Impact of subunit positioning on GABAA receptor function

The major isoforms of the GABAA (gamma-aminobutyric acid type A) receptor are composed of two alpha, two beta and one gamma subunit. Thus alpha and beta subunits occur twice in the receptor pentamer. As it is well documented that different isoforms of alpha and beta subunits can co-exist in the same pentamer, the question is raised whether the relative position of a subunit isoform affects the functional properties of the receptor. We have used subunit concatenation to engineer receptors of well-defined subunit arrangement to study this question. Although all five subunits may be concatenated, we have focused on the combination of triple and dual subunit constructs. We review here what is known so far on receptors containing simultaneously alpha1 and alpha6 subunits and receptors containing beta1 and beta2 subunits. Subunit concatenation may not only be used to study receptors containing two different subunit isoforms, but also to introduce a point mutation into a defined position in receptors containing either two alpha or beta subunits, or to study the receptor architecture of receptors containing unconventional GABAA receptor subunits. Similar approaches may be used to characterize other members of the pentameric ligand-gated ion channel family, including nicotinic acetylcholine receptors, glycine receptors and 5-HT3 (5-hydroxytryptamine) receptors.

A Surface Displacement Analysis for Volcan Pacaya from October 2001 through March 2013 by Means of 3-D Modeling of Precise Position GPS Data

Volcán Pacaya is one of three currently active volcanoes in Guatemala. Volcanic activity originates from the local tectonic subduction of the Cocos plate beneath the Caribbean plate along the Pacific Guatemalan coast. Pacaya is characterized by generally strombolian type activity with occasional larger vulcanian type eruptions approximately every ten years. One particularly large eruption occurred on May 27, 2010. Using GPS data collected for approximately 8 years before this eruption and data from an additional three years of collection afterwards, surface movement covering the period of the eruption can be measured and used as a tool to help understand activity at the volcano. Initial positions were obtained from raw data using the Automatic Precise Positioning Service provided by the NASA Jet Propulsion Laboratory. Forward modeling of observed 3-D displacements for three time periods (before, covering and after the May 2010 eruption) revealed that a plausible source for deformation is related to a vertical dike or planar surface trending NNW-SSE through the cone. For three distinct time periods the best fitting models describe deformation of the volcano: 0.45 right lateral movement and 0.55 m tensile opening along the dike mentioned above from October 2001 through January 2009 (pre-eruption); 0.55 m left lateral slip along the dike mentioned above for the period from January 2009 and January 2011 (covering the eruption); -0.025 m dip slip along the dike for the period from January 2011 through March 2013 (post-eruption). In all bestfit models the dike is oriented with a 75° westward dip. These data have respective RMS misfit values of 5.49 cm, 12.38 cm and 6.90 cm for each modeled period. During the time period that includes the eruption the volcano most likely experienced a combination of slip and inflation below the edifice which created a large scar at the surface down the northern flank of the volcano. All models that a dipping dike may be experiencing a combination of inflation and oblique slip below the edifice which augments the possibility of a westward collapse in the future.

Professionalism and Information Technology: Positioning and Mediation

The starting point of this paper is the assumption that - on the one hand - information technology (IT) is increasingly shaping the professional knowledge base and on the other the relation between organisation and profession. IT is changing the role, responsibilities and practices of social workers and therefore it is important to deal with the impact of IT on social work (representative for many: Harlow and Webb 2003; Burton and van den Broek 2008). Hence, the general aim of this paper is to stimulate a basic discussion on “IT application in social work“, or rather, in a more general way, on „technology and professions“. Secondly, it is about an analytical differentiation of the process of informatisation, respectively formalisation. Thirdly we want to discuss the assumption and overall combination of efficiency, effectiveness and IT. Therefore this paper is arranged as follows: After some opening remarks (chapter 1) we outline case management systems as research object (2). Further on, we confront the approach of reflexive professionalism (3) with the process of formalization (4). Subsequently, we touch on the debate of “technologies of care” (5) and conclude with some short remarks on a research program (6).

Left main coronary stent positioning using rapid transcoronary pacing

Temporary transcoronary unipolar pacing is a validated simple, effective, and safe alternative to temporary transvenous pacing of the right ventricle for the treatment of relevant bradyarrhythmias complicating percutaneous coronary intervention. We describe the use of rapid transcoronary pacing to aid precise placement of a stent in the left main coronary artery bifurcation.

Precise Orbit Determination of Low Earth Satellites at AIUB using GPS and SLR data

An ever increasing number of low Earth orbiting (LEO) satellites is, or will be, equipped with retro-reflectors for Satellite Laser Ranging (SLR) and on-board receivers to collect observations from Global Navigation Satellite Systems (GNSS) such as the Global Positioning Sys- tem (GPS) and the Russian GLONASS and the European Galileo systems in the future. At the Astronomical Insti- tute of the University of Bern (AIUB) LEO precise or- bit determination (POD) using either GPS or SLR data is performed for a wide range of applications for satellites at different altitudes. For this purpose the classical numeri- cal integration techniques, as also used for dynamic orbit determination of satellites at high altitudes, are extended by pseudo-stochastic orbit modeling techniques to effi- ciently cope with potential force model deficiencies for satellites at low altitudes. Accuracies of better than 2 cm may be achieved by pseudo-stochastic orbit modeling for satellites at very low altitudes such as for the GPS-based POD of the Gravity field and steady-state Ocean Circula- tion Explorer (GOCE).

Perioperative and Anesthetic Management of Complete Tracheal Rupture in One Dog and One Cat.

ABSTRACT The authors describe two animals (one dog and one cat) that were presented with severe respiratory distress after trauma. Computerized tomographic imaging under general anesthesia revealed, in both cases, complete tracheal transection. Hypoxic episodes during anesthesia were relieved by keeping the endotracheal tube (ETT) positioned in the cranial part of the transected trachea and by allowing spontaneous breathing. Surgical preparation was performed quickly, and patients were kept in a sternal position to improve ventilation and oxygenation, and were only turned into dorsal recumbency shortly before surgical incision. A sterile ETT was guided into the distal part of the transected trachea by the surgeon, at which point mechanical ventilation was started. Both animals were successfully discharged from hospital a few days after surgery. Rapid and well-coordinated teamwork seemed to contribute to the good outcome. Precise planning and communication between anesthetists, surgeons, and technicians, as well as a quick course of action prior to correct ETT positioning helped to overcome critical phases.

Aerial video geo-registration using terrain models from dense and coherent stereo matching

In the context of aerial imagery, one of the first steps toward a coherent processing of the information contained in multiple images is geo-registration, which consists in assigning geographic 3D coordinates to the pixels of the image. This enables accurate alignment and geo-positioning of multiple images, detection of moving objects and fusion of data acquired from multiple sensors. To solve this problem there are different approaches that require, in addition to a precise characterization of the camera sensor, high resolution referenced images or terrain elevation models, which are usually not publicly available or out of date. Building upon the idea of developing technology that does not need a reference terrain elevation model, we propose a geo-registration technique that applies variational methods to obtain a dense and coherent surface elevation model that is used to replace the reference model. The surface elevation model is built by interpolation of scattered 3D points, which are obtained in a two-step process following a classical stereo pipeline: first, coherent disparity maps between image pairs of a video sequence are estimated and then image point correspondences are back-projected. The proposed variational method enforces continuity of the disparity map not only along epipolar lines (as done by previous geo-registration techniques) but also across them, in the full 2D image domain. In the experiments, aerial images from synthetic video sequences have been used to validate the proposed technique.

Modelling and Control of Stepper Motors for High Accuracy Positioning Systems Used in Radioactive Environments

Hybrid Stepper Motors are widely used in open-loop position applications. They are the choice of actuation for the collimators in the Large Hadron Collider, the largest particle accelerator at CERN. In this case the positioning requirements and the highly radioactive operating environment are unique. The latter forces both the use of long cables to connect the motors to the drives which act as transmission lines and also prevents the use of standard position sensors. However, reliable and precise operation of the collimators is critical for the machine, requiring the prevention of step loss in the motors and maintenance to be foreseen in case of mechanical degradation. In order to make the above possible, an approach is proposed for the application of an Extended Kalman Filter to a sensorless stepper motor drive, when the motor is separated from its drive by long cables. When the long cables and high frequency pulse width modulated control voltage signals are used together, the electrical signals difer greatly between the motor and drive-side of the cable. Since in the considered case only drive-side data is available, it is therefore necessary to estimate the motor-side signals. Modelling the entire cable and motor system in an Extended Kalman Filter is too computationally intensive for standard embedded real-time platforms. It is, in consequence, proposed to divide the problem into an Extended Kalman Filter, based only on the motor model, and separated motor-side signal estimators, the combination of which is less demanding computationally. The efectiveness of this approach is shown in simulation. Then its validity is experimentally demonstrated via implementation in a DSP based drive. A testbench to test its performance when driving an axis of a Large Hadron Collider collimator is presented along with the results achieved. It is shown that the proposed method is capable of achieving position and load torque estimates which allow step loss to be detected and mechanical degradation to be evaluated without the need for physical sensors. These estimation algorithms often require a precise model of the motor, but the standard electrical model used for hybrid stepper motors is limited when currents, which are high enough to produce saturation of the magnetic circuit, are present. New model extensions are proposed in order to have a more precise model of the motor independently of the current level, whilst maintaining a low computational cost. It is shown that a significant improvement in the model It is achieved with these extensions, and their computational performance is compared to study the cost of model improvement versus computation cost. The applicability of the proposed model extensions is demonstrated via their use in an Extended Kalman Filter running in real-time for closed-loop current control and mechanical state estimation. An additional problem arises from the use of stepper motors. The mechanics of the collimators can wear due to the abrupt motion and torque profiles that are applied by them when used in the standard way, i.e. stepping in open-loop. Closed-loop position control, more specifically Field Oriented Control, would allow smoother profiles, more respectful to the mechanics, to be applied but requires position feedback. As mentioned already, the use of sensors in radioactive environments is very limited for reliability reasons. Sensorless control is a known option but when the speed is very low or zero, as is the case most of the time for the motors used in the LHC collimator, the loss of observability prevents its use. In order to allow the use of position sensors without reducing the long term reliability of the whole system, the possibility to switch from closed to open loop is proposed and validated, allowing the use of closed-loop control when the position sensors function correctly and open-loop when there is a sensor failure. A different approach to deal with the switched drive working with long cables is also presented. Switched mode stepper motor drives tend to have poor performance or even fail completely when the motor is fed through a long cable due to the high oscillations in the drive-side current. The design of a stepper motor output fillter which solves this problem is thus proposed. A two stage filter, one devoted to dealing with the diferential mode and the other with the common mode, is designed and validated experimentally. With this ?lter the drive performance is greatly improved, achieving a positioning repeatability even better than with the drive working without a long cable, the radiated emissions are reduced and the overvoltages at the motor terminals are eliminated.

Caracterización de Sistemas intensivos en Software desde un punto de vista de innovación=Characterizing Software-intensive Systems from the innovation point of view

La innovación en Sistemas Intesivos en Software está alcanzando relevancia por múltiples razones: el software está presente en sectores como automóvil, teléfonos móviles o salud. Las empresas necesitan conocer aquellos factores que afectan a la innovación para incrementar las probabilidades de éxito en el desarrollo de sus productos y, la evaluación de productos sofware es un mecanismo potente para capturar este conocimiento. En consecuencia, las empresas necesitan evaluar sus productos desde la perpectiva de innovación para reducir la distancia entre los productos desarrollados y el mercado. Esto es incluso más relevante en el caso de los productos intensivos en software, donde el tiempo real, la oportunidad, complejidad, interoperabilidad, capacidad de respuesta y compartción de recursos son características críticas de los nuevos sistemas. La evaluación de la innovación de productos ya ha sido estudiada y se han definido algunos esquemas de evaluación pero no son específicos para Sistemas intensivos en Sofwtare; además, no se ha alcanzado consenso en los factores ni el procedimiento de evaluación. Por lo tanto, tiene sentido trabajar en la definición de un marco de evaluación de innovación enfocado a Sistemas intesivos en Software. Esta tesis identifica los elementos necesarios para construir in marco para la evaluación de de Sistemas intensivos en Software desde el punto de vista de la innovación. Se han identificado dos componentes como partes del marco de evaluación: un modelo de referencia y una herramienta adaptativa y personalizable para la realización de la evaluación y posicionamiento de la innovación. El modelo de referencia está compuesto por cuatro elementos principales que caracterizan la evaluación de innovación de productos: los conceptos, modelos de innovación, cuestionarios de evaluación y la evaluación de productos. El modelo de referencia aporta las bases para definir instancias de los modelos de evaluación de innovación de productos que pueden se evaluados y posicionados en la herramienta a través de cuestionarios y que de forma automatizada aporta los resultados de la evaluación y el posicionamiento respecto a la innovación de producto. El modelo de referencia ha sido rigurosamente construido aplicando modelado conceptual e integración de vistas junto con la aplicación de métodos cualitativos de investigación. La herramienta ha sido utilizada para evaluar productos como Skype a través de la instanciación del modelo de referencia. ABSTRACT Innovation in Software intensive Systems is becoming relevant for several reasons: software is present embedded in many sectors like automotive, robotics, mobile phones or heath care. Firms need to have knowledge about factors affecting the innovation to increase the probability of success in their product development and the assessment of innovation in software products is a powerful mechanism to capture this knowledge. Therefore, companies need to assess products from an innovation perspective to reduce the gap between their developed products and the market. This is even more relevant in the case of SiSs, where real time, timeliness, complexity, interoperability, reactivity, and resource sharing are critical features of a new system. Many authors have analysed product innovation assessment and some schemas have been developed but they are not specific to SiSs; in addition, there is no consensus about the factors or the procedures for performing an assessment. Therefore, it has sense to work in the definition of a customized software product innovation evaluation framework. This thesis identifies the elements needed to build a framework to assess software products from the innovation perspective. Two components have been identified as part of the framework to assess Software intensive Systems from the innovation perspective: a reference-model and an adaptive and customizable tool to perform the assessment and to position product innovation. The reference-model is composed by four main elements characterizing product innovation assessment: concepts, innovation models, assessment questionnaires and product assessment. The reference model provides the umbrella to define instances of product innovation assessment models that can be assessed and positioned through questionnaires in the proposed tool that also provides automation in the assessment and positioning of innovation. The reference-model has been rigorously built by applying conceptual modelling and view integration integrated with qualitative research methods. The tool has been used to assess products like Skype through models instantiated from the reference-model.

Indoor positioning using Android Platform

In recent years, there has been a great increase in the development of wireless technologies and location services. For this reason, numerous projects in the location field, have arisen. In addition, with the appearance of the open Android operating system, wireless technologies are being developed faster than ever. This Project approaches the design and development of a system that combines the technologies of wireless, location and Android with the implementation of an indoor positioning system. As a result, an Android application has been obtained, which detects the position of a phone in a simple and useful way. The application is based on the WIFI manager API of Android. It combines the data stored in a SQL database with the wifi data received at any given time. Afterwards the position of the user is determined with the algorithm that has been implemented. This application is able to obtain the position of any person who is inside a building with Wi-Fi coverage, and display it on the screen of any device with the Android operating system. Besides the estimation of the position, this system displays a map that helps you see in which quadrant of the room are positioned in real time. This system has been designed with a simple interface to allow people without technology knowledge. Finally, several tests and simulations of the system have been carried out to see its operation and accuracy. The performance of the system has been verified in two different places and changes have been made in the Java code to improve its precision and effectiveness. As a result of the several tests, it has been noticed that the placement of the access point (AP) and the configuration of the Wireless network is an important point that should be taken into account to avoid interferences and errors as much as possible, in the estimation of the position. RESUMEN. En los últimos años, se ha producido un incremento en el desarrollo de tecnologías inalámbricas y en servicios de localización y posicionamiento. Por esta razón, han surgido numerosos proyectos relacionados con estas tecnologías. Por otra parte, un punto importante en el desarrollo de estas tecnologías ha sido la aparición del lenguaje Android que ha hecho que estas nuevas tecnologías se implementaran con una mayor rapidez. Este proyecto, se acerca al diseño y desarrollo de un sistema que combina tecnologías inalámbricas, de ubicación y uso de lenguaje Android para el desarrollo de una aplicación de un sistema de posicionamiento en interiores. Como consecuencia de esto se ha obtenido una aplicación Android que detecta la posición de un dispositivo móvil de una manera sencilla e intuititva. La aplicación se basa en la API WIFI de Android, que combina los datos almacenados en una base de datos SQL con los datos recibidos vía Wi-Fi en cualquier momento. A continuación, la posición del usuario se determina con el algoritmo que se ha implementado a lo largo de todo el proyecto utilizando código Android. Esta aplicación es capaz de obtener la posición de cualquier persona que se encuentra dentro de un edificio con cobertura Wi-Fi, mostrando por pantalla la ubicación del usuario en cualquier dispositivo que disponga de sistema operativo Android. Además de la estimación de la posición, este sistema muestra un mapa que le ayuda a ver en qué cuadrante de la sala está situado el usuario. Este sistema ha sido diseñado con una interfaz sencilla para permitir que usuarios sin conocimiento tecnológico o no acostumbrados al uso de los nuevos dispositivos de hoy en día puedan usarlo de una manera sencilla y de forma intuitiva. Por último, se han llevado a cabo varias pruebas y simulaciones del sistema para verificar su funcionamiento y precisión. El rendimiento del sistema se ha comprobado en dos puntos diferentes de la sala (lugar donde se han hecho todas las pruebas y desarrollado la aplicación) realizando cambios en el código Java para mejorar aún más la precisión y eficacia del posicionamiento. Como resultado de todo esto, se ha comprobado que la ubicación del punto de acceso (AP) y la configuración de la red inalámbrica es importante, y por ello se debe de tener en cuenta para evitar interferencias y tantos errores como sea posible en la estimación de la posición.

The importance of reactant positioning in enzyme catalysis: A hybrid quantum mechanics/molecular mechanics study of a haloalkane dehalogenase

Hybrid quantum mechanics/molecular mechanics calculations using Austin Model 1 system-specific parameters were performed to study the SN2 displacement reaction of chloride from 1,2-dichloroethane (DCE) by nucleophilic attack of the carboxylate of acetate in the gas phase and by Asp-124 in the active site of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. The activation barrier for nucleophilic attack of acetate on DCE depends greatly on the reactants having a geometry resembling that in the enzyme or an optimized gas-phase structure. It was found in the gas-phase calculations that the activation barrier is 9 kcal/mol lower when dihedral constraints are used to restrict the carboxylate nucleophile geometry to that in the enzyme relative to the geometries for the reactants without dihedral constraints. The calculated quantum mechanics/molecular mechanics activation barriers for the enzymatic reaction are 16.2 and 19.4 kcal/mol when the geometry of the reactants is in a near attack conformer from molecular dynamics and in a conformer similar to the crystal structure (DCE is gauche), respectively. This haloalkane dehalogenase lowers the activation barrier for dehalogenation of DCE by 2–4 kcal/mol relative to the single point energies of the enzyme's quantum mechanics atoms in the gas phase. SN2 displacements of this sort in water are infinitely slower than in the gas phase. The modest lowering of the activation barrier by the enzyme relative to the reaction in the gas phase is consistent with mutation experiments.

Use of binding energy by an RNA enzyme for catalysis by positioning and substrate destabilization.

A fundamental catalytic principle for protein enzymes in the use of binding interactions away from the site of chemical transformation for catalysis. We have compared the binding and reactivity of a series of oligonucleotide substrates and products of the Tetrahymena ribozyme, which catalyzes a site-specific phosphodiester cleavage reaction: CCCUCUpA+G<-->CCCUCU-OH+GpA. The results suggest that this RNA enzyme, like protein enzymes, can utilize binding interactions to achieve substantial catalysis via entropic fixation and substrate destabilization. The stronger binding of the all-ribose oligonucleotide product compared to an analog with a terminal 3' deoxyribose residue gives an effective concentration of 2200 M for the 3' hydroxyl group, a value approaching those obtained with protein enzymes and suggesting the presence of a structurally well defined active site capable of precise positioning. The stabilization from tertiary binding interactions is 40-fold less for the oligonucleotide substrate than the oligonucleotide product, despite the presence of the reactive phosphoryl group in the substrate. This destabilization is accounted for by a model in which tertiary interactions away from the site of bond cleavage position the electron-deficient 3' bridging phosphoryl oxygen of the oligonucleotide substrate next to an electropositive Mg ion. As the phosphodiester bond breaks and this 3' oxygen atom develops a negative charge in the transition state, the weak interaction of the substrate with Mg2+ becomes strong. These strategies of "substrate destabilization" and "transition state stabilization" provide estimated rate enhancements of approximately 280- and approximately 60-fold, respectively. Analogous substrate destabilization by a metal ion or hydrogen bond donor may be used more generally by RNA and protein enzymes catalyzing reactions of phosphate esters.

Evaluation of belt positioning booster seats and lap/shoulder belt test procedures. Final report.

Mode of access: Internet.

Rigid and Non-rigid Point-based Medical Image Registration

The primary goal of this dissertation is to develop point-based rigid and non-rigid image registration methods that have better accuracy than existing methods. We first present point-based PoIRe, which provides the framework for point-based global rigid registrations. It allows a choice of different search strategies including (a) branch-and-bound, (b) probabilistic hill-climbing, and (c) a novel hybrid method that takes advantage of the best characteristics of the other two methods. We use a robust similarity measure that is insensitive to noise, which is often introduced during feature extraction. We show the robustness of PoIRe using it to register images obtained with an electronic portal imaging device (EPID), which have large amounts of scatter and low contrast. To evaluate PoIRe we used (a) simulated images and (b) images with fiducial markers; PoIRe was extensively tested with 2D EPID images and images generated by 3D Computer Tomography (CT) and Magnetic Resonance (MR) images. PoIRe was also evaluated using benchmark data sets from the blind retrospective evaluation project (RIRE). We show that PoIRe is better than existing methods such as Iterative Closest Point (ICP) and methods based on mutual information. We also present a novel point-based local non-rigid shape registration algorithm. We extend the robust similarity measure used in PoIRe to non-rigid registrations adapting it to a free form deformation (FFD) model and making it robust to local minima, which is a drawback common to existing non-rigid point-based methods. For non-rigid registrations we show that it performs better than existing methods and that is less sensitive to starting conditions. We test our non-rigid registration method using available benchmark data sets for shape registration. Finally, we also explore the extraction of features invariant to changes in perspective and illumination, and explore how they can help improve the accuracy of multi-modal registration. For multimodal registration of EPID-DRR images we present a method based on a local descriptor defined by a vector of complex responses to a circular Gabor filter.

Automated Collection of Sign Inventory Information by Integrating Global Positioning System (GPS) with Videologging Data Collection Activities, 1995

Advances in communication, navigation and imaging technologies are expected to fundamentally change methods currently used to collect data. Electronic data interchange strategies will also minimize data handling and automatically update files at the point of capture. This report summarizes the outcome of using a multi-camera platform as a method to collect roadway inventory data. It defines basic system requirements as expressed by users, who applied these techniques and examines how the application of the technology met those needs. A sign inventory case study was used to determine the advantages of creating and maintaining the database and provides the capability to monitor performance criteria for a Safety Management System. The project identified at least 75 percent of the data elements needed for a sign inventory can be gathered by viewing a high resolution image.