Biomedical subjects
Publications and source records attributed to M Perrier.
The conclusions reached while considering various aspects of the implemented strategy in the identification procedures in the wake of the tsunami disaster of December 26, 2004 are outlined. The lessons to be learned are discussed.
A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was described as a function of intracellular concentration in cell building blocks. Intracellular transport and accumulation kinetics for major nutrients were included. The model uses intracellular nutrients as well as energy shuttles to describe metabolic regulation. Model calibration was performed using experimental data obtained from batch and medium exchange liquid cultures of C. roseus hairy root using a minimal medium in Petri dish. The model is efficient in estimating the growth rate.
Observer-based estimators (OBE) were used for estimation of state variables and kinetic parameters in an anaerobic digestion (AD) process. A simplified first-order model with time-varying kinetic parameters was used to design an OBE for kinetic parameter estimation. This approach was validated on a laboratory-scale anaerobic reactor equipped with a multiwavelength fluorometer for on-line measurements of COD and VFA concentrations in the reactor effluent. The proposed estimators provide continuous adjustment of kinetic parameters and can be used for predictions of state variables between samples acquisition and during sensor failure.
Anaerobic digestion model no.1 (ADM1) was used for tuning and performance analysis of the multi-model observer based estimator (mmOBE). The mmOBE was based on the variable structure model (VSM) of the anaerobic digestion model, which consists of several local submodels, each of which describes a typical process state. Depending on the hydraulic retention time, ADM1 simulated the methanogenic, organic overload, and acidogenic states of the process. These simulations allowed for optimising tunable parameters of the mmOBE. Owing to relatively slow process dynamics, a data acquisition interval as large as one day was sufficient to obtain acceptable accuracy. The simulations of mmOBE performance showed excellent rate of mmOBE convergence to ADM1 outputs. Moreover, mmOBE successfully estimated key kinetic parameters, such as maximal transformation rates of CODs, VFAs, and methane. These estimations can be used in the development of the advanced knowledge-based process system, which uses both available measurements and estimations of key kinetic parameters for extended diagnosis of failures and process trend analysis.
To meet increasing needs of adenovirus vectors for gene therapy programs, development of efficient and reproducible production processes is required. Perfusion cultures were employed to allow infection at greater cell concentrations. In an effort to define culture conditions resulting in enhanced productivities, experiments performed at different feed rates and infected at various cell densities were compared using metabolic flux analysis. The highest specific product yields were achieved in experiments performed at high perfusion rates and/or low cell concentrations. The intracellular flux analysis revealed that these experiments exhibited greater glycolytic fluxes, slightly higher TCA fluxes, and greater ATP production rates at the time of infection. In contrast, cultures infected at high cell density and/or low medium renewal rates were characterized by a more efficient utilization of glucose at the time of infection, but the specific product yields achieved were lower. The intracellular flux analysis provided a rational basis for the implementation of a feeding strategy that allowed successful infection at a density of 5x10(6)cells/ml.
Applicability of multi-wavelength fluorometry for anaerobic digestion process monitoring was investigated in a 3.5 L upflow anaerobic sludge bed (UASB) lab-scale reactor. Both off-line and on-line monitoring of key process parameters was tested. Off-line emission spectra were measured at an angle of 90 degrees to the excitation beam using a cuvette. On-line measurements were carried out using a fiber optic probe in the external recirculation line of the digester. Fluorescence spectra were correlated to available analytical measurements to obtain partial least square regression models. An independent set of measurements was used to validate the regression models. Model estimations showed reasonable agreement with analytical measurements with multiple determination coefficients (R2) between 0.6 and 0.95. Results showed that offline fluorescence measurements can be used for fast estimation of anaerobic digestor effluent quality. At the same time, the on-line implementation of multi-wavelength fluorescence measurements can be used for realtime process monitoring and, potentially, for on-line process control.
OBJECTIVE: To evaluate the effectiveness of morphine aerosols in the treatment of dyspnoea in the palliative care of patients with lung cancer. MATERIALS AND METHODS: During a randomised, double blind, cross-over study 12 patients receiving palliative care for lung cancer and suffering from dyspnoea despite conventional treatments were given, for two periods of 48 hours separated by a 24 hour wash-out period, 4 mls of morphine sulphate and 4 mls of normal saline 4 hourly by a jet nebuliser. Before and after each nebulisation respiratory rate and capillary oxygen saturation were measured and dyspnoea was quantified with the aid of a visual analogue scale by the patient and various other observers (doctors, students, nurses, care assistants and physiotherapists). RESULTS: The aerosols of normal saline and morphine produced the same improvements in the dyspnoea scores independently of the mass nebulised. Furthermore the nebulisations did not produce any significant change in respiratory rate or oxygen saturation. CONCLUSION: The fact that both aerosols lead to a similar improvement in dyspnoea scores suggests that humidification of the airways rather than a pharmacological action may be beneficial in the treatment of dyspnoea in terminally ill patients.
OBJECTIVES: To measure the frequencies of dental radiological examinations in Switzerland and to determine the associated collective radiation doses. METHODS: To evaluate the frequencies, a sample of 376 dental practitioners and other institutions performing dental radiology were requested to fill in questionnaires designed to measure, amongst others, frequencies of dental radiodiagnoses according to type of examination, patient age and gender, dental specialty and type of surgery. The associated collective radiation doses were determined by multiplying the relevant frequencies with dose estimates obtained from recent measurements and calculations. RESULTS: The total number of dental examinations performed in Switzerland in 1998 was 4.1 million (581 per 1000 population). Periapical, bitewing and panoramic radiographs were the most frequent types of dental examinations. The collective dose associated with dental radiology was 71 person.Sv. This amounts to an annual average effective dose to the population of 10 muSv per caput, which is in agreement with the figures reported for countries of similar healthcare level. Various features such as the age distribution of the radiographed patients, the forms of collimators used, film consumption and the use of digital imaging systems are presented. CONCLUSIONS: Several recommendations for dose reduction are made. These include the re-evaluation of the patterns and justification for prescribing some particular types of dental examinations as well as the avoidance of unnecessary irradiation by the use of rectangular collimation and high sensitivity F-speed films.
The objective of this study was to develop a reduced-order model of biodegradation in unsaturated soils that allows the estimation of contaminant depletion, using available on-line measurements. Hexadecane was chosen as a model compound for petroleum hydrocarbons. A two-compartment model was developed, decoupling the intrinsic biodegradation kinetics from limiting factors imposed by field conditions, such as oxygen transfer and contaminant bioavailability. Two new experimental protocols (one for the liquid phase and the other for the solid phase) were developed to monitor hexadecane depletion, hexadecane mineralization, total mineralization, and evolution of the degraders. Using the liquid-phase experiment, parameters of a Haldane kinetic model and yield coefficients were identified and used in the complete model of biodegradation in soil. Using the carbon dioxide production curve, a biocontact kinetic model was identified so that, despite the high sensitivity of the model outputs to variations in the parameters, hexadecane depletion could be correctly predicted with an average error on the entire time trajectory of about 8%. Moreover, the ratio between hexadecane mineralization and total mineralization remained constant after a brief transient period, indicating that hexadecane mineralization could be deduced from the total carbon dioxide measurement. Finally, the new model developed in this study allows real-time monitoring of contaminant biodegradation, using on-line carbon dioxide measurement.
The objective of this study was to develop a model-based estimator of biodegradation in unsaturated soil. This would allow real-time assessment of the efficiency of treatment bioprocesses, such as bioventilation and biopile, and eventually permit optimization through the implementation of control strategies. Based on a reduced-order model, an asymptotic observer was designed to estimate on-line the contaminant concentration, using carbon dioxide measurement. Two observer-based estimators were built to approximate: (1) the specific microbial growth rate; and (2) the biocontact kinetics representing the soil resistance to contaminant biodegradation. State observers and parameter estimators were confronted with the experimental results of biodegradation in microcosms. Hexadecane was used as the model compound, representing petroleum hydrocarbons. Three water contents, corresponding to 20%, 50% and 80% of the water-holding capacity, were tested. The asymptotic observer is able to predict hexadecane depletion with an error on the overall time trajectories of 13%, 8% and 4% for the dry, intermediate and wet soils, respectively, which is acceptable given that all the biokinetic parameters were identified from a biodegradation experiment in liquid phase. The observer-based estimator of the specific microbial growth rate, based on the CO(2) measurement, was successfully calibrated using the off-line measurements of hexadecane as validation data, and allowed estimation of the time when biodegradation switched from a microbial to a biocontact limitation. The biocontact kinetics was also identified on-line, using an estimator based on the hexadecane not in biocontact. These results are very encouraging with respect to the potential for on-line assessment of the performance of treatment bioprocesses in unsaturated soils.
In this study the metabolism of 293SF cells grown in serum-free and low-protein medium was analyzed. This cell line is known for its ability to replicate recombinant adenovirus, mainly used in gene therapy applications. A complete model composed of the main glycolytic, glutaminolytic, and amino acids pathways, as well as the internalization fluxes of certain compounds into the mitochondria, is used for metabolic flux calculations. The pentose-phosphate cycle is also added to the biochemical reactions set and was independently measured with labeled 14C-glucose. Different feeding strategies in two different media were analyzed with the model, and the theoretical ATP production was also calculated. The two media were similar in their glucose and amino acid composition, but one contained BSA at 1g/L whereas the other had a very low protein content. Use of low-protein medium resulted in up to fourfold higher adenoviral vector production. In this medium, glucose utilization was more efficient, as it entered the TCA cycle more efficiently. Also, lower glutamine and amino acids consumption were observed as well as lower lactate and ammonia production. This increased TCA activity led to a twofold higher ATP production in the low-protein medium.
A mathematical model, named A3DX, based on ASM3(A3) for C and N removal, on the bio-P metabolic model of the Technological University of Delft (D), and on extra processes (X) for chemical and biological phosphorus removal, was developed and used to simulate the treatment of a fermented cheese factory effluent by a sequencing batch reactor (SBR). Experimental data obtained from a pilot-scale SBR were used to calibrate the model. The model calibration was performed by changing a minimal number (four) of default values for parameters, and by introducing a Monod function to account for magnesium limitation. This study suggests that the value of stoichiometric and kinetic model parameters determined with municipal effluents or enriched bio-P cultures can be reasonably used with some agro-industrial effluents with minimal parameter adjustment for calibration.
On October 5, 1994, 48 members of the Sect of the Solar Temple were found dead at two different locations in Switzerland: 23 victims in Cheiry and 25 victims in Salvan. Our Institute was commissioned to solve the forensic problems presented by this tragedy. Our goals were to establish the time of death, determine its causes, help elucidate the surrounding circumstances and identify the victims. This work presented us with the following challenges. This catastrophe was of an 'open' type: there was no list of 'passengers'; the victims were of five different nationalities and many had just arrived in Switzerland to participate in this event; family ties were very complex within this group; half of the victims were burned and sometimes charred; the exceptionally intense media converage of the story put a lot of pressure on the investigators and our Institute. In spite of these difficulties, all the victims were positively identified within 1 month. In the present report, we describe the steps realized to progress in our work. A special section describes our relationship with the journalists and their invaluable help in our investigations. The importance of being prepared for such an event is discussed.
Metabolic flux analysis is a useful tool to analyze cell metabolism. In this study, we report the use of a metabolic model with 34 fluxes to study the 293 cell, in order to improve its growth capacity in a DMEM/F12 medium. A batch, fed-batch with glutamine feeding, fed-batch with essential amino acids, and finally a fed-batch experiment with both essential and nonessential amino acids were compared. The fed-batch with glutamine led to a maximum cell density of 2.4x10(6) cells/ml compared to 1.8x10(6) cells/ml achieved in a batch mode. In this fed-batch with glutamine, it was also found that 2.5 mM ammonia was produced compared to the batch which had a final ammonia concentration of 1 mM. Ammonia was found to be growth inhibiting for this cell line at a concentration starting at 1 mM. During the fed-batch with glutamine, the flux analysis shows that a majority of amino acid fluxes and Kreb's cycle fluxes, except for glutamine flux, are decreased. This observation led to the conclusion that the main nutrient used is glutamine and that during the batch there is an overflow in the Kreb's cycle. Thus, a fed-batch with glutamine permits a better utilization of this nutrient. A fed-batch with essential amino acid without glutamine was also assayed in order to reduce ammonia production. The maximum cell density was increased further to 3x10(6) cells/ml and ammonia production was reduced below 1 mM. Flux analysis shows that the cells could adapt to a medium with low glutamine by increasing the amino acid fluxes toward the Kreb's cycle. Adding nonessential amino acids during this feeding strategy did not improve growth further and the nonessential amino acids accumulated in the medium.
This case report describes severe dento-maxillofacial defects after chemoradiation therapy in a child aged 9 years 6 months with a parameningeal rhabdomyosarcoma. A clinical and radiologic (apical dental radiographs, orthopantograph, lateral skull roentgenogram) dental follow-up over 4 years showed such dental abnormalities as root blunting, mild to severe root shortening, premature closure of the root apices, and severe radiation caries. Craniofacial morphology evaluated by cephalometric analysis and dental models showed deficiency with mandibular and maxillary hypoplasia.
A method was developed to perform real-time analysis of cytosolic pH of arbuscular mycorrhizal fungi in culture using dye and ratiometric measurements (490/450 nm excitations). The study was mainly performed using photometric analysis, although some data were confirmed using image analysis. The use of nigericin allowed an in vivo calibration. Experimental parameters such as loading time and concentration of the dye were determined so that pH measurements could be made for a steady-state period on viable cells. A characteristic pH profile was observed along hyphae. For Gigaspora margarita, the pH of the tip (0-2 &mgr;m) was typically 6.7, increased sharply to 7.0 behind this region (9.5 &mgr;m), and decreased over the next 250 &mgr;m to a constant value of 6.6. A similar pattern was obtained for Glomus intraradices. The pH profile of G. margarita germ tubes was higher when cultured in the presence of carrot (Daucus carota) hairy roots (nonmycorrhizal). Similarly, extraradical hyphae of G. intraradices had a higher apical pH than the germ tubes. The use of a paper layer to prevent the mycorrhizal roots from being in direct contact with the medium selected hyphae with an even higher cytosolic pH. Results suggest that this method could be useful as a bioassay for studying signal perception and/or H+ cotransport of nutrients by arbuscular mycorrhizal hyphae.
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