Publishing Orthology and Diseases Information in the Linked Open Data Cloud

The Linked Data initiative offers a straight method to publish structured data in the World Wide Web and link it to other data, resulting in a world wide network of semantically codified data known as the Linked Open Data cloud. The size of the Linked Open Data cloud, i.e. the amount of data published using Linked Data principles, is growing exponentially, including life sciences data. However, key information for biological research is still missing in the Linked Open Data cloud. For example, the relation between orthologs genes and genetic diseases is absent, even though such information can be used for hypothesis generation regarding human diseases. The OGOLOD system, an extension of the OGO Knowledge Base, publishes orthologs/diseases information using Linked Data. This gives the scientists the ability to query the structured information in connection with other Linked Data and to discover new information related to orthologs and human diseases in the cloud.

Open multi-technology building energy management system

Energy Efficiency is one of the goals of the Smart Building initiatives. This paper presents an Open Energy Management System which consists of an ontology-based multi-technology platform and a wireless transducer network using 6LoWPAN communication technology. The system allows the integration of several building automation protocols and eases the development of different kind of services to make use of them. The system has been implemented and tested in the Energy Efficiency Research Facility at CeDInt-UPM.

Open Technologies for prototyping the Internet of Things

The worldwide "hyper-connection" of any object around us is the challenge that promises to cover the paradigm of the Internet of Things. If the Internet has colonized the daily life of more than 2000 million1 people around the globe, the Internet of Things faces of connecting more than 100000 million2 "things" by 2020. The underlying Internet of Things’ technologies are the cornerstone that promises to solve interrelated global problems such as exponential population growth, energy management in cities, and environmental sustainability in the average and long term. On the one hand, this Project has the goal of knowledge acquisition about prototyping technologies available in the market for the Internet of Things. On the other hand, the Project focuses on the development of a system for devices management within a Wireless Sensor and Actuator Network to offer some services accessible from the Internet. To accomplish the objectives, the Project will begin with a detailed analysis of various “open source” hardware platforms to encourage creative development of applications, and automatically extract information from the environment around them for transmission to external systems. In addition, web platforms that enable mass storage with the philosophy of the Internet of Things will be studied. The project will culminate in the proposal and specification of a service-oriented software architecture for embedded systems that allows communication between devices on the network, and the data transmission to external systems. Furthermore, it abstracts the complexities of hardware to application developers. RESUMEN. La “hiper-conexión” a nivel mundial de cualquier objeto que nos rodea es el desafío al que promete dar cobertura el paradigma de la Internet de las Cosas. Si la Internet ha colonizado el día a día de más de 2000 millones1 de personas en todo el planeta, la Internet de las Cosas plantea el reto de conectar a más de 100000 millones2 de “cosas” para el año 2020. Las tecnologías subyacentes de la Internet de las Cosas son la piedra angular que prometen dar solución a problemas globales interrelacionados como el crecimiento exponencial de la población, la gestión de la energía en las ciudades o la sostenibilidad del medioambiente a largo plazo. Este Proyecto Fin de Carrera tiene como principales objetivos por un lado, la adquisición de conocimientos acerca de las tecnologías para prototipos disponibles en el mercado para la Internet de las Cosas, y por otro lado el desarrollo de un sistema para la gestión de dispositivos de una red inalámbrica de sensores que ofrezcan unos servicios accesibles desde la Internet. Con el fin de abordar los objetivos marcados, el proyecto comenzará con un análisis detallado de varias plataformas hardware de tipo “open source” que estimulen el desarrollo creativo de aplicaciones y que permitan extraer de forma automática información del medio que les rodea para transmitirlo a sistemas externos para su posterior procesamiento. Por otro lado, se estudiarán plataformas web identificadas con la filosofía de la Internet de las Cosas que permitan el almacenamiento masivo de datos que diferentes plataformas hardware transfieren a través de la Internet. El Proyecto culminará con la propuesta y la especificación una arquitectura software orientada a servicios para sistemas empotrados que permita la comunicación entre los dispositivos de la red y la transmisión de datos a sistemas externos, así como facilitar el desarrollo de aplicaciones a los programadores mediante la abstracción de la complejidad del hardware.

An universal system to de-orbit satellites at end of life

A 3-year Project financed by the European Commission is aimed at developing a universal system to de-orbit satellites at their end of life, as a fundamental contribution to limit the increase of debris in the Space environment. The operational system involves a conductive tapetether left bare to establish anodic contact with the ambient plasma as a giant Langmuir probe. The Project will size the three disparate dimensions of a tape for a selected de-orbit mission and determine scaling laws to allow system design for a general mission. Starting at the second year, mission selection is carried out while developing numerical codes to implement control laws on tether dynamics in/off the orbital plane; performing numerical simulations and plasma chamber measurements on tether-plasma interaction; and completing design of subsystems: electronejecting plasma contactor, power module, interface elements, deployment mechanism, and tether-tape/end-mass. This will be followed by subsystems manufacturing and by currentcollection, free-fall, and hypervelocity impact tests.

Modelo Híbrido para la Ayuda al Capitán

En esta Tesis se plantea una nueva forma de entender la evacuación apoyándonos en tecnologías existentes y accesibles que nos permitirán ver este proceso como un ente dinámico. Se trata de una metodología que implica no solo el uso de herramientas de análisis que permitan la definición de planes de evacuación en tiempo real, sino que también se apunta hacia la creación de una infraestructura física que permita alimentar con información actualizada al sistema de forma que, según la situación y la evolución de la emergencia, sea posible realizar planes alternativos que se adapten a las nuevas circunstancias. En base a esto, el sistema asimilará toda esa información y aportará soluciones que faciliten la toma de decisiones durante toda la evolución del incidente. Las aportaciones originales de esta Tesis son múltiples y muy variadas, pudiéndolas resumir en los siguientes puntos: 1. Estudio completo del estado del arte: a. Detección y análisis de diferentes proyectos a nivel internacional que de forma parcial tratan algunos aspectos desarrollados en la Tesis. b. Completo estudio a nivel mundial del software desarrollado total o parcialmente para la simulación del comportamiento humano y análisis de procesos de evacuación. Se ha generado una base de datos que cataloga de forma exhaustiva estas aplicaciones, permitiendo realizar un completo análisis y posibilitando la evolución futura de los contenidos de la misma. En la tesis se han analizado casi un centenar de desarrollos, pero el objetivo es seguir completando esta base de datos debido a la gran utilidad y a las importantes posibilidades que ofrece. 2. Desarrollo de un importante capítulo que trata sobre la posibilidad de utilizar entornos virtuales como alternativa intermedia al uso de simuladores y simulacros. En esta sección se divide en dos bloques: a. Ensayos en entornos reales y virtuales. b. Ensayos en entornos virtuales (pruebas realizadas con varios entornos virtuales). 3. Desarrollo de e-Flow net design: paquete de herramientas desarrolladas sobre Rhinoceros para el diseño de la red de evacuación basada en los elementos definidos en la tesis: Nodes, paths, Relations y Areas. 4. Desarrollo de e-Flow Simulator: Conjunto de herramientas que transforman Rhinoceros en un simulador 3D de comportamiento humano. Este simulador, de desarrollo propio, incorpora un novedoso algoritmo de comportamiento a nivel de individuo que incluye aspectos que no se han encontrado en otros simuladores. Esta herramienta permite realizar simulaciones programadas de grupos de individuos cuyo comportamiento se basa en el análisis del entorno y en la presencia de referencias dinámicas. Incluye otras importantes novedades como por ejemplo: herramientas para análisis de la señalización, elementos de señalización dinámica, incorporación sencilla de obstáculos, etc. También se ha creado una herramienta que posibilita la implementación del movimiento del propio escenario simulando la oscilación del mismo, con objeto de reflejar la influencia del movimiento del buque en el desplazamiento de los individuos. 5. En una fase avanzada del desarrollo, se incorporó la posibilidad de generar un vídeo de toda la simulación, momento a partir del cual, se han documentado todas las pruebas (y se continúan documentando) en una base de datos que recoge todas las características de las simulaciones, los problemas detectados, etc. Estas pruebas constituyen, en el momento en que se ha cerrado la redacción de la Tesis, un total de 81 GB de datos. Generación y análisis de rutas en base a la red de evacuación creada con e-Flow Net design y las simulaciones realizadas con e-Flow Net simulator. a. Análisis para la optimización de la configuración de la red en base a los nodos por área existentes. b. Definición de procesos previos al cálculo de rutas posibles. c. Cálculo de rutas: i. Análisis de los diferentes algoritmos que existen en la actualidad para la optimización de rutas. ii. Desarrollo de una nueva familia de algoritmos que he denominado “Minimum Decision Algorithm (MDA)”, siendo los algoritmos que componen esta familia: 1. MDA básico. 2. MDA mínimo. 3. MDA de no interferencia espacial. 4. MDA de expansión. 5. MDA de expansión ordenada para un único origen. 6. MDA de expansión ordenada. iii. Todos estos algoritmos se han implementado en la aplicación e-Flow creada en la Tesis para el análisis de rutas y que constituye el núcleo del Sistema de Ayuda al Capitán. d. Determinación de las alternativas para el plan de evacuación. Tras la definición de las rutas posibles, se describen diferentes procesos existentes de análisis por ponderación en base a criterios, para pasar finalmente a definir el método de desarrollo propio propuesto en esta Tesis y cuyo objetivo es responder en base a la población de rutas posibles obtenidas mediante los algoritmos MDA, qué combinación de rutas constituyen el Plan o Planes más adecuados para cada situación. La metodología creada para la selección de combinaciones de rutas que determinan un Plan completo, se basa en cuatro criterios básicos que tras su aplicación ofrecen las mejores alternativas. En esta fase también se incluye un complejo análisis de evolución temporal que incorpora novedosas definiciones y formulaciones. e. Derivado de la definición de la metodología creada en esta Tesis para la realización de los análisis de evolución temporal, se ha podido definir un nuevo teorema matemático que se ha bautizado como “Familia de cuadriláteros de área constante”. 7. Especificación de la infraestructura física del Sistema de Ayuda al Capitán: parte fundamental de sistema es la infraestructura física sobre la que se sustentaría. Esta infraestructura estaría compuesta por sensores, actuadores, aplicaciones para dispositivos móviles, etc. En este capítulo se analizan los diferentes elementos que la constituirían y las tecnologías implicadas. 8. Especificación de la infraestructura de servicios. 9. Creación del Blog Virtual Environments (http://epcinnova-virtualenvironments.blogspot.com.es/) en el que se han publicado todas las pruebas realizadas en el capítulo que analiza los entornos virtuales como alternativa a los simuladores y a los ensayos en laboratorio o los simulacros, incluyendo en muchos casos la posibilidad de que el visitante del blog pueda realizar la simulación en el entorno virtual. Este blog también incluye otras secciones que se han trabajado durante la Tesis: • Recopilación de diferentes entornos virtuales existentes. • Diagrama que recopila información sobre accidentes tanto en el ámbito marítimo como en el terrestre (en desarrollo). • Esquema propuesto para el acopio de información obtenida a partir de un simulacro. 10. Esta Tesis es la base para el proyecto e-Flow (nombre de una de las aplicaciones que desarrolladas en esta obra), un proyecto en el que el autor de esta Tesis ha trabajado como Project Manager. En el proyecto participa un consorcio de empresas y la UPM, y tiene como objetivo trasladar a la realidad gran parte de los planteamientos e ideas presentadas en esta Tesis. Este proyecto incluye el desarrollo de la infraestructura física y de servicios que permitirán, entre otras cosas, implementar en infraestructuras complejas una plataforma que posibilita la evacuación dinámica y un control ubicuo de los sistemas de monitorización y actuación implementados. En estos momentos se está finalizando el proyecto, cuyo objetivo final es la implementación de un piloto en un Hospital. También destacamos los siguientes avances a nivel de difusión científico-tecnológico: • Ponencia en el “52 congreso de la Ingeniería Naval en España” presentando un artículo “e-Flow- Sistema integral inteligente de soporte a la evacuación”. En este artículo se trata tanto el proyecto e-Flow del que soy Project Manager, como esta Tesis Doctoral, al ser temas estrechamente vinculados. En 2014 se publicó en dos números de la Revista Ingeniería Naval el artículo presentado a estas jornadas. • Co-autor en el artículo “E-Flow: A communication system for user notification in dynamic evacuation scenarios” presentado en el 7th International Conference on Ubicuous Computing & Ambient Intelligence (UCAMI) celebrado en Costa Rica. Por último, una de las aportaciones más interesantes, es la definición de un gran número de líneas de investigación futuras en base a todos los avances realizados en esta Tesis. ABSTRACT With this Thesis a new approach for understanding evacuation process is considered, taking advantage of the existing and open technologies that will allow this process to be interpreted as a dynamic entity. The methodology involves not only tools that allows on.-time evacuation plans, but also creates a physical insfrastructure that makes possible to feed the system with information on real time so, considering in each moment the real situation as well as the specific emergency development it will be feasible to generate alternative plans that responds to the current emergency situation. In this respect, the system will store all this information and will feedback with solutions that will help the decision making along the evacuation process. The innovative and singular contributions of this Thesis are numerous and rich, summarised as follows: 1.- Complete state-of-art study: a. Detection and analysis of different projects on an international level that, although partially, deal with some aspects developed in this Thesis. b. Thorough study at a international level of the developed software - total or partially done - for the simulation of the human behaviour and evacuation processes analysis. A database has been generated that classifies in detail these applications allowing to perform a full analysis and leading to future evolution of its contents. Within the Thesis work, almost a hundred of developments have been analysed but the purpose is to keep up updating this database due to the broad applications and possibilities that it involves. 2. Development of an important chapter that studies the possibility of using virtual scenarios as mid-term alternative for the use of simulations. This section is divided in two blocks: a. Trials in virtual and real scenarios b. Trials in virutal scenarios (trials performed with several ones). 3. E-Flow net design development: Set of tools developed under Rhinoceros for the evacuation net design based on the elements defined in the Thesis: Nodes, Paths, Relations, Areas 4. E-Flow simulator development: Set of tools that uses Rhinoceros as a 3D simulator of human behaviour. This simulator, of my own design, includes a new and original algorithm of human behaviour that involves aspects that are not found in other simulators. This tool allows to perform groups programmed simulations which behaviour is based on their enviroment analysis and presence of dynamic references. It includes other important innovations as for example: tools for signals analysis, dynamic signal elements, easy obstacle adding etc... More over, a tool that allows the own scenario movement implementation has been created by simulating the own oscillation movement, with the purpose of playing the vessel movement's influences in the individuals' displacements. 5. In an advanced stage of the development, the possibility of generating a video recording of all the simulation was also integrated, then from that moment all tests have been filed (and keep on doing so) in a database that collects all simulation characteristics, failures detected, etc. These stored tests amounts to a total of 81 GB at the moment of finishing the Thesis work. Generation and analysis of paths regarding the evacuation net created with E-Flow design and the simulations performed with E-Flow net Simulator. a. Analysis for the optimisation of the network configuration based in the existing nodes per area. b. Definition of the processes previous to the calculation of the feasible paths c. Paths calculation: i. Analysis of the different algorithms on existance nowadays for the routes optimisation. ii. Development of a new family of algorithms that I have called “Minimum Decision Algorithm (MDA)”, being composed of: 1. MDA basic 2. MDA minimum 3. MDA of not spacial interference 4. MDA of expansion (es de extenderse) o enlargement ( es de crecimiento) 5. MDA of organised expansion for a single origin (of organised enlargement for a single origin) 6. MDA of organised expansion (of organised enlargement) iii. All these algorithms have been implemented in the E-Flow application created in the Thesis dfor the routes analysis and it is the core of the Captain's support system. d. Determination of the alternatives for the evacuation plan. After defining all possible paths, different processes of analysis existing for weighing-based criteria are described, thus to end defining the own development method proposed in this Thesis and that aims to respond in an agreggation of possible routes basis obtained by means of the MDA algorithms what is the routes' combination more suitable for the Plan or Plans in every situation. The methodology created fot the selection of the combinations of routes that determine a complete Plan is baesd in four basic criteria that after applying, offer the best alternatives. In this stage a complex analysis of the progress along time is also included, that adds original and innovative defintions and formulations. e. Originated from the methodology created in this Thesis for the perfoming of the analysy of the progress along time, a new mathematic theorem has been defined, that has been called as "Family of quadrilateral of constant area". 7. Specification of the physiscal infrastructure of the Captain's help system: essential part is this physical infrastructure that will support it. This system will be made of sensors, actuators, apps for mobile devices etc... Within this chapter the different elements and technologies that make up this infrastructure will be studied. 8. Specification for the services infrastructure. 9. Start up of the Blog. " Virtual Environments (http://epcinnova-virtualenvironments.blogspot.com.es/)" in which all tests performed have been published in terms of analysis of the virtual enviroments as alternative to the simulators as well as to the laboratory experiments or simulations, including in most of the cases the possibility that the visitor can perform the simulation within the virtual enviroment. This blog also includes other sections that have been worked along and within this Thesis: - Collection of different virtual scenarios existent. - Schema that gathers information concerning accidents for maritime and terrestrial areas (under development) - Schema proposed for the collecting of information obtained from a simulation. 10. This Thesis is the basis of the E-Flow project (name of one of the applications developed in this work), a project in which the Thesis' author has worked in as Project Manager. In the project takes part a consortium of firms as well as the UPM and the aim is to bring to real life most part of the approaches and ideas contained in this Thesis. This project includes the development of the physical infrastructure as well as the services that will allow, among others, implement in complex infrastrucutres a platform that will make possible a dynamic evacuation and a continuous control of the monitoring and acting systems implemented. At the moment the project is getting to an end which goal is the implementation of a pilot project in a Hospital. We also would like to highlight the following advances concerning the scientific-technology divulgation: • Talk in the " 52th Congress of the Naval Engineering in Spain" with the article "E-Flow . Intelligent system integrated for supporting evacuation". This paper is about project E-Flow which I am Project Manager of, as well as this Thesis for the Doctorate, being both closely related. Two papers published In 2014 in the Naval Engineering Magazine. • Co-author in the article “E-Flow: A communication system for user notification in dynamic evacuation scenarios” [17] introduced in the 7th International Conference on Ubicuous Computing & Ambient Intelligence (UCAMI) held in Costa Rica. Last, but not least, one of the more interesting contributions is the defintion of several lines of research in the future, based on the advances made in this Thesis.

A proposal for an Internet of Things-based monitoring system composed by low capability, open source and open hardware devices

The Internet of Things makes use of a huge disparity of technologies at very different levels that help one to the other to accomplish goals that were previously regarded as unthinkable in terms of ubiquity or scalability. If the Internet of Things is expected to interconnect every day devices or appliances and enable communications between them, a broad range of new services, applications and products can be foreseen. For example, monitoring is a process where sensors have widespread use for measuring environmental parameters (temperature, light, chemical agents, etc.) but obtaining readings at the exact physical point they want to be obtained from, or about the exact wanted parameter can be a clumsy, time-consuming task that is not easily adaptable to new requirements. In order to tackle this challenge, a proposal on a system used to monitor any conceivable environment, which additionally is able to monitor the status of its own components and heal some of the most usual issues of a Wireless Sensor Network, is presented here in detail, covering all the layers that give it shape in terms of devices, communications or services.

A Reliable Open-Source System Architecture for the Fast Designing and Prototyping of Autonomous Multi-UAV Systems: Simulation and Experimentation

During the process of design and development of an autonomous Multi-UAV System, two main problems appear. The first one is the difficulty of designing all the modules and behaviors of the aerial multi-robot system. The second one is the difficulty of having an autonomous prototype of the system for the developers that allows to test the performance of each module even in an early stage of the project. These two problems motivate this paper. A multipurpose system architecture for autonomous multi-UAV platforms is presented. This versatile system architecture can be used by the system designers as a template when developing their own systems. The proposed system architecture is general enough to be used in a wide range of applications, as demonstrated in the paper. This system architecture aims to be a reference for all designers. Additionally, to allow for the fast prototyping of autonomous multi-aerial systems, an Open Source framework based on the previously defined system architecture is introduced. It allows developers to have a flight proven multi-aerial system ready to use, so that they can test their algorithms even in an early stage of the project. The implementation of this framework, introduced in the paper with the name of “CVG Quadrotor Swarm”, which has also the advantages of being modular and compatible with different aerial platforms, can be found at https://​github.​com/​Vision4UAV/​cvg_​quadrotor_​swarm with a consistent catalog of available modules. The good performance of this framework is demonstrated in the paper by choosing a basic instance of it and carrying out simulation and experimental tests whose results are summarized and discussed in this paper.

Comment on “Effects of Arsenite during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Diseases in Male Mice” and “Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Trends and Scientific Gaps”

Peer reviewed

Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism

The puzzling linkage between genetic hemochromatosis and histocompatibility loci became even more so when the gene involved, HFE, was identified. Indeed, within the well defined, mainly peptide-binding, MHC class I family of molecules, HFE seems to perform an unusual yet essential function. As yet, our understanding of HFE function in iron homeostasis is only partial; an even more open question is its possible role in the immune system. To advance on both of these avenues, we report the deletion of HFE α1 and α2 putative ligand binding domains in vivo. HFE-deficient animals were analyzed for a comprehensive set of metabolic and immune parameters. Faithfully mimicking human hemochromatosis, mice homozygous for this deletion develop iron overload, characterized by a higher plasma iron content and a raised transferrin saturation as well as an elevated hepatic iron load. The primary defect could, indeed, be traced to an augmented duodenal iron absorption. In parallel, measurement of the gut mucosal iron content as well as iron regulatory proteins allows a more informed evaluation of various hypotheses regarding the precise role of HFE in iron homeostasis. Finally, an extensive phenotyping of primary and secondary lymphoid organs including the gut provides no compelling evidence for an obvious immune-linked function for HFE.

Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy

Objectives: To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding.

VIDA: a virus database system for the organization of animal virus genome open reading frames

VIDA is a new virus database that organizes open reading frames (ORFs) from partial and complete genomic sequences from animal viruses. Currently VIDA includes all sequences from GenBank for Herpesviridae, Coronaviridae and Arteriviridae. The ORFs are organized into homologous protein families, which are identified on the basis of sequence similarity relationships. Conserved sequence regions of potential functional importance are identified and can be retrieved as sequence alignments. We use a controlled taxonomical and functional classification for all the proteins and protein families in the database. When available, protein structures that are related to the families have also been included. The database is available for online search and sequence information retrieval at http://www.biochem.ucl.ac.uk/bsm/virus_database/VIDA.html.

Metabolism of Indole-3-Acetic Acid in Arabidopsis1

The metabolism of indole-3-acetic acid (IAA) was investigated in 14-d-old Arabidopsis plants grown in liquid culture. After ruling out metabolites formed as an effect of nonsterile conditions, high-level feeding, and spontaneous interconversions, a simple metabolic pattern emerged. Oxindole-3-acetic acid (OxIAA), OxIAA conjugated to a hexose moiety via the carboxyl group, and the conjugates indole-3-acetyl aspartic acid (IAAsp) and indole-3-acetyl glutamate (IAGlu) were identified by mass spectrometry as primary products of IAA fed to the plants. Refeeding experiments demonstrated that none of these conjugates could be hydrolyzed back to IAA to any measurable extent at this developmental stage. IAAsp was further oxidized, especially when high levels of IAA were fed into the system, yielding OxIAAsp and OH-IAAsp. This contrasted with the metabolic fate of IAGlu, since that conjugate was not further metabolized. At IAA concentrations below 0.5 μm, most of the supplied IAA was metabolized via the OxIAA pathway, whereas only a minor portion was conjugated. However, increasing the IAA concentrations to 5 μm drastically altered the metabolic pattern, with marked induction of conjugation to IAAsp and IAGlu. This investigation used concentrations for feeding experiments that were near endogenous levels, showing that the metabolic pathways controlling the IAA pool size in Arabidopsis are limited and, therefore, make good targets for mutant screens provided that precautions are taken to avoid inducing artificial metabolism.

Participation of Mitochondrial Metabolism in Photorespiration1 : Reconstituted System of Peroxisomes and Mitochondria from Spinach Leaves

In this study the interplay of mitochondria and peroxisomes in photorespiration was simulated in a reconstituted system of isolated mitochondria and peroxisomes from spinach (Spinacia oleracea L.) leaves. The mitochondria oxidizing glycine produced serine, which was reduced in the peroxisomes to glycerate. The required reducing equivalents were provided by the mitochondria via the malate-oxaloacetate (OAA) shuttle, in which OAA was reduced in the mitochondrial matrix by NADH generated during glycine oxidation. The rate of peroxisomal glycerate formation, as compared with peroxisomal protein, resembled the corresponding rate required during leaf photosynthesis under ambient conditions. When the reconstituted system produced glycerate at this rate, the malate-to-OAA ratio was in equilibrium with a ratio of NADH/NAD of 8.8 × 10−3. This low ratio is in the same range as the ratio of NADH/NAD in the cytosol of mesophyll cells of intact illuminated spinach leaves, as we had estimated earlier. This result demonstrates that in the photorespiratory cycle a transfer of redox equivalents from the mitochondria to peroxisomes, as postulated from separate experiments with isolated mitochondria and peroxisomes, can indeed operate under conditions of the very low reductive state of the NADH/NAD system prevailing in the cytosol of mesophyll cells in a leaf during photosynthesis.

Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system.

Various compounds that affect signal transduction regulate the relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.