Red blood cell lifespan, erythropoiesis and hemoglobin control

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

Interaction between Meristem Tissue Layers Controls Phyllotaxis

Phyllotaxis and vein formation are among the most conspicuous patterning processes in plants. The expression and polarization of the auxin efflux carrier PIN1 is the earliest marker for both processes, with mathematical models indicating that PIN1 can respond to auxin gradients and/or auxin flux. Here, we use cell-layer-specific PIN1 knockouts and partial complementation of auxin transport mutants to examine the interaction between phyllotactic patterning, which occurs primarily in the L1 surface layer of the meristem, and midvein specification in the inner tissues. We show that PIN1 expression in the L1 is sufficient for correct organ positioning, as long as the L1-specific influx carriers are present. Thus, differentiation of inner tissues can proceed without PIN1 or any of the known polar transporters. On theoretical grounds, we suggest that canalization of auxin flux between an auxin source and an auxin sink may involve facilitated diffusion rather than polar transport.

Groundwater age distributions at a public drinking water supply well field derived from multiple age tracers (⁸⁵Kr, ³H/³He, and ³⁹Ar)

Groundwater age is a key aspect of production well vulnerability. Public drinking water supply wells typically have long screens and are expected to produce a mixture of groundwater ages. The groundwater age distributions of seven production wells of the Holten well field (Netherlands) were estimated from tritium-helium (3H/3He), krypton-85 (85Kr), and argon-39 (39Ar), using a new application of a discrete age distribution model and existing mathematical models, by minimizing the uncertainty-weighted squared differences of modeled and measured tracer concentrations. The observed tracer concentrations fitted well to a 4-bin discrete age distribution model or a dispersion model with a fraction of old groundwater. Our results show that more than 75 of the water pumped by four shallow production wells has a groundwater age of less than 20 years and these wells are very vulnerable to recent surface contamination. More than 50 of the water pumped by three deep production wells is older than 60 years. 3H/3He samples from short screened monitoring wells surrounding the well field constrained the age stratification in the aquifer. The discrepancy between the age stratification with depth and the groundwater age distribution of the production wells showed that the well field preferentially pumps from the shallow part of the aquifer. The discrete groundwater age distribution model appears to be a suitable approach in settings where the shape of the age distribution cannot be assumed to follow a simple mathematical model, such as a production well field where wells compete for capture area.

Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). RESULTS: ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. CONCLUSION: These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance.

MODELLING β2AR REGULATION

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models can be classified into three classes; (i) Six quantitative models of SABA-induced G protein coupled receptor kinase (GRK)-mediated β2AR regulation; (ii) Three phenomenological models of salmeterol (a LABA)-induced GRK-mediated β2AR regulation; and (iii) One semi-quantitative, unified model of SABA-induced GRK-, protein kinase A (PKA)-, and phosphodiesterase (PDE)-mediated regulation of β2AR signalling. The various models were constrained with all or some of the following experimental data; (i) GRK-mediated β2AR phosphorylation in response to various LABAs/SABAs; (ii) dephosphorylation of the GRK site on the β2AR; (iii) β2AR internalisation; (iv) β2AR recycling; (v) β2AR desensitisation; (vi) β2AR resensitisation; (vii) PKA-mediated β2AR phosphorylation in response to a SABA; and (viii) LABA/SABA induced cAMP profile ± PDE inhibitors. The models of GRK-mediated β2AR regulation show that plasma membrane dephosphorylation and recycling of the phosphorylated β2AR are required to reconcile with the measured dephosphorylation kinetics. We further used a consensus model to predict the consequences of rapid pulsatile agonist stimulation and found that although resensitisation was rapid, the β2AR system retained the memory of prior stimuli and desensitised much more rapidly and strongly in response to subsequent stimuli. This could explain tachyphylaxis of SABAs over repeated use in rescue therapy of asthma patients. The LABA models show that the long action of salmeterol can be explained due to decreased stability of the arrestin/β2AR/salmeterol complex. This could explain long action of β-agonists used in maintenance therapy of asthma patients. Our consensus model of PKA/PDE/GRK-mediated β2AR regulation is being used to identify the dominant β2AR desensitisation pathways under different therapeutic regimens in human airway cells. In summary our models represent a significant advance towards understanding agonist-specific β2AR regulation that will aid in a more rational use of the β2AR agonists in the treatment of asthma.

The volume effect in irradiated mouse colorectum

Damage of the colorectum is the dose-limiting normal tissue complication following radiotherapy of prostate and cervical cancers. One approach for decreasing complications is to physically reduce the treatment volume. Mathematical models have been previously developed to describe the change in associated toxicity with a change in irradiated volume, i.e. the "volume effect", for serial-type normal tissues including the colorectum. The first goal of this thesis was to test the hypothesis that there would not be a threshold length in the development of obstruction after irradiation of mouse colorectum, as predicted by the Probability model of the volume effect. The second goal was to examine if there were differences in the threshold and in the incidence of colorectal obstruction after irradiation of two mouse strains, C57B1/6 (C57) and C3Hf/Kam (C3H), previously found to be fibrosis-prone and-resistant, respectively, after lung irradiation due, in part, to genetic differences. The hypothesis examined was that differences in incidence between strains were due to the differential expression of the fibrogenic cytokines $\rm TGF\beta$ and $\rm TNF\alpha.$ Various lengths of C57 and C3H mouse colorectum were irradiated and the incidence of colorectal obstruction was followed up to 15 months. A threshold length was observed for both mouse strains, in contradiction of model predictions. The mechanism of the threshold was epithelial regeneration after irradiation. C57 mice had significantly higher incidence of colorectal obstruction compared to C3H mice, especially at smaller irradiated lengths. Colorectal tissue was obtained at various times after irradiation and prepared for histology, immunohistochemistry and RNase protection assay for measurement of $\rm TGF\beta 1,$ 2, 3 and $\rm TNF\alpha$ mRNA. Distinct strain differences in the histological time of appearance and spatial locations of fibrosis were observed. However, there were no consistent strain difference in mRNA levels or immunolocalization for any of the cytokines examined. The data indicate the need for volume effect models that account for biologically important processes, such as the effect of epithelial regeneration after irradiation. As well, changes in fibrogenic cytokines at the mRNA level do not contribute to the strain difference in radiation-induced colorectal obstruction. ^

A glimpse into the future composition of marine phytoplankton communities

It is expected that climate change will have significant impacts on ecosystems. Most model projections agree that the ocean will experience stronger stratification and less nutrient supply from deep waters. These changes will likely affect marine phytoplankton communities and will thus impact on the higher trophic levels of the oceanic food web. The potential consequences of future climate change on marine microbial communities can be investigated and predicted only with the help of mathematical models. Here we present the application of a model that describes aggregate properties of marine phytoplankton communities and captures the effects of a changing environment on their composition and adaptive capacity. Specifically, the model describes the phytoplankton community in terms of total biomass, mean cell size, and functional diversity. The model is applied to two contrasting regions of the Atlantic Ocean (tropical and temperate) and is tested under two emission scenarios: SRES A2 or “business as usual” and SRES B1 or “local utopia.” We find that all three macroecological properties will decline during the next century in both regions, although this effect will be more pronounced in the temperate region. Being consistent with previous model predictions, our results show that a simple trait-based modeling framework represents a valuable tool for investigating how phytoplankton communities may reorganize under a changing climate.

BitWorker, a Decentralized Distributed Computing System based on BitTorrent

In this paper we present BitWorker, a platform for community distributed computing based on BitTorrent. Any splittable task can be easily specified by a user in a meta-information task file, such that it can be downloaded and performed by other volunteers. Peers find each other using Distributed Hash Tables, download existing results, and compute missing ones. Unlike existing distributed computing schemes relying on centralized coordination point(s), our scheme is totally distributed, therefore, highly robust. We evaluate the performance of BitWorker using mathematical models and real tests, showing processing and robustness gains. BitWorker is available for download and use by the community.

A common mechanism underlying food choice and social decisions

People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others’ benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

Respiratory rhythm generation: A modeling study of the respiratory central pattern generator and the phrenic motor neuron

The respiratory central pattern generator is a collection of medullary neurons that generates the rhythm of respiration. The respiratory central pattern generator feeds phrenic motor neurons, which, in turn, drive the main muscle of respiration, the diaphragm. The purpose of this thesis is to understand the neural control of respiration through mathematical models of the respiratory central pattern generator and phrenic motor neurons. ^ We first designed and validated a Hodgkin-Huxley type model that mimics the behavior of phrenic motor neurons under a wide range of electrical and pharmacological perturbations. This model was constrained physiological data from the literature. Next, we designed and validated a model of the respiratory central pattern generator by connecting four Hodgkin-Huxley type models of medullary respiratory neurons in a mutually inhibitory network. This network was in turn driven by a simple model of an endogenously bursting neuron, which acted as the pacemaker for the respiratory central pattern generator. Finally, the respiratory central pattern generator and phrenic motor neuron models were connected and their interactions studied. ^ Our study of the models has provided a number of insights into the behavior of the respiratory central pattern generator and phrenic motor neurons. These include the suggestion of a role for the T-type and N-type calcium channels during single spikes and repetitive firing in phrenic motor neurons, as well as a better understanding of network properties underlying respiratory rhythm generation. We also utilized an existing model of lung mechanics to study the interactions between the respiratory central pattern generator and ventilation. ^

The survival role and the potential therapeutic targeting of MET in multiple myeloma

Multiple myeloma (MM) is a debilitating and incurable B-cell malignancy. Previous studies have documented that the hepatocyte growth factor (HGF) plays a role in the pathobiology of MM. The receptor tyrosine kinase MET induced signaling initiates when its ligand HGF binds to the MET receptor. However, the direct importance of MET in MM has not been elucidated. The present work used three different but complementary approaches to reduce MET protein levels or its activity to demonstrate the importance of MET in MM. ^ In the first approach, MET transcript and protein levels were reduced by directly targeting the cellular MET transcripts using shRNA retroviral infection techniques. This direct reduction of MET mRNA leads to a reduction of MET protein levels, which caused an inhibition of growth and induction of cell death. ^ In the second approach, a global transcription inhibitor flavopiridol was used as a potential pharmacological tool to reduce MET levels. MET has a short half-life of 30 min for mRNA and 4 hours for protein; therefore using a RNA pol II inhibitor such as flavopiridol would be a viable option to reduce MET levels. When using flavopiridol in MM cell lines, there was a reduction of MET transcript and protein levels, which was associated with the induction of cell death. ^ Finally in the last strategy, MET kinase activity was suppressed by MP470, a small molecule inhibitor that binds to the ATP binding pocket in the kinase domain. At concentrations where phosphorylation of MET was inhibited there was induction of cell death in MM cell lines and primary cells from patients. In addition, in MM cell lines there was a decrease in phosphorylation of AKT (ser473) and caspase-9 (ser196); downstream of MET, suggesting that the mechanism of action for survival may be through these cascade of events. ^ Overall, this study provides a proof-of-principle that MET is important for the survival of MM cell lines as well as primary plasma cells obtained from patients. Therefore, targeting MET therapeutically may be a possible strategy to treat patients with this debilitating disease of MM. ^

(Table 1) 137Cs and 90Sr concentrations, salinity, and temperature in waters of the southeastern Baltic Sea on October 16, 2001

An analysis of variations in 137Cs and 90Sr concentrations in Baltic Sea surface waters after the accident at the Chernobyl nuclear power plant was performed. Instability of 137Cs concentrations during the short-term observations was found, when they differed 2- to 3-fold. Concentrations of 90Sr appeared to be more stable; meanwhile, their deviations sometimes exceeded ranges of experimental errors. By variations in the monthly average values of radionuclide concentrations in surface waters of the Baltic Sea in 1989-1995, no trend of water self-purification was observed. Theoretical results obtained confirmed a potential of formation and propagation of patches with increased concentrations of 137Cs in the southeastern Baltic Sea. The most reliable factor that controlled the process of self-purification of Baltic Sea water appeared to be the mean annual value of radionuclide concentration. Pronounced divergences were obtained between the measured and calculated mean annual concentrations of 137Cs and 90Sr in surface waters of the Baltic Sea in 1989-2001. These divergences are explained by potential influence of waters from the Gulf of Bothnia and by other additional supplies of radionuclides to marine environment, which were not included into mathematical models.

Thermal behaviour of Sunrise, a balloon-borne solar Telescope

Sunrise is a solar telescope, successfully flown in June 2009 with a long duration balloon from the Swedish Space Corporation Esrange launch site. The design of the thermal control of SUNRISE was quite critical because of the sensitivity to temperature of the optomechanical devices and the electronics. These problems got more complicated due the size and high power dissipation of the system. A detailed thermal mathematical model of SUNRISE was set up to predict temperatures. In this communication the thermal behaviour of SUNRISE during flight is presented. Flight temperatures of some devices are presented and analysed. The measured data have been compared with the predictions given by the thermal mathematical models. The main discrepancies between flight data and the temperatures predicted by the models have been identified. This allows thermal engineers to improve the knowledge of the thermal behaviour of the system for future missions.

Desarrollo de una aplicación software para laboratorios remotos

Las prácticas en laboratorios forman una parte muy importante de la formación en todos los programas docentes. A pesar de esta importancia, la creación de un laboratorio no es una tarea fácil, ya que el hecho de equipar un laboratorio puede suponer un gran gasto económico, tanto inicial como posterior. Como solución, surge la educación a distancia, y en concreto los laboratorios virtuales, es decir, simulaciones de un laboratorio real utilizando modelos matemáticos. Por sus características y flexibilidad se han ido desarrollando laboratorios virtuales en el ámbito docente, pero no todas las áreas cuentan con tantas posibilidades o facilidades como en la electrónica. La mayoría de los laboratorios accesibles desde Internet que hay en la actualidad dentro de la enseñanza a distancia o formación online, son virtuales. El laboratorio que se ha desarrollado tiene como principal ventaja la realización de prácticas controlando instrumentos y circuitos reales de forma remota. El proyecto consiste en realizar un sistema software para implementar un laboratorio remoto en el área de la electrónica analógica, que pueda ser utilizado como complemento a las actividades formativas que se realizan en los laboratorios de los centros de enseñanza. El sistema completo también consta de un hardware controlado mediante buses de comunicación estándar, que permite la implementación de distintos circuitos analógicos, de tal forma que se pueda realizar prácticas sobre circuitos físicos reales. Para desarrollar un laboratorio lo más real posible, la aplicación que maneja el estudiante es un visor 3D. Con la utilización de un visor 3D lo que se pretende es tener un aumento de la realidad a la hora de realizar las prácticas de laboratorio remotamente. El sistema desarrollado cuenta con un sistema de comunicación basado en un modelo cliente-servidor: • Servidor: se encarga de procesar las acciones que realiza el cliente y controla y monitoriza los instrumentos y dispositivos del sistema hardware. • Cliente: sería el usuario final, que mediante un visor 3D comunica las acciones a realizar al servidor para que éste las procese. Practices in laboratories are a very important part of training in all educational programs. Despite this importance, the establishment of a laboratory is not an easy task, since the fact of equipping a laboratory can be a great economic budget, both initial and subsequent spending. As a solution, appears the education at distance (online), and in particular the virtual labs, namely simulations of a real laboratory by using mathematical models. Virtual laboratories in the field of teaching have been developed for its features and flexibility, but not all areas have so many possibilities or facilities as in electronics. The most accessible laboratories from the Internet that are currently accessible within the distance or e-learning (on-line) are virtual. The laboratory which has been developed has as a main advantage to make practices or exercises in the fact of controlling instruments and real circuits remotely. The project consists of making a software system in order to implement a remote laboratory in the area of analog electronics that can be used as a complement to the others training activities to be carried out. The complete system also consists of a controlled hardware by standard communication buses that allow the implementation of several analog circuits, in such a way that practices can control real physical circuits. To develop a laboratory as more realistic as possible, the application that manages the student is a 3D viewer. With the use of a 3D viewer, is intended to have an increase in reality when any student wants to access to laboratory practices remotely. The developed system has a communication system based on a model Client/Server: • Server: The system that handles actions provided by the client and controls and monitors the instruments and devices in the hardware system. • Client: The end user, which using a 3D viewer, communicates the actions to be performed at the server so that it will process them.

Simulación de maniobras de buques con sistemas de propulsión no convencional en aguas poco profundas

Los requisitos cada vez más exigentes en cuanto a misiones, limitaciones operacionales y ambientales así como nuevas tecnologías, imponen permanentemente retos a los arquitectos navales para generar alternativas de buques y valorar su bondad en las primeras etapas del proyecto. Este es el caso de los Buques Patrulleros de Apoyo Fluvial Pesados PAF-P, que por requerimiento de la Armada Nacional de Colombia ha diseñado y construido COTECMAR. Los PAF-P, son buques fluviales cuya relación Manga-Calado excede la mayoría de los buques existentes (B/T=9,5), debido principalmente a las restricciones en el calado a consecuencia de la escasa profundidad de los ríos. Estos buques están equipados con sistemas de propulsión acimutales tipo “Pum-Jet”. Las particularidades del buque y del ambiente operacional, caracterizado por ríos tropicales con una variabilidad de profundidad dependiente del régimen de lluvias y sequía, así como la falta de canalización y la corriente, hacen que la maniobrabilidad y controlabilidad sean fundamentales para el cumplimiento de su misión; adicionalmente, no existen modelos matemáticos validados que permitan predecir en las primeras etapas del diseño la maniobrabilidad de este tipo de buques con los efectos asociados por profundidad. La presente tesis doctoral aborda el desarrollo de un modelo matemático para simulación de maniobrabilidad en aguas poco profundas de buques con relación manga-calado alta y con propulsores acimutales tipo “Pump-Jet”, cuyo chorro además de entregar el empuje necesario para el avance del buque, genera la fuerza de gobierno en función del ángulo de orientación del mismo, eliminando la necesidad de timones. El modelo matemático ha sido validado mediante los resultados obtenidos en las pruebas de maniobrabilidad a escala real del PAF-P, a través de la comparación de trayectorias, series temporales de las variables de estado más significativas y parámetros del círculo evolutivo como son diámetro de giro, diámetro táctico, avance y transferencia. El plan de pruebas se basó en técnicas de Diseño de Experimentos “DOE” para racionalizar el número de corridas en diferentes condiciones de profundidad, velocidad y orientación del chorro (ángulo de timón). En el marco de la presente investigación y para minimizar los errores por efectos ambientales y por inexactitud en los instrumentos de medición, se desarrolló un sistema de adquisición y procesamiento de datos de acuerdo con los lineamientos de ITTC. La literatura existente describe los efectos negativos de la profundidad en los parámetros de maniobrabilidad de buques convencionales (Efecto tipo S), principalmente las trayectorias descritas en los círculos evolutivos aumentan en la medida que disminuye la profundidad; no obstante, en buques de alta relación manga-calado, B/T=7,51 (Yoshimura, y otros, 1.988) y B/T=6,38 (Yasukawa, y otros, 1.995) ha sido reportado el efecto contrario (Efecto tipo NS Non Standart). Este último efecto sin embargo, ha sido observado mediante experimentación con modelos a escala pero no ha sido validado en pruebas de buques a escala real. El efecto tipo NS en buques dotados con hélice y timones, se atribuye al mayor incremento de la fuerza del timón comparativamente con las fuerzas del casco en la medida que disminuye la profundidad; en el caso de estudio, el fenómeno está asociado a la mejor eficiencia de la bomba de agua “Pump-Jet”, debido a la resistencia añadida en el casco por efecto de la disminución de la profundidad. Los resultados de las pruebas con buque a escala real validan el excelente desempeño de esta clase de buques, cumpliendo en exceso los criterios de maniobrabilidad existentes y muestran que el diámetro de giro y otras características de maniobrabilidad mejoran con la disminución de la profundidad en buques con alta relación manga-calado. ABSTRACT The increasingly demanding requirements in terms of missions, operational and environmental constraints as well as new technologies, constantly impose challenges to naval architects to generate alternatives and asses their performance in the early stages of design. That is the case of Riverine Support Patrol Vessel (RSPV), designed and built by COTECMAR for the Colombian Navy. RSPV are riverine ships with a Beam-Draft ratio exceeding most of existing ships (B/T=9,5), mainly due to the restrictions in draft as a result of shallow water environment. The ships are equipped with azimuthal propulsion system of the “Pump-Jet” type. The peculiarities of the ship and the operational environment, characterized by tropical rivers of variable depth depending on the rain and dry seasons, as well as the lack channels and the effect of water current, make manoeuvrability and controllability fundamental to fulfill its mission; on the other hand, there are not validated mathematical models available to predict the manoeuvrability of such ships with the associated water depth effects in the early stages of design. This dissertation addresses the development of a mathematical model for shallow waters’ manoeuvrability simulation of ships with high Beam-Draft ratio and azimuthal propulsion systems type “Pump-Jet”, whose stream generates the thrust required by the ship to advance and also the steering force depending on the orientation angle, eliminating the need of rudders. The mathematical model has been validated with the results of RSPV’s full scale manoeuvring tests, through a comparison of paths, time series of state variables and other parameters taken from turning tests, such as turning diameter, tactical diameter, advance and transfer. The test plan was developed applying techniques of Design of Experiments “DOE”, in order to rationalize the number of runs in different conditions of water depth, ship speed and jet stream orientation (rudder angle). A data acquisition and processing system was developed, following the guidelines of ITTC, as part of this research effort, in order to minimize errors by environmental effects and inaccuracy in measurement instruments, The negative effects of depth on manoeuvrability parameters for conventional ships (Effect Type S: the path described by the ship during turning test increase with decrease of water depth), has been documented in the open literature; however for wide-beam ships, B/T=7,51 (Yoshimura, y otros, 1.988) and B/T=6,38 (Yasukawa, y otros, 1.995) has been reported the opposite effect (Type NS). The latter effect has been observed thru model testing but until now had not been validated with full-scale results. In ships with propellers and rudders, type NS effect is due to the fact that increment of rudder force becomes larger than hull force with decrease of water depth; in the study case, the phenomenon is associated with better efficiency of the Pump-Jet once the vessel speed becomes lower, due to hull added resistance by the effect of the decrease of water depth. The results of full scale tests validates the excellent performance of this class of ships, fulfilling the manoeuvrability criteria in excess and showing that turning diameter and other parameters in high beam-draft ratio vessels do improve with the decrease of depth.