The Independence of CXCR4’s Pathways, Gαi and β-Arrestin2, and Their Modulation by AMD3100 and TC14012

CXCR4, a chemokine receptor involved in metastasis and homing of hematopoietic stem cells, signals through two major pathways: Gαi and β-arrestin2. β-arrestin2 terminates G-protein signaling and targets the receptor to endocytosis. This project proposed to study the effect of a previously described set of CXCR4 mutants on both these signaling pathways, as well as their localization. These mutants were assayed by different Bioluminescence Resonance Energy Transfer (BRET) systems. Using these systems, we confirmed that N119S is a constitutively active mutant (CAM), spontaneously activating Gαi. As well, we found that R134A is a constitutively inactive mutant (CIM), devoided of G-protein signaling, but spontaneously recruiting β-arrestin2. In addition, we studied the dependency of β-arrestin2 recruitment on the Gαi activity. By targeting R134A and N119S with pertussis toxin, an inhibitor of the Gαi activation, we showed efficient blocking of the Gαi pathway, while maintaining the constitutive recruitment of β-arrestin2. This demonstrated that for CXCR4, β-arrestin2 recruitment is independent of the Gαi pathway. Finally, two synthetic ligands of CXCR4, AMD3100 and TC14012 were tested for their ability to recruit β-arrestin2. AMD3100 is a clinically approved drug used for stem cell transplantation, with considerable side effects. We found it to be an antagonist on both Gαi and β-arrestin2 recruitment. On the other hand, TC14012 was found to be an inverse agonist on Gαi and an antagonist on β-arrestin2 recruitment. Based on this finding, it would be preferable to use of TC14012 as it will further reduce any basal Gαi activity, without affecting β-arrestin2 recruitment. These results support the development of TC14012 for stem cell mobilization trials.

Women and political change in kerala since independence

even after 45 years of independence, it is seen that women are still left cum the periphery cnf the political process. Effective and meaningful participation of women in politics remains elusive for most of them. The representation of women in the state legislatures and in both Houses of Parliament has been very marginal. The percentage of women members in the LokSabha to the total membership of the body has never touched a two-digit figure so far. Within these 45 years, India could field only five women as Union Cabinet Ministers. In the case of the various states also, the position of women's participation in political activities is not very different. On the whole, it is seen that in independent India the role played by women in the electoral politics of the country or in the day to day activities of the different political parties is very" ineffective and insignificant. The present study was undertaken to make an assessment of women's involvement in the political process of Kerala since independence. This small state in the southernmost part of India claims ‘that it possesses certain. unique features in its social fabric that makes it different from the rest of the country as far as the place of women in society is concerned.

A STUDY OF THE SHORT STORIES OF WOMEN WRITERS IN HINDI BEFORE INDEPENDENCE

hindi

RURAL LIFE IN HINDI NOVELS OF POST INDEPENDENCE PERIOD

HINDI

Social Dramas ()f Post Independence Period

HINDI

Probabilistic Independence Networks for Hidden Markov Probability Models

Graphical techniques for modeling the dependencies of randomvariables have been explored in a variety of different areas includingstatistics, statistical physics, artificial intelligence, speech recognition, image processing, and genetics.Formalisms for manipulating these models have been developedrelatively independently in these research communities. In this paper weexplore hidden Markov models (HMMs) and related structures within the general framework of probabilistic independencenetworks (PINs). The paper contains a self-contained review of the basic principles of PINs.It is shown that the well-known forward-backward (F-B) and Viterbialgorithms for HMMs are special cases of more general inference algorithms forarbitrary PINs. Furthermore, the existence of inference and estimationalgorithms for more general graphical models provides a set of analysistools for HMM practitioners who wish to explore a richer class of HMMstructures.Examples of relatively complex models to handle sensorfusion and coarticulationin speech recognitionare introduced and treated within the graphical model framework toillustrate the advantages of the general approach.

Intrinsic test of independence in contingency tables

A condition needed for testing nested hypotheses from a Bayesian viewpoint is that the prior for the alternative model concentrates mass around the small, or null, model. For testing independence in contingency tables, the intrinsic priors satisfy this requirement. Further, the degree of concentration of the priors is controlled by a discrete parameter m, the training sample size, which plays an important role in the resulting answer regardless of the sample size. In this paper we study robustness of the tests of independence in contingency tables with respect to the intrinsic priors with different degree of concentration around the null, and compare with other “robust” results by Good and Crook. Consistency of the intrinsic Bayesian tests is established. We also discuss conditioning issues and sampling schemes, and argue that conditioning should be on either one margin or the table total, but not on both margins. Examples using real are simulated data are given

Field dependence-independence (FDI) congnitive style : an analysis of attentional functioning. ' Estilo cognitivo dependencia-independencia de campo : un análisis del funcionamiento atencional'.

Resumen tomado de la publicación. Resumen también en inglés

Central Bank Independence and inflation: the case of Colombia. 1924 - 1998.

Este artículo evalúa el vínculo entre la independencia del banco central y la inflación, para el caso de Colombia. Se desarrolla un marco teórica relacionada con la independencia del Banco Central y la inflación. La conclusión es que la independencia del Banco Central es una característica importante de cara a la reducción de la inflación y con el fin de resolver parcialmente el problema de la inconsistencia temporal, y asumiendo la existencia de un régimen monetario dominante la independencia del Banco Central ha llevado a una reducción de la inflación y de su variabilidad en Colombia. No obstante, los resultados de la inflación en el último periodo no han sido tan impresionantes. Este artículo sugiere explicaciones alternativas a este resultado. La independencia real del Banco Central colombiano puede ser más baja que su independencia formal. Adicionalmente, otros factores pueden contribuir a explicar una inflación más elevada que la esperada, particularmente la existencia de un déficit fiscal financiado con recursos externos.

Towards independence : teacher's book 3.

Material de apoyo para la enseñanza de la lectura en toda la primaria. Es una guía esencial para orientar al profesor en cómo usar los recursos principalmente para alumnos de seis a siete años. Hay orientaciones detalladas fotocopiables para el profesorado y hojas de trabajo para los alumnos para trabajar con cada uno de los textos de la serie Cambridge reading.

Independence and equality : 1940 to 1968.

Forma parte de una serie que estudia la historia del hombre negro y de sus logros en el contexto histórico mundial, para lo cual utiliza material gráfico y biografías. El contenido de este recurso comienza en la década de los años treinta y cuarenta del siglo XX y finaliza en 1968 con la independencia de Mauritania y Guinea Ecuatorial. En el transcurso de estos años, se produce la descolonización de África, aunque en Sudáfrica se inicia en 1948 la política del apartheid, y la independencia del Caribe y de América del Sur; los afroamericanos luchan por la igualdad de derechos y para poner fin a la discriminación racial y la segregación; surge el movimiento por los Derechos Civiles y las protestas pacíficas en Estados Unidos.