Damping models in the truncated derivative nonlinear Schrödinger equation

Four-dimensional flow in the phase space of three amplitudes of circularly polarized Alfven waves and one relative phase, resulting from a resonant three-wave truncation of the derivative nonlinear Schrödinger equation, has been analyzed; wave 1 is linearly unstable with growth rate , and waves 2 and 3 are stable with damping 2 and 3, respectively. The dependence of gross dynamical features on the damping model as characterized by the relation between damping and wave-vector ratios, 2 /3, k2 /k3, and the polarization of the waves, is discussed; two damping models, Landau k and resistive k2, are studied in depth. Very complex dynamics, such as multiple blue sky catastrophes and chaotic attractors arising from Feigenbaum sequences, and explosive bifurcations involving Intermittency-I chaos, are shown to be associated with the existence and loss of stability of certain fixed point P of the flow. Independently of the damping model, P may only exist as against flow contraction just requiring.In the case of right-hand RH polarization, point P may exist for all models other than Landau damping; for the resistive model, P may exist for RH polarization only if 2+3/2.

Reduced three-wave model to study the hard transition to chaotic dynamics in Alfven wave-fronts

The derivative nonlinear Schrödinger (DNLS) equation, describing propagation of circularly polarized Alfven waves of finite amplitude in a cold plasma, is truncated to explore the coherent, weakly nonlinear, cubic coupling of three waves near resonance, one wave being linearly unstable and the other waves damped. In a reduced three-wave model (equal damping of daughter waves, three-dimensional flow for two wave amplitudes and one relative phase), no matter how small the growth rate of the unstable wave there exists a parametric domain with the flow exhibiting chaotic dynamics that is absent for zero growth-rate. This hard transition in phase-space behavior occurs for left-hand (LH) polarized waves, paralelling the known fact that only LH time-harmonic solutions of the DNLS equation are modulationally unstable.

Fully 3-wave model to study the hard transition to chaotic dynamics in alfven wave-fronts

The derivative nonlinear Schrödinger (DNLS) equation, describing propagation of circularly polarized Alfven waves of finite amplitude in a cold plasma, is truncated to explore the coherent, weakly nonlinear coupling of three waves near resonance, one wave being linearly unstable and the other waves damped. No matter how small the growth rate of the unstable wave, the four-dimensional flow for the three wave amplitudes and a relative phase, with both resistive damping and linear Landau damping, exhibits chaotic relaxation oscillations that are absent for zero growth-rate. This hard transition in phase-space behavior occurs for left-hand (LH) polarized waves, paralleling the known fact that only LH time-harmonic solutions of the DNLS equation are modulationally unstable. The parameter domain developing chaos is much broader than the corresponding domain in a reduced 3-wave model that assumes equal dampings of the daughter waves

Multi-fluid Eulerian model of an electrospray in a host gas.

An Eulerian multifluid model is used to describe the evolution of an electrospray plume and the flow induced in the surrounding gas by the drag of the electrically charged spray droplets in the space between an injection electrode containing the electrospray source and a collector electrode. The spray is driven by the voltage applied between the two electrodes. Numerical computations and order-of-magnitude estimates for a quiescent gas show that the droplets begin to fly back toward the injection electrode at a certain critical value of the flux of droplets in the spray, which depends very much on the electrical conditions at the injection electrode. As the flux is increased toward its critical value, the electric field induced by the charge of the droplets partially balances the field due to the applied voltage in the vicinity of the injection electrode, leading to a spray that rapidly broadens at a distance from its origin of the order of the stopping distance at which the droplets lose their initial momentum and the effect of their inertia becomes negligible. The axial component of the electric field first changes sign in this region, causing the fly back. The flow induced in the gas significantly changes this picture in the conditions of typical experiments. A gas plume is induced by the drag of the droplets whose entrainment makes the radius of the spray away from the injection electrode smaller than in a quiescent gas, and convects the droplets across the region of negative axial electric field that appears around the origin of the spray when the flux of droplets is increased. This suppresses fly back and allows much higher fluxes to be reached than are possible in a quiescent gas. The limit of large droplet-to-gas mass ratio is discussed. Migration of satellite droplets to the shroud of the spray is reproduced by the Eulerian model, but this process is also affected by the motion of the gas. The gas flow preferentially pushes satellite droplets from the shroud to the core of the spray when the effect of the inertia of the droplets becomes negligible, and thus opposes the well-established electrostatic/inertial mechanism of segregation and may end up concentrating satellite droplets in an intermediate radial region of the spray.

Methodology for assessing regional economic impacts of charging HGVs in Spain: an integrated approach through a random utility based multiregional input-output and a road transportation network model

An integrated approach composed of a random utility-based multiregional input-output model and a road transport network model was developed for evaluating the application of a fee to heavy-goods vehicles (HGVs) in Spain. For this purpose, a distance-based charge scenario (in euros per vehicle kilometer) for HGVs was evaluated for a selected motorway network in Spain. Although the aim of this charging policy was to increase the efficiency of transport, the approach strongly identified direct and indirect impacts on the regional economy. Estimates of the magnitude and extent of indirect effects on aggregated macroeconomic indicators (employment and gross domestic product) are provided. The macroeconomic effects of the charging policy were found to be positive for some regions and negative for other regions.

Las Opciones Reales en los Expedientes de Regulación de Empleo

Las empresas en situación económica negativa, recurren en España a los Expedientes de Regulación de Empleo que es la figura legal que permite ajustar sus plantillas y cuya utilización se acrecienta en épocas de crisis. El objetivo de esta investigación se focaliza en la integración de la Teoría de Opciones Reales en los proyectos organizativos de recursos humanos, en particular en el estudio y aplicación de la opción de contracción y de la opción de aplazamiento a los proyectos de desarrollo de los Expedientes de Regulación de Empleo. Las opciones reales son una herramienta de gestión, novedosa y contrastada, que posibilita realizar la valoración de los Expedientes de Regulación de Empleo tomando en consideración las incertidumbres futuras, lo que permite cuantificar mejor el resultado de la decisión y supone un avance sobre la valoración realizada de forma estática. Dos aspectos clave ha sido necesario resolver. En primer lugar determinar la fuente de incertidumbre que ponga en valor las opciones reales para este tipo de proyectos y como consecuencia desarrollar los procedimientos para obtener el valor de la opción. La puesta en valor de la opción de contracción permite, a partir de la consideración de la demanda como factor de incertidumbre, desarrollar un modelo que proporciona el valor óptimo del número de contratos de trabajo a extinguir, de modo que sitúa a la organización en la mejor posición para la toma de decisiones. La resolución del modelo se logra con la ayuda de la herramienta “The Newsvendor Model”, que facilita la obtención el valor óptimo. En la aplicación de la opción de aplazamiento se ha concluido asimismo, que la volatilidad de la demanda es la fuente de incertidumbre que hace viable la opción y a partir de dicha incertidumbre se ha desarrollado un procedimiento basado en el árbol binomial que permite obtener su valor. Una vez desarrollados los dos modelos para las opciones de contracción y aplazamiento, se ha elaborado un modelo conjunto con ambas opciones, integrando los resultados obtenidos en cada caso. Para validar los modelos obtenidos se presenta su aplicación al caso real de una empresa en situación económica negativa que requiere la necesidad de llevar a cabo un Expediente de Regulación de Empleo, lo que ha permitido comprobar la utilidad de dichos desarrollos, al obtener resultados que facilitan la toma de decisiones y que presentan soluciones que pueden ser más equilibradas para los trabajadores de la empresa, aspecto clave a tener en cuenta, dado el coste personal, familiar y social de este tipo de proyectos. La integración de las opciones reales en la gestión de recursos humanos tiene un amplio campo de aplicación, dadas las diferentes inversiones que se pueden llevar a cabo sobre el capital humano. Aunque esta investigación se ha focalizado en la opcionalidad de las inversiones para el ajuste de plantilla, existen otro tipo de inversiones en recursos humanos, como son las dedicadas a formación, motivación, adecuación o incorporación de personal, que también estarán sujetas a opcionalidad si existen incertidumbres a futuro. Con el objetivo de avanzar en el estudio y aplicación de las opciones reales a estas inversiones, se presenta un marco conceptual que identifica las bases de partida en lo referente a los retornos de las inversiones y las incertidumbres futuras. Con los resultados obtenidos en esta investigación se entiende que se ha conseguido el objetivo de aplicar la Teoría de Opciones Reales a los Expedientes de Regulación de Empleo y con ello establecer la posibilidad de mejorar las implicaciones sociales de estos proyectos dentro de la empresa y en la sociedad. ABSTRACT During crisis times, like the one Spain has been going through on the last years, the Collective Dismissal Procedure is an important issue to be considered within companies that are having a negative economic situation. This research focuses on the integration of the Real Options Theory for organizational projects in the management of human resources, and particularly the study and inclusion of the option to contract and the deferral option in Collective Dismissal Procedures. The Real Options Theory, an innovative management tool that has been proven as correct, help to improve the assessment of the Collective Dismissal Procedures using the dynamic demand instead of the static demand, giving a better quantification of the decision that is going to be taken. Two main issues which are hoped to be resolve are examined: the search for a source of uncertainty to make the real options viable for this type of projects, and consequently the development of a procedure to obtain the value of the option. The option to contract allows, from the consideration of the demand as a factor of uncertainty, to develop a model obtaining the optimal value in the reduction of the workforce, therefore allowing the organization to place itself in the best position for the decision making. The resolution of this model is achieved with the help of "The Newsvendor Model" tool, which facilitates obtaining the optimal value. The analysis performed in the deferral option also concluded that the volatility of demand is the source of the uncertainty that makes the option viable and the procedure developed by the binomial tree is the tool that enables the value of the option to be found. Once developed two models for contraction and deferment options, a joint model has been developed including both options by integrating the results obtained in each case. To validate the models, the real case of a company in negative economic situation requiring the need to carry out a procedure for collective redundancies is applied. This has demonstrated the usefulness of this kind of development that can deliver results to improve the decision making and provide more balanced solutions for company employees, key consideration given the impact on personal, family life and social environment of these Collective Dismissal Procedures. The integration of real options in the management of human resources has broad scope, given the different investments that can be performed on the human capital. Although this research has focused on the optionality of investments for downsizing, there are other investments in human resources for training, motivation, arrangement or incorporation of staff that are also subject to optionality if there are future uncertainties. With the aim of advancing the study and application of real options to these investments, a conceptual framework is presented that identifies the basis of research in terms of the investment returns and future uncertainties. With the results obtained on this research it is clearly defined the objectives for which this work was started for, the application of the Real Options Theory to the Collective Dismissal Procedure. And thereby achieve the final goal of improving the social impact of these projects within a company and society.

Estudio del rendimiento bajo presión en los tiros libres en baloncesto, y su influencia sobre el porcentaje de acierto durante el último minuto de juego

El minuto final de un partido ajustado de baloncesto es un momento crítico que está sujeto a multitud de factores que influyen en su desarrollo. Así, el porcentaje de acierto en los tiros libres durante ese periodo de tiempo va a determinar, en muchas ocasiones, el resultado final del partido. La disminución de rendimiento (drop) en esta faceta de juego en condiciones de presión, puede estar relacionada con múltiples variables propias del contexto deportivo estudiado, como por ejemplo: los segundos restantes de posesión, la situación en el marcador (ir ganando, empatando o perdiendo), la localización del partido (jugar en casa o fuera), la fase de competición (fase regular o eliminatorias) o el nivel del equipo (mejores/peores equipos). Además, las características del jugador que realiza los lanzamientos tienen una gran importancia respecto a su edad y años de experiencia para afrontar los momentos críticos, así como el puesto de juego que ocupa en el equipo. En este sentido, la combinación de factores del contexto y del jugador, permiten interactuar en el rendimiento del lanzador en los momentos finales de partido durante sus lanzamientos de tiro libre. El presente trabajo de tesis doctoral tiene como objetivo encontrar aquellas variables más relacionadas con la disminución de rendimiento del jugador en los tiros libres durante el último minuto de juego, y la última serie de tiros libres en los partidos ajustados de baloncesto. Para alcanzar el objetivo del estudio se analizaron 124 partidos ajustados (diferencias iguales o inferiores a 2 puntos) de todas las competiciones (fase regular, playoff y copa del Rey) de la liga ACB durante las temporadas 2011-2012 a 2014-2015. Para el registro de variables se analizó el porcentaje de acierto en los tiros libres del lanzador en la liga regular, partido completo, último minuto y última serie. De este modo se trató de analizar qué variables del contexto y del jugador permitían explicar el rendimiento en los tiros libres durante el último minuto, y la última serie de tiros libres del partido. Por otro lado, se trató de conocer el grado de asociación entre el descenso del rendimiento (drop) en los momentos finales de partido, y las variables estudiadas del jugador: puesto de juego, edad, y años de experiencia profesional; mientras que las variables situacionales consideradas fueron: fase de competición, localización, clasificación, tiempo restante, y diferencia parcial en el marcador. Para el análisis de los datos se realizaron dos modelos estadísticos: 1º) un modelo de regresión lineal múltiple para conocer el efecto de las variables independientes en el porcentaje de aciertos del lanzador en el último minuto, y en la última serie de tiros libres del partido; y 2º) un análisis de regresión logística binomial para analizar la relación existente entre la probabilidad de tener un drop (disminución del rendimiento) y las características del lanzador, y las variables situacionales. Los resultados del modelo de regresión lineal múltiple mostraron efectos negativos significativos en el porcentaje de acierto en los tiros libres durante el último minuto, cuando los lanzadores son los pívots (-19,45%). Por otro lado, los resultados durante la última serie mostraron el efecto negativo significativo sobre la posición de pívot (- 19,30%) y la diferencia parcial en el marcador (-3,33%, para cada punto de diferencia en el marcador) en el porcentaje de acierto en los tiros libres. Las variables independientes edad, experiencia profesional, clasificación en la liga regular, fase de competición, localización, y tiempo restante, no revelaron efectos significativos en los modelos de regresión lineal. Los resultados de la regresión logística binomial revelaron que las variables experiencia profesional entre 13 y 18 años (OR = 4,63), jugar de alero (OR = 23,01), y jugar de base (OR = 10,68) están relacionadas con una baja probabilidad de disminuir el rendimiento durante el último minuto del partido; mientras que ir ganando, aumenta esta probabilidad (OR = 0,06). Además, los resultados de la última serie mostraron una menor disminución del rendimiento del jugador cuando tiene entre 13 y 18 años de experiencia (OR = 4,28), y juega de alero (OR = 8,06) o base (OR = 6,34). Por el contrario, las variables situacionales relacionadas con esa disminución del rendimiento del jugador son las fases eliminatorias (OR = 0,22) e ir ganando (OR = 0,04). Los resultados principales del estudio mostraron que existe una disminución del rendimiento del jugador en su porcentaje de acierto en los tiros libres durante el último minuto y en la última serie de lanzamientos del partido, y que está relacionada significativamente con la edad, experiencia profesional, puesto de juego del jugador, y diferencia parcial en el marcador. Encontrando relación también con la fase de competición, durante la última serie de tiros libres del partido. Esta información supone una valiosa información para el entrenador, y su aplicación en el ámbito competitivo real. En este sentido, la creación de simulaciones en el apartado de aplicaciones prácticas, permite predecir el porcentaje de acierto en los tiros libres de un jugador durante los momentos de mayor presión del partido, en base a su perfil de rendimiento. Lo que puede servir para realizar una toma de decisiones más idónea, con el objetivo de lograr el mejor resultado. Del mismo modo, orienta el tipo de proceso de entrenamiento que se ha de seguir, en relación a los jugadores más tendentes al drop, con el objetivo de minimizar el efecto de la presión sobre su capacidad para rendir adecuadamente en la ejecución de los tiros libres, y lograr de esta manera un rendimiento más homogéneo en todos los jugadores del equipo en esta faceta del juego, durante el momento crítico del final de partido. ABSTRACT. The final minute of a close game in basketball is a critical moment which is subject to many factors that influence its development. Thus, the success rate in free-throws during that period will determine, in many cases, the outcome of the game. Decrease of performance (drop) in this facet of play under pressure conditions, may be related to studied own multiple sports context variables, such as the remaining seconds of possession, the situation in the score (to be winning, drawing, or losing) the location of the match (playing at home or away), the competition phase (regular season or playoffs) or team level (best/worst teams). In addition, the characteristics of the player are very important related to his age and years of experience to face the critical moments, as well as his playing position into team. In this sense, the combination of factors in context and player, allows interact about performance of shooter in the final moments of the game during his free-throw shooting. The aim of this present doctoral thesis was find the most related variables to player´s drop in free throws in the last minute of the game and the last row of free-throws in closed games of basketball. To achieve the objective of the study, 124 closed games (less or equal than 2 points difference) were analyzed in every copetition in ACB league (regular season, playoff and cup) from 2011-2012 to 2014-2015 seasons. To record the variables, the percentage of success of the shooter in regular season, full game, last minute, and last row were analyzed. This way, it is tried to analyze which player and context variables explain the free-throw performance in last minute and last row of the game. On the other hand, it is tried to determine the degree of association between decrease of performance (drop) of the player in the final moments, and studied player variables: playing position, age, and years of professional experience; while considered situational variables considered were: competition phase, location, classification, remaining time, and score-line. For data analysis were performed two statistical models: 1) A multiple linear regression model to determine the effect of the independent variables in the succsess percentage of shooter at the last minute, and in the last row of free-throws in the game; and 2) A binomial logistic regression analysis to analyze the relationship between the probability of a drop (lower performance) and the characteristics of the shooter and situational variables. The results of multiple linear regression model showed significant negative effects on the free-throw percentage during last minute, when shooters are centers (-19.45%). On the other hand, results in the last series showed the significant negative effect on the center position (-19.30%) and score-line (-3.33% for each point difference in the score) in the free-throw percentage. The independent variables age, professional experience, ranking in the regular season, competition phase, location, and remaining time, revealed no significant effects on linear regression models. The results of the binomial logistic regression showed that the variables professional experience between 13 and 18 years (OR = 4.63), playing forward (OR = 23.01) and playing guard (OR = 10.68) are related to reduce the probability to decrease the performance during the last minute of the game. While wining, increases it (OR = 0.06). Furthermore, the results of the last row showed a reduction in performance degradation when player is between 13 and 18 years of experience (OR = 4.28), and playing forward (OR = 8.06) or guard (OR = 6.34). By contrast, the variables related to the decrease in performance of the player are the knockout phases (OR = 0.22) and wining (OR = 0.04). The main results of the study showed that there is a decrease in performance of the player in the percentage of success in free-throws in the last minute and last row of the game, and it is significantly associated with age, professional experience, and player position. Finding relationship with the competition phase, during last row of free-throws of the game too. This information is a valuable information for the coach, for applying in real competitive environment. In this sense, create simulations in the section of practical applications allows to predict the success rate of free-throw of a player during the most pressing moments of the game, based on their performance profile. What can be used to take more appropriate decisions in order to achieve the best result. Similarly, guides the type of training process must be followed in relation to the most favorable players to drop, in order to minimize the effect of pressure on their ability to perform properly in the execution of the free-throws. And to achieve, in this way, a more consistent performance in all team players in this facet of the game, during the critical moment in the final of the game.

Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog

Phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.

Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: No accentuation by apolipoprotein(a)

We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [LDLR−/−] and express a human apolipoprotein B-100 (apoB) transgene [Tg(apoB+/+)] with or without an apo(a) transgene [Tg(apoa+/−)]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (i) LDLR−/−, (ii) LDLR−/−;Tg(apoa+/−), (iii) LDLR−/−;Tg(apoB+/+), and (iv)LDLR−/−;Tg(apoB+/+);Tg(apo+/−). The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the LDLR−/− and LDLR−/−;Tg(apoa+/−) mice (1.0 ± 0.2% vs. 1.4 ± 0.3%). However, the LDLR−/−;Tg(apoB+/+) mice had ≈15-fold greater mean lesion area than the LDLR−/− mice. No significant difference was found in percent lesion area in the LDLR−/−;Tg(apoB+/+) mice whether or not they expressed apo(a) [18.5 ± 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 ± 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of LDLR−/−;Tg(apoB+/+) mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that LDLR−/−; Tg(apoB+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.

A variant of DNA polymerase β acts as a dominant negative mutant

In eukaryotic cells, DNA polymerase β (polβ) carries out base-excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. A specific deletion in one allele in the coding sequence of the polβ gene occurs in colorectal and breast carcinomas. The 87-bp deleted region encodes amino acid residues 208–236 in the catalytic domain of the enzyme. Here, we report evidence for expression of the wild-type (WT) and the truncated polβ proteins in colorectal tumors. To elucidate the potential functional consequences of polβ truncation, stable HeLa cell lines were established from cloned WT and variant polβΔ208–236. Cells expressing the variant protein exhibited substantially decreased BER activity. To test our hypothesis that truncated polβ may disrupt the function of the WT enzyme, we stably transfected mouse embryonic fibroblast 16.3 cells with polβΔ208–236 cDNA. Reverse transcription–PCR and Western blot analyses showed that the new cell line, 16.3ΔP, expresses the WT and the truncated polβ mRNA and proteins. BER and binding activities were undetectable in these cells. Furthermore, in vivo the 16.3ΔP cells were more sensitive to N-methyl-N′-nitro-N-nitrosoguanidine than the 16.3 cells. On adding increasing amounts of 16.3ΔP protein extracts, the BER and DNA binding activities of extracts of the parent 16.3 cell line progressively declined. These results strongly suggest that truncated polβ acts as a dominant negative mutant. The defective polβ may facilitate accumulation of mutations, leading to the expression of a mutator phenotype in tumor cells.

Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation

The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-Å resolution. The crystals comprise residues 44–243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic α-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 × 80 × 40 Å. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein.

Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons

We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using adenovirus-mediated gene transfer. A recombinant virus directed the expression of both a GFP reporter protein and TrkB.T1, a C-terminal truncated dominant negative TrkB neurotrophin receptor. When expressed in the presynaptic cell at synapses between embryonic hippocampal neurons in culture, the dominant negative TrkB.T1 inhibited two forms of synaptic potentiation induced by the neurotrophin brain-derived neurotrophic factor (BDNF): (i) greater evoked synaptic transmission and (ii) higher frequency of spontaneous miniature synaptic currents. These inhibition effects are not seen if the transgene is expressed only in the postsynaptic cell. We conclude that BDNF-TrkB signal transduction in the presynaptic terminal leads to both types of potentiation and is therefore the primary cause of synaptic enhancement by BDNF in these neurons.

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0–12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12–24 hr, P implant removed; 24–36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3α-hydroxy-5α-pregnan-20-one, which operates through the type A γ-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.

A model for amplification of hair-bundle motion by cyclical binding of Ca2+ to mechanoelectrical-transduction channels

Amplification of auditory stimuli by hair cells augments the sensitivity of the vertebrate inner ear. Cell-body contractions of outer hair cells are thought to mediate amplification in the mammalian cochlea. In vertebrates that lack these cells, and perhaps in mammals as well, active movements of hair bundles may underlie amplification. We have evaluated a mathematical model in which amplification stems from the activity of mechanoelectrical-transduction channels. The intracellular binding of Ca2+ to channels is posited to promote their closure, which increases the tension in gating springs and exerts a negative force on the hair bundle. By enhancing bundle motion, this force partially compensates for viscous damping by cochlear fluids. Linear stability analysis of a six-state kinetic model reveals Hopf bifurcations for parameter values in the physiological range. These bifurcations signal conditions under which the system’s behavior changes from a damped oscillatory response to spontaneous limit-cycle oscillation. By varying the number of stereocilia in a bundle and the rate constant for Ca2+ binding, we calculate bifurcation frequencies spanning the observed range of auditory sensitivity for a representative receptor organ, the chicken’s cochlea. Simulations using prebifurcation parameter values demonstrate frequency-selective amplification with a striking compressive nonlinearity. Because transduction channels occur universally in hair cells, this active-channel model describes a mechanism of auditory amplification potentially applicable across species and hair-cell types.

Acyl-homoserine lactone quorum sensing in Gram-negative bacteria: A signaling mechanism involved in associations with higher organisms

Recent advances in studies of bacterial gene expression have brought the realization that cell-to-cell communication and community behavior are critical for successful interactions with higher organisms. Species-specific cell-to-cell communication is involved in successful pathogenic or symbiotic interactions of a variety of bacteria with plant and animal hosts. One type of cell–cell signaling is acyl-homoserine lactone quorum sensing in Gram-negative bacteria. This type of quorum sensing represents a dedicated communication system that enables a given species to sense when it has reached a critical population density in a host, and to respond by activating expression of genes necessary for continued success in the host. Acyl-homoserine lactone signaling in the opportunistic animal and plant pathogen Pseudomonas aeruginosa is a model for the relationships among quorum sensing, pathogenesis, and community behavior. In the P. aeruginosa model, quorum sensing is required for normal biofilm maturation and for virulence. There are multiple quorum-sensing circuits that control the expression of dozens of specific genes that represent potential virulence loci.