out against two bacterial strains: Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, by the broth dilution method. Cell viability was evaluated by the MTT procedure after exposure of MCF7 breast cancer cells and HT29 or HCT116 human colon adenocarcinoma cells to each endophytic extract. Of interest, Byssochlamys spectabilis isolated from Euphorbia prostata showed cytotoxicity (IC50 = 1.51 ± 0.2 μg mL(-1)) against MCF7 cells, but had a low effect against HT29 or HCT116 cells (IC50 > 20 μg mL(-1)). Cladosporium cladosporioides 2, isolated from Vernonia amygdalina leaves, showed antiproliferative activities against MCF7 cells (IC50 = 10.5 ± 1.5 μg mL(-1)) only. On the other hand, B. spectabilis and Alternaria sp. extract had antibacterial activities against the S. aureus strain. The findings of this work revealed that endophytic fungi associated with medicinal plants from Sudan could be considered as an attractive source of new therapeutic compounds.
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http://dx.doi.org/10.1093/femsle/fnw089DOI Listing
June 2016

Left atrial remodelling assessed by 2D and 3D echocardiography identifies paroxysmal atrial fibrillation.

Eur Heart J Cardiovasc Imaging 2017 Jan 13;18(1):46-53. Epub 2016 Mar 13.

INSERM UMR-1060, CarMeN Laboratory, Université Claude Bernard Lyon1, Lyon F-69373, France.

Aims: Paroxysmal atrial fibrillation (PAF) is common, often silent, and can be difficult to detect. Echocardiographic parameters assessing left atrial (LA) remodelling correlated with atrial fibrosis in permanent AF, but less is known about earlier stages such as PAF. We aimed to evaluate whether 2D and 3D echocardiographic (2DE and 3DE) assessment of LA anatomy and function is able to identify patients with PAF.

Methods And Results: This case-control study included 102 patients without overt heart disease, 44 patients with PAF. Anatomical remodelling was assessed using indexed maximal, minimal, and pre-atrial contraction volumes. Reservoir, conduit, and pump functions were assessed by volume and strain methods. All parameters were assessed by 2DE and 3DE and were compared between the two groups. Receiver-operating characteristic curves were constructed for each parameter for PAF prediction. PAF patients had bigger LA volumes than non-PAF group. Using 3DE, all atrial functions were impaired in the PAF group, regardless of the parameters used (all P < 0.05), whereas using 2DE, conduit function did not reach significant difference. Areas under the curve (AUCs) for 3D parameters were higher than those for equivalent 2DE parameters. PAF was best predicted by LA minimal indexed volume assessed by 2DE or 3DE (AUC 0.82 and 0.86, respectively) and 3D-LA ejection fraction and area strain (AUC = 0.82 and 0.81, respectively).

Conclusion: Anatomical and functional LA remodelling assessed by 2DE and 3DE is independently and strongly associated with PAF, suggesting that these parameters can help identify PAF.
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http://dx.doi.org/10.1093/ehjci/jew028DOI Listing
January 2017

Vaccination of healthcare workers: A review.

Hum Vaccin Immunother 2015 ;11(11):2522-37

a Service d'Hygiène, Epidémiologie et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon ; Lyon , France.

Vaccine-preventable diseases are a significant cause of morbidity and mortality. As new vaccines are proving to be effective and as the incidence of some infections decreases, vaccination practices are changing. Healthcare workers (HCWs) are particularly exposed to and play a role in nosocomial transmission, which makes them an important target group for vaccination. Most vaccine-preventable diseases still carry a significant risk of resurgence and have caused outbreaks in recent years. While many professional societies favor vaccination of HCWs as well as the general population, recommendations differ from country to country. In turn, vaccination coverage varies widely for each microorganism and for each country, making hospitals and clinics vulnerable to outbreaks. Vaccine mandates and non-mandatory strategies are the subject of ongoing research and controversies. Optimal approaches to increase coverage and turn the healthcare workforce into an efficient barrier against infectious diseases are still being debated.
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http://dx.doi.org/10.1080/21645515.2015.1082014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685699PMC
August 2016

Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

Nat Genet 2015 Sep 27;47(9):969-978. Epub 2015 Jul 27.

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.
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http://dx.doi.org/10.1038/ng.3360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564951PMC
September 2015

Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach.

Transgenic Res 2015 Oct 16;24(5):921-7. Epub 2015 Jul 16.

Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK.

With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects.
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http://dx.doi.org/10.1007/s11248-015-9897-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569667PMC
October 2015

Metabolic and cardiac phenotype characterization in 37 atypical Dunnigan patients with nonfarnesylated mutated prelamin A.

Am Heart J 2015 Apr 7;169(4):587-93. Epub 2015 Jan 7.

Service de Rythmologie, Hôpital Cardiologique Louis-Pradel, Bron, France.

Background: Laminopathies are associated with a broad spectrum of clinical manifestations, from lipodystrophy to cardiac diseases. The purpose of this study was to assess genotype-phenotype correlations in a lipodystrophic laminopathy caused by the Lamin A (LMNA) mutation T655fsX49. This mutation leads to synthesis of nonfarnesylated-mutated prelamin A that does not undergo the physiologic lamin A maturation process.

Methods And Results: We studied 35 patients originating from Reunion Island who carried the LMNA T655fsX49 mutation. Comparisons of cardiac and endocrinologic features were made between homozygous and heterozygous patients. Homozygous patients presented more overlapping syndromes with severe cardiac phenotypes, defined by cardiolaminopathy, early atheroma with coronary heart disease (CHD) and high-degree conduction disorder compared with heterozygous (40% vs 4%; P = .016). Moreover, homozygous patients had earlier onset (49.6 vs 66 years old; P = .0002). Left ventricle lowered ejection fraction associated with heart failure was more frequent in homozygous than in heterozygous patients (40% vs 0%, respectively). Lipodystrophic traits were more marked in the homozygous group but only reached statistical significance for L4 subcutaneous fat measurement (2.8 ± 2.16 vs 18.7 ± 8.9 mm; P = .008) and leptin levels (2.45 ± 1.6 vs 11.26 ± 7.2 ng/mL; P = .0001).

Conclusions: Our results suggest that there is a relationship between mutated prelamin-A accumulation and the severity of the phenotypes in homozygous familial partial lipodystrophy type 2 patients who harbor the LMNA T655fsX49 mutation. A dose-dependent effect seems likely.
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http://dx.doi.org/10.1016/j.ahj.2014.12.021DOI Listing
April 2015

CD47 activation-induced UHRF1 over-expression is associated with silencing of tumor suppressor gene p16INK4A in glioblastoma cells.

Anticancer Res 2015 Jan;35(1):149-57

CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, Illkirch, France

CD47, an integrin-associated protein is over-expressed in several tumors including glioblastomas. Activation of CD47 induces proliferation of human astrocytoma cells but not normal astrocytes via an Akt-dependent way. However, the pathways mediating this process are still unknown. The epigenetic integrator UHRF1 (Ubiquitin-like containing PHD and RING Finger 1) is over-expressed in various cancers and plays a vital role in the silencing of numerous tumor suppressor genes including p16(INK4A), thereby promoting cell proliferation. The aim of the present study was to investigate the role of UHRF1 and p16(INK4A) in CD47-induced effects. Herein we showed that activation of CD47 in human astrocytoma cell lines U87 and CCF- STTG1 (Grade IV), up-regulated the expression of UHRF1 with subsequent down-regulation of p16(INK4A), thus promoting cell proliferation. Blockage of CD47 using a blocking antibody down-regulated UHRF1 expression, accompanied by a re-expression of p16(INK4A), conducting to decreased cell proliferation in both cancer cell lines. Neither CD47 activation nor its blocking has any effect on UHRF1/p16(INK4A) expression in normal human astrocytes. Depletion of CD47 in the U87 cell line resulted in down-regulation of UHRF1. We also found that CD47 activated the inflammatory genes IL-6, IL-7 and MCP-1 by a NF-κB-dependent mechanism in human astrocytoma but not in normal astrocytes. In conclusion, the present findings indicate that CD47 activation increases expression of UHRF1 and suggest, for the first time, that CD47 regulates the epigenetic code by targeting UHRF1. This could represent a new pathway towards cell proliferation and metastasis.
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January 2015

Effect of ball-milling and Fe-/Al-doping on the structural aspect and visible light photocatalytic activity of TiO2 towards Escherichia coli bacteria abatement.

Mater Sci Eng C Mater Biol Appl 2014 May 22;38:11-9. Epub 2014 Jan 22.

Institut de Physique et Chimie des Matériaux de Strasbourg IPCMS, UMR 7504, CNRS-ECPM-Université de Strasbourg, 23 rue du loess BP 43 67034 Strasbourg cedex 2, France. Electronic address:

Escherichia coli abatement was studied in liquid phase under visible light in the presence of two commercial titania photocatalysts, and of Fe- and Al-doped titania samples prepared by high energy ball-milling. The two commercial titania photocatalysts, Aeroxide P25 (Evonik industries) exhibiting both rutile and anatase structures and MPT625 (Ishihara Sangyo Kaisha), a Fe-, Al-, P- and S-doped titania exhibiting only the rutile phase, are active suggesting that neither the structure nor the doping is the driving parameter. Although the MPT625 UV-visible spectrum is shifted towards the visible domain with respect to the P25 one, the effect on bacteria is not increased. On the other hand, the ball milled iron-doped P25 samples exhibit low activities in bacteria abatement under visible light due to charge recombinations unfavorable to catalysis as shown by photoluminescence measurements. While doping elements are in interstitial positions within the rutile structure in MPT625 sample, they are located at the surface in ball milled samples and in isolated octahedral units according to (57)Fe Mössbauer spectrometry. The location of doping elements at the surface is suggested to be responsible for the sample cytotoxicity observed in the dark.
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http://dx.doi.org/10.1016/j.msec.2014.01.026DOI Listing
May 2014

TiO2 photocatalysis damages lipids and proteins in Escherichia coli.

Appl Environ Microbiol 2014 Apr 14;80(8):2573-81. Epub 2014 Feb 14.

Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS and Strasbourg University, Illkirch, France.

This study investigates the mechanisms of UV-A (315 to 400 nm) photocatalysis with titanium dioxide (TiO2) applied to the degradation of Escherichia coli and their effects on two key cellular components: lipids and proteins. The impact of TiO2 photocatalysis on E. coli survival was monitored by counting on agar plate and by assessing lipid peroxidation and performing proteomic analysis. We observed through malondialdehyde quantification that lipid peroxidation occurred during the photocatalytic process, and the addition of superoxide dismutase, which acts as a scavenger of the superoxide anion radical (O2·(-)), inhibited this effect by half, showing us that O2·(-) radicals participate in the photocatalytic antimicrobial effect. Qualitative analysis using two-dimensional electrophoresis allowed selection of proteins for which spot modifications were observed during the applied treatments. Two-dimensional electrophoresis highlighted that among the selected protein spots, 7 and 19 spots had already disappeared in the dark in the presence of 0.1 g/liter and 0.4 g/liter TiO2, respectively, which is accounted for by the cytotoxic effect of TiO2. Exposure to 30 min of UV-A radiation in the presence of 0.1 g/liter and 0.4 g/liter TiO2 increased the numbers of missing spots to 14 and 22, respectively. The proteins affected by photocatalytic oxidation were strongly heterogeneous in terms of location and functional category. We identified several porins, proteins implicated in stress response, in transport, and in bacterial metabolism. This study reveals the simultaneous effects of O2·(-) on lipid peroxidation and on the proteome during photocatalytic treatment and therefore contributes to a better understanding of molecular mechanisms in antibacterial photocatalytic treatment.
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http://dx.doi.org/10.1128/AEM.03995-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993174PMC
April 2014

Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes.

Diabetes 2014 Feb 23;63(2):446-55. Epub 2013 Aug 23.

Vactech Ltd., Tampere, Finland.

The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.
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http://dx.doi.org/10.2337/db13-0619DOI Listing
February 2014

Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not supported when data are stratified by age.

Clin Infect Dis 2013 Dec 15;57(11):1658-60. Epub 2013 Aug 15.

Department of Epidemiology, Sanofi Pasteur, Lyon, France.

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http://dx.doi.org/10.1093/cid/cit552DOI Listing
December 2013

On the use of capillary cytometry for assessing the bactericidal effect of TiO2. Identification and involvement of reactive oxygen species.

Photochem Photobiol Sci 2013 Apr;12(4):610-20

Laboratoire de Biophotonique et de Pharmacologie, CNRS and Strasbourg University, 74 route du Rhin, Illkirch, France.

The photocatalytic antimicrobial properties of TiO2 were studied on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacterial strains taken as model strains for pathogenic species mainly implied in nosocomial infections. Capillary cytometry, coupled to a double-staining method for visualizing membrane integrity as a cell viability indicator, was highlighted as a rapid, easy-to-use, and automated numeration technique for quantitative and reproducible determination of cellular viability and thus, was able to give an accurate evaluation of the bactericidal effect of UV-A photocatalysis. Cytometry also enabled the study of TiO2-bacteria interactions and aggregation in the dark as well as TiO2 cytotoxicity. Compared with the traditional agar plate cultivation method, a significatively weaker reduction in cell viability was recorded by cytometry whatever the bacteria, TiO2 concentration, and duration of the photocatalytic treatment. The mismatch between both numeration methods was attributed to: (i) the presence of mixed bacteria-TiO2 aggregates that could interfere with bacteria measurement on plates, (ii) prolonged contact of the bacteria with TiO2 during incubation, which could cause additional cytotoxic damage to the bacterial wall, and (iii) the counting of viable but non-culturable bacteria as live bacteria in cytometry, whereas they cannot grow on solid media. A more pronounced difference was observed for P. aeruginosa and S. aureus bacteria, for which 2.9 and 1.9 log10 survival reduction overestimations were measured by plate counting, respectively. Using chemiluminescence, full restoration of cell viability by controlled addition of the O2˙(-) scavenger superoxide dismutase enzyme suggests that O2˙(-) acts, in our conditions, as the main reactive oxygen species responsible for the photocatalytic attack towards the targeted bacteria.
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http://dx.doi.org/10.1039/c2pp25189bDOI Listing
April 2013

Interferometric identification of a pre-brown dwarf.

Science 2012 Jul;337(6090):69-72

Laboratoire d'Astrophysique, Instrumentation et Modélisation (AIM), Commissariat à l'Energie Atomique (CEA)/Direction des Sciences de la Matière (DSM)-CNRS-Université Paris Diderot, Gif-sur-Yvette, France.

It is not known whether brown dwarfs [stellar-like objects with masses less than the hydrogen-burning limit, 0.075 solar mass (M)[symbol:see text]] are formed in the same way as solar-type stars or by some other process. Here we report the clear-cut identification of a self-gravitating condensation of gas and dust with a mass in the brown-dwarf regime, made through millimeter interferometric observations. The level of thermal millimeter continuum emission detected from this object indicates a mass ~0.02 to 0.03 M[symbol:see text], whereas the small radius, <460 astronomical units, and narrow spectral lines imply a dynamical mass of 0.015 to 0.02 M[symbol:see text]. The identification of such a pre-brown dwarf core supports models according to which brown dwarfs are formed in the same manner as hydrogen-burning stars.
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http://dx.doi.org/10.1126/science.1222602DOI Listing
July 2012

Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt-dependent pathway.

Glia 2011 Feb;59(2):308-19

Université de Strasbourg, CNRS UMR 7213-Pharmacologie, Faculté de Pharmacie, 74 rte du Rhin, Illkirch, France.

CD47 is a membrane receptor that plays pivotal roles in many pathophysiological processes, including infection, inflammation, cell spreading, proliferation, and apoptosis. We show that activation of CD47 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. CD47 function-blocking antibodies inhibit proliferation of untreated U87 and U373 cells but not normal astrocytes, suggesting that CD47 may be constitutively activated in astrocytoma. CD47 expression levels were similar in our three cell types. CD47 couples to G-proteins in astrocytes and astrocytoma and especially to the Gβγ dimer. Downstream signaling following CD47 activation involves Gβγ dimer-dependent activation of the PI3K/Akt pathway in astrocytoma cells but not in normal astrocytes. This pathway is known to be deregulated in astrocytoma, leading to cell proliferation and enhanced survival signals. Putative PLIC-1 interaction with CD47 in astrocytoma cells but not astrocytes may contribute to the proliferative effect observed upon activation of CD47. Our data indicate that CD47 receptors have a stimulatory role in cell proliferation and demonstrate for the first time that CD47 signals via the PI3K/Akt pathway in cancerous cells but not normal cells.
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http://dx.doi.org/10.1002/glia.21102DOI Listing
February 2011

A new approach to estimate vaccine efficacy based on immunogenicity data applied to influenza vaccines administered by the intradermal or intramuscular routes.

Hum Vaccin 2010 Oct 1;6(10):841-8. Epub 2010 Oct 1.

Sanofi Pasteur, Lyon, France.

Background: Despite their pivotal role in the assessment of influenza vaccines, limited attempts have been made to use haemagglutination inhibition (HI) titers for predicting vaccine efficacy against laboratory-confirmed influenza. We present here the second step of a two-step approach allowing performing such predictions and use it to compare a new trivalent inactivated influenza vaccine administered by the intradermal (ID) route (INTANZA® /IDFlu®) with the vaccine administered by the classical intramuscular (IM) route.

Methods: The first step corresponding to the estimation of the level of protection against laboratory-confirmed influenza that can be linked to each HI titer, referred to as the HI protection curve, was achieved by using a meta-analytical approach based on published information. Vaccine efficacy and differences in vaccine efficacy are predicted in a second step using this HI protection curve alongside the results of two randomized clinical trials providing comparative information on the immunogenicity of trivalent inactivated influenza vaccines administered ID or IM in 3503 & 1645 elderly participants, respectively.

Results: Pooling all available immunogenicity data, the predicted vaccine efficacy was 63.3% [CI: 58.1; 68.7] for ID route and 54.4% [CI: 49.4; 59.2] for IM route. The corresponding relative increase in efficacy that is of 16.5% [CI: 12.7; 20.1]. Predicted vaccine efficacies decreased with age for both vaccines, but the decrease was less marked by ID route: the relative increase in efficacy for subjects aged 70 years and above is of 18.0% [CI:12;24].

Conclusion: The analysis performed confirmed that the superior immune response provided by the vaccine using the ID route should translate into a higher vaccine efficacy against laboratory-confirmed influenza.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056065PMC
http://dx.doi.org/10.4161/hv.6.10.12636DOI Listing
October 2010

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model.

BMC Med Res Methodol 2010 Mar 8;10:18. Epub 2010 Mar 8.

Sanofi pasteur, 2 avenue Pont Pasteur F-69367 Lyon cedex 07 France.

Background: Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.

Methods: We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.

Results: A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.

Conclusion: Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.
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http://dx.doi.org/10.1186/1471-2288-10-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851702PMC
March 2010

3D-pharmacophere models for CC chemokine receptor 1 antagonists.

Med Chem 2009 Jul;5(4):318-24

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

The CC Chemokine Receptor 1 (CCR1) is closely related to various chronic inflammatory diseases like rheumatoid arthritis and multiple sclerosis, and plays a crucial role in transplant rejection. Inhibiting its activity with CCR1 antagonists has been proved to be effective in preventing some diseases. A number of in vivo experiments have been carried out to shed light on the underlying mechanism of the interactions between the CCR1 and its ligands. However, their conclusions are still controversial. In this study, ligand-based computational drug design is applied as a new and effective way to study the structure-activity relationship of CCR1 antagonists. Three-dimensional pharmacophore models were generated for CCR1 antagonists, using both HypoGen and HipHop algorithms in Catalyst software. Two optimal pharmacophore models were defined through careful qualification processes. Both of them have four features: one hydrogen-bond acceptor, one positive ionable and two hydrophobic groups. Additional information was obtained through comparison between the two models. Our results can be valuable tools for the discovery and development of specific, highly potent CCR1 antagonists. For Supplement material, please see the online version of the article.
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http://dx.doi.org/10.2174/157340609788681502DOI Listing
July 2009

Embedded silver ions-containing liposomes in polyelectrolyte multilayers: cargos films for antibacterial agents.

Langmuir 2008 Sep 13;24(18):10209-15. Epub 2008 Aug 13.

Département de Chimie Bioorganique, Institut Gilbert Laustriat, UMR 7175 CNRS/Université Louis Pasteur, Illkirch, France.

A new antibacterial coating made of poly(L-lysine)/hyaluronic acid (PLL/HA) multilayer films and liposome aggregates loaded with silver ions was designed. Liposomes filled with an AgNO 3 solution were first aggregated by the addition of PLL in solution. The obtained micrometer-sized aggregates were then deposited on a PLL/HA multilayer film, playing the role of a spacer with the support. Finally, HA/PLL/HA capping layers were deposited on top of the architecture to form a composite AgNO 3 coating. Release of encapsulated AgNO 3 from this composite coating was followed and triggered upon temperature increase over the transition temperature of vesicles, found to be equal to 34 degrees C. After determination of the minimal inhibitory concentration (MIC) of AgNO 3 in solution, the antibacterial activity of the AgNO 3 coating was investigated against Escherichia coli. A 4-log reduction in the number of viable E. coli cells was observed after contact for 120 min with a 120 ng/cm (2) AgNO 3 coating. In comparison, no bactericidal activity was found for PLL/HA films previously dipped in an AgNO 3 solution and for PLL/HA films with liposome aggregates containing no AgNO 3 solution. The strong bactericidal effect could be linked to the diffusion of silver ions out of the AgNO 3 coating, leading to an important bactericidal concentration close to the membrane of the bacteria. A simple method to prepare antibacterial coatings loaded with a high and controlled amount of AgNO 3 is therefore proposed. This procedure is far superior to that soaking AgNO 3 or Ag nanoparticles into a coating. In principle, other small bactericidal chemicals like antibiotics could be encapsulated by this method. This study opens a new route to modify surfaces with small solutes that are not permeating phospholipid membranes below the phase transition temperature.
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http://dx.doi.org/10.1021/la8014755DOI Listing
September 2008

Comparison of serological and real-time PCR assays to diagnose Bordetella pertussis infection in 2007.

J Clin Microbiol 2008 May 26;46(5):1672-7. Epub 2008 Mar 26.

Sanofi Pasteur, 2 Avenue Pont Pasteur, 69367 Lyon Cedex 07, France.

Bacterial culture for diagnosing pertussis infection has high specificity but poor sensitivity and is slow. Highly sensitive real-time PCR assays and single-serum pertussis serology have been developed to overcome these limitations, but there are few data available on the relative sensitivities and specificities of such assays for pertussis diagnosis. Using data on 195 participants (>or=7 years old) from an epidemiological study, we assessed the sensitivity, specificity, and performance (Youden index) for pertussis diagnosis of the pertussis toxin enzyme-linked immunosorbent assay (using single and paired serology) and of real-time PCR assays (using the IS481 and ptxA-Pr targets). All available diagnostic information (clinical and laboratory) was pooled to serve as the gold standard. Single serology was the most efficient diagnostic test (Youden index, 0.57 to 0.58), with relatively high sensitivity (>64%) and high specificity (>90%), independent of the cutoff level. IS481 PCR performance was superior to that of ptxA-Pr PCR, and it was the second-most-efficient tool (Youden index, 0.30). Performing both ptxA-Pr and IS481 PCRs did not improve diagnostic performance. The greatest test efficiency (Youden index, 0.69 to 0.74) was achieved when single-serum serology was used in combination with IS481 or ptxA-Pr PCR or paired serology. Combining single serology with one PCR or paired serology increased the sensitivity with an associated limited decrease in specificity. The most specific tests for diagnosis of pertussis were single serology and ptxA-Pr PCR, and the most sensitive diagnostic tool was the combination of IS481 PCR with single serology.
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http://dx.doi.org/10.1128/JCM.02187-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395107PMC
May 2008

Gamma-glutamyltransferase activity and development of the metabolic syndrome (International Diabetes Federation Definition) in middle-aged men and women: Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort.

Diabetes Care 2007 Sep 22;30(9):2355-61. Epub 2007 Jun 22.

Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 780-IFR69, Epidemiological and Biostatistical Research, Villejuif, France.

Objective: Among hepatic enzymes, gamma-glutamyltransferase (GGT) is the main predictor of type 2 diabetes incidence, although it has not been shown that GGT predicts pre-diabetes states. Our aim was to study the association of GGT with the development of the metabolic syndrome (MetS).

Research Design And Methods: We analyzed the 3-year data from the Data from Epidemiological Study on the Insulin Resistance Syndrome prospective cohort of 1,656 men and 1,889 women without MetS at baseline, according to the International Diabetes Federation definition.

Results: Over 3 years, 309 participants developed the MetS. After adjustment for age, alcohol intake, physical activity, smoking habits, and alanine aminotransferase (ALT), the odds ratios for incident MetS increased across baseline GGT quartiles (1, 1.96, 2.25, and 3.81 in men, P < 0.03; and 1, 1.23, 1.80, and 1.58 in women, P < 0.05). After additional adjustment for insulin resistance markers (fasting insulin or homeostasis model assessment of insulin resistance index), the association was attenuated and the linear relation no longer significant in both sexes (P = 0.08, P = 0.16). However, men in the highest in comparison to the lowest quartile of GGT retained a significant risk for incident MetS. In women, there was no longer a significant risk. GGT was significantly associated with the 3-year incidence of individual components of the MetS. The incidence of the MetS also increased with ALT, but after adjustment on GGT this association remained significant only in women.

Conclusions: GGT, a predictor of type 2 diabetes, was associated with a risk of incident MetS. This association was mainly related with insulin resistance but was independent of other confounding factors.
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http://dx.doi.org/10.2337/dc07-0440DOI Listing
September 2007

Ferritin and transferrin are associated with metabolic syndrome abnormalities and their change over time in a general population: Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR).

Diabetes Care 2007 Jul 6;30(7):1795-801. Epub 2007 Apr 6.

Institut National de la Santé et de la Recherche Médicale, Unité 780-IFR69, Epidemiological and Biostatistical Research, Villejuif, France.

Objective: The aim of this work was to study cross-sectional and longitudinal relations between iron stocks (ferritin) and the iron transport protein (transferrin) with the metabolic syndrome and its abnormalities.

Research Design And Methods: A total of 469 men and 278 premenopausal and 197 postmenopausal women from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, aged 30-65 years, were followed over 6 years.

Results: Higher concentrations of both ferritin and transferrin were associated with the International Diabetes Federation (IDF) and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III original and revised definitions of the metabolic syndrome at baseline: for the IDF definition of the metabolic syndrome, the standardized, age-adjusted odds ratios (95% CI) for log(ferritin) were 1.49 (1.14-1.94) for men, 2.10 (1.27-3.48) for premenopausal women, and 1.80 (1.21-2.68) for postmenopausal women; for transferrin they were, respectively, 1.94 (1.53-2.47), 2.22 (1.32-3.75), and 2.14 (1.47-3.10). After 6 years of follow-up, the change in the presence of the metabolic syndrome was associated with higher baseline values in all three groups: log(ferritin), 1.46 (1.13-1.89), 1.28 (0.85-1.94), and 1.62 (1.10-2.38); and transferrin, 1.41 (1.10-1.81), 1.63 (1.05-2.52), and 1.51 (1.02-2.22). Among syndrome components, hypertriglyceridemia at 6 years was the component most strongly associated with baseline ferritin and transferrin. The odds of an incident IDF-defined metabolic syndrome after 6 years was more than fourfold higher when ferritin and transferrin values were both above the group-specific top tertile, in comparison with participants with both parameters below these thresholds.

Conclusions: This is the first prospective study associating ferritin and transferrin with the metabolic syndrome and its components. When both markers of the iron metabolism are elevated, the incidence of the metabolic syndrome is increased in men and both pre- and postmenopausal women.
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http://dx.doi.org/10.2337/dc06-2312DOI Listing
July 2007

Chemiluminescence of enterococci isolates from freshwater.

FEMS Microbiol Lett 2005 Apr;245(1):123-9

U.F.R. des Sciences Pharmaceutiques, UE-3429, 74 route du Rhin, B.P. 24, 67401 Illkirch Cedex, France.

All Enterococcus spp., isolated from environmental water samples (n=81), emitted a high chemiluminescence signal in the presence of luminol (10(-2) M). Kinetic studies of chemiluminescence show a close correlation between chemiluminescence and growth curves during the exponential phase, with a maximum chemiluminescence reached just before bacterial growth entered in the stationary phase. On the other hand, genera closely related to Enterococcus such as Streptococcus or Lactococcus produced a very weak chemiluminescent signal. Chemiluminescence of enterococci could therefore offer a rapid test, in aiding the identification of the genus Enterococcus and in the survey of the microbiological quality of water supplies.
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http://dx.doi.org/10.1016/j.femsle.2005.02.036DOI Listing
April 2005

A neural network controller for hydronic heating systems of solar buildings.

Neural Netw 2004 Apr;17(3):427-40

Section of Applied Physics, Department of Physics, University of Patras, GR-256 00 Patras, Greece.

An artificial neural network (ANN)-based controller for hydronic heating plants of buildings is presented. The controller has forecasting capabilities: it includes a meteorological module, forecasting the ambient temperature and solar irradiance, an indoor temperature predictor module, a supply temperature predictor module and an optimizing module for the water supply temperature. All ANN modules are based on the Feed Forward Back Propagation (FFBP) model. The operation of the controller has been tested experimentally, on a real-scale office building during real operating conditions. The operation results were compared to those of a conventional controller. The performance was also assessed via numerical simulation. The detailed thermal simulation tool for solar systems and buildings TRNSYS was used. Both experimental and numerical results showed that the expected percentage of energy savings with respect to a conventional controller is of about 15% under North European weather conditions.
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http://dx.doi.org/10.1016/j.neunet.2003.07.001DOI Listing
April 2004