Study of the thermal effects induced by magnetic resonance on endocardial leads: numerical models and experimental validation

Magnetic resonance imaging (MRI) is today precluded to patients bearing active implantable medical devices AIMDs). The great advantages related to this diagnostic modality, together with the increasing number of people benefiting from implantable devices, in particular pacemakers(PM)and carioverter/defibrillators (ICD), is prompting the scientific community the study the possibility to extend MRI also to implanted patients. The MRI induced specific absorption rate (SAR) and the consequent heating of biological tissues is one of the major concerns that makes patients bearing metallic structures contraindicated for MRI scans. To date, both in-vivo and in-vitro studies have demonstrated the potentially dangerous temperature increase caused by the radiofrequency (RF) field generated during MRI procedures in the tissues surrounding thin metallic implants. On the other side, the technical evolution of MRI scanners and of AIMDs together with published data on the lack of adverse events have reopened the interest in this field and suggest that, under given conditions, MRI can be safely performed also in implanted patients. With a better understanding of the hazards of performing MRI scans on implanted patients as well as the development of MRI safe devices, we may soon enter an era where the ability of this imaging modality may be more widely used to assist in the appropriate diagnosis of patients with devices. In this study both experimental measures and numerical analysis were performed. Aim of the study is to systematically investigate the effects of the MRI RF filed on implantable devices and to identify the elements that play a major role in the induced heating. Furthermore, we aimed at developing a realistic numerical model able to simulate the interactions between an RF coil for MRI and biological tissues implanted with a PM, and to predict the induced SAR as a function of the particular path of the PM lead. The methods developed and validated during the PhD program led to the design of an experimental framework for the accurate measure of PM lead heating induced by MRI systems. In addition, numerical models based on Finite-Differences Time-Domain (FDTD) simulations were validated to obtain a general tool for investigating the large number of parameters and factors involved in this complex phenomenon. The results obtained demonstrated that the MRI induced heating on metallic implants is a real risk that represents a contraindication in extending MRI scans also to patient bearing a PM, an ICD, or other thin metallic objects. On the other side, both experimental data and numerical results show that, under particular conditions, MRI procedures might be consider reasonably safe also for an implanted patient. The complexity and the large number of variables involved, make difficult to define a unique set of such conditions: when the benefits of a MRI investigation cannot be obtained using other imaging techniques, the possibility to perform the scan should not be immediately excluded, but some considerations are always needed.

Integrated analysis of cooling water systems: Modeling and experimental validation

Cooling towers are widely used in many industrial and utility plants as a cooling medium, whose thermal performance is of vital importance. Despite the wide interest in cooling tower design, rating and its importance in energy conservation, there are few investigations concerning the integrated analysis of cooling systems. This work presents an approach for the systemic performance analysis of a cooling water system. The approach combines experimental design with mathematical modeling. An experimental investigation was carried out to characterize the mass transfer in the packing of the cooling tower as a function of the liquid and gas flow rates, whose results were within the range of the measurement accuracy. Then, an integrated model was developed that relies on the mass and heat transfer of the cooling tower, as well as on the hydraulic and thermal interactions with a heat exchanger network. The integrated model for the cooling water system was simulated and the temperature results agree with the experimental data of the real operation of the pilot plant. A case study illustrates the interaction in the system and the need for a systemic analysis of cooling water system. The proposed mathematical and experimental analysis should be useful for performance analysis of real-world cooling water systems. (C) 2009 Elsevier Ltd. All rights reserved.

Determination of regional flow by use of intravascular PET tracers: Microvascular theory and experimental validation for pig livers

Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared with the standard model in a pig liver study. Methods: Eight pigs underwent a 5-min dynamic PET study after O-15-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual-inlet concentration was calculated as the flow-weighted inlet concentration. Dynamic PET data were analyzed with a traditional single-compartment model and 2 microvascular models. Results: Microvascular models provided a better fit of the tissue activity of an intravascular tracer than did the compartment model. In particular, the early dynamic phase after a tracer bolus injection was much improved. The regional hepatic blood flow estimates provided by the microvascular models (1.3 +/- 0.3 mL min(-1) mL(-1) for the single-capillary model and 1.14 +/- 0.14 min(-1) mL(-1) for the multiple-capillary model) (mean +/- SEM mL of blood min(-1) mL of liver tissue(-1)) were in agreement with the total blood flow measured by flow meters and normalized to liver weight (1.03 +/- 0.12 mL min(-1) mL(-1)). Conclusion: Compared with the standard compartment model, the 2 microvascular models provide a superior description of tissue activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional flow estimates in agreement with flow measurements.

Development and experimental validation of a finite element model of total ankle replacement.

Total ankle replacement remains a less satisfactory solution compared to other joint replacements. The goal of this study was to develop and validate a finite element model of total ankle replacement, for future testing of hypotheses related to clinical issues. To validate the finite element model, an experimental setup was specifically developed and applied on 8 cadaveric tibias. A non-cemented press fit tibial component of a mobile bearing prosthesis was inserted into the tibias. Two extreme anterior and posterior positions of the mobile bearing insert were considered, as well as a centered one. An axial force of 2kN was applied for each insert position. Strains were measured on the bone surface using digital image correlation. Tibias were CT scanned before implantation, after implantation, and after mechanical tests and removal of the prosthesis. The finite element model replicated the experimental setup. The first CT was used to build the geometry and evaluate the mechanical properties of the tibias. The second CT was used to set the implant position. The third CT was used to assess the bone-implant interface conditions. The coefficient of determination (R-squared) between the measured and predicted strains was 0.91. Predicted bone strains were maximal around the implant keel, especially at the anterior and posterior ends. The finite element model presented here is validated for future tests using more physiological loading conditions.

Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

Theoretical Analysis and Experimental Validation of the Scholte Wave Propagation in Immersed Plates for the Characterization of Viscous Fluids

This work reports the study of an attractive interfacial wave for application in ultrasonic NDE techniques for inspection and fluid characterization. This wave, called quasi-Scholte mode, is a kind of flexural wave in a plate in contact with a fluid which presents a good sensitivity to the fluid properties. In order to explore this feature, the phase velocity curve of quasi-Scholte mode is experimentally measured in a plate in contact with a viscous fluid, showing a good agreement with theory.

Modeling, control and experimental validation of a novel actuator based on shape memory alloys

The paper presents the development of a mechanical actuator using a shape memory alloy with a cooling system based on the thermoelectric effect (Seebeck-Peltier effect). Such a method has the advantage of reduced weight and requires a simpler control strategy as compared to other forced cooling systems. A complete mathematical model of the actuator was derived, and an experimental prototype was implemented. Several experiments are used to validate the model and to identify all parameters. A robust and nonlinear controller, based on sliding-mode theory, was derived and implemented. Experiments were used to evaluate the actuator closed-loop performance, stability, and robustness properties. The results showed that the proposed cooling system and controller are able to improve the dynamic response of the actuator. (C) 2009 Elsevier Ltd. All rights reserved.

Dimensionless spray flux in wet granulation: Monte-Carlo simulations and experimental validation

Dimensionless spray flux Ψa is a dimensionless group that characterises the three most important variables in liquid dispersion: flowrate, drop size and powder flux through the spray zone. In this paper, the Poisson distribution was used to generate analytical solutions for the proportion of nuclei formed from single drops (fsingle) and the fraction of the powder surface covered by drops (fcovered) as a function of Ψa. Monte-Carlo simulations were performed to simulate the spray zone and investigate how Ψa, fsingle and fcovered are related. The Monte-Carlo data was an excellent match with analytical solutions of fcovered and fsingle as a function of Ψa. At low Ψa, the proportion of the surface covered by drops (fcovered) was equal to Ψa. As Ψa increases, drop overlap becomes more dominant and the powder surface coverage levels off. The proportion of nuclei formed from single drops (fsingle) falls exponentially with increasing Ψa. In the ranges covered, these results were independent of drop size, number of drops, drop size distribution (mono-sized, bimodal and trimodal distributions), and the uniformity of the spray. Experimental data of nuclei size distributions as a function of spray flux were fitted to the analytical solution for fsingle by defining a cutsize for single drop nuclei. The fitted cutsizes followed the spray drop sizes suggesting that the method is robust and that the cutsize does indicate the transition size between single drop and agglomerate nuclei. This demonstrates that the nuclei distribution is determined by the dimensionless spray flux and the fraction of drop controlled nuclei can be calculated analytically in advance.

Growth regime map for liquid-bound granules: further development and experimental validation

An attempt was made to quantify the boundaries and validate the granule growth regime map for liquid-bound granules recently proposed by Iveson and Litster (AlChE J. 44 (1998) 1510). This regime map postulates that the type of granule growth behaviour is a function of only two dimensionless groups: the amount of granule deformation during collision (characterised by a Stokes deformation number, St(def)) and the maximum granule pore saturation, s(max). The results of experiments performed with a range of materials (glass ballotini, iron ore fines, copper chalcopyrite powder and a sodium sulphate and cellulose mixture) using both drum and high shear mixer granulators were examined. The drum granulation results gave good agreement with the proposed regime map. The boundary between crumb and steady growth occurs at St(def) of order 0.1 and the boundary between steady and induction growth occurs at St(def) of order 0.001. The nucleation only boundary occurs at pore saturations that increase from 70% to 80% with decreasing St(def). However, the high shear mixer results all had St(def) numbers which were too large. This is most likely to be because the chopper tip-speed is an over-estimate of the average impact velocity granules experience and possibly also due to the dynamic yield strength of the materials being significantly greater than the yield strengths measured at low strain rates. Hence, the map is only a useful tool for comparing the granulation behaviour of different materials in the same device. Until we have a better understanding of the flow patterns and impact velocities in granulators, it cannot be used to compare different types of equipment. Theoretical considerations also revealed that several of the regime boundaries are also functions of additional parameters not explicitly contained on the map, such as binder viscosity. (C) 2001 Elsevier Science B.V. All rights reserved.

Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [O-15] CO or injections of diffusible 3-O[ C-11] methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time ( T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: (T) over bar = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.

A traffic differentiation add-on to the IEEE 802.15.4 protocol: implementation and experimental validation over a real-time operating system

The IEEE 802.15.4 is the most widespread used protocol for Wireless Sensor Networks (WSNs) and it is being used as a baseline for several higher layer protocols such as ZigBee, 6LoWPAN or WirelessHART. Its MAC (Medium Access Control) supports both contention-free (CFP, based on the reservation of guaranteed time-slots GTS) and contention based (CAP, ruled by CSMA/CA) access, when operating in beacon-enabled mode. Thus, it enables the differentiation between real-time and best-effort traffic. However, some WSN applications and higher layer protocols may strongly benefit from the possibility of supporting more traffic classes. This happens, for instance, for dense WSNs used in time-sensitive industrial applications. In this context, we propose to differentiate traffic classes within the CAP, enabling lower transmission delays and higher success probability to timecritical messages, such as for event detection, GTS reservation and network management. Building upon a previously proposed methodology (TRADIF), in this paper we outline its implementation and experimental validation over a real-time operating system. Importantly, TRADIF is fully backward compatible with the IEEE 802.15.4 standard, enabling to create different traffic classes just by tuning some MAC parameters.

Strength prediction and experimental validation of adhesive joints including polyethylene, carbon-epoxy and aluminium adherends

Polyolefins are especially difficult to bond due to their non-polar, non-porous and chemically inert surfaces. Acrylic adhesives used in industry are particularly suited to bond these materials, including many grades of polypropylene (PP) and polyethylene (PE), without special surface preparation. In this work, the tensile strength of single-lap PE and mixed joints bonded with an acrylic adhesive was investigated. The mixed joints included PE with aluminium (AL) or carbon fibre reinforced plastic (CFRP) substrates. The PE substrates were only cleaned with isopropanol, which assured cohesive failures. For the PE CFRP joints, three different surfaces preparations were employed for the CFRP substrates: cleaning with acetone, abrasion with 100 grit sand paper and peel-ply finishing. In the PE AL joints, the AL bonding surfaces were prepared by the following methods: cleaning with acetone, abrasion with 180 and 320 grit sand papers, grit blasting and chemical etching with chromic acid. After abrasion of the CFRP and AL substrates, the surfaces were always cleaned with acetone. The tensile strengths were compared with numerical results from ABAQUS® and a mixed mode (I+II) cohesive damage model. A good agreement was found between the experimental and numerical results, except for the PE AL joints, since the AL surface treatments were not found to be effective.

Análisis comparativo entre actividades de aprendizaje diseñadas con Estudio de Casos y Aprendizaje Basado en Problemas, y actividades de tipo tradicional, como dispositivos didácticos en Educación a Distancia. Comparative analysis of learning activities designed with Problem Based Learning and Case Study approaches, and activities designed with traditional methods, in Distance Education.

Identificación y caracterización del problema: El problema que guía este proyecto, pretende dar respuesta a interrogantes tales como: ¿De qué modo el tipo de actividades que se diseñan, se constituyen en dispositivos posibilitadores de la comprensión de los temas propios de cada asignatura, por parte de los alumnos? A partir de esta pregunta, surge la siguiente: Al momento de resolver las actividades, ¿qué estrategias cognitivas ponen en juego los estudiantes? y ¿cuáles de ellas favorecen procesos de construcción del conocimiento? Hipótesis: - Las asignaturas cuyas actividades están elaboradas bajo la metodología de Aprendizaje Basado en Problemas y Estudio de Casos, propician aprendizajes significativos por parte de los estudiantes. - Las actividades elaboradas bajo la metodología del Aprendizaje Basado en Problemas y el Estudio de Casos requieren de procesos cognitivos más complejos que los que se implementan en las de tipo tradicional. Objetivo: - Identificar el impacto que tienen las actividades de aprendizaje de tipo tradicional y las elaboradas bajo la metodología de Aprendizaje Basado en Problemas y Estudio de Casos, en el aprendizaje de los alumnos. Materiales y Métodos: a) Análisis de las actividades de aprendizaje del primero y segundo año de la carrera de Abogacía, bajo lamodalidad a Distancia. b) Entrevistas tanto a docentes contenidistas como así también a los tutores. c) Encuestas y entrevistas a los alumnos. Resultados esperados: Se pretende confirmar que las actividades de aprendizaje, diseñadas bajo la metodología del Aprendizaje Basado en Problemas y el Estudio de Casos, promueven aprendizajes significativos en los alumnos. Importancia del proyecto y pertinencia: La relevancia del presente proyecto se podría identificar a través de dos grandes variables vinculadas entre sí: la relacionada con el dispositivo didáctico (estrategias implementadas por los alumnos) y la referida a lo institucional (carácter innovador de la propuesta de enseñanza y posibilidad de extenderla a otras cátedras). El presente proyecto pretende implementar mejoras en el diseño de las actividades de aprendizaje, a fin de promover en los alumnos la generación de ideas y soluciones responsables y el desarrollo de su capacidad analítica y reflexiva.

Seasonal fluctuations of bacterial community diversity in agricultural soil and experimental validation by laboratory disturbance experiments.

Natural fluctuations in soil microbial communities are poorly documented because of the inherent difficulty to perform a simultaneous analysis of the relative abundances of multiple populations over a long time period. Yet, it is important to understand the magnitudes of community composition variability as a function of natural influences (e.g., temperature, plant growth, or rainfall) because this forms the reference or baseline against which external disturbances (e.g., anthropogenic emissions) can be judged. Second, definition of baseline fluctuations in complex microbial communities may help to understand at which point the systems become unbalanced and cannot return to their original composition. In this paper, we examined the seasonal fluctuations in the bacterial community of an agricultural soil used for regular plant crop production by using terminal restriction fragment length polymorphism profiling (T-RFLP) of the amplified 16S ribosomal ribonucleic acid (rRNA) gene diversity. Cluster and statistical analysis of T-RFLP data showed that soil bacterial communities fluctuated very little during the seasons (similarity indices between 0.835 and 0.997) with insignificant variations in 16S rRNA gene richness and diversity indices. Despite overall insignificant fluctuations, between 8 and 30% of all terminal restriction fragments changed their relative intensity in a significant manner among consecutive time samples. To determine the magnitude of community variations induced by external factors, soil samples were subjected to either inoculation with a pure bacterial culture, addition of the herbicide mecoprop, or addition of nutrients. All treatments resulted in statistically measurable changes of T-RFLP profiles of the communities. Addition of nutrients or bacteria plus mecoprop resulted in bacteria composition, which did not return to the original profile within 14 days. We propose that at less than 70% similarity in T-RFLP, the bacterial communities risk to drift apart to inherently different states.

Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.