Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate

Background: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. Methods: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). Results: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. Conclusions: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required. © 2014 Cancer Research UK. All rights reserved.

Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server. © 2013 Magdalena Molero-Abraham et al.

The migration crisis: representation of a border conflict in Hungarian, German and Pan-European television new coverage

In this article we review the methods used by television news channels in their reporting of the clashes between the Hungarian police and refugees at the Serbian-Hungarian border on 16th of September 2015. With the help of content analysis we examine the techniques used by each editorial board to portray events differently,resulting in dissimilar effects on recipients. During the analysis we examine news coverage for one specific day as presented by Hungarian, German and pan-European broadcasters. German news programs were chosen for comparison with Hungarian ones due to the fact that most of the refugees were heading towards Germany. We conclude that there are significant differences between the information that was broadcast according to television channels; owner expectations presumably play an important role in this.

Remembering Pedro Pan: Faith, Family, and Freedom in Cuban-American Collective Memory , Lecture by Anita Casavantes Bradford

This flyer promotes the event "Remembering Pedro Pan: Faith, Family, and Freedom in Cuban-American Collective Memory Lecture by Anita Casavantes Bradford" and cosponsored by the Latin American and Caribbean Center and the Green Library

Legacy of Operation Pedro Pan, Lecture by Anita Casavantes Bradford

This flyer promotes the event "Legacy of Operation Pedro Pan", a lecture by author Anita Casavantes Bradford.

Operation Pedro Pan Exodus: A Testimonial, lecture by Eloísa Echazábal

Lecture by Eloísa Echazábal, founding member of Operation Pedro Pan Group, Inc., in which she shares a brief film and shares personal testimony of the ordeals she and others endured as part of Operation Pedro Pan.

Parámetros clínicos de chimpancé ("Pan troglodytes") en programas de rehabilitación y reintroducción en su medio natural

Genéticamente, los chimpancés y los bonobos son los parientes vivos más cercanos a los seres humanos, que comparten un ancestro común que vivió hace unos seis millones de años. Los chimpancés se consideran en peligro de extinción por la IUCN y numerosos programas de conservación en África trabajan hacia la protección de la especie y su hábitat. Amenazado por la caza furtiva y la destrucción del hábitat, las cifras de población de chimpancés salvajes siguen disminuyendo. Como consecuencia, un importante flujo de chimpancés en vivo que son víctimas de la caza furtiva son enviados a centros de rehabilitación en África donde viven en semilibertad y en ocasiones son reintroducidos en el medio natural. Un objetivo primordial en estos centros de rescate y rehabilitación es proporcionar a los primates en cautividad con altos estándares de bienestar. La realización de tratamientos médicos adecuados y una gestión cuidadosa contribuye a su buen estado de salud, que a su vez permite a estos centros para garantizar el bienestar óptimo chimpancé. A un nivel veterinaria, la implementación de un tratamiento rápido y efectivo para una enfermedad requiere las herramientas de diagnóstico adecuadas, así como los valores de referencia correctos correspondientes a la especie. El objetivo de la presente tesis es establecer rangos de referencia de los diferentes parámetros clínicos para el chimpancé común (Pan troglodytes), que viven en semi-libertad en su hábitat natural. A fin de establecer valores de referencia, hemos utilizado los datos obtenidos durante los controles de rutina del brezo en chimpancés realizados durante diez años, en Tchimpounga Centro de Rehabilitación de chimpancé. Todos los chimpancés en el Centro de Rehabilitación Tchimpounga someten a controles de salud a su llegada al centro y en adelante cada tres años. Los análisis se llevan a cabo para asegurar la buena salud de la comunidad, y mejorar el control de la transmisión de enfermedades infecciosas, como la tuberculosis. Los análisis incluyen la recogida de sangre de la muestra, electrocardiogramas, radiografías de tórax, ecografía abdominal y pruebas serológicas y bacteriológicas. Estos análisis requieren la inmovilización química del individuo. A su vez, otros controles de salud que no requieren inmovilización química se realizan a diario en el centro por personal cualificado. Estos incluyen el análisis de las heces y la orina, y la exploración física general. La exploración global incluye tomar la temperatura corporal diaria de los chimpancés menores de 10 años en virtud de condicionamiento positivo...

We Are the Ones We Have Been Waiting for: Pan-African Consciousness Raising and Organizing in the United States and Venezuela

We Are the Ones We Have Been Waiting for: Pan-African Consciousness Raising and Organizing in the United States and Venezuela, draws on fifteen months of field research accompanying organizers, participating in protests, planning/strategy meetings, state-run programs, academic conferences and everyday life in these two countries. Through comparative examination of the processes by which African Diaspora youth become radically politicized, this work deconstructs tendencies to deify political s/heroes of eras past by historicizing their ascent to political acclaim and centering the narratives of present youth leading movements for Black/African liberation across the Diaspora. I employ Manuel Callahan’s description of “encuentros”, “the disruption of despotic democracy and related white middle-class hegemony through the reconstruction of the collective subject”; “dialogue, insurgent learning, and convivial research that allows for a collective analysis and vision to emerge while affirming local struggles” to theorize the moments of encounter, specifically, the moments (in which) Black/African youth find themselves becoming politically radicalized and by what. I examine the ways in which Black/African youth organizing differs when responding to their perpetual victimization by neoliberal, genocidal state-politics in the US, and a Venezuelan state that has charged itself with the responsibility of radically improving the quality of life of all its citizens. Through comparative analysis, I suggest the vertical structures of “representative democracy” dominating the U.S. political climate remain unyielding to critical analyses of social stratification based on race, gender, and class as articulated by Black youth. Conversely, I contend that present Venezuelan attempts to construct and fortify more horizontal structures of “popular democracy” under what Hugo Chavez termed 21st Century Socialism, have resulted in social fissures, allowing for a more dynamic and hopeful negation between Afro-Venezuelan youth and the state.

Design and analysis of a compliant parallel pan-tilt platform

In combination of the advantages of both parallel mechanisms and compliant mechanisms, a compliant parallel mechanism with two rotational DOFs (degrees of freedom) is designed to meet the requirement of a lightweight and compact pan-tilt platform. Firstly, two commonly-used design methods i.e. direct substitution and FACT (Freedom and Constraint Topology) are applied to design the configuration of the pan-tilt system, and similarities and differences of the two design alternatives are compared. Then inverse kinematic analysis of the candidate mechanism is implemented by using the pseudo-rigid-body model (PRBM), and the Jacobian related to its differential kinematics is further derived to help designer realize dynamic analysis of the 8R compliant mechanism. In addition, the mechanism’s maximum stress existing within its workspace is tested by finite element analysis. Finally, a method to determine joint damping of the flexure hinge is presented, which aims at exploring the effect of joint damping on actuator selection and real-time control. To the authors’ knowledge, almost no existing literature concerns with this issue.

Qué Peter Pan conocemos y cómo : Recorridos de un fenómeno intermedial desde su origen

Fil: Pérez, Soledad. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.

Qué Peter Pan conocemos y cómo : Recorridos de un fenómeno intermedial desde su origen

Fil: Pérez, Soledad. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.

Qué Peter Pan conocemos y cómo : Recorridos de un fenómeno intermedial desde su origen

Fil: Pérez, Soledad. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.