Showing papers by "Olivier Bernard published in 2001"

Dynamical model development and parameter identification for an anaerobic wastewater treatment process

Abstract: This paper deals with the development and the parameter identification of an anaerobic digestion process model. A two-step (acidogenesis-methanization) mass-balance model has been considered. The model incorporates electrochemical equilibria in order to include the alkalinity, which has to play a central role in the related monitoring and control strategy of a treatment plant. The identification is based on a set of dynamical experiments designed to cover a wide spectrum of operating conditions that are likely to take place in the practical operation of the plant. A step by step identification procedure to estimate the model parameters is presented. The results of 70 days of experiments in a 1-m(3) fermenter are then used to validate the model. (C) 2001 John Wiley & Sons, Inc.

A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.

Abstract: FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia (ALL), whereas it was not observed in B ALL samples. This translocation is present in five out of 23 (22%) children and adolescents with T ALL tested. RanBP17, a gene coding for a member of the importin β protein family, and Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5 breakpoints and CTIP2, which is highly expressed during normal T cell differentiation, was localized in the vicinity of the chromosome 14 breakpoints. The Hox11L2 gene was found to be transcriptionally activated as a result of the translocation, probably under the influence of CTIP2 transcriptional regulation elements. These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis.

Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia

Abstract: The recurrent t(1;22)(p13;q13) translocation is exclusively associated with infant acute megakaryoblastic leukemia. We have identified the two genes involved in this translocation. Both genes possess related sequences in the Drosophila genome. The chromosome 22 gene (megakaryocytic acute leukemia, MAL) product is predicted to be involved in chromatin organization, and the chromosome 1 gene (one twenty-two, OTT) product is related to the Drosophila split-end (spen) family of proteins. Drosophila genetic experiments identified spen as involved in connecting the Raf and Hox pathways. Because almost all of the sequences and all of the identified domains of both OTT and MAL proteins are included in the predicted fusion protein, the OTT-MAL fusion could aberrantly modulate chromatin organization, Hox differentiation pathways, or extracellular signaling.

Outcome of liver disease in children with Alagille syndrome: a study of 163 patients

Abstract: BACKGROUND AND AIMS—Various opinions have been expressed as to the long term prognosis of liver disease associated with Alagille syndrome (AGS). PATIENTS AND METHODS—We reviewed the outcome of 163 children with AGS and liver involvement, investigated from 1960 to 2000, the end point of the study (median age 10 years (range 2 months to 44 years)) being death, liver transplantation, or the last visit. RESULTS—At the study end point, of the 132 patients who presented with neonatal cholestatic jaundice, 102 remained jaundiced, 112 had poorly controlled pruritus, and 40 had xanthomas; cirrhosis was found in 35/76 livers, varices in 25/71 patients, and liver transplantation had been carried out in 44 patients (33%). Forty eight patients died, 17 related to complications of liver disease. Of 31 patients who did not present with neonatal cholestatic jaundice, five were jaundiced at the study end point, 17 had well controlled pruritus, and none had xanthomas; cirrhosis was found in 6/18 patients, varices in 4/11, and none underwent liver transplantation. Nine patients died, two of liver disease. In the whole series, actuarial survival rates with native liver were 51% and 38% at 10 and 20 years, respectively, and overall survival rates were 68% and 62%, respectively. Neonatal cholestatic jaundice was associated with poorer survival with native liver (p=0.0004). CONCLUSIONS—The prognosis of liver disease in AGS is worse in children who present with neonatal cholestatic jaundice. However, severe liver complications are possible even after late onset of liver disease, demanding follow up throughout life. Keywords: Alagille syndrome; cholestasis; end stage liver disease; liver transplantation

Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway.

Abstract: Signal Transducer and Activator of Transcription (STATs) are important mediators of cytokine and growth factor-induced signal transduction. STAT5A and STAT5B have been shown to play a role in survival and proliferation of hematopoietic cells both in vitro and in vivo and to contribute to the growth and viability of cells transformed by the TEL-JAK2 oncoprotein. In this study, we investigated the molecular mechanisms by which constitutively active STAT5 proteins induce cell proliferation and survival of Ba/F3 cell lines expressing either dominant positive STAT5A or STAT5B variants or TEL-JAK2 or TEL-ABL fusion proteins. Our results showed that active STAT5 constitutively interacted with p85, the regulatory subunit of the PI 3-kinase. A constitutive activity of the PI 3-kinase/Akt pathway was observed in these cells and required for their cell cycle progression. In contrast, while activity of the PI 3-kinase/Akt pathway was required for survival of Ba/F3 cells expressing the constitutively active forms of STAT5A or STAT5B, it was dispensable for cells transformed by TEL-JAK2 or TEL-ABL fusion proteins, suggesting that additional survival pathways take place in these transformed cells.

Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic leukemia.

Abstract: Fluorescence in situ hybridization (FISH) studies were performed in three cases of acute lymphoblastic leukemia (ALL) with marker chromosomes to analyze the contribution of chromosome 21 in these markers. FISH with a chromosome 21 painting probe confirmed that chromosome 21 was involved in all three cases. FISH with YAC probes showed that the number of extra copies varied according to their location on chromosome 21. Attention was focused on the AML1 gene, which was present as five copies in most of the cells exhibiting the marker chromosomes. As controls, 11 cases of childhood ALL were studied with PAC probes covering AML1. The results agreed with the banded karyotypes in 10 patients. FISH uncovered a clone with four copies of AML1 which were only observed by FISH analysis of interphase nuclei in one patient. No point mutation was detected in exons 3–5, encoding the runt domain of AML1, in the three cases, suggesting an oncogenic role of wild-type AML1 amplification. © 2001 Wiley-Liss, Inc.

Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a study of 5 children.

Abstract: Background. Liver involvement in mitochondrial respiratory chain disorders (MRCD) frequently ends in liver failure and death. Because of the high risk of extrahepatic, particularly neuromuscular, manifestations of the disease, the indication of orthotopic liver transplantation (OLT) in these patients remains controversial. We report on 5 such children in whom OLT was carried out, in an attempt to help clarify the matter. Patients. Patients 1 and 2 presented with fulminant liver failure at ages 7 and 6 months respectively. Emergency liver transplantation was performed before etiological investigations were completed. Retrospective examination of the explanted livers showed defects in complexes I, III and IV. In patient 1, severe neurological deterioration occurred 2 months after OLT with fatal outcome 9 months later. Patient 2 is alive 22 months after OLT with moderate motor impairment. Patients 3, 4 and 5 presented with progressive liver failure before 6 months of age. Surgical liver biopsies displayed a 50% defect in complex IV (patient 3), a defect in complexes I, IV (patient 4) and in complexes I, III, IV (patient 5). Because there was no clinical extrahepatic involvement on investigations, OLT was carried out in these patients. Patient 3 died of multiple organ failure soon after OLT, patients 4 and 5 are alive respectively 21 months and 12 months after OLT with normal neurological examination. Conclusion. OLT may be a valid therapeutic option in infants with delayed liver cell failure due to MRCD, only after performing in emergency a thorough investigation to exclude clinically significant extrahepatic, especially neuromuscular, involvement.

The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells.

Abstract: The leukemia-associated TEL-Jak2 fusion protein possesses a constitutive tyrosine kinase activity and transforming properties in hematopoietic cell lines and animal models. In the murine pro-B Ba/F3 cell line, this fusion constitutively activates the Signal Transducer and Activator of Transcription 5 (Stat5) factors and, as a consequence, induces the sustained expression of various Stat5-target genes including the Cytokine Inducible SH2-containing protein (Cis) gene, which codes for a member of the Suppressor of Cytokine Signaling (Socs) protein family. In TEL-Jak2-transformed Ba/F3 cells, we also observed the upregulation of the Socs1 gene, whose product has been reported to negatively regulate the Jak kinase activity. In transient transfection experiments, Socs1 physically interacts with TEL-Jak2 and interferes with the TEL-Jak2-induced phosphorylation and activation of Stat5 factors, probably through the Socs1-induced proteasome-mediated degradation of the fusion protein. Interestingly, TEL-Jak2-expressing Ba/F3 cells were found to be resistant to the anti-proliferative activities of gamma interferon (IFN-gamma) seemingly as a consequence of Socs1 constitutive expression. These results indicate that the Socs1-dependent cytokine feedback loop, although active, is bypassed by the TEL-Jak2 fusion, but may play a role in the leukemogenic process by altering the cytokine responses of the leukemic cells. Our results also suggest that Socs1 plays a role in shutting down the signaling from the normally activated Jak2 kinase by inducing its proteasome-dependent degradation.

Discrimination of semi-quantitative models by experiment selection: method and application in population biology

Abstract: Modeling an experimental system often results in a number of alternative models that are justified equally well by the experimental data. In order to discriminate between these models, additional experiments are needed. We present a method for the discrimination of models in the form of semiquantitative differential equations. The method is a generalization of previous work in model discrimination. It is based on an entropy criterion for the selection of the most informative experiment which can handle cases where the models predict multiple qualitative behaviors. The applicability of the method is demonstrated on a real-life example, the discrimination of a set of competing models of the growth of phytoplankton in a bioreactor.

Mechanical behaviour of a multilayer system for microelectronic applications

Abstract: Thin PLT (Pb 0.9 La 0.1 TiO 3 ) ferroelectric films have been deposited by a PVD process on SrTiO 3 (STO) substrates and on a superconducting interlayer. Cross sections of the different films were observed by TEM and it allowed to determine the thickness of the coatings and to characterise their microstructure. Vickers microindentation and nano-indentation tests were performed on the substrate, on the PLT films and on the PLT/YBa 2 Cu 3 O 7 /STO system. All these tests showed an anisotropy in the mechanical behaviour, with peculiar fracture distribution and cleavage. The Young's modulus and the hardness of these systems were measured using the nano-indentation, with different imposed depths, These experiments show a very interesting phenomenon with the superconducting interlayer addition: the film delamination observed without an interlayer during indentation experiments disappears for the multilayered material, due to the presence of the superconducting ceramic. This work offers the advantage to characterise for the first time peculiar mechanical properties of multilayered ceramics.