Inverse agonism and neutral antagonism at alpha(1a)- and alpha(1b)-adrenergic receptor subtypes.

We have characterized the pharmacological antagonism, i.e., neutral antagonism or inverse agonism, displayed by a number of alpha-blockers at two alpha1-adrenergic receptor (AR) subtypes, alpha(1a)- and alpha(1b)-AR. Constitutively activating mutations were introduced into the alpha(1a)-AR at the position homologous to A293 of the alpha(1b)-AR where activating mutations were previously described. Twenty-four alpha-blockers differing in their chemical structures were initially tested for their effect on the agonist-independent inositol phosphate response mediated by the constitutively active A271E and A293E mutants expressed in COS-7 cells. A selected number of drugs also were tested for their effect on the small, but measurable spontaneous activity of the wild-type alpha(1a)- and alpha(1b)-AR expressed in COS-7 cells. The results of our study demonstrate that a large number of structurally different alpha-blockers display profound negative efficacy at both the alpha(1a)- and alpha(1b)-AR subtypes. For other drugs, the negative efficacy varied at the different constitutively active mutants. The most striking difference concerns a group of N-arylpiperazines, including 8-[2-[4-(5-chloro-2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4, 5] decane-7,9-dione (REC 15/3039), REC 15/2739, and REC 15/3011, which are inverse agonists with profound negative efficacy at the wild-type alpha(1b)-AR, but not at the alpha(1a)-AR.

CoDaPack. An Excel and Visual Basic based software of compositional data analysis. Current version and discussion form upcoming versions

In the eighties, John Aitchison (1986) developed a new methodological approach for the statistical analysis of compositional data. This new methodology was implemented in Basic routines grouped under the name CODA and later NEWCODA inMatlab (Aitchison, 1997). After that, several other authors have published extensions to this methodology: Marín-Fernández and others (2000), Barceló-Vidal and others (2001), Pawlowsky-Glahn and Egozcue (2001, 2002) and Egozcue and others (2003). (...)

The European Union in North Korea: Current Realities and Paths for Future Engagement – A Qualitative and Quantitative Study

Malgrat la rellevància estratègica i el paper desestabilitzador de Corea del Nord a la regió econòmicament més dinàmica del món, la UE no compta amb cap estratègia clara per involucrar-se amb aquest país. Combinant tècniques d’anàlisi qualitatives i quantitatives, aquest treball pretén descobrir possibles contradiccions internes que impedeixin la definició d'una política exterior europea coherent i efectiva amb respecte a Corea del Nord, així com discrepàncies entre les percepcions d’actors interns de la UE i les d’actors externs. S'han detectat importants diferències d’expectatives i mancances en termes de coherència, tant entre les visions expressades pels actors interns com entre les opinions d’aquests actors i les dels futurs líders sudcoreans enquestats – diferències que fins i tot afecten la promoció dels drets humans

Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era.

New delay-dependent stability criteria for uncertain neutral systems with mixed time-varying delays and nonlinear perturbations

The problem of stability analysis for a class of neutral systems with mixed time-varying neutral, discrete and distributed delays and nonlinear parameter perturbations is addressed. By introducing a novel Lyapunov-Krasovskii functional and combining the descriptor model transformation, the Leibniz-Newton formula, some free-weighting matrices, and a suitable change of variables, new sufficient conditions are established for the stability of the considered system, which are neutral-delay-dependent, discrete-delay-range dependent, and distributeddelay-dependent. The conditions are presented in terms of linear matrix inequalities (LMIs) and can be efficiently solved using convex programming techniques. Two numerical examples are given to illustrate the efficiency of the proposed method

Behavioural Flexibility: evolutionary past and its role in a changing world

A través de la historia de la vida, gran parte de los organismos han desarrollado estrategias para responder a un mundo en constante cambio. Hoy en día, las actividades humanas producen cambios ambientales a una velocidad sin precedentes, lo cual se traduce en grandes desafíos para la persistencia de biodiversidad. Esta investigación evalúa las respuesta de los animales a los cambios ambientales enfocándose en la flexibilidad del comportamiento como estrategia adaptativa. En una primera aproximación a una escala evolutiva, se otorgan evidencias del vínculo hasta ahora tenue entre la cognición e historias de vida, entregando un claro apoyo a la relación entre longevidad, vida reproductiva y el tamaño del cerebro en mamíferos. La longevidad es el centro de muchas hipótesis respecto a las ventajas de desarrollar un cerebro grande, como por ejemplo en la hipótesis del buffer cognitivo y las respuestas flexibles frente a nuevos ambientes. En un segundo nivel, se abordan factores extrínsecos e intrínsecos que podrían explicar las diferencias individuales en innovación, un componente clave en la flexibilidad del comportamiento. Por medio de una aproximación experimental, se evalúan potenciales escenarios que podrían conducir a consistentes diferencias individuales en uno de los principales factores subyacentes a la innovación (i.e. la motivación), y el potencial control endocrino sobre estos escenarios. Posteriormente, con el objetivo de evaluar la respuesta de los animales frente a los cambios ambientales actuales, se explora la respuesta de los animales frente a una de las actividades humanas mas disruptivas sobre los ecosistemas, la urbanización. Por medio de un analisis filogenetico comparativo a nivel global en aves se abordan los mecanismos implicados en la perdida de biodiversidad observada en ambientes urbanos. Los resultados entregan evidencias sobre la importancia de procesos de dispersión local junto con el papel clave de los rasgos de historia de vida, pero en un sentido diferente al clasicamente pensado. Finalmente por medio de una revisión bibliográfica se entregan evidencias teóricas y empíricas que respaldan el rol clave de la flexibilidad del comportamiento en confrontar los desafíos de una vida urbana. La integración de estos resultados muestra cómo el pasado evolutivo contribuye a hacer frente a los retos ambientales actuales, y pone de relieve posibles consecuencias ante un planeta más cambiante que nunca.

An LMI approach to H∞ synchronization of second-order neutral master-slave systems

The H∞ synchronization problem of the master and slave structure of a second-order neutral master-slave systems with time-varying delays is presented in this paper. Delay-dependent sufficient conditions for the design of a delayed output-feedback control are given by Lyapunov-Krasovskii method in terms of a linear matrix inequality (LMI). A controller, which guarantees H∞ synchronization of the master and slave structure using some free weighting matrices, is then developed. A numerical example has been given to show the effectiveness of the method

Postmortem angiography: review of former and current methods.

OBJECTIVE: Postmortem investigations are becoming more and more sophisticated. CT and MRI are already being used in pathology and forensic medicine. In this context, the impact of postmortem angiography increases because of the rapid evaluation of organ-specific vascular patterns, vascular alteration under pathologic and physiologic conditions, and tissue changes induced by artificial and unnatural causes. CONCLUSION: In this article, the advantages and disadvantages of former and current techniques and contrast agents are reviewed.

La Gestió policial als esdeveniments públics en espais urbans a l'Àfrica: situació actual i perspectives = Policing public events in urban spaces in Africa : an analysis of the current situation and a perspective on follow-up action

L’informe que es presenta en aquest llibre és el resultat d’un nou acord de col·laboració entre el Programa de les Nacions Unides per als Assentaments Humans (ONU-Habitat) i l’Institut de Seguretat Pública de Catalunya, impulsat amb l’objectiu de millorar la seguretat en esdeveniments públics en els espais urbans a l’Àfrica. La fase pilot es va dur a terme el 2010, durant els dos seminaris de formació realitzats a Mollet del Vallès (Barcelona) com a part de la Plataforma Policia per al Desenvolupament Urbà (PPUD). En aquest informe es descriuen els orígens i l’estat de la iniciativa i resumeix els resultats. També s’inclouen algunes recomanacions per a millorar la seguretat d’esdeveniments públics. Font d'informació: http://www.onuhabitat.org.

Personnes âgées aux urgences: défis actuels et futurs [Older patients at the emergency department: current and future challenges].

Emergency departments are and will be at the front line to face the forthcoming increased use of the health care system by the aging baby boomers cohort. Emergency department services will need to adjust on a quantitative as well as on a qualitative basis to manage the impact of these demographic changes. Various models of care have been developed to improve the care of older geriatric patients in the Emergency department that resulted in favorable results on functional, health, as well as health services utilization outcomes. Key components of these successful models have been identified that require a high level of integration between geriatric and emergency teams.

Light-regulated plant growth and development.

Plants are sessile and photo-autotrophic; their entire life cycle is thus strongly influenced by the ever-changing light environment. In order to sense and respond to those fluctuating conditions higher plants possess several families of photoreceptors that can monitor light from UV-B to the near infrared (far-red). The molecular nature of UV-B sensors remains unknown, red (R) and far-red (FR) light is sensed by the phytochromes (phyA-phyE in Arabidopsis) while three classes of UV-A/blue photoreceptors have been identified: cryptochromes, phototropins, and members of the Zeitlupe family (cry1, cry2, phot1, phot2, ZTL, FKF1, and LKP2 in Arabidopsis). Functional specialization within photoreceptor families gave rise to members optimized for a wide range of light intensities. Genetic and photobiological studies performed in Arabidopsis have shown that these light sensors mediate numerous adaptive responses (e.g., phototropism and shade avoidance) and developmental transitions (e.g., germination and flowering). Some physiological responses are specifically triggered by a single photoreceptor but in many cases multiple light sensors ensure a coordinated response. Recent studies also provide examples of crosstalk between the responses of Arabidopsis to different external factors, in particular among light, temperature, and pathogens. Although the different photoreceptors are unrelated in structure, in many cases they trigger similar signaling mechanisms including light-regulated protein-protein interactions or light-regulated stability of several transcription factors. The breath and complexity of this topic forced us to concentrate on specific aspects of photomorphogenesis and we point the readers to recent reviews for some aspects of light-mediated signaling (e.g., transition to flowering).

Eddy current effects on a clinical 7T-68 cm bore scanner.

INTRODUCTION: Eddy currents induced by switching of magnetic field gradients can lead to distortions in short echo-time spectroscopy or diffusion weighted imaging. In small bore magnets, such as human head-only systems, minimization of eddy current effects is more demanding because of the proximity of the gradient coil to conducting structures. METHODS: In the present study, the eddy current behavior achievable on a recently installed 7 tesla-68 cm bore head-only magnet was characterized. RESULTS: Residual effects after compensation were shown to be on the same order of magnitude as those measured on two whole body systems (3 and 4.7 T), while using two to three fold increased gradient slewrates.

Iowa Airport Directory, 2003 ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***

Iowa has 8 commercial service airports and 105 general aviation airports, of which three serve as reliever airports. ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***