Characterization of the dose distribution in the halo region of a clinical proton pencil beam using emulsion film detectors

Proton therapy is a high precision technique in cancer radiation therapy which allows irradiating the tumor with minimal damage to the surrounding healthy tissues. Pencil beam scanning is the most advanced dose distribution technique and it is based on a variable energy beam of a few millimeters FWHM which is moved to cover the target volume. Due to spurious effects of the accelerator, of dose distribution system and to the unavoidable scattering inside the patient's body, the pencil beam is surrounded by a halo that produces a peripheral dose. To assess this issue, nuclear emulsion films interleaved with tissue equivalent material were used for the first time to characterize the beam in the halo region and to experimentally evaluate the corresponding dose. The high-precision tracking performance of the emulsion films allowed studying the angular distribution of the protons in the halo. Measurements with this technique were performed on the clinical beam of the Gantry1 at the Paul Scherrer Institute. Proton tracks were identified in the emulsion films and the track density was studied at several depths. The corresponding dose was assessed by Monte Carlo simulations and the dose profile was obtained as a function of the distance from the center of the beam spot.

Emulsion detectors for the antihydrogen detection in AEgIS

The AEgIS experiment at CERN aims to perform the first direct measurement of gravitational interaction between matter and antimatter by measuring the deviation of a cold antihydrogen beam in the Earth gravitational field. The design of the experiment has been recently updated to include emulsion films as position sensitive detector. The submicrometric position accuracy of emulsions leads indeed to a significant improvement of the experimental sensitivity. We present results of preliminary tests and discuss perspectives for the final measurement.

Room temperature absorption in laterally biased Quantum Infrared Detectors fabricated by MBE regrowth

In this paper, we show room temperature operation of a quantum well infrared photodetector (QWIP) using lateral conduction through ohmic contacts deposited at both sides of two n-doped quantum wells. To reduce the dark current due to direct conduction in the wells, we apply an electric field between the quantum wells and two pinch-off Schottky gates, in a fashion similar to a field effect device. Since the normal incidence absorption is strongly reduced in intersubband transitions in quantum wells, we first analyze the response of a detector based on quantum dots (QD). This QD device shows photocurrent signal up to 150 K when it is processed in conventional vertical detector. However, it is possible to observe room temperature signal when it is processed in a lateral structure. Finally, the room temperature photoresponse of the QWIP is demonstrated, and compared with theory. An excellent agreement between the estimated and measured characteristics of the device is found

Projector Model for Efficient List-Mode Reconstruction in PET Scanners with Parallel Planar Detectors

We have developed a new projector model specifically tailored for fast list-mode tomographic reconstructions in Positron emission tomography (PET) scanners with parallel planar detectors. The model provides an accurate estimation of the probability distribution of coincidence events defined by pairs of scintillating crystals. This distribution is parameterized with 2D elliptical Gaussian functions defined in planes perpendicular to the main axis of the tube of response (TOR). The parameters of these Gaussian functions have been obtained by fitting Monte Carlo simulations that include positron range, acolinearity of gamma rays, as well as detector attenuation and scatter effects. The proposed model has been applied efficiently to list-mode reconstruction algorithms. Evaluation with Monte Carlo simulations over a rotating high resolution PET scanner indicates that this model allows to obtain better recovery to noise ratio in OSEM (ordered-subsets, expectation-maximization) reconstruction, if compared to list-mode reconstruction with symmetric circular Gaussian TOR model, and histogram-based OSEM with precalculated system matrix using Monte Carlo simulated models and symmetries.

Applications for wireless sensor networks : tracking with binary proximity sensors

El interés cada vez mayor por las redes de sensores inalámbricos pueden ser entendido simplemente pensando en lo que esencialmente son: un gran número de pequeños nodos sensores autoalimentados que recogen información o detectan eventos especiales y se comunican de manera inalámbrica, con el objetivo final de entregar sus datos procesados a una estación base. Los nodos sensores están densamente desplegados dentro del área de interés, se pueden desplegar al azar y tienen capacidad de cooperación. Por lo general, estos dispositivos son pequeños y de bajo costo, de modo que pueden ser producidos y desplegados en gran numero aunque sus recursos en términos de energía, memoria, velocidad de cálculo y ancho de banda están enormemente limitados. Detección, tratamiento y comunicación son tres elementos clave cuya combinación en un pequeño dispositivo permite lograr un gran número de aplicaciones. Las redes de sensores proporcionan oportunidades sin fin, pero al mismo tiempo plantean retos formidables, tales como lograr el máximo rendimiento de una energía que es escasa y por lo general un recurso no renovable. Sin embargo, los recientes avances en la integración a gran escala, integrado de hardware de computación, comunicaciones, y en general, la convergencia de la informática y las comunicaciones, están haciendo de esta tecnología emergente una realidad. Del mismo modo, los avances en la nanotecnología están empezando a hacer que todo gire entorno a las redes de pequeños sensores y actuadores distribuidos. Hay diferentes tipos de sensores tales como sensores de presión, acelerómetros, cámaras, sensores térmicos o un simple micrófono. Supervisan las condiciones presentes en diferentes lugares tales como la temperatura, humedad, el movimiento, la luminosidad, presión, composición del suelo, los niveles de ruido, la presencia o ausencia de ciertos tipos de objetos, los niveles de tensión mecánica sobre objetos adheridos y las características momentáneas tales como la velocidad , la dirección y el tamaño de un objeto, etc. Se comprobara el estado de las Redes Inalámbricas de Sensores y se revisaran los protocolos más famosos. Así mismo, se examinara la identificación por radiofrecuencia (RFID) ya que se está convirtiendo en algo actual y su presencia importante. La RFID tiene un papel crucial que desempeñar en el futuro en el mundo de los negocios y los individuos por igual. El impacto mundial que ha tenido la identificación sin cables está ejerciendo fuertes presiones en la tecnología RFID, los servicios de investigación y desarrollo, desarrollo de normas, el cumplimiento de la seguridad y la privacidad y muchos más. Su potencial económico se ha demostrado en algunos países mientras que otros están simplemente en etapas de planificación o en etapas piloto, pero aun tiene que afianzarse o desarrollarse a través de la modernización de los modelos de negocio y aplicaciones para poder tener un mayor impacto en la sociedad. Las posibles aplicaciones de redes de sensores son de interés para la mayoría de campos. La monitorización ambiental, la guerra, la educación infantil, la vigilancia, la micro-cirugía y la agricultura son solo unos pocos ejemplos de los muchísimos campos en los que tienen cabida las redes mencionadas anteriormente. Estados Unidos de América es probablemente el país que más ha investigado en esta área por lo que veremos muchas soluciones propuestas provenientes de ese país. Universidades como Berkeley, UCLA (Universidad de California, Los Ángeles) Harvard y empresas como Intel lideran dichas investigaciones. Pero no solo EE.UU. usa e investiga las redes de sensores inalámbricos. La Universidad de Southampton, por ejemplo, está desarrollando una tecnología para monitorear el comportamiento de los glaciares mediante redes de sensores que contribuyen a la investigación fundamental en glaciología y de las redes de sensores inalámbricos. Así mismo, Coalesenses GmbH (Alemania) y Zurich ETH están trabajando en diversas aplicaciones para redes de sensores inalámbricos en numerosas áreas. Una solución española será la elegida para ser examinada más a fondo por ser innovadora, adaptable y polivalente. Este estudio del sensor se ha centrado principalmente en aplicaciones de tráfico, pero no se puede olvidar la lista de más de 50 aplicaciones diferentes que ha sido publicada por la firma creadora de este sensor específico. En la actualidad hay muchas tecnologías de vigilancia de vehículos, incluidos los sensores de bucle, cámaras de video, sensores de imagen, sensores infrarrojos, radares de microondas, GPS, etc. El rendimiento es aceptable, pero no suficiente, debido a su limitada cobertura y caros costos de implementación y mantenimiento, especialmente este ultimo. Tienen defectos tales como: línea de visión, baja exactitud, dependen mucho del ambiente y del clima, no se puede realizar trabajos de mantenimiento sin interrumpir las mediciones, la noche puede condicionar muchos de ellos, tienen altos costos de instalación y mantenimiento, etc. Por consiguiente, en las aplicaciones reales de circulación, los datos recibidos son insuficientes o malos en términos de tiempo real debido al escaso número de detectores y su costo. Con el aumento de vehículos en las redes viales urbanas las tecnologías de detección de vehículos se enfrentan a nuevas exigencias. Las redes de sensores inalámbricos son actualmente una de las tecnologías más avanzadas y una revolución en la detección de información remota y en las aplicaciones de recogida. Las perspectivas de aplicación en el sistema inteligente de transporte son muy amplias. Con este fin se ha desarrollado un programa de localización de objetivos y recuento utilizando una red de sensores binarios. Esto permite que el sensor necesite mucha menos energía durante la transmisión de información y que los dispositivos sean más independientes con el fin de tener un mejor control de tráfico. La aplicación se centra en la eficacia de la colaboración de los sensores en el seguimiento más que en los protocolos de comunicación utilizados por los nodos sensores. Las operaciones de salida y retorno en las vacaciones son un buen ejemplo de por qué es necesario llevar la cuenta de los coches en las carreteras. Para ello se ha desarrollado una simulación en Matlab con el objetivo localizar objetivos y contarlos con una red de sensores binarios. Dicho programa se podría implementar en el sensor que Libelium, la empresa creadora del sensor que se examinara concienzudamente, ha desarrollado. Esto permitiría que el aparato necesitase mucha menos energía durante la transmisión de información y los dispositivos sean más independientes. Los prometedores resultados obtenidos indican que los sensores de proximidad binarios pueden formar la base de una arquitectura robusta para la vigilancia de áreas amplias y para el seguimiento de objetivos. Cuando el movimiento de dichos objetivos es suficientemente suave, no tiene cambios bruscos de trayectoria, el algoritmo ClusterTrack proporciona un rendimiento excelente en términos de identificación y seguimiento de trayectorias los objetos designados como blancos. Este algoritmo podría, por supuesto, ser utilizado para numerosas aplicaciones y se podría seguir esta línea de trabajo para futuras investigaciones. No es sorprendente que las redes de sensores de binarios de proximidad hayan atraído mucha atención últimamente ya que, a pesar de la información mínima de un sensor de proximidad binario proporciona, las redes de este tipo pueden realizar un seguimiento de todo tipo de objetivos con la precisión suficiente. Abstract The increasing interest in wireless sensor networks can be promptly understood simply by thinking about what they essentially are: a large number of small sensing self-powered nodes which gather information or detect special events and communicate in a wireless fashion, with the end goal of handing their processed data to a base station. The sensor nodes are densely deployed inside the phenomenon, they deploy random and have cooperative capabilities. Usually these devices are small and inexpensive, so that they can be produced and deployed in large numbers, and so their resources in terms of energy, memory, computational speed and bandwidth are severely constrained. Sensing, processing and communication are three key elements whose combination in one tiny device gives rise to a vast number of applications. Sensor networks provide endless opportunities, but at the same time pose formidable challenges, such as the fact that energy is a scarce and usually non-renewable resource. However, recent advances in low power Very Large Scale Integration, embedded computing, communication hardware, and in general, the convergence of computing and communications, are making this emerging technology a reality. Likewise, advances in nanotechnology and Micro Electro-Mechanical Systems are pushing toward networks of tiny distributed sensors and actuators. There are different sensors such as pressure, accelerometer, camera, thermal, and microphone. They monitor conditions at different locations, such as temperature, humidity, vehicular movement, lightning condition, pressure, soil makeup, noise levels, the presence or absence of certain kinds of objects, mechanical stress levels on attached objects, the current characteristics such as speed, direction and size of an object, etc. The state of Wireless Sensor Networks will be checked and the most famous protocols reviewed. As Radio Frequency Identification (RFID) is becoming extremely present and important nowadays, it will be examined as well. RFID has a crucial role to play in business and for individuals alike going forward. The impact of ‘wireless’ identification is exerting strong pressures in RFID technology and services research and development, standards development, security compliance and privacy, and many more. The economic value is proven in some countries while others are just on the verge of planning or in pilot stages, but the wider spread of usage has yet to take hold or unfold through the modernisation of business models and applications. Possible applications of sensor networks are of interest to the most diverse fields. Environmental monitoring, warfare, child education, surveillance, micro-surgery, and agriculture are only a few examples. Some real hardware applications in the United States of America will be checked as it is probably the country that has investigated most in this area. Universities like Berkeley, UCLA (University of California, Los Angeles) Harvard and enterprises such as Intel are leading those investigations. But not just USA has been using and investigating wireless sensor networks. University of Southampton e.g. is to develop technology to monitor glacier behaviour using sensor networks contributing to fundamental research in glaciology and wireless sensor networks. Coalesenses GmbH (Germany) and ETH Zurich are working in applying wireless sensor networks in many different areas too. A Spanish solution will be the one examined more thoroughly for being innovative, adaptable and multipurpose. This study of the sensor has been focused mainly to traffic applications but it cannot be forgotten the more than 50 different application compilation that has been published by this specific sensor’s firm. Currently there are many vehicle surveillance technologies including loop sensors, video cameras, image sensors, infrared sensors, microwave radar, GPS, etc. The performance is acceptable but not sufficient because of their limited coverage and expensive costs of implementation and maintenance, specially the last one. They have defects such as: line-ofsight, low exactness, depending on environment and weather, cannot perform no-stop work whether daytime or night, high costs for installation and maintenance, etc. Consequently, in actual traffic applications the received data is insufficient or bad in terms of real-time owed to detector quantity and cost. With the increase of vehicle in urban road networks, the vehicle detection technologies are confronted with new requirements. Wireless sensor network is the state of the art technology and a revolution in remote information sensing and collection applications. It has broad prospect of application in intelligent transportation system. An application for target tracking and counting using a network of binary sensors has been developed. This would allow the appliance to spend much less energy when transmitting information and to make more independent devices in order to have a better traffic control. The application is focused on the efficacy of collaborative tracking rather than on the communication protocols used by the sensor nodes. Holiday crowds are a good case in which it is necessary to keep count of the cars on the roads. To this end a Matlab simulation has been produced for target tracking and counting using a network of binary sensors that e.g. could be implemented in Libelium’s solution. Libelium is the enterprise that has developed the sensor that will be deeply examined. This would allow the appliance to spend much less energy when transmitting information and to make more independent devices. The promising results obtained indicate that binary proximity sensors can form the basis for a robust architecture for wide area surveillance and tracking. When the target paths are smooth enough ClusterTrack particle filter algorithm gives excellent performance in terms of identifying and tracking different target trajectories. This algorithm could, of course, be used for different applications and that could be done in future researches. It is not surprising that binary proximity sensor networks have attracted a lot of attention lately. Despite the minimal information a binary proximity sensor provides, networks of these sensing modalities can track all kinds of different targets classes accurate enough.

Failure Detectors in Homonymous Distributed Systems (with an Application to Consensus).

This paper is on homonymous distributed systems where processes are prone to crash failures and have no initial knowledge of the system membership (?homonymous? means that several processes may have the same identi?er). New classes of failure detectors suited to these systems are ?rst de?ned. Among them, the classes H? and H? are introduced that are the homonymous counterparts of the classes ? and ?, respectively. (Recall that the pair h?,?i de?nes the weakest failure detector to solve consensus.) Then, the paper shows how H? and H? can be implemented in homonymous systems without membership knowledge (under different synchrony requirements). Finally, two algorithms are presented that use these failure detectors to solve consensus in homonymous asynchronous systems where there is no initial knowledge ofthe membership. One algorithm solves consensus with hH?, H?i, while the other uses only H?, but needs a majority of correct processes. Observe that the systems with unique identi?ers and anonymous systems are extreme cases of homonymous systems from which follows that all these results also apply to these systems. Interestingly, the new failure detector class H? can be implemented with partial synchrony, while the analogous class A? de?ned for anonymous systems can not be implemented (even in synchronous systems). Hence, the paper provides us with the ?rst proof showing that consensus can be solved in anonymous systems with only partial synchrony (and a majority of correct processes).

Design of a training tool for improving the use of hand-held detectors in humanitarian demining

Purpose – The purpose of this paper is to introduce the design of a training tool intended to improve deminers' technique during close-in detection tasks. Design/methodology/approach – Following an introduction that highlights the impact of mines and improvised explosive devices (IEDs), and the importance of training for enhancing the safety and the efficiency of the deminers, this paper considers the utilization of a sensory tracking system to study the skill of the hand-held detector expert operators. With the compiled information, some critical performance variables can be extracted, assessed, and quantified, so that they can be used afterwards as reference values for the training task. In a second stage, the sensory tracking system is used for analysing the trainee skills. The experimentation phase aims to test the effectiveness of the elements that compose the sensory system to track the hand-held detector during the training sessions. Findings – The proposed training tool will be able to evaluate the deminers' efficiency during the scanning tasks and will provide important information for improving their competences. Originality/value – This paper highlights the need of introducing emerging technologies for enhancing the current training techniques for deminers and proposes a sensory tracking system that can be successfully utilised for evaluating trainees' performance with hand-held detectors.

A function using cubic splines for the analysis of alpha--particles spectra from silicon detectors

A function based on the characteristics of the alpha-particle lines obtained with silicon semiconductor detectors and modi"ed by using cubic splines is proposed to parametrize the shape of the peaks. A reduction in the number of parameters initially considered in other proposals was carried out in order to improve the stability of the optimization process. It was imposed by the boundary conditions for the cubic splines term. This function was then able to describe peaks with highly anomalous shapes with respect to those expected from this type of detector. Some criteria were implemented to correctly determine the area of the peaks and their errors. Comparisons with other well-established functions revealed excellent agreement in the "nal values obtained from both "ts. Detailed studies on reliability of the "tting results were carried out and the application of the function is proposed. Although the aim was to correct anomalies in peak shapes, the peaks showing the expected shapes were also well "tted. Accordingly, the validity of the proposal is quite general in the analysis of alpha-particle spectrometry with semiconductor detectors.

Neighborhood mobility: A Long-Gone Pardigm? Approaching proximity and land use mix using data from home based surveys.

El WCTR es un congreso de reconocido prestigio internacional en el ámbito de la investigación del transporte y aunque las actas publicadas están en formato digital y sin ISSN ni ISBN, lo consideramos lo suficientemente importante como para que se considere en los indicadores. Policies trying to increase walking within urban mobility modal split usually highlight the importance of the functional patterns and the environmental quality of the urban space as major drivers of citizens modal choices. Functional characteristics would be mainly associated to an appropriate mix of land uses within neighbourhoods, whereas environmental quality would be associated to the characteristics of urban spaces. The purpose of this research is threefold: first, to identify relevant proxy indicators, which could characterize pedestrian-friendly land use mix and environmental quality. Second, to assess, for both traits, existing disparities among neighbourhoods in a major metropolitan area. And finally, to explore the association between both indicators and children mobility patterns: according to their built environment, which neighbourhoods have a greater proportion of children and, how is their mobility? Using data from the 2004 household mobility survey in the 128 neighbourhoods of the municipality of Madrid, this paper concludes that potentially favourable conditions at the neighbourhood level seem to have only a modest influence in,mobility patterns , in terms of both, selection of closer destinations and a higher share of walking within modal split. The citys policy choices, with intensive investment in road and public transport infrastructure may explain why short-distance mobility is not as important as it could have been expected in those neighbourhoods with more pedestrian-friendly conditions. The metropolitan transport system is providing mobility conditions, which make far-away destinations attractive to most citizens.

Neighbourhood mobility: a longgone Paradigm? Approaching "proximity" and "land use mix" using data from home-based surveys

Policies trying to increase walking within urban mobility modal split usually highlight the importance of the functional patterns and the environmental quality of the urban space as major drivers of citizens modal choices. Functional characteristics would be mainly associated to an appropriate mix of land uses within neighbourhoods, whereas environmental quality would be associated to the characteristics of urban spaces. The purpose of this research is threefold: first, to identify relevant proxy indicators, which could characterize pedestrian-friendly land use mix and environmental quality. Second, to assess, for both traits, existing disparities among neighbourhoods in a major metropolitan area. And finally, to explore the association between both indicators and children mobility patterns: according to their built environment, which neighbourhoods have a greater proportion of children and, how is their mobility? Using data from the 2004 household mobility survey in the 128 neighbourhoods of the municipality of Madrid, this paper concludes that potentially favourable conditions at the neighbourhood level seem to have only a modest influence in,mobility patterns , in terms of both, selection of closer destinations and a higher share of walking within modal split. The city s policy choices, with intensive investment in road and public transport infrastructure may explain why short-distance mobility is not as important as it could have been expected in those neighbourhoods with more pedestrian-friendly conditions. The metropolitan transport system is providing mobility conditions, which make far-away destinations attractive to most citizens.

Real-time Surveillance Application by Multiple Detectors and Compressive Trackers

A real-time surveillance system for IP network cameras is presented. Motion, part-body, and whole-body detectors are efficiently combined to generate robust and fast detections, which feed multiple compressive trackers. The generated trajectories are then improved using a reidentification strategy for long term operation.

Detection of Biological CO2 and 1,3-Pentadiene Using Non-refrigerated Low-Cost MWIR Detectors

The early detection of spoiling metabolic products in contaminated food is a very important tool to control quality. Some volatile compounds produce unpleasant odours at very low concentrations, making their early detection very challenging. This is the case of 1,3-pentadiene produced by microorganisms through decarboxylation of the preservative sorbate. In this work, we have developed a methodology to use the data produced by a low-cost, compact MWIR (Mid-Wave IR) spectrometry device without moving parts, which is based on a linear array of 128 elements of VPD PbSe coupled to a linear variable filter (LVF) working in the spectral range between 3 and 4.6 ?m. This device is able to analyze food headspace gases through dedicated sample presentation setup. This methodology enables the detection of CO2 and the volatile compound 1,3-pentadiene, as compared to synthetic patrons. Data analysis is based on an automated multidimensional dynamic processing of the MWIR spectra. Principal component and discriminant analysis allow segregating between four yeast strains including producers and no producers. The segregation power is accounted as a measure of the discrimination quality.

PRIM: Proximity imaging of green fluorescent protein-tagged polypeptides

We report a serendipitous discovery that extends the impressive catalog of reporter functions performed by green fluorescent protein (GFP) or its derivatives. When two GFP molecules are brought into proximity, changes in the relative intensities of green fluorescence emitted upon excitation at 395 vs. 475 nm result. These spectral changes provide a sensitive ratiometric index of the extent of self-association that can be exploited to quantitatively image homo-oligomerization or clustering processes of GFP-tagged proteins in vivo. The method, which we term proximity imaging (PRIM), complements fluorescence resonance energy transfer between a blue fluorescent protein donor and a GFP acceptor, a powerful method for imaging proximity relationships between different proteins. However, unlike fluorescence resonance energy transfer (which is a spectral interaction), PRIM depends on direct contact between two GFP modules, which can lead to structural perturbations and concomitant spectral changes within a module. Moreover, the precise spatial arrangement of the GFP molecules within a given dimer determines the magnitude and direction of the spectral change. We have used PRIM to detect FK1012-induced dimerization of GFP fused to FK506-binding protein and clustering of glycosylphosphatidylinositol-anchored GFP at cell surfaces.

Caspase activation: The induced-proximity model

Members of the caspase family of proteases transmit the events that lead to apoptosis of animal cells. Distinct members of the family are involved in both the initiation and execution phases of cell death, with the initiator caspases being recruited to multicomponent signaling complexes. Initiation of apoptotic events depends on the ability of the signaling complexes to generate an active protease. The mechanism of activation of the caspases that constitute the different apoptosis-signaling complexes can be explained by an unusual property of the caspase zymogens to autoprocess to an active form. This autoprocessing depends on intrinsic activity that resides in the zymogens of the initiator caspases. We review evidence for a hypothesis—the induced-proximity model—that describes how the first proteolytic signal is produced after adapter-mediated clustering of initiator caspase zymogens.

Structure and function in rhodopsin: correct folding and misfolding in point mutants at and in proximity to the site of the retinitis pigmentosa mutation Leu-125-->Arg in the transmembrane helix C.

L125R is a mutation in the transmembrane helix C of rhodopsin that is associated with autosomal dominant retinitis pigmentosa. To probe the orientation of the helix and its packing in the transmembrane domain, we have prepared and studied the mutations E122R, I123R, A124R, S127R, L125F, and L125A at, and in proximity to, the above mutation site. Like L125R, the opsin expressed in COS-1 cells from E122R did not bind 11-cis-retinal, whereas those from I123R and S127R formed the rhodopsin chromophore partially. A124R opsin formed the rhodopsin chromophore (lambda max 495 nm) in the dark, but the metarhodopsin II formed on illumination decayed about 6.5 times faster than that of the wild type and was defective in transducin activation. The mutant opsins from L125F and L125A bound 11-cis-retinal only partially, and in both cases, the mixtures of the proteins produced were separated into retinal-binding and non-retinal-binding (misfolded) fractions. The purified mutant rhodopsin from L125F showed lambda max at 500 nm, whereas that from L125A showed lambda max at 503 nm. The mutant rhodopsin L125F showed abnormal bleaching behavior and both mutants on illumination showed destabilized metarhodopsin II species and reduced transducin activation. Because previous results have indicated that misfolding in rhodopsin is due to the formation of a disulfide bond other than the normal disulfide bond between Cys-110 and Cys-187 in the intradiscal domain, we conclude from the misfolding in mutants L125F and L125A that the folding in vivo in the transmembrane domain is coupled to that in the intradiscal domain.