Commitment to natural killer cells requires the helix–loop–helix inhibitor Id2

We have previously described how T and natural killer (NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2−/− mice that exhibit defective NK cell development. In the Id2−/− FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2−/− FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2−/− fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2−/− and Id2+/+ embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T/NK progenitors to the NK cell lineage.

Virtual Power Player Using Demand Response to Deal with Unexpected Low Wind Power Generation

Demand response is assumed as an essential resource to fully achieve the smart grids operating benefits, namely in the context of competitive markets and of the increasing use of renewable-based energy sources. Some advantages of Demand Response (DR) programs and of smart grids can only be achieved through the implementation of Real Time Pricing (RTP). The integration of the expected increasing amounts of distributed energy resources, as well as new players, requires new approaches for the changing operation of power systems. The methodology proposed in this paper aims the minimization of the operation costs in a distribution network operated by a virtual power player that manages the available energy resources focusing on hour ahead re-scheduling. When facing lower wind power generation than expected from day ahead forecast, demand response is used in order to minimize the impacts of such wind availability change. In this way, consumers actively participate in regulation up and spinning reserve ancillary services through demand response programs. Real time pricing is also applied. The proposed model is especially useful when actual and day ahead wind forecast differ significantly. Its application is illustrated in this paper implementing the characteristics of a real resources conditions scenario in a 33 bus distribution network with 32 consumers and 66 distributed generators.

Short-term Wind Forecasting to Support Virtual Power Player Operation

This paper proposes a wind speed forecasting model that contributes to the development and implementation of adequate methodologies for Energy Resource Man-agement in a distribution power network, with intensive use of wind based power generation. The proposed fore-casting methodology aims to support the operation in the scope of the intraday resources scheduling model, name-ly with a time horizon of 10 minutes. A case study using a real database from the meteoro-logical station installed in the GECAD renewable energy lab was used. A new wind speed forecasting model has been implemented and it estimated accuracy was evalu-ated and compared with a previous developed forecast-ing model. Using as input attributes the information of the wind speed concerning the previous 3 hours enables to obtain results with high accuracy for the wind short-term forecasting.

Maximizing the Social Welfare of Virtual Power Players Operation in Case of Excessive Wind Power

The integration of growing amounts of distributed generation in power systems, namely at distribution networks level, has been fostered by energy policies in several countries around the world, including in Europe. This intensive integration of distributed, non-dispatchable, and natural sources based generation (including wind power) has caused several changes in the operation and planning of power systems and of electricity markets. Sometimes the available non-dispatchable generation is higher than the demand. This generation must be used; otherwise it is wasted if not stored or used to supply additional demand. New policies and market rules, as well as new players, are needed in order to competitively integrate all the resources. The methodology proposed in this paper aims at the maximization of the social welfare in a distribution network operated by a virtual power player that aggregates and manages the available energy resources. When facing a situation of excessive non-dispatchable generation, including wind power, real time pricing is applied in order to induce the increase of consumption so that wind curtailment is minimized. This method is especially useful when actual and day-ahead resources forecast differ significantly. The distribution network characteristics and concerns are addressed by including the network constraints in the optimization model. The proposed methodology has been implemented in GAMS optimization tool and its application is illustrated in this paper using a real 937-bus distribution network with 20.310 consumers and 548 distributed generators, some of them non-dispatchable and with must take contracts. The implemented scenario corresponds to a real day in Portuguese power system.

Energy resources management in three distinct time horizons considering a large variation in wind power

The intensive use of distributed generation based on renewable resources increases the complexity of power systems management, particularly the short-term scheduling. Demand response, storage units and electric and plug-in hybrid vehicles also pose new challenges to the short-term scheduling. However, these distributed energy resources can contribute significantly to turn the shortterm scheduling more efficient and effective improving the power system reliability. This paper proposes a short-term scheduling methodology based on two distinct time horizons: hour-ahead scheduling, and real-time scheduling considering the point of view of one aggregator agent. In each scheduling process, it is necessary to update the generation and consumption operation, and the storage and electric vehicles status. Besides the new operation condition, more accurate forecast values of wind generation and consumption are available, for the resulting of short-term and very short-term methods. In this paper, the aggregator has the main goal of maximizing his profits while, fulfilling the established contracts with the aggregated and external players.

La force motrice hydraulique au service du développement économique helvétique : L'exemple du réseau d'eau sous pression à Lausanne 1868-1914

The success story of hydroelectricity long influenced and dominated Swiss scholarly literature devoted to the history of technology. This means of conducting power, which emerged at the end of the 19th century and is still dominating today, has attracted much more attention than technologies that have been shadowed by its success. In spite of their important contribution to Swiss economic development, the distribution networks of pressurized water have been neglected by scholars. This article contributes to close this historiographic gap by analyzing the introduction of pressurized water distribution in 1876 in Lausanne, in the context of the building of the first Swiss cable funicular between Lausanne and Ouchy. This article shows how pressurized water distribution transformed socio-economic practices in the urban areas in which it was adopted. Indeed, this innovation, which allowed the use of distant hydraulic resources, enabled the rationalization of industrial and artisanal production as well as improved the density of the urban industrial base. By facilitating the introduction of electric lighting, pressurized water networks played a key role in the early development, and further successes, of the Swiss hydroelectric industry.

Growth promoting signaling by tenascin-C [corrected].

Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of beta-catenin and stimulated the expression of the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.

Transcriptional regulation of effector CD8+ T cell differentiation and molecular dysfunction during HIV-1 infection

Les cellules T CD8+ jouent un rôle primordial dans le contrôle des infections virales en limitant la dissémination des cellules infectées. Lors de l’infection chronique par le virus HIV, les cellules T CD8+ HIV-spécifiques ne se différencient pas en cellules effectrices fonctionnelles capables de tuer les cellules infectées par le virus ; ces cellules ne sont plus capables de proliférer ou de produire l’ IL-2. Ces cellules expriment PD-1 et l’engagement de PD-1, par son ligand, aboutit a plusieurs de ces déficits fonctionnels des cellules T . Le rôle de PD-1 dans la régulation d'évènements transcriptionnels contrôlant la différentiation et l'obtention des fonction effectrices des cellules T CD8+ reste à démontrer. Id2 joue un rôle central dans la différenciation des cellules T CD8+ effectrices. Nous avons émis l’hypothèse que le défaut de maturation observé chez les cellules T CD8+ PD-1 high HIV-spécifiques (CD8+PD-1hi) au cours de l’infection chronique par le virus HIV pouvait être lié à la diminution d’expression du régulateur Id2. Nous avons ainsi démontré que l'engagement de PD-1 contribuait à une diminution d'expression de Id2 et de ses cibles transcriptionnelles. La surexpression de Id2 de ces cellules a permis de restaurer l'expression de marqueurs tels que Granzyme B et Bcl-2 et diminuir l’expression du marqueur de maturation de CD27. La famille des cytokines à chaine gamma joue un rôle clef dans la survie et l’homéostasie des cellules T. Dans ce travail, nous avons démontré que l’IL-15 était unique grâce à ses capacités de stimulation de l’expression d’Id2 et ses propriétés favorisant la survie ainsi que la différenciation des cellules T CD8+ effectrices. l’IL-15 induit la prolifération de toutes les populations de cellules T mémoires provenant de donneurs sains. L’addition de cette cytokine aux sous-populations cellulaires Ttm et Tem a permis leur différenciation en cellules effectrices capables de produire Granzyme B alors que la stimulation par l’IL-15 des cellules Tcm ne favorise pas leur différenciation. Un test de cytotoxicitié par cytométrie en flux nous a permis de confirmer que la stimulation de cellules T CD8+ HIV spécifiques par l’IL-15 favorisait l’expression de Id2 et restaurait les fonctions cytotoxiques des cellules T CD8+ HIV spécifiques. En conclusion, nous avons pour la première fois dans cette thèse défini les mécanismes moléculaires impliqués dans la modulation de l’expression du régulateur transcriptionnel Id2 par l’IL-15. Nous avons également révélé comment l’engagement de PD-1 conduisait a une altération de l’expression et de la fonction d’Id2 et favorisait la diminution des fonctions effectrices des cellules T CD8-HIV spécifiques. Une perspective de traitement avec des agents tels que l’IL-15 ou le bloquage de PD-1, en combinaison avec les traitements conventionnels, pourrait contribuer à une meilleure stimulation des réponses immunes favorisant ainsi la réactivation des cellules T CD8+ et permettant la destruction de cellules T CD4+ infectées de manière latente.

Estudo das alterações funcionais respiratórias em pacientes submetidos à colecistectomia videolaparoscópica

Pós-graduação em Bases Gerais da Cirurgia - FMB