Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice.

Morphine induces antinociception by activating mu opioid receptors (muORs) in spinal and supraspinal regions of the CNS. (Beta)arrestin-2 (beta)arr2), a G-protein-coupled receptor-regulating protein, regulates the muOR in vivo. We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. To determine the general applicability of the (beta)arr2-muOR interaction in other neuronal systems, we have, in the present study, tested (beta)arr2 knock-out ((beta)arr2-KO) mice using the warm water tail-immersion paradigm, which primarily assesses spinal reflexes to painful thermal stimuli. In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Interestingly, however, after a delayed onset, they do ultimately develop morphine tolerance, although to a lesser degree than the wild-type (WT) controls. In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. These findings provide in vivo evidence that the muOR is differentially regulated in diverse regions of the CNS. Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent.

Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice.

The reinforcing and psychomotor effects of morphine involve opiate stimulation of the dopaminergic system via activation of mu-opioid receptors (muOR). Both mu-opioid and dopamine receptors are members of the G-protein-coupled receptor (GPCR) family of proteins. GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of beta(arrestins), which prevents further receptor-G-protein coupling. Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. However, whether abrogating muOR desensitization affects the reinforcing and psychomotor properties of morphine has remained unexplored. In the present study, we examined this question by assessing the effects of morphine and cocaine on locomotor activity, behavioral sensitization, conditioned place preference, and striatal dopamine release in beta(arr2) knock-out (beta(arr2)-KO) mice and their wild-type (WT) controls. Cocaine treatment resulted in very similar neurochemical and behavioral responses between the genotypes. However, in the beta(arr2)-KO mice, morphine induced more pronounced increases in striatal extracellular dopamine than in WT mice. Moreover, the rewarding properties of morphine in the conditioned place preference test were greater in the beta(arr2)-KO mice when compared with the WT mice. Thus, beta(arr2) appears to play a more important role in the dopaminergic effects mediated by morphine than those induced by cocaine.

TRANSCENDING FACH: A SEARCH FOR IDENTITY INSIDE AND OUT OF MEZZO-SOPRANO REPERTOIRE

The German Fach system is a tool to classify voices in classical singing. This dissertation comprises three different programs that reflect my search for identity as a mezzo-soprano and my desire to transcend the limitations of Fach. The three programs, all presented at The Clarice Performing Arts Center, contain repertoire written for male and female voices thus allowing me to explore areas outside of the mezzo-soprano Fach, gain a better understanding of the Fach system and guide me as I strive to become a more mature performer. In my first program, I sang the role of Sesto, a role that was composed originally for a castrate, in the opera La Clemenza di Tito by W.A. Mozart. The Maryland Opera Studio production took place April 30, May 2,4&6,2003. Performing this gender-bending role provided an experience of physical behavior from the male view point along with the demands of coloratura singing. Program two (November 30,2004) contained the song cycle Dichterliebe by Robert Schumann and songs by Ludwig van Beethoven, Franz Schubert and Felix Mendelssohn, which are usually sung by male voices. This program experimented with extended range, tessitura and a gender-bending performance in the art song arena. 8 In program three (April 21 &23,2005), I sang the contralto role of Cornelia from Giulio Cesare in Egitto by George Frederic Handel. The role of Cornelia is psychologically complex, expressing emotions such as love, melancholy, rage, malice, joy and fear. To convey these emotions a voice needs warmth and darkness of quality. Although the range is close to that of the mezzo-soprano, Handel wrote Cornelia for contralto voice because he wanted a dark timbre and this role allowed me to develop my lower register and manage suitable ornamentations. The programs are documented in a digital format available on compact disc and are accompanied by the oral presentation at the defense of this dissertation.

Where does energy R&D come from? Examining crowding out from energy R&D

Recent efforts to endogenize technological change in climate policy models demonstrate the importance of accounting for the opportunity cost of climate R&D investments. Because the social returns to R&D investments are typically higher than the social returns to other types of investment, any new climate mitigation R&D that comes at the expense of other R&D investment may dampen the overall gains from induced technological change. Unfortunately, there has been little empirical work to guide modelers as to the potential magnitude of such crowding out effects. This paper considers both the private and social opportunity costs of climate R&D. Addressing private costs, we ask whether an increase in climate R&D represents new R&D spending, or whether some (or all) of the additional climate R&D comes at the expense of other R&D. Addressing social costs, we use patent citations to compare the social value of alternative energy research to other types of R&D that may be crowded out. Beginning at the industry level, we find no evidence of crowding out across sectors-that is, increases in energy R&D do not draw R&D resources away from sectors that do not perform R&D. Given this, we proceed with a detailed look at alternative energy R&D. Linking patent data and financial data by firm, we ask whether an increase in alternative energy patents leads to a decrease in other types of patenting activity. While we find that increases in alternative energy patents do result in fewer patents of other types, the evidence suggests that this is due to profit-maximizing changes in research effort, rather than financial constraints that limit the total amount of R&D possible. Finally, we use patent citation data to compare the social value of alternative energy patents to other patents by these firms. Alternative energy patents are cited more frequently, and by a wider range of other technologies, than other patents by these firms, suggesting that their social value is higher. © 2011 Elsevier B.V.

Lechería ovina en la Argentina : identificación y análisis de los puntos de conflicto en las transacciones productor - industria e industria - distribución y su impacto sobre la sostenibilidad del negocio en Argentina

El estancamiento y presumible retroceso de la actividad lechera ovina en la Argentina suele explicarse desde los aspectos productivos y reproductivos y, en forma incipiente, desde los aspectos institucionales y organizacionales. Los conflictos entre actores, posible causa de la baja sostenibilidad de los negocios de tipo artesanal, han sido poco explorados en la Argentina y en el mundo. El objetivo del presente trabajo es identificar y estudiar los principales puntos de conflicto en las transacciones productor - industria (T2) e industria - distribución (T3) en el negocio de los lácteos ovinos en la Argentina y su impacto sobre la sostenibilidad de este Agronegocio. La metodología de trabajo utilizada fue la epistemología fenomenológica, combinando la investigación cualitativa con la cuantitativa. Se encuestaron 19 tambos ovinos de la provincia de Buenos Aires seleccionados en base a un muestreo aleatorio estratificado por escala de producción. Las encuestas se analizaron a partir del software PC-ORD con técnicas de análisis multivariado: Análisis de Componentes Principales (ACP). A partir del ACP se retuvieron los dos primeros autovalores por acumular el 59,6 por ciento del total de la varianza. Dos componentes principales explicaron el 60 por ciento de la variabilidad total arrojando tres grupos de productores similares en las variables en torno a F1 (estructura de gobernancia) y F2 (nivel de especialización). En T2 los puntos de conflicto giraron en torno a la calidad de la materia prima, el precio, el plazo de pago y la dificultad de cambiar de comprador de leche, mientras que en T3 estos giraron en torno a la calidad de la materia prima, volumen comercializado y regularidad en el abastecimiento del producto. En ambas transacciones se observó una falta de alineación. La elevada especificidad del activo involucrado (leche en T2 y quesos en T3) propició la aparición de comportamientos oportunistas por parte del eslabón siguiente de la cadena, generando cuasi rentas expropiables y potenciando los conflictos entre actores. La ausencia de mecanismos híbridos como las redes de contratos, cooperativas u otras formas de organización, afectó en forma negativa el nivel de especialización, la competitividad y, por lo tanto, la sostenibilidad de los emprendimientos.

Análisis de las transacciones industria-distribución y producción-industria del SAG lácteo argentino : estructuras de gobernancia y conflictos en un contexto de políticas de intervención

El favorable contexto internacional en las últimas décadas permitió el crecimiento de la producción mundial de leche especialmente en países como Nueva Zelanda y Brasil. Sin embargo en Argentina el sector presenta desde hace diez años un estancamiento en los niveles de producción en torno de los 8 y 10 mil millones de litros anuales. El Sistema de Agronegocios Lácteo argentino (SAG) ocupa un lugar importante en la economía, no solo como generador de empleo y riquezas sino por la importancia que tiene el consumo de lácteos a nivel local como productos de primera necesidad. Esta tesis tiene como objetivo general analizar las principales restricciones y limitaciones en la alineación de dos transacciones clave en el SAG lácteo argentino -Producción - Industria e Industria - Distribución - a partir del análisis de las estructuras de gobernancia presentes en términos de precio, plazos, salvaguardas y activos específicos involucrados y de las relaciones de poder y dependencia existentes en ambas interfaces. Para ello se desarrolla y aplica un modelo teórico-metodológico que incorpora conceptos de La Nueva Economía Institucional y conceptos desde la literatura de los canales de distribución. Se encontró que las transacciones bajo estudio suceden en un ambiente institucional de por sí incapaz de proveer un marco regulatorio que pueda dar soluciones a las mismas, y además altamente turbulento, especialmente a partir de la intervención estatal desde 2005. La dependencia 'hacia adelante' entre los eslabones es una de las principales limitaciones del SAG, llevando a que los ajustes, esto es el ejercicio de poder, -manifestado a su vez en la apropiación de cuasi rentas- se trasladen hacia atrás en el SAG, recayendo predominantemente en los productores y las PyMEs industriales, existiendo un conflicto permanente. Las fallas en la fijación del precio, los plazos de contratación que no están acordes con la amortización de los activos específicos, la falta de salvaguardas que reduzcan la incertidumbre y activos específicos que no son bien remunerados en un ambiente institucional altamente turbulento, son las principales fallas en estas relaciones.

Cooperación entre la industria e instituciones de investigación : el caso del Convenio de vinculación tecnológica INTA-Apache SA

p.175-180

Análisis de las transacciones industria-distribución y producción-industria del SAG lácteo argentino : estructuras de gobernancia y conflictos en un contexto de políticas de intervención

El favorable contexto internacional en las últimas décadas permitió el crecimiento de la producción mundial de leche especialmente en países como Nueva Zelanda y Brasil. Sin embargo en Argentina el sector presenta desde hace diez años un estancamiento en los niveles de producción en torno de los 8 y 10 mil millones de litros anuales. El Sistema de Agronegocios Lácteo argentino (SAG)ocupa un lugar importante en la economía, no solo como generador de empleo y riquezas sino por la importancia que tiene el consumo de lácteos a nivel local como productos de primera necesidad. Esta tesis tiene como objetivo general analizar las principales restricciones y limitaciones en la alineación de dos transacciones clave en el SAG lácteo argentino -Producción - Industria e Industria - Distribución - a partir del análisis de las estructuras de gobernancia presentes en términos de precio, plazos, salvaguardas y activos específicos involucrados y de las relaciones de poder y dependencia existentes en ambas interfaces. Para ello se desarrolla y aplica un modelo teórico-metodológico que incorpora conceptos de La Nueva Economía Institucional y conceptos desde la literatura de los canales de distribución. Se encontró que las transacciones bajo estudio suceden en un ambiente institucional de por sí incapaz de proveer un marco regulatorio que pueda dar soluciones a las mismas, y además altamente turbulento, especialmente a partir de la intervención estatal desde 2005. La dependencia 'hacia adelante' entre los eslabones es una de las principales limitaciones del SAG, llevando a que los ajustes, esto es el ejercicio de poder, -manifestado a su vez en la apropiación de cuasi rentas- se trasladen hacia atrás en el SAG, recayendo predominantemente en los productores y las PyMEs industriales, existiendo un conflicto permanente. Las fallas en la fijación del precio, los plazos de contratación que no están acordes con la amortización de los activos específicos, la falta de salvaguardas que reduzcan la incertidumbre y activos específicos que no son bien remunerados en un ambiente institucional altamente turbulento, son las principales fallas en estas relaciones.

Acción del CIPC y otros factores en la pérdida de peso durante el almacenamiento de papa para la industria

p.103-113

The knowledge is out there

Review Essay. On Bourdieu, education and society, by Derek Robbins, Oxford, The Bardwell Press, 2006, 596 pp., £75, ISBN 0-95-486836-6. Bringing knowledge back in, from social constructivism to social realism in the sociology of education, by Michael Young, London, Routledge, 2008, 247 pp.,£23.99, ISBN 9-78-041532-121-1. Personal knowledge, towards a post-critical philosophy, by Michael Polanyi, Chicago, University of Chicago Press, 1962, 428 pp., £18.99, ISBN 0-22-667288-3.

We could make a meal out of nothing: contested explanations of inequalities in health

This paper reports on the qualitative findings from a comparative study of public health and lifestyles in South East England and Northern France, regions with similar geographic and economic characteristics. Data from health surveys showed that both countries had an increasing BMI with age, particularly in Northern France. This was despite the finding that the percentage eating fresh fruit and vegetable at least five days a week in Northern France increased with age (from well over 50% to over 90%) compared to around 50% to around 75% in South East England. Qualitative data on health inequalities and how they could be addressed were gathered by focus groups sampling from five tiers using the Townsend Index for comparability (14 in England with 106 participants overall; 13 in France with 143 participants). Both had about two thirds women participants, with a preponderance of middle aged and older people. There was a striking difference in the salience of diet between the two countries; in the French data it was raised only 14 times, whereas in England there were 165 occurrences, and these were often distinguished by their use of narrative. Older respondents contrasted the pressures on families today and the expense of fresh fruit and vegetables with their own childhood or childrearing, when cheap meals could be created using skills which have now been lost. These data therefore provide further evidence that providing food is a moral activity.

To fit in or stand out? The interaction between mortality salience, dissent and self esteem on social projection

Social projection (SP) refers to our tendency to assume that others think the same as we do, but the effect can also be used to detect the extent to which participants want to see themselves as similar to others. Simon et al (1997) found that participants informed that they were deviant increased their SP but those told that they were conformist reduced theirs. This compensatory function supports Brewer’s optimal distinctiveness which states that a balance must be struck between competing desires to feel similar and unique. In line with terror management theory, the effect was particularly apparent under conditions of mortality salience (MS). So far SP has only been examined on measures that target personal identity so this experiment developed a measure to target social identity as well. Participants were provided with either minority or majority dissent feedback, in MS or control conditions, and their SP on items relevant to personal and social identity were recorded. Results showed that group feedback only impacted upon participants SP on social identity measures and interacted with MS and self-esteem; those with high self-esteem had higher SP scores following minority dissent under conditions of mortality salience, indicating an attempt to assert their individuality. On SP measures targeting personal identity, MS and self-esteem interacted; the death prime increased SP scores for those with low self-esteem but decreased it for those with high self-esteem. Findings are interpreted in terms of TMT and optimal distinctiveness theory and their applications.