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Article ; Online: System for quantitative evaluation of DAB&H-stained breast cancer biopsy digital images (CHISEL).

Roszkowiak, Lukasz / Korzynska, Anna / Siemion, Krzysztof / Zak, Jakub / Pijanowska, Dorota / Bosch, Ramon / Lejeune, Marylene / Lopez, Carlos

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9291

Abstract: ... along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based ... sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been ...

Abstract	This study presents CHISEL (Computer-assisted Histopathological Image Segmentation and EvaLuation), an end-to-end system capable of quantitative evaluation of benign and malignant (breast cancer) digitized tissue samples with immunohistochemical nuclear staining of various intensity and diverse compactness. It stands out with the proposed seamless segmentation based on regions of interest cropping as well as the explicit step of nuclei cluster splitting followed by a boundary refinement. The system utilizes machine learning and recursive local processing to eliminate distorted (inaccurate) outlines. The method was validated using two labeled datasets which proved the relevance of the achieved results. The evaluation was based on the IISPV dataset of tissue from biopsy of breast cancer patients, with markers of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based on the comparison of the ground truth with the results of the detected and classified objects, we conclude that the proposed method can achieve better or similar results as the state-of-the-art methods. This system deals with the complex problem of nuclei quantification in digitalized images of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been prepared with user-friendly graphical interface and was optimized to fully utilize the available computing power, while being accessible to users with fewer resources than needed by deep learning techniques.
MeSH term(s)	3,3'-Diaminobenzidine ; Algorithms ; Biopsy ; Breast Neoplasms/pathology ; Cell Nucleus/ultrastructure ; Female ; Hematoxylin ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Machine Learning ; Staining and Labeling
Chemical Substances	3,3'-Diaminobenzidine (2RV4T6KHQI) ; Hematoxylin (YKM8PY2Z55)
Language	English
Publishing date	2021-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-88611-y
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Article ; Online: System for quantitative evaluation of DAB&H-stained breast cancer biopsy digital images (CHISEL)

Lukasz Roszkowiak / Anna Korzynska / Krzysztof Siemion / Jakub Zak / Dorota Pijanowska / Ramon Bosch / Marylene Lejeune / Carlos Lopez

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 14

Abstract: ... of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients ... of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples ...

Abstract	Abstract This study presents CHISEL (Computer-assisted Histopathological Image Segmentation and EvaLuation), an end-to-end system capable of quantitative evaluation of benign and malignant (breast cancer) digitized tissue samples with immunohistochemical nuclear staining of various intensity and diverse compactness. It stands out with the proposed seamless segmentation based on regions of interest cropping as well as the explicit step of nuclei cluster splitting followed by a boundary refinement. The system utilizes machine learning and recursive local processing to eliminate distorted (inaccurate) outlines. The method was validated using two labeled datasets which proved the relevance of the achieved results. The evaluation was based on the IISPV dataset of tissue from biopsy of breast cancer patients, with markers of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based on the comparison of the ground truth with the results of the detected and classified objects, we conclude that the proposed method can achieve better or similar results as the state-of-the-art methods. This system deals with the complex problem of nuclei quantification in digitalized images of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been prepared with user-friendly graphical interface and was optimized to fully utilize the available computing power, while being accessible to users with fewer resources than needed by deep learning techniques.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article: The H-NS protein is involved in the biogenesis of flagella in Escherichia coli.

Bertin, P / Terao, E / Lee, E H / Lejeune, P / Colson, C / Danchin, A / Collatz, E

Journal of bacteriology

1994 Volume 176, Issue 17, Page(s) 5537–5540

Abstract: ... the flagellum synthesis independent of the cAMP-CAP complex. These results suggest that the H-NS protein acts ...

Abstract	The function of the flagellum-chemotaxis regulon requires the expression of many genes and is positively regulated by the cyclic AMP-catabolite activator protein (cAMP-CAP) complex. In this paper, we show that motile behavior was affected in Escherichia coli hns mutants. The loss of motility resulted from a complete lack of flagella. A decrease in the level of transcription of the flhD and fliA genes, which are both required for the synthesis of flagella, was observed in the presence of an hns mutation. Furthermore, the Fla- phenotype was not reversed to the wild type in the presence of a cfs mutation which renders the flagellum synthesis independent of the cAMP-CAP complex. These results suggest that the H-NS protein acts as a positive regulator of genes involved in the biogenesis of flagella by a mechanism independent of the cAMP-CAP pathway.
MeSH term(s)	Bacterial Outer Membrane Proteins/biosynthesis ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins ; Cell Movement/genetics ; Cyclic AMP/metabolism ; Cyclic AMP Receptor Protein/metabolism ; DNA-Binding Proteins/biosynthesis ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Escherichia coli/genetics ; Escherichia coli/physiology ; Escherichia coli/ultrastructure ; Flagella/physiology ; Flagella/ultrastructure ; Genes, Bacterial ; Genotype ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Mutagenesis ; Phenotype ; Regulon ; Species Specificity ; Transcription, Genetic
Chemical Substances	Bacterial Outer Membrane Proteins ; Bacterial Proteins ; Cyclic AMP Receptor Protein ; DNA-Binding Proteins ; H-NS protein, bacteria ; Cyclic AMP (E0399OZS9N)
Language	English
Publishing date	1994-09
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/jb.176.17.5537-5540.1994
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Article: Interactions of (+)- and (-)-8- and 7-hydroxy-2-(di-n-propylamino)tetralin at human (h)D3, hD2 and h serotonin1A receptors and their modulation of the activity of serotoninergic and dopaminergic neurones in rats.

Lejeune, F / Newman-Tancredi, A / Audinot, V / Millan, M J

The Journal of pharmacology and experimental therapeutics

1997 Volume 280, Issue 3, Page(s) 1241–1249

Abstract: ... interactions with cloned, human (h)5-HT1A, hD3 and hD2 receptors. In binding studies, racemic 8-OH-DPAT showed ...

Abstract	The aminotetralins, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 7-OH-DPAT behave as preferential agonists at serotonin (5-HT)1A and dopamine D3 and D2 receptors, respectively. In our study, we evaluated the influence of their (+)- and (-) isomers on the electrical activity of serotoninergic neurones of the dorsal raphe nucleus (DRN), which bear 5-HT1A autoreceptors, and of dopaminergic neurones of the ventral tegmental area (VTA), which possess inhibitory D3 and D2 receptors. These actions were compared to their in vitro interactions with cloned, human (h)5-HT1A, hD3 and hD2 receptors. In binding studies, racemic 8-OH-DPAT showed 100-fold selectivity for h5-HT1A vs. hD2 and hD3 receptors and there was little difference between its (+)- and (-)-isomers either in terms of their potency at 5-HT1A receptors or of their selectivity at 5-HT1A vs hD2/hD3 sites. Nevertheless, the (+)-isomer was markedly more efficacious than its (-)-counterpart in stimulating the binding of guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]-GTPgammaS) at h5-HT1A receptors, a measure of coupling to G-proteins; 90 vs. 57% maximal stimulation respectively, relative to 5-HT = 100%. Also the (+)-isomer was ca. 3-fold more potent than the (-)-isomer in inhibiting the firing rate of DRN neurones. These actions were abolished by the 5-HT1A antagonist, (-)-tertatolol, but unaffected by the hD2/hD3 antagonist, haloperidol. Whereas (+)-8-OH-DPAT stimulated VTA neurone firing with a bell-shaped dose response curve, the (-)-isomer only inhibited VTA firing. The (+)-isomer-induced stimulation was blocked by (-)-tertatolol but not haloperidol, whereas the (-)-isomer-induced inhibition was abolished by haloperidol and unaffected by (-)-tertatolol. In contrast to 8-OH-DPAT, the (+)- and (-)isomers of 7-OH-DPAT showed marked stereoselectivity inasmuch as the latter bound with 20-fold less potency than the former at hD3 and, at higher concentrations, hD2 receptors. Correspondingly, (+)-7-OH-DPAT was 20-fold more potent than (-)-7-OH-DPAT in reducing VTA firing. Concerning 5-HT1A receptors, the (+)-isomer showed 20-fold lower affinity than at hD3 receptors and, accordingly, it inhibited DRN firing at 20-fold higher doses than for inhibition of VTA firing. (-)-7-OH-DPAT showed even less (5-fold) selectivity for hD3 vs. 5-HT1A sites and for inhibition of VTA vs. DRN firing. The inhibition of VTA and DRN neurone firing by (+)-7-OH-DPAT was abolished by haloperidol and (-)-tertatolol, respectively. Finally, in line with this inhibition of DRN firing, both (+)- and (-)-7-OH-DPAT showed substantial efficacy ([35S]-GTPgammaS binding, 76 and 53%, respectively) at h5-HT1A receptors. In conclusion, for these substituted aminotetralins, stereospecificity is a more marked feature of interactions at hD3 (and hD2) than at h5-HT1A receptors and is more pronounced for 7- as compared to 8-OH-DPAT. Neither (+)- nor (-)-7-OH-DPAT show substantial selectivity for hD3 vs. 5-HT1A receptors and their inhibition of the firing of VTA as compared to DRN neurones is mediated by hD3/hD2 and 5-HT1A receptors, respectively. Finally, VTA neurones are stimulated by (+)-8-OH-DPAT via 5-HT1A receptors and inhibited by (-)-8-OH-DPAT via hD3 and/or hD2 receptors.
MeSH term(s)	8-Hydroxy-2-(di-n-propylamino)tetralin/metabolism ; 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Humans ; Male ; Neurons/drug effects ; Neurons/metabolism ; Neurons/physiology ; Rats ; Rats, Wistar ; Receptors, Dopamine/drug effects ; Receptors, Dopamine/metabolism ; Receptors, Serotonin/drug effects ; Receptors, Serotonin/metabolism ; Recombinant Proteins/metabolism ; Serotonin Antagonists/pharmacology ; Serotonin Receptor Agonists/pharmacology ; Tetrahydronaphthalenes/metabolism ; Tetrahydronaphthalenes/pharmacology
Chemical Substances	Dopamine Agonists ; Dopamine Antagonists ; Receptors, Dopamine ; Receptors, Serotonin ; Recombinant Proteins ; Serotonin Antagonists ; Serotonin Receptor Agonists ; Tetrahydronaphthalenes ; 8-Hydroxy-2-(di-n-propylamino)tetralin (78950-78-4) ; 7-hydroxy-2-N,N-dipropylaminotetralin (RR7D75YDF4)
Language	English
Publishing date	1997-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
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Article: Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber.

Lejeune, Manuela P G M / Westerterp, Klaas R / Adam, Tanja C M / Luscombe-Marsh, Natalie D / Westerterp-Plantenga, Margriet S

The American journal of clinical nutrition

2006 Volume 83, Issue 1, Page(s) 89–94

Abstract: ... was to investigate 24-h satiety and related hormones and energy and substrate metabolism during a high ... in a randomized crossover design. Substrate oxidation, 24-h energy expenditure (EE), appetite profile, and ghrelin ... a tendency for a greater 24-h EE during the HP diet (P = 0.05). Although energy intake was not significantly ...

Abstract	Background: The mechanism of protein-induced satiety remains unclear. Objective: The objective was to investigate 24-h satiety and related hormones and energy and substrate metabolism during a high-protein (HP) diet in a respiration chamber. Design: Twelve healthy women aged 18-40 y were fed in energy balance an adequate-protein (AP: 10%, 60%, and 30% of energy from protein, carbohydrate, and fat, respectively) or an HP (30%, 40%, and 30% of energy from protein, carbohydrate, and fat, respectively) diet in a randomized crossover design. Substrate oxidation, 24-h energy expenditure (EE), appetite profile, and ghrelin and glucagon-like peptide 1 (GLP-1) concentrations were measured. Results: Sleeping metabolic rate (6.40 +/- 0.47 compared with 6.12 +/- 0.40 MJ/d; P < 0.05), diet-induced thermogenesis (0.91 +/- 0.25 compared with 0.69 +/- 0.24 MJ/d; P < 0.05), and satiety were significantly higher, and activity-induced EE (1.68 +/- 0.32 compared with 1.86 +/- 0.41; P < 0.05), respiratory quotient (0.84 +/- 0.02 compared with 0.88 +/- 0.03; P < 0.0005), and hunger were significantly lower during the HP diet. There was a tendency for a greater 24-h EE during the HP diet (P = 0.05). Although energy intake was not significantly different between the diet groups, the subjects were in energy balance during the HP diet and in positive energy balance during the AP diet. Satiety was related to 24-h protein intake (r2 = 0.49, P < 0.05) only during the HP diet. Ghrelin concentrations were not significantly different between diets. GLP-1 concentrations after dinner were higher during the HP than during the AP diet (P < 0.05). Conclusion: An HP diet, compared with an AP diet, fed at energy balance for 4 d increased 24-h satiety, thermogenesis, sleeping metabolic rate, protein balance, and fat oxidation. Satiety was related to protein intake, and incidentally to ghrelin and GLP-1 concentrations, only during the HP diet.
MeSH term(s)	Adolescent ; Adult ; Amino Acids/metabolism ; Area Under Curve ; Basal Metabolism/drug effects ; Basal Metabolism/physiology ; Body Composition/physiology ; Calorimetry, Indirect/methods ; Cross-Over Studies ; Dietary Proteins/administration & dosage ; Dose-Response Relationship, Drug ; Energy Intake ; Energy Metabolism/physiology ; Environment, Controlled ; Female ; Ghrelin ; Glucagon-Like Peptide 1/blood ; Humans ; Oxidation-Reduction ; Oxygen Consumption ; Peptide Hormones/blood ; Satiation/drug effects ; Satiation/physiology ; Single-Blind Method ; Thermogenesis/drug effects ; Thermogenesis/physiology
Chemical Substances	Amino Acids ; Dietary Proteins ; Ghrelin ; Peptide Hormones ; Glucagon-Like Peptide 1 (89750-14-1)
Language	English
Publishing date	2006-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1093/ajcn/83.1.89
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Article ; Online: Chemotherapies and male infertility.

Plotton, Ingrid / Renault, Lucie / Lapoirie, Marion / Lejeune, Hervé

Annales d'endocrinologie

2023 Volume 84, Issue 4, Page(s) 481–482

MeSH term(s)	Humans ; Male ; Infertility, Male/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Language	English
Publishing date	2023-05-18
Publishing country	France
Document type	Journal Article
ZDB-ID	299-9
ISSN	2213-3941 ; 0003-4266
ISSN (online)	2213-3941
ISSN	0003-4266
DOI	10.1016/j.ando.2023.05.001
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Article: The Escherichia coli DNA-binding protein H-NS is one of the first proteins to be synthesized after a nutritional upshift.

Laurent-Winter, C / Lejeune, P / Danchin, A

Research in microbiology

1995 Volume 146, Issue 1, Page(s) 5–16

Abstract: ... in this work was a strong and transient synthesis of H-NS in the wild-type strain just after the nutritional ...

Abstract	Using two-dimensional electrophoresis, the patterns of polypeptide expression of a wild type and an hns mutant of Escherichia coli were examined in exponential and late stationary phases. The same procedure was used for a kinetic study of proteins synthesized during the first 60 min following inoculation into fresh complete medium. The present study focusses on 35 polypeptides differentially synthesized according to the strain and/or the growth phase. One of the most striking and unexpected observations in this work was a strong and transient synthesis of H-NS in the wild-type strain just after the nutritional upshift.
MeSH term(s)	Autoradiography ; Bacterial Proteins ; DNA-Binding Proteins/biosynthesis ; DNA-Binding Proteins/chemistry ; Electrophoresis, Gel, Two-Dimensional ; Escherichia coli/growth & development ; Escherichia coli/metabolism ; In Vitro Techniques ; Mutation ; Nuclear Proteins/biosynthesis ; Nuclear Proteins/chemistry
Chemical Substances	Bacterial Proteins ; DNA-Binding Proteins ; H-NS protein, bacteria ; Nuclear Proteins
Language	English
Publishing date	1995-01
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1004220-9
ISSN	1769-7123 ; 0923-2508
ISSN (online)	1769-7123
ISSN	0923-2508
DOI	10.1016/0923-2508(96)80266-x
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Article: The H-NS protein modulates the activation of the ilvIH operon of Escherichia coli K12 by Lrp, the leucine regulatory protein.

Levinthal, M / Lejeune, P / Danchin, A

Molecular & general genetics : MGG

1994 Volume 242, Issue 6, Page(s) 736–743

Abstract: The H-NS protein, the product of the hns gene, plays a central role in the cellular response ... as a repressor. We demonstrate that H-NS can decrease the activity of Lrp in stationary phase and under ...

Abstract	The H-NS protein, the product of the hns gene, plays a central role in the cellular response of bacteria to environmental stresses such as modification of osmolarity and temperature. The leucine regulatory protein (Lrp) controls a wide array of operons both as an activator (e.g. ilvIH) and as a repressor. We demonstrate that H-NS can decrease the activity of Lrp in stationary phase and under conditions of high osmolarity. Strains containing hns mutations have higher levels of Lrp-activated ilvIH transcription, while strains carrying the hns+ allele on a pBR322 plasmid have lower activity of Lrp-directed ilvIH gene expression.
MeSH term(s)	Alleles ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Proteins/genetics ; DNA-Binding Proteins/genetics ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Escherichia coli/metabolism ; Escherichia coli Proteins ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Leucine-Responsive Regulatory Protein ; Multigene Family ; Mutation ; Operon ; Regulon ; Transcription Factors ; Transcription, Genetic ; Transcriptional Activation ; Water-Electrolyte Balance/genetics
Chemical Substances	Bacterial Outer Membrane Proteins ; Bacterial Proteins ; DNA-Binding Proteins ; Escherichia coli Proteins ; H-NS protein, bacteria ; Lrp protein, E coli ; Transcription Factors ; Leucine-Responsive Regulatory Protein (138791-20-5)
Language	English
Publishing date	1994-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2169-6
ISSN	1432-1874 ; 1617-4623 ; 0026-8925
ISSN (online)	1432-1874 ; 1617-4623
ISSN	0026-8925
DOI	10.1007/bf00283429
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Article ; Online: Portées théoriques et incarnations des valeurs épistémiques et ontologiques de la durabilité forte dans les politiques environnementales

Caroline Lejeune

Développement Durable et Territoires (2019)

2019

Abstract: Strong sustainability is a concept that originates from the fields of ecological economics and environmental ethics. The pragmatist currents of environmental ethics and ecological economics have deepened what could be a conception of sustainability, ... ...

Abstract	Strong sustainability is a concept that originates from the fields of ecological economics and environmental ethics. The pragmatist currents of environmental ethics and ecological economics have deepened what could be a conception of sustainability, taking into account thresholds of irreversibility and the finiteness of nature in the process of knowledge production. The concept of strong sustainability has therefore been formalized by bridging the gap between theory and environmental policy practice. However, the term “strong sustainability” has never been used as such in environmental public policies. The purpose of this article is to analyze the ontological and epistemic consideration of the concept of strong sustainability and its modes of embeddedness in environmental policies. We will study the consequences of scientific logics and the political effects of strong sustainability.
Keywords	strong sustainability ; ecological economic ; environmental ethic ; environmental politics ; epistemics cultures ; Environmental sciences ; GE1-350 ; Social Sciences ; H
Subject code	333
Language	French
Publishing date	2019-04-01T00:00:00Z
Publisher	Réseau Développement Durable et Territoires Fragiles
Document type	Article ; Online
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Article: Switching or gating? The attentional challenge in cognitive models of psychological time.

Lejeune, H

Behavioural processes

2014 Volume 44, Issue 2, Page(s) 127–145

Abstract: This paper briefly outlines theories dealing with attentional processes, before the status of attention is evaluated within cognitive models of psychological time. Particular emphasis is put on comparing the temporal information processing model (TIP) ... ...

Abstract	This paper briefly outlines theories dealing with attentional processes, before the status of attention is evaluated within cognitive models of psychological time. Particular emphasis is put on comparing the temporal information processing model (TIP) and the attentional gate model (AGM). It is argued that certain functional attributes that the AGM splits between an `attentional gate' and the switch located at the clock level of the TIP model were already ascribed to the switch and supported by previous animal data. Thus, the notion of an `attentional switch' is favored over adding a `gate'. This does not exclude the possibility that the TIP model may be adapted to accommodate both prospective and retrospective timing data.
Language	English
Publishing date	2014-06-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	196999-7
ISSN	1872-8308 ; 0376-6357
ISSN (online)	1872-8308
ISSN	0376-6357
DOI	10.1016/s0376-6357(98)00045-x
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