A Shepherd`s Dream. From The Play The "Lost Sheep"

B. Thomashefsky

Her Confession. The Great Hit of Kessler`s Second Ave. Theatre from Jos. Lateiner`s Play

H.Altman

Bone marrow-derived stem/progenitor cells play an important role in the growth of Ewing's sarcoma tumors

Both angiogenesis and vasculogenesis contribute to the formation and expansion of tumor neovasculature. We demonstrated that bone marrow (BM)-derived cells migrated to TC71 Ewing's tumors and differentiated into endothelial cells lining perfused, functional tumor neovessels. In addition, a substantial fraction of recruited, BM-derived cells resided in the vessel vicinity but did not demonstrate endothelial differentiation. Rather, these perivascular cells expressed desmin and PDGFR-β, implying pericyte-like/vascular smooth muscle cell differentiation. No defined, consensus set of markers exists for endothelial progenitor cells (EPCs) and the specific subsets of BM cells that participate in vessel formation are poorly understood. We used a functional in vivo assay to investigate the roles performed by specific human- and murine-derived stem/progenitor subpopulations within Ewing's sarcoma tumors. CD34 +45+, CD34+38-, VEGFR2 + and Sca1+Gr1+ cells were demonstrated to establish residence within the expanding tumor vascular network and differentiate into endothelial cells and pericytes. By constrast, CD34-45 + and Sca1-Gr1+ cells predominantly localized to sites outside the Ewing's tumor vasculature, and differentiated into macrophages. Cytokines, such as VEGF, influence the recruitment of BM cells and their incorporation into the tumor vasculature. VEGF165-inhibited TC/siVEGF7-1 Ewing's tumors showed delayed in vivo tumor growth, decreased vessel density, and reduced infiltration of BM progenitor cells. We tested whether another chemoattractant, Stromal Cell-Derived Factor-1 (SDF-1), could augment the growth of these VEGF165-inhibited TC/siVEGF 7-1 tumors by enhancing the recruitment of BM cells and stimulating neovasculature expansion. SDF-1 promoted progenitor cell chemotaxis and retainment of BM-derived pericyte precursors in close association with functional, perfused tumor blood vessels. Treatment of TC/siVEGF7-1 tumors with adenovirus-SDF-1α resulted in augmented tumor size, enhanced pericyte coverage of tumor neovessels, remodeling of vascular endothelium into larger, functional structures, and upregulation of PDGF-BB, with no effect on VEGF165. Taken together, these findings suggest that the recruitment of BM stem/progenitor cells plays an important role in the growth of Ewing's tumors. ^

Alex Garvie. Aeschylus' Supplices. Play and Trilogy, Bristol Phoenix Press, UK, 2006, i-xxiv + 279 pp.

Fil: Fernández Deagustini, María del Pilar. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Alex Garvie. Aeschylus' Supplices. Play and Trilogy, Bristol Phoenix Press, UK, 2006, i-xxiv + 279 pp.

Fil: Fernández Deagustini, María del Pilar. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Contribución a los Modelos y Metodologías para la Estimación de la Calidad Percibida por los Usuarios (QoE) a partir de Parámetros de Calidad de Red/Servicio (QoS) en Servicios Convergentes Multimedia (Triple-Play)

Esta Tesis constituye una contribución a los Modelos y Metodologías para la Estimación de la Calidad Percibida por los Usuarios, o Calidad de Experiencia (QoE), a partir de Parámetros de Calidad y/o Rendimiento de Red y/o Servicio (QoS) en Servicios Multimedia, y específicamente en servicios Triple-Play (3P): servicios de Televisión (TV), Telefonía y Datos ofrecidos por un mismo operador como un paquete único. En particular, se centra en los servicios Triple-Play convergentes (desplegados sobre una Red de Transporte común basada en IP, gestionada por un único operador como un Sistema Autónomo (SA)), y la relación entre la Calidad Percibida por los usuarios de dichos servicios y los parámetros de rendimiento de la Red de Transporte IP subyacente. Específicamente, contribuye a la estimación ‘en línea’ (es decir, durante la prestación del servicio, en tiempo real o casi-real) de dicha calidad. La calidad de experiencia de los usuarios es un factor determinante para el éxito o fracaso de estos servicios, y su adecuada gestión resulta por tanto un elemento crucial para el despliegue exitoso de los mismos. La calidad de experiencia resulta fácil de entender, pero compleja de implementar en sistemas reales, debido principalmente a la dificultad de su modelado, evaluación, y traducción en términos de parámetros de calidad de servicio. Mientras que la calidad de servicio puede medirse, monitorizarse y controlarse fácilmente, la calidad de experiencia es todavía muy difícil de gestionar. Una metodología completa de gestión de la calidad de experiencia debe incluir al menos: monitorización de la experiencia de los usuarios durante el consumo del servicio; adaptación de la provisión de contenidos a las condiciones variables del contexto; predicción del nivel de degradación potencial de la calidad de experiencia; y recuperación de la degradación debida a cambios en el sistema. Para conseguir un control completo de la experiencia de los usuarios finales, todas estas tareas deben ser realizadas durante la prestación del servicio y de forma coordinada. Por lo tanto, la capacidad de medir, estimar y monitorizar la calidad percibida en tiempo casi-real, y relacionarla con las condiciones de servicio de la red, resulta crítica para los proveedores de este tipo de servicios, especialmente en el caso de los más exigentes, tales como la difusión de Televisión sobre IP (IPTV). Para ello se ha seleccionado un modelo ya existente, de tipo matricial, para la estimación de la Calidad Global en servicios complejos a partir de los parámetros de funcionamiento interno de los agentes que proporcionan los servicios. Este modelo, definido en términos de servicios y sus componentes, percepciones de los usuarios, capacidades de los agentes, indicadores de rendimiento y funciones de evaluación, permite estimar la calidad global de un conjunto de servicios convergentes, tal como la perciben uno o más grupos de usuarios. Esto se consigue combinando los resultados de múltiples modelos parciales, tales que cada uno de ellos proporciona la valoración de la calidad percibida para uno de los servicios componentes, obtenida a partir de un conjunto de parámetros de rendimiento y/o Calidad de Servicio de la red de transporte IP convergente. El modelo se basa en la evaluación de las percepciones de los usuarios a partir de Factores de Valoración, calculados a partir de Indicadores de Rendimiento, que se derivan a su vez de Parámetros de Funcionamiento Interno correspondientes a las capacidades de los distintos agentes que intervienen en la prestación de los servicios. El trabajo original incluye la aplicación del modelo a un servicio 3P (datos+voz+vídeo). En este trabajo, sin embargo, el servicio de vídeo (Vídeo bajo Demanda, VoD) se considera poco importante y es finalmente ignorado. En el caso de los usuarios residenciales, el servicio de voz (Voz sobre IP, VoIP) se considera asimismo poco importante y es también ignorado, por lo que el servicio global se reduce finalmente a los servicios de datos (Acceso a Internet y juegos interactivos). Esta simplificación era razonable en su momento, pero la evolución del mercado de servicios convergentes ha hecho que en la actualidad las razones que la justificaban no sean ya aplicables. En esta Tesis, por lo tanto, hemos considerado un servicio ‘Triple-Play��� completo, incluyendo servicios de datos, voz y vídeo. Partiendo de dicho modelo, se ha procedido a actualizar los servicios considerados, eliminando los no relevantes e incluyendo otros no considerados, así como a incluir nuevos elementos (percepciones) para la estimación de la calidad de los servicios; actualizar, extender y/o mejorar los modelos de estimación de los servicios ya incluidos; incluir modelos de estimación para los nuevos servicios y elementos añadidos; desarrollar nuevos modelos de estimación para aquellos servicios o elementos para los que no existen modelos adecuados; y por último, extender, actualizar y/o mejorar los modelos para la estimación de la calidad global. Con todo ello se avanza apreciablemente en la modelización y estimación de la Calidad de Experiencia (QoE) en Servicios Multimedia a partir de Parámetros de Calidad de Servicio (QoS) y/o Rendimiento de la Red, y específicamente en la estimación ‘en línea’, en tiempo casi-real, de dicha calidad en servicios Triple-Play convergentes. La presente Tesis Doctoral se enmarca en la línea de investigación sobre Calidad de Servicio del grupo de Redes y Servicios de Telecomunicación e Internet, dentro del Departamento de Ingeniería de Sistemas Telemáticos (DIT) de la Universidad Politécnica de Madrid (UPM).

Security of plug-and-play QKD arrangements with finite resources

The security of a passive plug-and-play QKD arrangement in the case of finite (resources) key lengths is analysed. It is assumed that the eavesdropper has full access to the channel so an unknown and untrusted source is assumed. To take into account the security of the BB84 protocol under collective attacks within the framework of quantum adversaries, a full treatment provides the well-known equations for the secure key rate. A numerical simulation keeping a minimum number of initial parameters constant as the total error sought and the number of pulses is carried out. The remaining parameters are optimized to produce the maximum secure key rate. Two main strategies are addressed: with and without two-decoy-states including the optimization of signal to decoy relationship.

What role does climate change play in agricultural market uncertainty? An integrated assessment taking into account market-driven adjustments

Recent studies point to climate change being one of the long-term drivers of agricultural market uncertainty. To advance in the understanding of the influence of climate change on future agricultural market developments, we compare a reference scenario for 2030 with alternative simulation scenarios that differ regarding: (1) emission scenarios; (2) climate projections; and (3) the consideration of carbon fertilization effects. For each simulation scenario, the CAPRI model provides global and EU-wide impacts of climate change on agricultural markets. Results show that climate change would considerably affect agrifood markets up to 2030. Nevertheless, market-driven adaptation strategies (production intensification, trade adjustments) would soften the impact of yield shocks on supply and demand. As a result, regional changes in production would be lower than foreseen by other studies focused on supply effects.

Low-status monkeys “play dumb” when learning in mixed social groups

Many primates, including humans, live in complex hierarchical societies where social context and status affect daily life. Nevertheless, primate learning studies typically test single animals in limited laboratory settings where the important effects of social interactions and relationships cannot be studied. To investigate the impact of sociality on associative learning, we compared the individual performances of group-tested rhesus monkeys (Macaca mulatta) across various social contexts. We used a traditional discrimination paradigm that measures an animal’s ability to form associations between cues and the obtaining of food in choice situations; but we adapted the task for group testing. After training a 55-member colony to separate on command into two subgroups, composed of either high- or low-status families, we exposed animals to two color discrimination problems, one with all monkeys present (combined condition), the other in their “dominant” and “subordinate” cohorts (split condition). Next, we manipulated learning history by testing animals on the same problems, but with the social contexts reversed. Monkeys from dominant families excelled in all conditions, but subordinates performed well in the split condition only, regardless of learning history. Subordinate animals had learned the associations, but expressed their knowledge only when segregated from higher-ranking animals. Because aggressive behavior was rare, performance deficits probably reflected voluntary inhibition. This experimental evidence of rank-related, social modulation of performance calls for greater consideration of social factors when assessing learning and may also have relevance for the evaluation of human scholastic achievement.

The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation

cABL is a protooncogene, activated in a subset of human leukemias, whose protein product is a nonreceptor tyrosine kinase of unknown function. cABL has a complex structure that includes several domains and motifs found in proteins implicated in signal transduction pathways. An approach to elucidate cABL function is to identify proteins that interact directly with cABL and that may serve as regulators or effectors of its activity. To this end, a protein-interaction screen of a phage expression library was undertaken to identify proteins that interact with specific domains of cABL. An SH3-domain-containing protein has been identified that interacts with sequences in the cABL carboxyl terminus. The cDNA encoding ALP1 (amphiphysin-like protein 1) was isolated from a 16-day mouse embryo. ALP1 has high homology to BIN1, a recently cloned myc-interacting protein, and also shows significant homology to amphiphysin, a neuronal protein cloned from human and chicken. The amino terminus has homology to two yeast proteins, Rvs167 and Rvs161, which are involved in cell entry into stationary phase and cytoskeletal organization. ALP1 binds cABL in vitro and in vivo. Expression of ALP1 results in morphological transformation of NIH 3T3 fibroblasts in a cABL-dependent manner. The properties of ALP1 suggest that it may be involved in possible cytoskeletal functions of the cABL kinase. Additionally, these results provide further evidence for the importance of the cABL carboxyl terminus and its binding proteins in the regulation of cABL function.

Lumenal and Transmembrane Domains Play a Role in Sorting Type I Membrane Proteins on Endocytic Pathways

Previous studies have shown that when the cytosolic domains of the type I membrane proteins TGN38 and lysosomal glycoprotein 120 (lgp120) are added to a variety of reporter molecules, the resultant chimeric molecules are localized to the trans-Golgi network (TGN) and to lysosomes, respectively. In the present study we expressed chimeric constructs of rat TGN38 and rat lgp120 in HeLa cells. We found that targeting information in the cytosolic domain of TGN38 could be overridden by the presence of the lumenal and transmembrane domains of lgp120. In contrast, the presence of the transmembrane and cytosolic domains of TGN38 was sufficient to deliver the lumenal domain of lgp120 to the trans-Golgi network. On the basis of steady-state localization of the various chimeras and antibody uptake experiments, we propose that there is a hierarchy of targeting information in each molecule contributing to sorting within the endocytic pathway. The lumenal and cytosolic domains of lgp120 contribute to sorting and delivery to lysosomes, whereas the transmembrane and cytosolic domains of TGN38 contribute to sorting and delivery to the trans-Golgi network.

Two Distinct Signaling Pathways Downstream of Janus Kinase 2 Play Redundant Roles for Antiapoptotic Activity of Granulocyte-Macrophage Colony-stimulating Factor

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains the viability of the mouse interleukin-3-dependent cell line BA/F3 expressing the hGM-CSF receptor. Analysis of the antiapoptosis activity of GM-CSF receptor βc mutants showed that box1 but not the C-terminal region containing tyrosine residues is essential for GM-CSF-dependent antiapoptotic activity. Because βc mutants, which activate Janus kinase 2 but neither signal transducer and activator of transcription 5 nor the MAPK cascade sustain antiapoptosis activity, involvement of Janus kinase 2, excluding the above molecules, in antiapoptosis activity seems likely. GM-CSF activates phosphoinositide-3-OH kinase as well as Akt, and activation of both was suppressed by addition of wortmannin. Interestingly, wortmannin did not affect GM-CSF-dependent antiapoptosis, thus indicating that the phosphoinositide-3-OH kinase pathway is not essential for cell surivival. Analysis using the tyrosine kinase inhibitor genistein and a MAPK/extracellular signal-regulated kinase (ERK) kinase 1 inhibitor, PD98059, indicates that activation of either the genistein-sensitive signaling pathway or the PD98059-sensitive signaling pathway from βc may be sufficient to suppress apoptosis. Wild-type and a βc mutant lacking tyrosine residues can induce expression of c-myc and bcl-xL genes; however, drug sensitivities for activation of these genes differ from those for antiapoptosis activity of GM-CSF, which means that these gene products may be involved yet are inadequate to promote cell survival.

Molecular genetics of pattern formation in the inner ear: Do compartment boundaries play a role?

The membranous labyrinth of the inner ear establishes a precise geometrical topology so that it may subserve the functions of hearing and balance. How this geometry arises from a simple ectodermal placode is under active investigation. The placode invaginates to form the otic cup, which deepens before pinching off to form the otic vesicle. By the vesicle stage many genes expressed in the developing ear have assumed broad, asymmetrical expression domains. We have been exploring the possibility that these domains may reflect developmental compartments that are instrumental in specifying the location and identity of different parts of the ear. The boundaries between compartments are proposed to be the site of inductive interactions required for this specification. Our work has shown that sensory organs and the endolymphatic duct each arise near the boundaries of broader gene expression domains, lending support to this idea. A further prediction of the model, that the compartment boundaries will also represent lineage-restriction compartments, is supported in part by fate mapping the otic cup. Our data suggest that two lineage-restriction boundaries intersect at the dorsal pole of the otocyst, a convergence that may be critical for the specification of endolymphatic duct outgrowth. We speculate that the patterning information necessary to establish these two orthogonal boundaries may emanate, in part, from the hindbrain. The compartment boundary model of ear development now needs to be tested through a variety of experimental perturbations, such as the removal of boundaries, the generation of ectopic boundaries, and/or changes in compartment identity.