TGF-beta1 in Aplysia: role in long-term changes in the excitability of sensory neurons and distribution of TbetaR-II-like immunoreactivity.

Exogenous recombinant human transforming growth factor beta-1 (TGF-beta1) induced long-term facilitation of Aplysia sensory-motor synapses. In addition, 5-HT-induced facilitation was blocked by application of a soluble fragment of the extracellular portion of the TGF-beta1 type II receptor (TbetaR-II), which presumably acted by scavenging an endogenous TGF-beta1-like molecule. Because TbetaR-II is essential for transmembrane signaling by TGF-beta, we sought to determine whether Aplysia tissues contained TbetaR-II and specifically, whether neurons expressed the receptor. Western blot analysis of Aplysia tissue extracts demonstrated the presence of a TbetaR-II-immunoreactive protein in several tissue types. The expression and distribution of TbetaR-II-immunoreactive proteins in the central nervous system was examined by immunohistochemistry to elucidate sites that may be responsive to TGF-beta1 and thus may play a role in synaptic plasticity. Sensory neurons in the ventral-caudal cluster of the pleural ganglion were immunoreactive for TbetaR-II, as well as many neurons in the pedal, abdominal, buccal, and cerebral ganglia. Sensory neurons cultured in isolation and cocultured sensory and motor neurons were also immunoreactive. TGF-beta1 affected the biophysical properties of cultured sensory neurons, inducing an increase of excitability that persisted for at least 48 hr. Furthermore, exposure to TGF-beta1 resulted in a reduction in the firing threshold of sensory neurons. These results provide further support for the hypothesis that TGF-beta1 plays a role in long-term synaptic plasticity in Aplysia.

Apoptosis of hippocampal neurons in organotypic slice culture models: direct effect of bacteria revisited

Neurons of the hippocampal dentate gyrus selectively undergo programmed cell death in patients suffering from bacterial meningitis and in experimental models of pneumococcal meningitis in infant rats. In the present study, a membrane-based organotypic slice culture system of rat hippocampus was used to test whether this selective vulnerability of neurons of the dentate gyrus could be reproduced in vitro. Apoptosis was assessed by nuclear morphology (condensed and fragmented nuclei), by immunochemistry for active caspase-3 and deltaC-APP, and by proteolytic caspase-3 activity. Co-incubation of the cultures with live pneumococci did not induce neuronal apoptosis unless cultures were kept in partially nutrient-deprived medium. Complete nutrient deprivation alone and staurosporine independently induced significant apoptosis, the latter in a dose-response way. In all experimental settings, apoptosis occurred preferentially in the dentate gyrus. Our data demonstrate that factors released by pneumococci per se failed to induce significant apoptosis in vitro. Thus, these factors appear to contribute to a multifactorial pathway, which ultimately leads to neuronal apoptosis in bacterial meningitis.

The influence of formal and informal sales controls on customer-directed selling behaviors and sales unit effectiveness

Adaptive selling (AS) and customer-oriented selling (COS) constitute two key customer-directed selling behaviors for the success of the modern sales force. However, knowledge regarding the organizational factors that can induce salespeople to engage in those behaviors is strikingly limited. Against this background, we develop a comprehensive model that delineates the influences of formal and informal sales controls on AS and COS and, through them, on sales unit effectiveness. Based on a sample of sales managers in a major European Union country, we present new evidence that (a) formal and informal sales controls exert differential impact on salespeople's AS and COS behaviors; (b) AS directly and positively influences sales unit effectiveness; (c) COS affects sales unit effectiveness only indirectly, i.e. by fostering AS; and (d) outcome and cultural controls directly improve sales unit effectiveness. We conclude with a discussion of our findings for academics and practitioners.

The Emergence of Formal Control Specificity in Information Systems Outsourcing: A Process-View

Information systems (IS) outsourcing projects often fail to achieve initial goals. To avoid project failure, managers need to design formal controls that meet the specific contextual demands of the project. However, the dynamic and uncertain nature of IS outsourcing projects makes it difficult to design such specific formal controls at the outset of a project. It is hence crucial to translate high-level project goals into specific formal controls during the course of a project. This study seeks to understand the underlying patterns of such translation processes. Based on a comparative case study of four outsourced software development projects, we inductively develop a process model that consists of three unique patterns. The process model shows that the performance implications of emergent controls with higher specificity depend on differences in the translation process. Specific formal controls have positive implications for goal achievement if only the stakeholder context is adapted, while they are negative for goal achievement if in the translation process tasks are unintendedly adapted. In the latter case projects incrementally drift away from their initial direction. Our findings help to better understand control dynamics in IS outsourcing projects. We contribute to a process theoretic understanding of IS outsourcing governance and we derive implications for control theory and the IS project escalation literature.

Artificial Neural Nets with Interaction of Afferents

The aim is to obtain computationally more powerful, neuro physiologically founded, artificial neurons and neural nets. Artificial Neural Nets (ANN) of the Perceptron type evolved from the original proposal by McCulloch an Pitts classical paper [1]. Essentially, they keep the computing structure of a linear machine followed by a non linear operation. The McCulloch-Pitts formal neuron (which was never considered by the author’s to be models of real neurons) consists of the simplest case of a linear computation of the inputs followed by a threshold. Networks of one layer cannot compute anylogical function of the inputs, but only those which are linearly separable. Thus, the simple exclusive OR (contrast detector) function of two inputs requires two layers of formal neurons

Towards a concurrent semantics-based analysis of CC and CLP. principles and practice of constraint programming

Abstract is not available.

Multiple attractors, long chaotic transients, and failure in small-world networks of excitable neurons.

We study the dynamical states of a small-world network of recurrently coupled excitable neurons, through both numerical and analytical methods. The dynamics of this system depend mostly on both the number of long-range connections or ?shortcuts?, and the delay associated with neuronal interactions. We find that persistent activity emerges at low density of shortcuts, and that the system undergoes a transition to failure as their density reaches a critical value. The state of persistent activity below this transition consists of multiple stable periodic attractors, whose number increases at least as fast as the number of neurons in the network. At large shortcut density and for long enough delays the network dynamics exhibit exceedingly long chaotic transients, whose failure times follow a stretched exponential distribution. We show that this functional form arises for the ensemble-averaged activity if the failure time for each individual network realization is exponen- tially distributed

Applications of Formal Languages to Management of Manned and Unmanned Aircraft

En el futuro, la gestión del tráfico aéreo (ATM, del inglés air traffic management) requerirá un cambio de paradigma, de la gestión principalmente táctica de hoy, a las denominadas operaciones basadas en trayectoria. Un incremento en el nivel de automatización liberará al personal de ATM —controladores, tripulación, etc.— de muchas de las tareas que realizan hoy. Las personas seguirán siendo el elemento central en la gestión del tráfico aéreo del futuro, pero lo serán mediante la gestión y toma de decisiones. Se espera que estas dos mejoras traigan un incremento en la eficiencia de la gestión del tráfico aéreo que permita hacer frente al incremento previsto en la demanda de transporte aéreo. Para aplicar el concepto de operaciones basadas en trayectoria, el usuario del espacio aéreo (la aerolínea, piloto, u operador) y el proveedor del servicio de navegación aérea deben negociar las trayectorias mediante un proceso de toma de decisiones colaborativo. En esta negociación, es necesaria una forma adecuada de compartir dichas trayectorias. Compartir la trayectoria completa requeriría un gran ancho de banda, y la trayectoria compartida podría invalidarse si cambiase la predicción meteorológica. En su lugar, podría compartirse una descripción de la trayectoria independiente de las condiciones meteorológicas, de manera que la trayectoria real se pudiese calcular a partir de dicha descripción. Esta descripción de la trayectoria debería ser fácil de procesar usando un programa de ordenador —ya que parte del proceso de toma de decisiones estará automatizado—, pero también fácil de entender para un operador humano —que será el que supervise el proceso y tome las decisiones oportunas—. Esta tesis presenta una serie de lenguajes formales que pueden usarse para este propósito. Estos lenguajes proporcionan los medios para describir trayectorias de aviones durante todas las fases de vuelo, desde la maniobra de push-back (remolcado hasta la calle de rodaje), hasta la llegada a la terminal del aeropuerto de destino. También permiten describir trayectorias tanto de aeronaves tripuladas como no tripuladas, incluyendo aviones de ala fija y cuadricópteros. Algunos de estos lenguajes están estrechamente relacionados entre sí, y organizados en una jerarquía. Uno de los lenguajes fundamentales de esta jerarquía, llamado aircraft intent description language (AIDL), ya había sido desarrollado con anterioridad a esta tesis. Este lenguaje fue derivado de las ecuaciones del movimiento de los aviones de ala fija, y puede utilizarse para describir sin ambigüedad trayectorias de este tipo de aeronaves. Una variante de este lenguaje, denominada quadrotor AIDL (QR-AIDL), ha sido desarrollada en esta tesis para permitir describir trayectorias de cuadricópteros con el mismo nivel de detalle. Seguidamente, otro lenguaje, denominado intent composite description language (ICDL), se apoya en los dos lenguajes anteriores, ofreciendo más flexibilidad para describir algunas partes de la trayectoria y dejar otras sin especificar. El ICDL se usa para proporcionar descripciones genéricas de maniobras comunes, que después se particularizan y combinan para formar descripciones complejas de un vuelo. Otro lenguaje puede construirse a partir del ICDL, denominado flight intent description language (FIDL). El FIDL especifica requisitos de alto nivel sobre las trayectorias —incluyendo restricciones y objetivos—, pero puede utilizar características del ICDL para proporcionar niveles de detalle arbitrarios en las distintas partes de un vuelo. Tanto el ICDL como el FIDL han sido desarrollados en colaboración con Boeing Research & Technology Europe (BR&TE). También se ha desarrollado un lenguaje para definir misiones en las que interactúan varias aeronaves, el mission intent description language (MIDL). Este lenguaje se basa en el FIDL y mantiene todo su poder expresivo, a la vez que proporciona nuevas semánticas para describir tareas, restricciones y objetivos relacionados con la misión. En ATM, los movimientos de un avión en la superficie de aeropuerto también tienen que ser monitorizados y gestionados. Otro lenguaje formal ha sido diseñado con este propósito, llamado surface movement description language (SMDL). Este lenguaje no pertenece a la jerarquía de lenguajes descrita en el párrafo anterior, y se basa en las clearances (autorizaciones del controlador) utilizadas durante las operaciones en superficie de aeropuerto. También proporciona medios para expresar incertidumbre y posibilidad de cambios en las distintas partes de la trayectoria. Finalmente, esta tesis explora las aplicaciones de estos lenguajes a la predicción de trayectorias y a la planificación de misiones. El concepto de trajectory language processing engine (TLPE) se usa en ambas aplicaciones. Un TLPE es una función de ATM cuya principal entrada y salida se expresan en cualquiera de los lenguajes incluidos en la jerarquía descrita en esta tesis. El proceso de predicción de trayectorias puede definirse como una combinación de TLPEs, cada uno de los cuales realiza una pequeña sub-tarea. Se le ha dado especial importancia a uno de estos TLPEs, que se encarga de generar el perfil horizontal, vertical y de configuración de la trayectoria. En particular, esta tesis presenta un método novedoso para la generación del perfil vertical. El proceso de planificar una misión también se puede ver como un TLPE donde la entrada se expresa en MIDL y la salida consiste en cierto número de trayectorias —una por cada aeronave disponible— descritas utilizando FIDL. Se ha formulado este problema utilizando programación entera mixta. Además, dado que encontrar caminos óptimos entre distintos puntos es un problema fundamental en la planificación de misiones, también se propone un algoritmo de búsqueda de caminos. Este algoritmo permite calcular rápidamente caminos cuasi-óptimos que esquivan todos los obstáculos en un entorno urbano. Los diferentes lenguajes formales definidos en esta tesis pueden utilizarse como una especificación estándar para la difusión de información entre distintos actores de la gestión del tráfico aéreo. En conjunto, estos lenguajes permiten describir trayectorias con el nivel de detalle necesario en cada aplicación, y se pueden utilizar para aumentar el nivel de automatización explotando esta información utilizando sistemas de soporte a la toma de decisiones. La aplicación de estos lenguajes a algunas funciones básicas de estos sistemas, como la predicción de trayectorias, han sido analizadas. ABSTRACT Future air traffic management (ATM) will require a paradigm shift from today’s mainly tactical ATM to trajectory-based operations (TBOs). An increase in the level of automation will also relieve humans —air traffic control officers (ATCOs), flight crew, etc.— from many of the tasks they perform today. Humans will still be central in this future ATM, as decision-makers and managers. These two improvements (TBOs and increased automation) are expected to provide the increase in ATM performance that will allow coping with the expected increase in air transport demand. Under TBOs, trajectories are negotiated between the airspace user (an airline, pilot, or operator) and the air navigation service provider (ANSP) using a collaborative decision making (CDM) process. A suitable method for sharing aircraft trajectories is necessary for this negotiation. Sharing a whole trajectory would require a high amount of bandwidth, and the shared trajectory might become invalid if the weather forecast changed. Instead, a description of the trajectory, decoupled from the weather conditions, could be shared, so that the actual trajectory could be computed from this trajectory description. This trajectory description should be easy to process using a computing program —as some of the CDM processes will be automated— but also easy to understand for a human operator —who will be supervising the process and making decisions. This thesis presents a series of formal languages that can be used for this purpose. These languages provide the means to describe aircraft trajectories during all phases of flight, from push back to arrival at the gate. They can also describe trajectories of both manned and unmanned aircraft, including fixedwing and some rotary-wing aircraft (quadrotors). Some of these languages are tightly interrelated and organized in a language hierarchy. One of the key languages in this hierarchy, the aircraft intent description language (AIDL), had already been developed prior to this thesis. This language was derived from the equations of motion of fixed-wing aircraft, and can provide an unambiguous description of fixed-wing aircraft trajectories. A variant of this language, the quadrotor AIDL (QR-AIDL), is developed in this thesis to allow describing a quadrotor aircraft trajectory with the same level of detail. Then, the intent composite description language (ICDL) is built on top of these two languages, providing more flexibility to describe some parts of the trajectory while leaving others unspecified. The ICDL is used to provide generic descriptions of common aircraft manoeuvres, which can be particularized and combined to form complex descriptions of flight. Another language is built on top of the ICDL, the flight intent description language (FIDL). The FIDL specifies high-level requirements on trajectories —including constraints and objectives—, but can use features of the ICDL to provide arbitrary levels of detail in different parts of the flight. The ICDL and FIDL have been developed in collaboration with Boeing Research & Technology Europe (BR&TE). Also, the mission intent description language (MIDL) has been developed to allow describing missions involving multiple aircraft. This language is based on the FIDL and keeps all its expressive power, while it also provides new semantics for describing mission tasks, mission objectives, and constraints involving several aircraft. In ATM, the movement of aircraft while on the airport surface also has to be monitored and managed. Another formal language has been designed for this purpose, denoted surface movement description language (SMDL). This language does not belong to the language hierarchy described above, and it is based on the clearances used in airport surface operations. Means to express uncertainty and mutability of different parts of the trajectory are also provided. Finally, the applications of these languages to trajectory prediction and mission planning are explored in this thesis. The concept of trajectory language processing engine (TLPE) is used in these two applications. A TLPE is an ATM function whose main input and output are expressed in any of the languages in the hierarchy described in this thesis. A modular trajectory predictor is defined as a combination of multiple TLPEs, each of them performing a small subtask. Special attention is given to the TLPE that builds the horizontal, vertical, and configuration profiles of the trajectory. In particular, a novel method for the generation of the vertical profile is presented. The process of planning a mission can also be seen as a TLPE, where the main input is expressed in the MIDL and the output consists of a number of trajectory descriptions —one for each aircraft available in the mission— expressed in the FIDL. A mixed integer linear programming (MILP) formulation for the problem of assigning mission tasks to the available aircraft is provided. In addition, since finding optimal paths between locations is a key problem to mission planning, a novel path finding algorithm is presented. This algorithm can compute near-shortest paths avoiding all obstacles in an urban environment in very short times. The several formal languages described in this thesis can serve as a standard specification to share trajectory information among different actors in ATM. In combination, these languages can describe trajectories with the necessary level of detail for any application, and can be used to increase automation by exploiting this information using decision support tools (DSTs). Their applications to some basic functions of DSTs, such as trajectory prediction, have been analized.

Glial cell line-derived neurotrophic factor promotes the development of adrenergic neurons in mouse neural crest cultures

Growth of mouse neural crest cultures in the presence of glial cell line-derived neurotrophic factor (GDNF) resulted in a dramatic dose-dependent increase in the number of tyrosine hydroxylase (TH)-positive cells that developed when 5% chicken embryo extract was present in the medium. In contrast, growth in the presence of bone morphogenetic protein (BMP)-2, BMP-4, BMP-6, transforming growth factor (TGF) β1, TGF-β2, and TGF-β3 elicited no increase in the number of TH-positive cells. The TH-positive cells that developed in the presence of GDNF had neuronal morphology and contained the middle and low molecular weight neurofilament proteins. Numerous TH-negative cells with the morphology of neurons also were observed in GDNF-treated cultures. Analysis revealed that the period from 6 to 12 days in vitro was the critical time for exposure to GDNF to generate the increase in TH-positive cell number. The growth factors neurotrophin-3 and fibroblast growth factor-2 elicited increases in the number of TH-positive cells similar to that seen in response to GDNF. In contrast, nerve growth factor was unable to substitute for GDNF. These findings extend the previously reported biological activities of GDNF by showing that it can act on mouse neural crest cultures to promote the development of neurons.

Reelin controls position of autonomic neurons in the spinal cord

Mutation of the reeler gene (Reln) disrupts neuronal migration in several brain regions and gives rise to functional deficits such as ataxic gait and trembling in the reeler mutant mouse. Thus, the Reln product, reelin, is thought to control cell–cell interactions critical for cell positioning in the brain. Although an abundance of reelin transcript is found in the embryonic spinal cord [Ikeda, Y. & Terashima, T. (1997) Dev. Dyn. 210, 157–172; Schiffmann, S. N., Bernier, B. & Goffinet, A. M. (1997) Eur. J. Neurosci. 9, 1055–1071], it is generally thought that neuronal migration in the spinal cord is not affected by reelin. Here, however, we show that migration of sympathetic preganglionic neurons in the spinal cord is affected by reelin. This study thus indicates that reelin affects neuronal migration outside of the brain. Moreover, the relationship between reelin and migrating preganglionic neurons suggests that reelin acts as a barrier to neuronal migration.

Modifications of retinal neurons in a mouse model of retinitis pigmentosa

Animal models of retinitis pigmentosa include the rd mouse, in which a mutation of a rod-specific phosphodiesterase leads to the rapid loss of photoreceptors during the early postnatal life. Very little is known about changes occurring in inner retinal neurons after photoreceptor loss. These changes are important in view of the possibility of restoring vision in retinas with photoreceptor degeneration by means of cell transplantation or direct stimulation of inner layers. In this paper, we show that bipolar and horizontal cells of the rd mouse retina undergo dramatic morphological modifications accompanying photoreceptor loss, demonstrating a dependence of second order neurons on these cells. While describing modifications of the rd retina, we also provide quantitative information about neurons of the wild-type mouse retina, useful for future studies on genetically altered animals.