Annexins sense changes in intracellular pH during hypoxia

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators.

The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction

The central nervous system (CNS) is tightly sealed from the changeable milieu of blood by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB). While the BBB is considered to be localized at the level of the endothelial cells within CNS microvessels, the BCSFB is established by choroid plexus epithelial cells. The BBB inhibits the free paracellular diffusion of water-soluble molecules by an elaborate network of complex tight junctions (TJs) that interconnects the endothelial cells. Combined with the absence of fenestrae and an extremely low pinocytotic activity, which inhibit transcellular passage of molecules across the barrier, these morphological peculiarities establish the physical permeability barrier of the BBB. In addition, a functional BBB is manifested by a number of permanently active transport mechanisms, specifically expressed by brain capillary endothelial cells that ensure the transport of nutrients into the CNS and exclusion of blood-borne molecules that could be detrimental to the milieu required for neural transmission. Finally, while the endothelial cells constitute the physical and metabolic barrier per se, interactions with adjacent cellular and acellular layers are prerequisites for barrier function. The fully differentiated BBB consists of a complex system comprising the highly specialized endothelial cells and their underlying basement membrane in which a large number of pericytes are embedded, perivascular antigen-presenting cells, and an ensheathment of astrocytic endfeet and associated parenchymal basement membrane. Endothelial cell morphology, biochemistry, and function thus make these brain microvascular endothelial cells unique and distinguishable from all other endothelial cells in the body. Similar to the endothelial barrier, the morphological correlate of the BCSFB is found at the level of unique apical tight junctions between the choroid plexus epithelial cells inhibiting paracellular diffusion of water-soluble molecules across this barrier. Besides its barrier function, choroid plexus epithelial cells have a secretory function and produce the CSF. The barrier and secretory function of the choroid plexus epithelial cells are maintained by the expression of numerous transport systems allowing the directed transport of ions and nutrients into the CSF and the removal of toxic agents out of the CSF. In the event of CNS pathology, barrier characteristics of the blood-CNS barriers are altered, leading to edema formation and recruitment of inflammatory cells into the CNS. In this review we will describe current knowledge on the cellular and molecular basis of the functional and dysfunctional blood-CNS barriers with focus on CNS autoimmune inflammation.

Zellulare Transportfahrzeuge für flexible und wandelbare Intralogistiksysteme

Aufgrund stetig wechselnder Leistungsanforderungen volatiler Märkte ist die Flexibilisierung des in-nerbetrieblichen Materialflusses eine Notwendigkeit. Klassische Fördermittel, wie zentral gesteuerte Stetig-fördertechniksysteme, stoßen dabei an ihre Grenzen. Auch die planerische Auslegung von starren Material-flusssystemen ist damit vor eine nicht lösbare Aufgabe gestellt. Zellulare Intralogistiksysteme sind die heutigen Antworten auf diese Anforderungen. Die Zellularen Transportfahrzeuge „Multishuttle Move“ sollen Stetigfördersysteme und manuelle Transporte dort ablösen, wo ein hohes Maß an Flexibilität und Wandelbarkeit gefragt ist, die Planungssicherheit nicht gewährleistet ist oder aufgrund mangelnder Flexibilität nicht automatisiert werden kann. In diesem Beitrag werden diese Systeme vorgestellt und deren Eigenschaften aufgezeigt.

Kollaborative Planung dezentral gesteuerter Materialflusssysteme in der Intralogistik

Der Beitrag stellt eine Kollaborationssoftware vor, die im Rahmen des AiF-Forschungsprojektes „KoDeMat“ entwickelt wurde. Der Fokus wird auf die Problemfelder der fehlenden Standardisierung und Anpassbarkeit im Bereich von fördertechnischen Anlagen gerichtet. Ziel ist, unter Zuhilfenahme von standardisierten, kollaborativen Engineeringprozessen, eine unternehmensübergreifende Planung, Realisierung und einen Umbau von komplexen dezentral gesteuerten Intralogistiksystemen sowie deren Betrieb effizient zu ermöglichen.

VuLF – Entwicklung eines Versuchsstandes zur Fehlerminimierung durch Fahrzeuganalyse

Fahrerlose Transportsysteme (FTS) kommen in der Intralogistik immer mehr zum Einsatz. Dabei wer-den neue Anforderungen an die FTS gestellt, die bisherige Aufgaben weit übersteigen. Der Transport von schweren Lasten und die Fahrt mehrere FTS in einer Formation sind dabei nur der Anfang einer Menge zukünftiger Einsatzgebiete. Große Probleme stellen dabei Schlupf und Verschleiß dar, die bisher noch kaum erforscht sind, welche die Performance der Fahrzeuge jedoch stark beeinträchtigen. Um diese Fehlerquellen besser verstehen zu können, wurde ein Versuchsstand entwickelt, mit dessen Hilfe Einzelfahrten aber auch Formationsfahrten in Bezug auf Schlupf und Verschleiß besser untersucht werden können. Dabei kann ein sehr breites Spektrum an Fahrzeugarten abgedeckt werden, da Parameter wie Lenksysteme oder Bereifung variabel gewählt werden können.

(Lifelong) learning in your pocket?

Der Beitrag fokussiert die Entwicklung, den Einsatz und die Nutzung von innovativen Technologien zur Unterstützung von Bildungsszenarien in Schule, Hochschule und Weiterbildung. Ausgehend von den verschiedenen Phasen des Corporate Learning, Social Learning, Mobile Learning und Intelligent Learning wird in einem ersten Abschnitt das Nutzungsverhalten von Technologien durch Kinder, Jugendliche und (junge) Erwachsene in Schule, Studium und Lehre betrachtet. Es folgt die Darstellung technologischer Entwicklungen auf Basis des Technology Life Cycle und die Konsequenzen von unterschiedlichen Entwicklungszuständen und Reifegraden von Technologien wie Content Learning Management, sozialen Netzwerken, mobilen Endgeräten, multidimensionalen und -modalen Räumen bis hin zu Anwendungen augmentierter Realität und des Internets der Dinge, Dienste und Daten für den Einsatz und die Nutzung in Bildungsszenarien. Nach der Darstellung von Anforderungen an digitale Technologien hinsichtlich Inhalte, Didaktik und Methodik wie etwa hinsichtlich der Erstellung von Inhalten, deren Wiederverwendung, Digitalisierung und Auffindbarkeit sowie Standards werden methodische Hinweise zur Nutzung digitaler Technologien zur Interaktion von Lernenden, von Lehrenden, sozialer Interaktion, kollaborativem Autorieren, Kommentierung, Evaluation und Begutachtung gegeben. Abschließend werden - differenziert für Schule und Hochschule - Erkenntnisse zu Rahmenbedingungen, Einflussgrößen, hemmenden und fördernden Faktoren sowie Herausförderungen bei der Einführung und nachhaltigen Implementation digitaler Technologien im schulischen Unterricht, in Lehre, Studium und Weiterbildung im Überblick zusammengefasst.

Targeting the Blood-brain Barrier with a Non-canonical Iron-mimicry Mechanism

Treatment of central nervous system (CNS) diseases is limited by the blood-brain barrier (BBB), a selective vascular interface restricting passage of most molecules from blood into brain. Specific transport systems have evolved allowing circulating polar molecules to cross the BBB and gain access to the brain parenchyma. However, to date, few ligands exploiting such systems have proven clinically viable in the setting of CNS diseases. We reasoned that combinatorial phage-display screenings in vivo would yield peptides capable of crossing the BBB and allow for the development of ligand-directed targeting strategies of the brain. Here we show the identification of a peptide mediating systemic targeting to the normal brain and to an orthotopic human glioma model. We demonstrate that this peptide functionally mimics iron through an allosteric mechanism and that a non-canonical association of (i) transferrin, (ii) the iron-mimic ligand motif, and (iii) transferrin receptor mediates binding and transport of particles across the BBB. We also show that in orthotopic human glioma xenografts, a combination of transferrin receptor over-expression plus extended vascular permeability and ligand retention result in remarkable brain tumor targeting. Moreover, such tumor targeting attributes enables Herpes simplex virus thymidine kinase-mediated gene therapy of intracranial tumors for molecular genetic imaging and suicide gene delivery with ganciclovir. Finally, we expand our data by analyzing a large panel of primary CNS tumors through comprehensive tissue microarrays. Together, our approach and results provide a translational avenue for the detection and treatment of brain tumors.

High affinity amino acid transporters specifically expressed in xylem parenchyma and developing seeds of Arabidopsis

Arabidopsis amino acid transporters (AAPs) show individual temporal and spatial expression patterns. A new amino acid transporter, AAP8 was isolated by reverse transcription-PCR. Growth and transport assays in comparison to AAP1-5 characterize AAP8 and AAP6 as high affinity amino acid transport systems from Arabidopsis. Histochemical promoter-beta-glucuronidase (GUS) studies identified AAP6 expression in xylem parenchyma, cells requiring high affinity transport due to the low amino acid concentration in xylem sap. AAP6 may thus function in uptake of amino acids from xylem. Histochemical analysis of AAP8 revealed stage-dependent expression in siliques and developing seeds. Thus AAP8 is probably responsible for import of organic nitrogen into developing seeds. The only missing transporter of the family AAP7 was nonfunctional in yeast with respect to amino acid transport, and expression was not detectable. Therefore, AAP6 and -8 are the only members of the family able to transport aspartate with physiologically relevant affinity. AAP1, -6 and -8 are the closest AAP paralogs. Although AAP1 and AAP8 originate from a duplicated region on chromosome I, biochemical properties and expression pattern diverged. Overlapping substrate specificities paired with individual properties and expression patterns point to specific functions of each of the AAP genes in nitrogen distribution rather than to mere redundancy.

A Conceptual Model to Combine Creativity Techniques with Fuzzy Cognitive Maps for Enhanced Knowledge Management

This chapter introduces a conceptual model to combine creativity techniques with fuzzy cognitive maps (FCMs) and aims to support knowledge management methods by improving expert knowledge acquisition and aggregation. The aim of the conceptual model is to represent acquired knowledge in a manner that is as computer-understandable as possible with the intention of developing automated reasoning in the future as part of intelligent information systems. The formal represented knowledge thus may provide businesses with intelligent information integration. To this end, we introduce and evaluate various creativity techniques with a list of attributes to define the most suitable to combine with FCMs. This proposed combination enables enhanced knowledge management through the acquisition and representation of expert knowledge with FCMs. Our evaluation indicates that the creativity technique known as mind mapping is the most suitable technique in our set. Finally, a scenario from stakeholder management demonstrates the combination of mind mapping with FCMs as an integrated system.

Éxitos y desafíos en política de transporte público : análisis comparativo de las innovaciones en la prestación del servicio de transporte público de pasajeros en las ciudades de Curitiba, Brasil; Santiago de Chile, Chile y Rosario, Argentina

En esta artículo realizamos un análisis comparativo de los sistemas de servicio de transporte público de pasajeros en las ciudades de Curitiba, Brasil; Santiago de Chile, Chile y Rosario, Argentina para poder comparar las similitudes, diferencias y dificultades que presentan estos sistemas en la etapa de implementación de las políticas públicas; como así también presentar una sistematización de las políticas, instrumentos y acciones que permitieron gestionar con éxito las reestructuraciones de los sistemas de transporte y sus aportes para el desarrollo de una Política pública de transporte en el Gran Mendoza.

Pollen analysis of surface sediment off northwest Africa

Over 100 samples of recent surface sediments from the bottomn of the Atlantic Ocean offshore NW Africa between 34° and 6° N have been analysed palynologically. The objective of this study was to reveal the relation between source areas, transport systems, and resulting distribution patterns of pollen and spores in marine sediments off NW Africa, in order to lay a sound foundation for the interpretation of pollen records of marine cores from this area. The clear zonation of the NW-African vegetation (due to the distinct climatic gradient) is helpful in determining main source areas, and the presence of some major wind belts facilitates the registration of the average course of wind trajectories. The present circulation pattern is driven by the intertropical front (ITCZ) which shifts over the continent between c. 22° N (summer position) and c. 4° N (winter position) in the course of the year. Determination of the period of main pollen release and the average atmospheric circulation pattern effective at that time of the years is of prime importance. The distribution patterns in recent marine sediments of pollen of a series of genera and families appear to record climatological/ecological variables, such as the trajectory of the NE trade, January trades, African Easterly Jet (Saharan Air Layer), the northernmost and southernmost position of the intertropical convergence zone, and the extent and latitudinal situation of the NW-African vegetation belt. Pollen analysis of a series of dated deep-sea cores taken between c. 35° and the equator off NW African enable the construction of paleo-distribution maps for time slices of the past, forming a register of paleoclimatological/paleoecological information.

Detection and Tracking of Traffic Signs Using a Recursive Bayesian Decision Framework

In this paper we propose a new method for the automatic detection and tracking of road traffic signs using an on-board single camera. This method aims to increase the reliability of the detections such that it can boost the performance of any traffic sign recognition scheme. The proposed approach exploits a combination of different features, such as color, appearance, and tracking information. This information is introduced into a recursive Bayesian decision framework, in which prior probabilities are dynamically adapted to tracking results. This decision scheme obtains a number of candidate regions in the image, according to their HS (Hue-Saturation). Finally, a Kalman filter with an adaptive noise tuning provides the required time and spatial coherence to the estimates. Results have shown that the proposed method achieves high detection rates in challenging scenarios, including illumination changes, rapid motion and significant perspective distortion

Two Novel Methods For The Determination Of The Number Of Components In Independent Components Analysis Models

Independent Components Analysis is a Blind Source Separation method that aims to find the pure source signals mixed together in unknown proportions in the observed signals under study. It does this by searching for factors which are mutually statistically independent. It can thus be classified among the latent-variable based methods. Like other methods based on latent variables, a careful investigation has to be carried out to find out which factors are significant and which are not. Therefore, it is important to dispose of a validation procedure to decide on the optimal number of independent components to include in the final model. This can be made complicated by the fact that two consecutive models may differ in the order and signs of similarly-indexed ICs. As well, the structure of the extracted sources can change as a function of the number of factors calculated. Two methods for determining the optimal number of ICs are proposed in this article and applied to simulated and real datasets to demonstrate their performance.

On-board and Ground Visual Pose Estimation Techniques for UAV Control

In this paper, two techniques to control UAVs (Unmanned Aerial Vehicles), based on visual information are presented. The first one is based on the detection and tracking of planar structures from an on-board camera, while the second one is based on the detection and 3D reconstruction of the position of the UAV based on an external camera system. Both strategies are tested with a VTOL (Vertical take-off and landing) UAV, and results show good behavior of the visual systems (precision in the estimation and frame rate) when estimating the helicopter¿s position and using the extracted information to control the UAV.

Automatic lateral control for unmanned vehicles via genetic algorithms

It is known that the techniques under the topic of Soft Computing have a strong capability of learning and cognition, as well as a good tolerance to uncertainty and imprecision. Due to these properties they can be applied successfully to Intelligent Vehicle Systems; ITS is a broad range of technologies and techniques that hold answers to many transportation problems. The unmannedcontrol of the steering wheel of a vehicle is one of the most important challenges facing researchers in this area. This paper presents a method to adjust automatically a fuzzy controller to manage the steering wheel of a mass-produced vehicle; to reach it, information about the car state while a human driver is handling the car is taken and used to adjust, via iterative geneticalgorithms an appropriated fuzzy controller. To evaluate the obtained controllers, it will be considered the performance obtained in the track following task, as well as the smoothness of the driving carried out.