[DOTA]Somatostatin-14 analogs and their (111)In-radioligands: effects of decreasing ring-size on sst1-5 profile, stability and tumor targeting.

Multiple somatostatin receptor (sst)-subtype expression has been manifested in several human tumors. Hence, the availability of radiopeptides retaining the full pansomatostatin profile of the native hormone (SS14) is expected to increase the sensitivity and broaden the clinical indications of currently applied sst2-preferring cyclic octapeptide radioligands, like OctreoScan(®) ([(111)In-DTPA]octreotide). On the other hand, SS14 has been excluded from clinical use due to its rapid in vivo degradation. We herein present a small library of seven novel cyclic SS14-mimics carrying at their N-terminus the universal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for stable binding of medically useful radiometals, like (111)In. By decreasing the number of amino acids composing the ring in their structure from 12 up to 6 AA, we induced important changes in key-biological parameters in vitro and in vivo. In particular, we observed unexpected changes and even total loss of sst1-5-affinity (6AA-ring), as well as weaker sst2-internalization efficacy as the ring size decreased. In contrast, in vivo stability increased with decreasing ring size, reaching its maximum in the 6AA-ring analogs. Interestingly, only the 12AA- and 9AA-ring members of this series showed sst2-specific uptake in AR4-2J tumors in mice revealing the prominent role of ring size on the biological response of tested SS14-derived radioligands.

Oligodeoxynucleotide Duplexes Containing (5′S)-5′-C-Alkyl-Modified 2′-Deoxynucleosides: Can an Alkyl Zipper across the DNA Minor-Groove Enhance Duplex Stability?

10.1002/hlca.200390311.abs A series of oligonucleotides containing (5′S)-5′-C-butyl- and (5′S)-5′-C-isopentyl-substituted 2′-deoxyribonucleosides were designed, prepared, and characterized with the intention to explore alkyl-zipper formation between opposing alkyl chains across the minor groove of oligonucleotide duplexes as a means to modulate DNA-duplex stability. From four possible arrangements of the alkyl groups that differ in the density of packing of the alkyl chains across the minor groove, three (duplex types I–III, Fig. 2) could experimentally be realized and their duplex-forming properties analyzed by UV-melting curves, CD spectroscopy, and isothermal titration calorimetry (ITC), as well as by molecular modeling. The results show that all arrangements of alkyl residues within the minor groove of DNA are thermally destabilizing by 1.5–3°/modification in Tm. We found that, within the proposed duplexes with more loosely packed alkyl groups (type-III duplexes), accommodation of alkyl residues without extended distorsion of the helical parameters of B-DNA is possible but does not lead to higher thermodynamic stability. The more densely packed and more unevenly distributed arrangement (type-II duplexes) seems to suffer from ecliptic positioning of opposite alkyl groups, which might account for a systematic negative contribution to stability due to steric interactions. The decreased stability in the type-III duplexes described here may be due either to missing hydrophobic interactions of the alkyl groups (not bulky enough to make close contacts), or to an overcompensation of favorable alkyl-zipper formation presumably by loss of structured H2O in the minor groove.

(Table 1) Isotopic and geochemical parameters of gas phase from underground fluids of the Baikal rift and its framing

Results of studying isotopic composition of helium in underground fluids of the Baikal-Mongolian region during the last quarter of XX century are summarized. Determinations of 3He/4He ratio in 139 samples of gas phase from fluids, collected at 104 points of the Baikal rift zone and adjacent structures are given. 3He/4He values lie within the range from 1x10**-8 (typical for crustal radiogenic helium) to 1.1x10**-5 (close to typical MORB reservoir). Repeated sampling in some points during more than 20 years showed stability of helium isotopic composition in time in each of them at any level of 3He/4He values. There is no systematic differences of 3He/4He in samples from surface water sources and deeper intervals of boreholes in the same areas. Universal relationship between isotopic composition of helium and general composition of gas phase is absent either, but the minimum 3He/4He values occurred in methane gas of hydrocarbon deposits, whereas in nitrogen and carbon dioxide gases of helium composition varied (in the latter maximum 3He/4He values have been measured). According to N2/Ar_atm ratio nitrogen gases are atmospheric. In carbonic gas fN2/fNe ratio indicates presence of excessive (non-atmogenic) nitrogen, but the attitude CO2/3He differs from one in MORB. Comparison of helium isotopic composition with its concentration and composition of the main components of gas phase from fluids shows that it is formed under influence of fractionation of components with different solubility in the gas-water system and generation/consumption of reactive gases in the crust. Structural and tectonic elements of the region differ from the spectrum of 3He/4He values. At the pre-Riphean Siberian Platform the mean 3He/4He = (3.6+/-0.9)x10**- 8 is very close to radiogenic one. In the Paleozoic crust of Khangay 3He/4He = (16.3+/-4.6)x10**-8, and the most probable estimate is (12.3+/-2.9)x10**-8. In structures of the eastern flank of the Baikal rift zone (Khentei, Dauria) affected by the Mz-Kz activization 3He/4He values range from 4.4x10**-8 to 2.14x10**-6 (average 0.94x10**-6). Distribution of 3He/4He values across the strike of the Baikal rift zone indicates advective heat transfer from the mantle not only in the rift zone, but also much further to the east. In fluids of the Baikal rift zone range of 3He/4He values is the widest: from 4x10**-8 to 1.1x10**-5. Their variations along the strike of the rift zone are clearly patterned, namely, decrease of 3He/4He values in both directions from the Tunka depression. Accompanied by decrease in density of conductive heat flow and in size of rift basins, this trend indicates decrease in intensity of advective heat transfer from the mantle to peripheral segments of the rift zone. Comparing this trend with data on other continental rift zones and mid-ocean ridges leads to the conclusion about fundamental differences in mechanisms of interaction between the crust and the mantle in these environments.

Effects of seawater pCO2 and temperature on shell growth, shell stability, condition and cellular stress of Western Baltic Sea Mytilus edulis (L.) and Arctica islandica (L.)

Acidification of the World's oceans may directly impact reproduction, performance and shell formation of marine calcifying organisms. In addition, since shell production is costly and stress in general draws on an organism's energy budget, shell growth and stability of bivalves should indirectly be affected by environmental stress. The aim of this study was to investigate whether a combination of warming and acidification leads to increased physiological stress (lipofuscin accumulation and mortality) and affects the performance [shell growth, shell breaking force, condition index (Ci)] of young Mytilus edulis and Arctica islandica from the Baltic Sea. We cultured the bivalves in a fully-crossed 2-factorial experimental setup (seawater (sw) pCO2 levels "low", "medium" and "high" for both species, temperature levels 7.5, 10, 16, 20 and 25 °C for M. edulis and 7.5, 10 and 16 °C for A. islandica) for 13 weeks in summer. Mytilus edulis and A. islandica appeared to tolerate wide ranges of sw temperature and pCO2. Lipofuscin accumulation of M. edulis increased with temperature while the Ci decreased, but shell growth of the mussels only sharply decreased while its mortality increased between 20 and 25 °C. In A. islandica, lipofuscin accumulation increased with temperature, whereas the Ci, shell growth and shell breaking force decreased. The pCO2 treatment had only marginal effects on the measured parameters of both bivalve species. Shell growth of both bivalve species was not impaired by under-saturation of the sea water with respect to aragonite and calcite. Furthermore, independently of water temperatures shell breaking force of both species and shell growth of A. islandica remained unaffected by the applied elevated sw pCO2 for several months. Only at the highest temperature (25 °C), growth arrest of M. edulis was recorded at the high sw pCO2 treatment and the Ci of M. edulis was slightly higher at the medium sw pCO2 treatment than at the low and high sw pCO2 treatments. The only effect of elevated sw pCO2 on A. islandica was an increase in lipofuscin accumulation at the high sw pCO2 treatment compared to the medium sw pCO2 treatment. Our results show that, despite this robustness, growth of both M. edulis and A. islandica can be reduced if sw temperatures remain high for several weeks in summer. As large body size constitutes an escape from crab and sea star predation, this can make bivalves presumably more vulnerable to predation with possible negative consequences on population growth. In M. edulis, but not in A. islandica, this effect is amplified by elevated sw pCO2. We follow that combined effects of elevated sw pCO2 and ocean warming might cause shifts in future Western Baltic Sea community structures and ecosystem services; however, only if predators or other interacting species do not suffer as strong from these stressors.

Characterization cement pastes degraded in lanoratory solutions and physiochemical parameters employed for modeling the process

Previously degradation studies carried out, over a number of different mortars by the research team, have shown that observed degradation does not exclusively depend on the solution equilibrium pH, nor the aggressive anions relative solubility. In our tests no reason was found that could allow us to explain, why same solubility anions with a lower pH are less aggressive than others. The aim of this paper is to study cement pastes behavior in aggressive environments. As observed in previous research, this cement pastes behaviors are not easily explained only taking into account only usual parameters, pH, solubility etc. Consequently the paper is about studying if solution physicochemical characteristics are more important in certain environments than specific pH values. The paper tries to obtain a degradation model, which starting from solution physicochemical parameters allows us to interpret the different behaviors shown by different composition cements. To that end, the rates of degradation of the solid phases were computed for each considered environment. Three cement have been studied: CEM I 42.5R/SR, CEM II/A-V 42.5R and CEM IV/B-(P-V) 32.5 N. The pastes have been exposed to five environments: sodium acetate/acetic acid 0.35 M, sodium sulfate solution 0.17 M, a solution representing natural water, saturated calcium hydroxide solution and laboratory environment. The attack mechanism was meant to be unidirectional, in order to achieve so; all sides of cylinders were sealed except from the attacked surface. The cylinders were taking out of the exposition environments after 2, 4, 7, 14, 30, 58 and 90 days. Both aggressive solution variations in solid phases and in different depths have been characterized. To each age and depth the calcium, magnesium and iron contents have been analyzed. Hydrated phases evolution studied, using thermal analysis, and crystalline compound changes, using X ray diffraction have been also analyzed. Sodium sulphate and water solutions stabilize an outer pH near to 8 in short time, however the stability of the most pH dependent phases is not the same. Although having similar pH and existing the possibility of forming a plaster layer near to the calcium leaching surface, this stability is greater than other sulphate solutions. Stability variations of solids formed by inverse diffusion, determine the rate of degradation.

The scenario of two-dimensional instabilities of the cylinder wake under EHD forcing: A linear stability analysis

We propose to study the stability properties of an air flow wake forced by a dielectric barrier discharge (DBD) actuator, which is a type of electrohydrodynamic (EHD) actuator. These actuators add momentum to the flow around a cylinder in regions close to the wall and, in our case, are symmetrically disposed near the boundary layer separation point. Since the forcing frequencies, typical of DBD, are much higher than the natural shedding frequency of the flow, we will be considering the forcing actuation as stationary. In the first part, the flow around a circular cylinder modified by EHD actuators will be experimentally studied by means of particle image velocimetry (PIV). In the second part, the EHD actuators have been numerically implemented as a boundary condition on the cylinder surface. Using this boundary condition, the computationally obtained base flow is then compared with the experimental one in order to relate the control parameters from both methodologies. After validating the obtained agreement, we study the Hopf bifurcation that appears once the flow starts the vortex shedding through experimental and computational approaches. For the base flow derived from experimentally obtained snapshots, we monitor the evolution of the velocity amplitude oscillations. As to the computationally obtained base flow, its stability is analyzed by solving a global eigenvalue problem obtained from the linearized Navier–Stokes equations. Finally, the critical parameters obtained from both approaches are compared.

X-parameters based analytical design of non-linear microwave circuits Application to oscillator design

Resumen El diseño clásico de circuitos de microondas se basa fundamentalmente en el uso de los parámetros s, debido a su capacidad para caracterizar de forma exitosa el comportamiento de cualquier circuito lineal. La relación existente entre los parámetros s con los sistemas de medida actuales y con las herramientas de simulación lineal han facilitado su éxito y su uso extensivo tanto en el diseño como en la caracterización de circuitos y subsistemas de microondas. Sin embargo, a pesar de la gran aceptación de los parámetros s en la comunidad de microondas, el principal inconveniente de esta formulación reside en su limitación para predecir el comportamiento de sistemas no lineales reales. En la actualidad, uno de los principales retos de los diseñadores de microondas es el desarrollo de un contexto análogo que permita integrar tanto el modelado no lineal, como los sistemas de medidas de gran señal y los entornos de simulación no lineal, con el objetivo de extender las capacidades de los parámetros s a regímenes de operación en gran señal y por tanto, obtener una infraestructura que permita tanto la caracterización como el diseño de circuitos no lineales de forma fiable y eficiente. De acuerdo a esta filosofía, en los últimos años se han desarrollado diferentes propuestas como los parámetros X, de Agilent Technologies, o el modelo de Cardiff que tratan de proporcionar esta plataforma común en el ámbito de gran señal. Dentro de este contexto, uno de los objetivos de la presente Tesis es el análisis de la viabilidad del uso de los parámetros X en el diseño y simulación de osciladores para transceptores de microondas. Otro aspecto relevante en el análisis y diseño de circuitos lineales de microondas es la disposición de métodos analíticos sencillos, basados en los parámetros s del transistor, que permitan la obtención directa y rápida de las impedancias de carga y fuente necesarias para cumplir las especificaciones de diseño requeridas en cuanto a ganancia, potencia de salida, eficiencia o adaptación de entrada y salida, así como la determinación analítica de parámetros de diseño clave como el factor de estabilidad o los contornos de ganancia de potencia. Por lo tanto, el desarrollo de una formulación de diseño analítico, basada en los parámetros X y similar a la existente en pequeña señal, permitiría su uso en aplicaciones no lineales y supone un nuevo reto que se va a afrontar en este trabajo. Por tanto, el principal objetivo de la presente Tesis consistiría en la elaboración de una metodología analítica basada en el uso de los parámetros X para el diseño de circuitos no lineales que jugaría un papel similar al que juegan los parámetros s en el diseño de circuitos lineales de microondas. Dichos métodos de diseño analíticos permitirían una mejora significativa en los actuales procedimientos de diseño disponibles en gran señal, así como una reducción considerable en el tiempo de diseño, lo que permitiría la obtención de técnicas mucho más eficientes. Abstract In linear world, classical microwave circuit design relies on the s-parameters due to its capability to successfully characterize the behavior of any linear circuit. Thus the direct use of s-parameters in measurement systems and in linear simulation analysis tools, has facilitated its extensive use and success in the design and characterization of microwave circuits and subsystems. Nevertheless, despite the great success of s-parameters in the microwave community, the main drawback of this formulation is its limitation in the behavior prediction of real non-linear systems. Nowadays, the challenge of microwave designers is the development of an analogue framework that allows to integrate non-linear modeling, large-signal measurement hardware and non-linear simulation environment in order to extend s-parameters capabilities to non-linear regimen and thus, provide the infrastructure for non-linear design and test in a reliable and efficient way. Recently, different attempts with the aim to provide this common platform have been introduced, as the Cardiff approach and the Agilent X-parameters. Hence, this Thesis aims to demonstrate the X-parameter capability to provide this non-linear design and test framework in CAD-based oscillator context. Furthermore, the classical analysis and design of linear microwave transistorbased circuits is based on the development of simple analytical approaches, involving the transistor s-parameters, that are able to quickly provide an analytical solution for the input/output transistor loading conditions as well as analytically determine fundamental parameters as the stability factor, the power gain contours or the input/ output match. Hence, the development of similar analytical design tools that are able to extend s-parameters capabilities in small-signal design to non-linear ap- v plications means a new challenge that is going to be faced in the present work. Therefore, the development of an analytical design framework, based on loadindependent X-parameters, constitutes the core of this Thesis. These analytical nonlinear design approaches would enable to significantly improve current large-signal design processes as well as dramatically decrease the required design time and thus, obtain more efficient approaches.

Improvement of compatibility and stability on polyethylene-modified bitumen by use of an aromatic extra as compatibilizer.

Bitumen modification by polyethylene addition usually improves the mechanical properties of the binder and, therefore, the behavior in service of the bituminous mix: thermal susceptibility and rutting can be diminished, whilst the resistance to low temperature cracking may increase. To achieve this improvement it is necessary a good compatibility between the base bitumen and the polyethylene. Low compatibility between bitumen and polyethylene can lead to phase separation: the polymer- asphalt incompatibility translates into a deterioration of ultimate properties. The object of this research project was to determine if these problems can be diminished by using certain compatibilizer agents, e.g. an aromatic extract from the oil refinery. Compatibility and stability of the polyethylene modified bitumen were studied using conventional test methods and dynamic shear reometer (DSR). Blends of bitumen and polyethylene were prepared with neat bitumen (PMB) or bitumen with compatibilizer as component of the binder (PMBC) and then compared. The experimental results show that “colloid instability index”(IC) is a parameter that can be used to control the compatibility between bitumen and polyethylene. From polyethylene point of view, one of the parameters that govern is the “melt flow index” (MFI). Experimental results show that PMBC formulated with low IC bitumen and hi gh MFI lineal polyethylene can be considered as stable binder.

Variable structure control with chattering elimination and guaranteed stability for a generalized T-S model

In this paper, a fuzzy based Variable Structure Control (VSC) with guaranteed stability is presented. The main objective is to obtain an improved performance of highly non-linear unstable systems. The main contribution of this work is that, firstly, new functions for chattering reduction and error convergence without sacrificing invariant properties are proposed, which is considered the main drawback of the VSC control. Secondly, the global stability of the controlled system is guaranteed.The well known weighting parameters approach, is used in this paper to optimize local and global approximation and modeling capability of T-S fuzzy model.A one link robot is chosen as a nonlinear unstable system to evaluate the robustness, effectiveness and remarkable performance of optimization approach and the high accuracy obtained in approximating nonlinear systems in comparison with the original T-S model. Simulation results indicate the potential and generality of the algorithm. The application of the proposed FLC-VSC shows that both alleviation of chattering and robust performance are achieved with the proposed FLC-VSC controller. The effectiveness of the proposed controller is proven in front of disturbances and noise effects.

Stability and mechanical evaluation of bovine pericardium cross-linked with polyurethane prepolymer in aqueous medium

The present study investigates the potential use of non-catalyzed water-soluble blocked polyurethane prepolymer (PUP) as a bifunctional cross-linker for collagenous scaffolds. The effect of concentration (5, 10, 15 and 20%), time (4, 6, 12 and 24 h), medium volume (50, 100, 200 and 300%) and pH (7.4, 8.2, 9 and 10) over stability, microstructure and tensile mechanical behavior of acellular pericardial matrix was studied. The cross-linking index increased up to 81% while the denaturation temperature increased up to 12 °C after PUP crosslinking. PUP-treated scaffold resisted the collagenase degradation (0.167 ± 0.14 mmol/g of liberated amine groups vs. 598 ± 60 mmol/g for non-cross-linked matrix). The collagen fiber network was coated with PUP while viscoelastic properties were altered after cross-linking. The treatment of the pericardial scaffold with PUP allows (i) different densities of cross-linking depending of the process parameters and (ii) tensile properties similar to glutaraldehyde method.

Influence of aerodynamic characteristics of H beams on galloping stability

This paper presents the experimental study developed on a prismatic beam with H section, sometimes used in bridges as suspenders, vertical bars or decks. The purpose of this study is to understand the physical behavior of the air around this type of section, in order to reduce the aerodynamic loads, the onset speed of galloping and even to avoid it. To achieve this, a study of the influence of all geometric parameters that define the section has been developed. Previously, the most interesting configurations have been selected using a smoke flow visualization technique in the wind-tunnel, then the corresponding static aerodynamic loads were measured, completed with dynamic tests and, finally, the parameters governing the phenomenon of galloping determined.

Static and Dynamic Experimental Analysis of the Galloping Stability of Porous H-Section Beams

The phenomenon of self-induced vibrations of prismatic beams in a cross-flow has been studied for decades, but it is still of great interest due to their important effects in many different industrial applications. This paper presents the experimental study developed on a prismatic beam with H-section.The aim of this analysis is to add some additional insight into the behaviour of the flow around this type of bodies, in order to reduce galloping and even to avoid it. The influence of some relevant geometrical parameters that define the H-section on the translational galloping behaviour of these beams has been analysed. Wind loads coefficients have been measured through static wind tunnel tests and the Den Hartog criterion applied to elucidate the influence of geometrical parameters on the galloping properties of the bodies under consideration.These results have been completed with surface pressure distribution measurements and, besides, dynamic tests have been also performed to verify the static criterion. Finally, the morphology of the flow past the tested bodies has been visualised by using smoke visualization techniques. Since the rectangular section beam is a limiting case of the H-section configuration, the results here obtained are compared with the ones published in the literature concerning rectangular configurations; the agreement is satisfactory.

Asymptotic stability of a mathematical model of cell population

We consider a simplified system of a growing colony of cells described as a free boundary problem. The system consists of two hyperbolic equations of first order coupled to an ODE to describe the behavior of the boundary. The system for cell populations includes non-local terms of integral type in the coefficients. By introducing a comparison with solutions of an ODE's system, we show that there exists a unique homogeneous steady state which is globally asymptotically stable for a range of parameters under the assumption of radially symmetric initial data.

Fishing effort control regulations influence on stability, safety and operability of small fishing vessels: study of a series of stability related accidents occurred in Spain between 2004 and 2007

Entre los años 2004 y 2007 se hundieron por problemas de estabilidad cinco pesqueros españoles de pequeña eslora, de características parecidas, de relativamente poca edad, que habían sido construidos en un intervalo de pocos años. La mayoría de los tripulantes de esos pesqueros fallecieron o desaparecieron en esos accidentes. Este conjunto de accidentes tuvo bastante repercusión social y mediática. Entre ingenieros navales y marinos del sector de la pesca se relacionó estos accidentes con los condicionantes a los diseños de los pesqueros impuestos por la normativa de control de esfuerzo pesquero. Los accidentes fueron investigados y publicados sus correspondientes informes; en ellos no se exploró esta supuesta relación. Esta tesis pretende investigar la relación entre esos accidentes y los cambios de la normativa de esfuerzo pesquero. En la introducción se expone la normativa de control de esfuerzo pesquero analizada, se presentan datos sobre la estructura de la flota pesquera en España y su accidentalidad, y se detallan los criterios de estabilidad manejados durante el trabajo, explicando su relación con la seguridad de los pesqueros. Seguidamente se realiza un análisis estadístico de la siniestralidad en el sector de la pesca para establecer si el conjunto de accidentes estudiados supone una anomalía, o si por el contrario el conjunto de estos accidentes no es relevante desde el punto de vista estadístico. Se analiza la siniestralidad a partir de diversas bases de datos de buques pesqueros en España y se concluye que el conjunto de accidentes estudiados supone una anomalía estadística, ya que la probabilidad de ocurrencia de los cinco sucesos es muy baja considerando la frecuencia estimada de pérdidas de buques por estabilidad en el subsector de la flota pesquera en el que se encuadran los cinco buques perdidos. A continuación el trabajo se centra en la comparación de los buques accidentados con los buques pesqueros dados de baja para construir aquellos, según exige la normativa de control de esfuerzo pesquero; a estos últimos buques nos referiremos como “predecesores” de los buques accidentados. Se comparan las dimensiones principales de cada buque y de su predecesor, resultando que los buques accidentados comparten características de diseño comunes que son sensiblemente diferentes en los buques predecesores, y enlazando dichas características de diseño con los requisitos de la nueva normativa de control del esfuerzo pesquero bajo la que se construyeron estos barcos. Ello permite establecer una relación entre los accidentes y el mencionado cambio normativo. A continuación se compara el margen con que se cumplían los criterios reglamentarios de estabilidad entre los buques accidentados y los predecesores, encontrándose que en cuatro de los cinco casos los predecesores cumplían los criterios de estabilidad con mayor holgura que los buques accidentados. Los resultados obtenidos en este punto permiten establecer una relación entre el cambio de normativa de esfuerzo pesquero y la estabilidad de los buques. Los cinco buques accidentados cumplían con los criterios reglamentarios de estabilidad en vigor, lo que cuestiona la relación entre esos criterios y la seguridad. Por ello se extiende la comparativa entre pesqueros a dos nuevos campos relacionados con la estabilidad y la seguridad delos buques: • Movimientos a bordo (operatividad del buque), y • Criterios de estabilidad en condiciones meteorológicas adversas El estudio de la operatividad muestra que los buques accidentados tenían, en general, una mayor operatividad que sus predecesores, contrariamente a lo que sucedía con el cumplimiento de los criterios reglamentarios de estabilidad. Por último, se comprueba el desempeño de los diez buques en dos criterios específicos de estabilidad en caso de mal tiempo: el criterio IMO de viento y balance intenso, y un criterio de estabilidad de nueva generación, incluyendo la contribución original del autor de considerar agua en cubierta. Las tendencias observadas en estas dos comparativas son opuestas, lo que permite cuestionar la validez del último criterio sin un control exhaustivo de los parámetros de su formulación, poniendo de manifiesto la necesidad de más investigaciones sobre ese criterio antes de su adopción para uso regulatorio. El conjunto de estos resultados permite obtener una serie de conclusiones en la comparativa entre ambos conjuntos de buques pesqueros. Si bien los resultados de este trabajo no muestran que la aprobación de la nueva normativa de esfuerzo pesquero haya significado una merma general de seguridad en sectores enteros de la flota pesquera, sí se concluye que permitió que algunos diseños de buques pesqueros, posiblemente en busca de la mayor eficiencia compatible con dicha normativa, quedaran con una estabilidad precaria, poniendo de manifiesto que la relación entre seguridad y criterios de estabilidad no es unívoca, y la necesidad de que éstos evolucionen y se adapten a los nuevos diseños de buques pesqueros para continuar garantizando su seguridad. También se concluye que la estabilidad es un aspecto transversal del diseño de los buques, por lo que cualquier reforma normativa que afecte al diseño de los pesqueros o su forma de operar debería estar sujeta a evaluación por parte de las autoridades responsables de la seguridad marítima con carácter previo a su aprobación. ABSTRACT Between 2004 and 2007 five small Spanish fishing vessels sank in stability related accidents. These vessels had similar characteristics, had relatively short age, and had been built in a period of a few years. Most crewmembers of these five vessels died or disappeared in those accidents. This set of accidents had significant social and media impact. Among naval architects and seamen of the fishing sector these accidents were related to the design constraints imposed by the fishing control effort regulations. The accidents were investigated and the official reports issued; this alleged relationship was not explored. This thesis aims to investigate the relationship between those accidents and changes in fishing effort control regulations. In the introduction, the fishing effort control regulation is exposed, data of the Spanish fishing fleet structure and its accident rates are presented, and stability criteria dealt with in this work are explained, detailing its relationship with fishing vessel safety. A statistical analysis of the accident rates in the fishing sector in Spain is performed afterwards. The objective is determining whether the set of accidents studied constitute an anomaly or, on the contrary, they are not statistically relevant. Fishing vessels accident rates is analyzed from several fishing vessel databases in Spain. It is concluded that the set of studied accidents is statistically relevant, as the probability of occurrence of the five happenings is extremely low, considering the loss rates in the subsector of the Spanish fishing fleet where the studied vessels are fitted within. From this point the thesis focuses in comparing the vessels lost and the vessels that were decommissioned to build them as required by the fishing effort control regulation; these vessels will be referred to as “predecessors” of the sunk vessels. The main dimensions between each lost vessel and her predecessor are compared, leading to the conclusion that the lost vessels share design characteristics which are sensibly different from the predecessors, and linking these design characteristics with the requirements imposed by the new fishing control effort regulations. This allows establishing a relationship between the accidents and this regulation change. Then the margin in fulfilling the regulatory stability criteria among the vessels is compared, resulting, in four of the five cases, that predecessors meet the stability criteria with greater clearance than the sunk vessels. The results obtained at this point would establish a relationship between the change of fishing effort control regulation and the stability of vessels. The five lost vessels complied with the stability criteria in force, so the relation between these criteria and safety is put in question. Consequently, the comparison among vessels is extended to other fields related to safety and stability: • Motions onboard (operability), and • Specific stability criteria in rough weather The operability study shows that the lost vessels had in general greater operability than their predecessors, just the opposite as when comparing stability criteria. Finally, performance under specific rough weather stability criteria is checked. The criteria studied are the IMO Weather Criterion, and one of the 2nd generation stability criteria under development by IMO considering in this last case the presence of water on deck, which is an original contribution by the author. The observed trends in these two cases are opposite, allowing to put into question the last criterion validity without an exhaustive control of its formulation parameters; indicating that further research might be necessary before using it for regulatory purposes. The analysis of this set of results leads to some conclusions when comparing both groups of fishing vessels. While the results obtained are not conclusive in the sense that the entry into force of a new fishing effort control in 1998 caused a generalized safety reduction in whole sectors of the Spanish fishing fleet, it can be concluded that it opened the door for some vessel designs resulting with precarious stability. This evidences that the relation between safety and stability criteria is not univocal, so stability criteria needs to evolve for adapting to new fishing vessels designs so their safety is still guaranteed. It is also concluded that stability is a transversal aspect to ship design and operability, implying that any legislative reform affecting ship design or operating modes should be subjected to assessing by the authorities responsible for marine safety before being adopted.