One-dimensional self-similar solution of the dynamics of axisymmetric slender liquid bridges

In this paper the dynamics of axisymmetric, slender, viscous liquid bridges having volume close to the cylindrical one, and subjected to a small gravitational field parallel to the axis of the liquid bridge, is considered within the context of one-dimensional theories. Although the dynamics of liquid bridges has been treated through a numerical analysis in the inviscid case, numerical methods become inappropriate to study configurations close to the static stability limit because the evolution time, and thence the computing time, increases excessively. To avoid this difficulty, the problem of the evolution of these liquid bridges has been attacked through a nonlinear analysis based on the singular perturbation method and, whenever possible, the results obtained are compared with the numerical ones.

Morphological Functions with Parallel Sets for the Pore Space of X-ray CT Images of Soil Columns

During the last few decades, new imaging techniques like X-ray computed tomography have made available rich and detailed information of the spatial arrangement of soil constituents, usually referred to as soil structure. Mathematical morphology provides a plethora of mathematical techniques to analyze and parameterize the geometry of soil structure. They provide a guide to design the process from image analysis to the generation of synthetic models of soil structure in order to investigate key features of flow and transport phenomena in soil. In this work, we explore the ability of morphological functions built over Minkowski functionals with parallel sets of the pore space to characterize and quantify pore space geometry of columns of intact soil. These morphological functions seem to discriminate the effects on soil pore space geometry of contrasting management practices in a Mediterranean vineyard, and they provide the first step toward identifying the statistical significance of the observed differences.

A computational model coupling mechanics and electrophysiology in spinal cord injury

Traumatic brain injury and spinal cord injury have recently been put under the spotlight as major causes of death and disability in the developed world. Despite the important ongoing experimental and modeling campaigns aimed at understanding the mechanics of tissue and cell damage typically observed in such events, the differentiated roles of strain, stress and their corresponding loading rates on the damage level itself remain unclear. More specifically, the direct relations between brain and spinal cord tissue or cell damage, and electrophysiological functions are still to be unraveled. Whereas mechanical modeling efforts are focusing mainly on stress distribution and mechanistic-based damage criteria, simulated function-based damage criteria are still missing. Here, we propose a new multiscale model of myelinated axon associating electrophysiological impairment to structural damage as a function of strain and strain rate. This multiscale approach provides a new framework for damage evaluation directly relating neuron mechanics and electrophysiological properties, thus providing a link between mechanical trauma and subsequent functional deficits

El paralelo. Bosquejo de un método gráfico = The parallel. Sketch of a graphical method

El paralelo gráfico ha sido -y continúa siendo- un excepcional método para conocer, aprender, investigar y difundir la forma arquitectónica y urbana. Aquí intentamos esbozar los principios que rigen su elaboración y echar un leve vistazo a alguno de los jalones de su intensa historia, que merecería una atención más pausada.

Parallel Virtual Urban Workshops A “resasonable-cost” methodology for academic internationalization in problem-solving oriented postgraduate subjects

Descripción y análisis critic de una metodología de taller de posgrado a realizar entre dos universidades en idioma ingles y con el apoyo de las nuevas tecnologías

Multiphase Parallel Interleaved And Primary-Parallel Secondary-Series Forward Micro-Inverter Comparison.

Using multiphase technique is interesting in PV AC-module application due to light-load efficiency improvement by applying phase shedding, and the possibility of low-profile implementation. This paper presents a comparison, in terms of size and efficiency, of the parallel interleaved and the parallel-series connected multiphase configurations, as a function of the number of phases, for a forward micro-inverter operated in DCM. 8-phase prototypes of both multiphase configurations are built and compared between them and with the single phase forward micro-inverter, validating the presented analysis.

A framework for adaptive e-learning for continuum mechanics and structural analysis

This paper presents a project for providing the students of Structural Engineering with the flexibility to learn outside classroom schedules. The goal is a framework for adaptive E-learning based on a repository of open educational courseware with a set of basic Structural Engineering concepts and fundamentals. These are paramount for students to expand their technical knowledge and skills in structural analysis and design of tall buildings, arch-type structures as well as bridges. Thus, concepts related to structural behaviour such as linearity, compatibility, stiffness and influence lines have traditionally been elusive for students. The objective is to facilitate the student a teachinglearning process to acquire the necessary intuitive knowledge, cognitive skills and the basis for further technological modules and professional development in this area. As a side effect, the system is expected to help the students improve their preparation for exams on the subject. In this project, a web-based open-source system for studying influence lines on continuous beams is presented. It encompasses a collection of interactive user-friendly applications accessible via Web, written in JavaScript under JQuery and Dygraph Libraries, taking advantage of their efficiency and graphic capabilities. It is performed in both Spanish and English languages. The student is enabled to set the geometric, topologic, boundary and mechanic layout of a continuous beam. While changing the loading and the support conditions, the changes in the beam response prompt on the screen, so that the effects of the several issues involved in structural analysis become apparent. This open interaction with the user allows the student to simulate and virtually infer the structural response. Different levels of complexity can be handled, whereas an ongoing help is at hand for any of them. Students can freely boost their experiential learning on this subject at their own pace, in order to further share, process, generalize and apply the relevant essential concepts of Structural Engineering analysis. Besides, this collection is being added to the "Virtual Lab of Continuum Mechanics" of the UPM, launched in 2013 (http://serviciosgate.upm.es/laboratoriosvirtuales/laboratorios/medios-continuos-en-construcci%C3%B3n)

Comparative theoretical analysis between parallel and perpendicular geometries for 2D particle patterning in photovoltaic ferroelectric substrates

This paper describes the dielectrophoretic potential created by the evanescent electric field acting on a particle near a photovoltaic crystal surface depending on the crystal cut. This electric field is obtained from the steady state solution of the Kukhtarev equations for the photovoltaic effect, where the diffusion term has been disregarded. First, the space charge field generated by a small, square, light spot where d _ l (being d a side of the square and l the crystal thickness) is studied. The surface charge density generated in both geometries is calculated and compared as their relation determines the different properties of the dielectrophoretic potential for both cuts. The shape of the dielectrophoretic potential is obtained and compared for several distances to the sample. Afterwards other light patterns are studied by the superposition of square spots, and the resulting trapping profiles are analysed. Finally the surface charge densities and trapping profiles for different d/l relations are studied.

Advanced Control Strategies for a 6 DoF Hydraulic Parallel Robot Based on the Dynamic Model

Nowadays robots have made their way into real applications that were prohibitive and unthinkable thirty years ago. This is mainly due to the increase in power computations and the evolution in the theoretical field of robotics and control. Even though there is plenty of information in the current literature on this topics, it is not easy to find clear concepts of how to proceed in order to design and implement a controller for a robot. In general, the design of a controller requires of a complete understanding and knowledge of the system to be controlled. Therefore, for advanced control techniques the systems must be first identified. Once again this particular objective is cumbersome and is never straight forward requiring of great expertise and some criteria must be adopted. On the other hand, the particular problem of designing a controller is even more complex when dealing with Parallel Manipulators (PM), since their closed-loop structures give rise to a highly nonlinear system. Under this basis the current work is developed, which intends to resume and gather all the concepts and experiences involve for the control of an Hydraulic Parallel Manipulator. The main objective of this thesis is to provide a guide remarking all the steps involve in the designing of advanced control technique for PMs. The analysis of the PM under study is minced up to the core of the mechanism: the hydraulic actuators. The actuators are modeled and experimental identified. Additionally, some consideration regarding traditional PID controllers are presented and an adaptive controller is finally implemented. From a macro perspective the kinematic and dynamic model of the PM are presented. Based on the model of the system and extending the adaptive controller of the actuator, a control strategy for the PM is developed and its performance is analyzed with simulation.

Coupled Nonlinear Ginzburg-Landau and Mechanics Model for Martensitic Transformations in Polycrystals

Las transformaciones martensíticas (MT) se definen como un cambio en la estructura del cristal para formar una fase coherente o estructuras de dominio multivariante, a partir de la fase inicial con la misma composición, debido a pequeños intercambios o movimientos atómicos cooperativos. En el siglo pasado se han descubierto MT en diferentes materiales partiendo desde los aceros hasta las aleaciones con memoria de forma, materiales cerámicos y materiales inteligentes. Todos muestran propiedades destacables como alta resistencia mecánica, memoria de forma, efectos de superelasticidad o funcionalidades ferroicas como la piezoelectricidad, electro y magneto-estricción etc. Varios modelos/teorías se han desarrollado en sinergia con el desarrollo de la física del estado sólido para entender por qué las MT generan microstructuras muy variadas y ricas que muestran propiedades muy interesantes. Entre las teorías mejor aceptadas se encuentra la Teoría Fenomenológica de la Cristalografía Martensítica (PTMC, por sus siglas en inglés) que predice el plano de hábito y las relaciones de orientación entre la austenita y la martensita. La reinterpretación de la teoría PTMC en un entorno de mecánica del continuo (CM-PTMC) explica la formación de los dominios de estructuras multivariantes, mientras que la teoría de Landau con dinámica de inercia desentraña los mecanismos físicos de los precursores y otros comportamientos dinámicos. La dinámica de red cristalina desvela la reducción de la dureza acústica de las ondas de tensión de red que da lugar a transformaciones débiles de primer orden en el desplazamiento. A pesar de las diferencias entre las teorías estáticas y dinámicas dado su origen en diversas ramas de la física (por ejemplo mecánica continua o dinámica de la red cristalina), estas teorías deben estar inherentemente conectadas entre sí y mostrar ciertos elementos en común en una perspectiva unificada de la física. No obstante las conexiones físicas y diferencias entre las teorías/modelos no se han tratado hasta la fecha, aun siendo de importancia crítica para la mejora de modelos de MT y para el desarrollo integrado de modelos de transformaciones acopladas de desplazamiento-difusión. Por lo tanto, esta tesis comenzó con dos objetivos claros. El primero fue encontrar las conexiones físicas y las diferencias entre los modelos de MT mediante un análisis teórico detallado y simulaciones numéricas. El segundo objetivo fue expandir el modelo de Landau para ser capaz de estudiar MT en policristales, en el caso de transformaciones acopladas de desplazamiento-difusión, y en presencia de dislocaciones. Comenzando con un resumen de los antecedente, en este trabajo se presentan las bases físicas de los modelos actuales de MT. Su capacidad para predecir MT se clarifica mediante el ansis teórico y las simulaciones de la evolución microstructural de MT de cúbicoatetragonal y cúbicoatrigonal en 3D. Este análisis revela que el modelo de Landau con representación irreducible de la deformación transformada es equivalente a la teoría CM-PTMC y al modelo de microelasticidad para predecir los rasgos estáticos durante la MT, pero proporciona una mejor interpretación de los comportamientos dinámicos. Sin embargo, las aplicaciones del modelo de Landau en materiales estructurales están limitadas por su complejidad. Por tanto, el primer resultado de esta tesis es el desarrollo del modelo de Landau nolineal con representación irreducible de deformaciones y de la dinámica de inercia para policristales. La simulación demuestra que el modelo propuesto es consistente fcamente con el CM-PTMC en la descripción estática, y también permite una predicción del diagrama de fases con la clásica forma ’en C’ de los modos de nucleación martensítica activados por la combinación de temperaturas de enfriamiento y las condiciones de tensión aplicada correlacionadas con la transformación de energía de Landau. Posteriomente, el modelo de Landau de MT es integrado con un modelo de transformación de difusión cuantitativa para elucidar la relajación atómica y la difusión de corto alcance de los elementos durante la MT en acero. El modelo de transformaciones de desplazamiento y difusión incluye los efectos de la relajación en borde de grano para la nucleación heterogenea y la evolución espacio-temporal de potenciales de difusión y movilidades químicas mediante el acoplamiento de herramientas de cálculo y bases de datos termo-cinéticos de tipo CALPHAD. El modelo se aplica para estudiar la evolución microstructural de aceros al carbono policristalinos procesados por enfriamiento y partición (Q&P) en 2D. La microstructura y la composición obtenida mediante la simulación se comparan con los datos experimentales disponibles. Los resultados muestran el importante papel jugado por las diferencias en movilidad de difusión entre la fase austenita y martensita en la distibución de carbono en las aceros. Finalmente, un modelo multi-campo es propuesto mediante la incorporación del modelo de dislocación en grano-grueso al modelo desarrollado de Landau para incluir las diferencias morfológicas entre aceros y aleaciones con memoria de forma con la misma ruptura de simetría. La nucleación de dislocaciones, la formación de la martensita ’butterfly’, y la redistribución del carbono después del revenido son bien representadas en las simulaciones 2D del estudio de la evolución de la microstructura en aceros representativos. Con dicha simulación demostramos que incluyendo las dislocaciones obtenemos para dichos aceros, una buena comparación frente a los datos experimentales de la morfología de los bordes de macla, la existencia de austenita retenida dentro de la martensita, etc. Por tanto, basado en un modelo integral y en el desarrollo de códigos durante esta tesis, se ha creado una herramienta de modelización multiescala y multi-campo. Dicha herramienta acopla la termodinámica y la mecánica del continuo en la macroescala con la cinética de difusión y los modelos de campo de fase/Landau en la mesoescala, y también incluye los principios de la cristalografía y de la dinámica de red cristalina en la microescala. ABSTRACT Martensitic transformation (MT), in a narrow sense, is defined as the change of the crystal structure to form a coherent phase, or multi-variant domain structures out from a parent phase with the same composition, by small shuffles or co-operative movements of atoms. Over the past century, MTs have been discovered in different materials from steels to shape memory alloys, ceramics, and smart materials. They lead to remarkable properties such as high strength, shape memory/superelasticity effects or ferroic functionalities including piezoelectricity, electro- and magneto-striction, etc. Various theories/models have been developed, in synergy with development of solid state physics, to understand why MT can generate these rich microstructures and give rise to intriguing properties. Among the well-established theories, the Phenomenological Theory of Martensitic Crystallography (PTMC) is able to predict the habit plane and the orientation relationship between austenite and martensite. The re-interpretation of the PTMC theory within a continuum mechanics framework (CM-PTMC) explains the formation of the multivariant domain structures, while the Landau theory with inertial dynamics unravels the physical origins of precursors and other dynamic behaviors. The crystal lattice dynamics unveils the acoustic softening of the lattice strain waves leading to the weak first-order displacive transformation, etc. Though differing in statics or dynamics due to their origins in different branches of physics (e.g. continuum mechanics or crystal lattice dynamics), these theories should be inherently connected with each other and show certain elements in common within a unified perspective of physics. However, the physical connections and distinctions among the theories/models have not been addressed yet, although they are critical to further improving the models of MTs and to develop integrated models for more complex displacivediffusive coupled transformations. Therefore, this thesis started with two objectives. The first one was to reveal the physical connections and distinctions among the models of MT by means of detailed theoretical analyses and numerical simulations. The second objective was to expand the Landau model to be able to study MTs in polycrystals, in the case of displacive-diffusive coupled transformations, and in the presence of the dislocations. Starting with a comprehensive review, the physical kernels of the current models of MTs are presented. Their ability to predict MTs is clarified by means of theoretical analyses and simulations of the microstructure evolution of cubic-to-tetragonal and cubic-to-trigonal MTs in 3D. This analysis reveals that the Landau model with irreducible representation of the transformed strain is equivalent to the CM-PTMC theory and microelasticity model to predict the static features during MTs but provides better interpretation of the dynamic behaviors. However, the applications of the Landau model in structural materials are limited due its the complexity. Thus, the first result of this thesis is the development of a nonlinear Landau model with irreducible representation of strains and the inertial dynamics for polycrystals. The simulation demonstrates that the updated model is physically consistent with the CM-PTMC in statics, and also permits a prediction of a classical ’C shaped’ phase diagram of martensitic nucleation modes activated by the combination of quenching temperature and applied stress conditions interplaying with Landau transformation energy. Next, the Landau model of MT is further integrated with a quantitative diffusional transformation model to elucidate atomic relaxation and short range diffusion of elements during the MT in steel. The model for displacive-diffusive transformations includes the effects of grain boundary relaxation for heterogeneous nucleation and the spatio-temporal evolution of diffusion potentials and chemical mobility by means of coupling with a CALPHAD-type thermo-kinetic calculation engine and database. The model is applied to study for the microstructure evolution of polycrystalline carbon steels processed by the Quenching and Partitioning (Q&P) process in 2D. The simulated mixed microstructure and composition distribution are compared with available experimental data. The results show that the important role played by the differences in diffusion mobility between austenite and martensite to the partitioning in carbon steels. Finally, a multi-field model is proposed by incorporating the coarse-grained dislocation model to the developed Landau model to account for the morphological difference between steels and shape memory alloys with same symmetry breaking. The dislocation nucleation, the formation of the ’butterfly’ martensite, and the redistribution of carbon after tempering are well represented in the 2D simulations for the microstructure evolution of the representative steels. With the simulation, we demonstrate that the dislocations account for the experimental observation of rough twin boundaries, retained austenite within martensite, etc. in steels. Thus, based on the integrated model and the in-house codes developed in thesis, a preliminary multi-field, multiscale modeling tool is built up. The new tool couples thermodynamics and continuum mechanics at the macroscale with diffusion kinetics and phase field/Landau model at the mesoscale, and also includes the essentials of crystallography and crystal lattice dynamics at microscale.

Hydrostatic instabilities in floating zone cristal growth process

If only Fluid Mechanics aspects are considered, the configuration appearing in the floating zone technique for crystal growth can be modelled as a mass of liquid spanning between two solid rods. Besides, if now the influence of temperature gradients and heat flow are not considered, the simplest fluid model consists of an isothermal liquid mass of constant properties (density and surface tension) held by capillary forces between two solid disks placed a distance L apart: the so called liquid bridge. As it is well known, if both supporting disks were parallel, coaxial and of the same diameter, 2R, the volume of liquid, V, were equal to that of a cylinder of the same L and R (V=KR~L) and no body forces were acting on the liquid column, the fluid configuration (under these conditions of cylindrical shape) will become unstable when the distance between the disks equals the length of the circumference of the supporting disks (L=2KR, the so-called Rayleigh stability limit). One should be aware that the Rayleigh stability limit can be dramatically modified when the geometry differs from the above described cylinder (due to having non-coaxial disks, different diameter disks, liquid volume different from the cylindrical one, etc) or when other external effects like accelerations either axial or lateral are considered. In this paper the stability limits of liquid bridges considering different types of perturbations are reviewed.

Parallel Computer Vision Algorithms for Graphics Processing Units

La evolución de los teléfonos móviles inteligentes, dotados de cámaras digitales, está provocando una creciente demanda de aplicaciones cada vez más complejas que necesitan algoritmos de visión artificial en tiempo real; puesto que el tamaño de las señales de vídeo no hace sino aumentar y en cambio el rendimiento de los procesadores de un solo núcleo se ha estancado, los nuevos algoritmos que se diseñen para visión artificial han de ser paralelos para poder ejecutarse en múltiples procesadores y ser computacionalmente escalables. Una de las clases de procesadores más interesantes en la actualidad se encuentra en las tarjetas gráficas (GPU), que son dispositivos que ofrecen un alto grado de paralelismo, un excelente rendimiento numérico y una creciente versatilidad, lo que los hace interesantes para llevar a cabo computación científica. En esta tesis se exploran dos aplicaciones de visión artificial que revisten una gran complejidad computacional y no pueden ser ejecutadas en tiempo real empleando procesadores tradicionales. En cambio, como se demuestra en esta tesis, la paralelización de las distintas subtareas y su implementación sobre una GPU arrojan los resultados deseados de ejecución con tasas de refresco interactivas. Asimismo, se propone una técnica para la evaluación rápida de funciones de complejidad arbitraria especialmente indicada para su uso en una GPU. En primer lugar se estudia la aplicación de técnicas de síntesis de imágenes virtuales a partir de únicamente dos cámaras lejanas y no paralelas—en contraste con la configuración habitual en TV 3D de cámaras cercanas y paralelas—con información de color y profundidad. Empleando filtros de mediana modificados para la elaboración de un mapa de profundidad virtual y proyecciones inversas, se comprueba que estas técnicas son adecuadas para una libre elección del punto de vista. Además, se demuestra que la codificación de la información de profundidad con respecto a un sistema de referencia global es sumamente perjudicial y debería ser evitada. Por otro lado se propone un sistema de detección de objetos móviles basado en técnicas de estimación de densidad con funciones locales. Este tipo de técnicas es muy adecuada para el modelado de escenas complejas con fondos multimodales, pero ha recibido poco uso debido a su gran complejidad computacional. El sistema propuesto, implementado en tiempo real sobre una GPU, incluye propuestas para la estimación dinámica de los anchos de banda de las funciones locales, actualización selectiva del modelo de fondo, actualización de la posición de las muestras de referencia del modelo de primer plano empleando un filtro de partículas multirregión y selección automática de regiones de interés para reducir el coste computacional. Los resultados, evaluados sobre diversas bases de datos y comparados con otros algoritmos del estado del arte, demuestran la gran versatilidad y calidad de la propuesta. Finalmente se propone un método para la aproximación de funciones arbitrarias empleando funciones continuas lineales a tramos, especialmente indicada para su implementación en una GPU mediante el uso de las unidades de filtraje de texturas, normalmente no utilizadas para cómputo numérico. La propuesta incluye un riguroso análisis matemático del error cometido en la aproximación en función del número de muestras empleadas, así como un método para la obtención de una partición cuasióptima del dominio de la función para minimizar el error. ABSTRACT The evolution of smartphones, all equipped with digital cameras, is driving a growing demand for ever more complex applications that need to rely on real-time computer vision algorithms. However, video signals are only increasing in size, whereas the performance of single-core processors has somewhat stagnated in the past few years. Consequently, new computer vision algorithms will need to be parallel to run on multiple processors and be computationally scalable. One of the most promising classes of processors nowadays can be found in graphics processing units (GPU). These are devices offering a high parallelism degree, excellent numerical performance and increasing versatility, which makes them interesting to run scientific computations. In this thesis, we explore two computer vision applications with a high computational complexity that precludes them from running in real time on traditional uniprocessors. However, we show that by parallelizing subtasks and implementing them on a GPU, both applications attain their goals of running at interactive frame rates. In addition, we propose a technique for fast evaluation of arbitrarily complex functions, specially designed for GPU implementation. First, we explore the application of depth-image–based rendering techniques to the unusual configuration of two convergent, wide baseline cameras, in contrast to the usual configuration used in 3D TV, which are narrow baseline, parallel cameras. By using a backward mapping approach with a depth inpainting scheme based on median filters, we show that these techniques are adequate for free viewpoint video applications. In addition, we show that referring depth information to a global reference system is ill-advised and should be avoided. Then, we propose a background subtraction system based on kernel density estimation techniques. These techniques are very adequate for modelling complex scenes featuring multimodal backgrounds, but have not been so popular due to their huge computational and memory complexity. The proposed system, implemented in real time on a GPU, features novel proposals for dynamic kernel bandwidth estimation for the background model, selective update of the background model, update of the position of reference samples of the foreground model using a multi-region particle filter, and automatic selection of regions of interest to reduce computational cost. The results, evaluated on several databases and compared to other state-of-the-art algorithms, demonstrate the high quality and versatility of our proposal. Finally, we propose a general method for the approximation of arbitrarily complex functions using continuous piecewise linear functions, specially formulated for GPU implementation by leveraging their texture filtering units, normally unused for numerical computation. Our proposal features a rigorous mathematical analysis of the approximation error in function of the number of samples, as well as a method to obtain a suboptimal partition of the domain of the function to minimize approximation error.

Grid-Connected Forward Microinverter With Primary-Parallel Secondary-Series Transformer

This paper presents a primary-parallel secondaryseries multicore forward microinverter for photovoltaic ac-module application. The presented microinverter operates with a constant off-time boundary mode control, providing MPPT capability and unity power factor. The proposed multitransformer solution allows using low-profile unitary turns ratio transformers. Therefore, the transformers are better coupled and the overall performance of the microinverter is improved. Due to the multiphase solution, the number of devices increases but the current stress and losses per device are reduced contributing to an easier thermal management. Furthermore, the decoupling capacitor is split among the phases, contributing to a low-profile solution without electrolytic capacitors suitable to be mounted in the frame of a PV module. The proposed solution is compared to the classical parallel-interleaved approach, showing better efficiency in a wide power range and improving the weighted efficiency.

Comparing in vitro, in situ, and in vivo experimental data in a three-dimensional model of mammalian cochlear mechanics

Normal mammalian hearing is refined by amplification of the motion of the cochlear partition. This partition, comprising the organ of Corti sandwiched between the basilar and tectorial membranes, contains the outer hair cells that are thought to drive this amplification process. Force generation by outer hair cells has been studied extensively in vitro and in situ, but, to understand cochlear amplification fully, it is necessary to characterize the role played by each of the components of the cochlear partition in vivo. Observations of cochlear partition motion in vivo are severely restricted by its inaccessibility and sensitivity to surgical trauma, so, for the present study, a computer model has been used to simulate the operation of the cochlea under different experimental conditions. In this model, which uniquely retains much of the three-dimensional complexity of the real cochlea, the motions of the basilar and tectorial membranes are fundamentally different during in situ- and in vivo-like conditions. Furthermore, enhanced outer hair cell force generation in vitro leads paradoxically to a decrease in the gain of the cochlear amplifier during sound stimulation to the model in vivo. These results suggest that it is not possible to extrapolate directly from experimental observations made in vitro and in situ to the normal operation of the intact organ in vivo.

From ab initio quantum mechanics to molecular neurobiology: A cation–π binding site in the nicotinic receptor

The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that cation–π interactions may be involved in binding the quaternary ammonium group of the agonist, acetylcholine. Here we show a compelling correlation between: (i) ab initio quantum mechanical predictions of cation–π binding abilities and (ii) EC50 values for acetylcholine at the receptor for a series of tryptophan derivatives that were incorporated into the receptor by using the in vivo nonsense-suppression method for unnatural amino acid incorporation. Such a correlation is seen at one, and only one, of the aromatic residues—tryptophan-149 of the α subunit. This finding indicates that, on binding, the cationic, quaternary ammonium group of acetylcholine makes van der Waals contact with the indole side chain of α tryptophan-149, providing the most precise structural information to date on this receptor. Consistent with this model, a tethered quaternary ammonium group emanating from position α149 produces a constitutively active receptor.