Microenvironment and microvascular wall modulate cancer cell progression

Tumour progression is a complex process that frequently brings to cancer metastasis, the first cause of poor prognosis of cancer affected patients. Metastasis are generated by cells escaped from a primary mass and able to enter in the circulation, survive and proliferate in a new, distant site of the organism. To reach all these goal, many different phenomena had occur within both the cancer cells and the surrounding microenvironment. In the first part of this thesis, the focus was pointed on the metastatic potential of a leiomyosarcoma cell model. The studied cancer cells demonstrated a strong invasive capacity of the ECM in vitro, principally by production of matrix metalloproteinases 2 and 9, and robust pro-angiogenic activity in the chick CAM model, that facilitate its dissemination through same chick embryo internal organs. This study, with the title “MMPs and angiogenesis affect the metastatic potential of a human vulvar leiomyosarcoma cell line”, is presented in the published form. In the second part of this work, the emphasis was given to the microvascular element of the tumour microenvironment and specifically to the perivascular pericytes. These are intriguing cells due to their uncertain involvement in the biology of cancer. It is not clear how pericytes change within the tumour microenvironment and which is their contribute during the tumour dissemination. After the characterization of the chosen pericytic cell model, an in vitro study of the interaction between pericytes and different cancer cell lines where performed. Indirect and direct cell-cell interaction as well as movement of cancer cells in presence of pericytes conditioned media was analysed, in order to investigate the reciprocal influence of pericytes and tumour cells in the context of cancer progression.

Personaje y empatía en la animación actual: influencias de Chaplin y Keaton en Wall-E

En la presente investigación pretendemos analizar las influencias del cine cómico mudo de los primeros años de Hollywood en algunas películas de animación actuales en cuanto a la creación de los personajes. La película de 2008 dirigida por Andrew Stanton, Wall·E, será el elemento principal de nuestro análisis y a ella será a la que apliquemos nuestras hipótesis puesto que creemos que es un ejemplo muy válido para corroborarlo. La idea principal es comprobar cómo se produce esa influencia en la creación del personaje, cuáles son los principales artistas del mudo que han sido tomados como referencia para ello, y sobre todo cuál es la razón principal de que se haya creado esta película de esta determinada manera: los intentos por conseguir que el espectador tome parte en la historia es lo que han producido este tipo de trabajo de personajes. La empatía con el espectador es un elemento muy importante en nuestra investigación, ya que creemos que toda la creación de la película, las influencias en los personajes, su diseño, las subtramas que viven y las emociones que expresan están realizados con una única finalidad: conseguir conectar emocionalmente con el espectador para hacerle partícipe de la historia...

Single wall carbon nanotubes loaded with Pd and NiPd nanoparticles for H2 sensing at room temperature

Pd and bimetallic Ni50Pd50 nanoparticles protected by polyvinylpyrrolidone (PVP) have been synthesized by the reduction-by-solvent method and deposited on single wall carbon nanotubes (SWCNTs) to be tested as H2 sensors. The SWCNTs were deposited by drop casting from different suspensions. The Pd nanoparticles-based sensors show a very reproducible performance with good sensitivity and very low response times (few seconds) for different H2 concentrations, ranging from 0.2% to 5% vol. H2 in air at atmospheric pressure. The influence of the metal nanoparticle composition, the quality of SWCNTs suspension and the metal loading have been studied, observing that all these parameters play an important role in the H2 sensor performance. Evidence for water formation during the H2 detection on Pd nanoparticles has been found, and its repercussion on the behaviour of the assembled sensors is discussed. The sensor preparation procedure detailed in this work has proven to be simple and reproducible to prepare cost-effective and highly efficient H2 sensors that perform very well under real application conditions.

Electrochemical behaviour of different redox probes on single wall carbon nanotube buckypaper-modified electrodes

In the present work, the electrochemical properties of single-walled carbon nanotube buckypapers (BPs) were examined in terms of carbon nanotubes nature and preparation conditions. The performance of the different free-standing single wall carbon nanotube sheets was evaluated via cyclic voltammetry of several redox probes in aqueous electrolyte. Significant differences are observed in the electron transfer kinetics of the buckypaper-modified electrodes for both the outer- and inner-sphere redox systems. These differences can be ascribed to the nature of the carbon nanotubes (nanotube diameter, chirality and aspect ratio), surface oxidation degree and type of functionalities. In the case of dopamine, ferrocene/ferrocenium, and quinone/hydroquinone redox systems the voltammetric response should be thought as a complex contribution of different tips and sidewall domains which act as mediators for the electron transfer between the adsorbate species and the molecules in solution. In the other redox systems only nanotube ends are active sites for the electron transfer. It is also interesting to point out that a higher electroactive surface area not always lead to an improvement in the electron transfer rate of various redox systems. In addition, the current densities produced by the redox reactions studied here are high enough to ensure a proper electrochemical signal, which enables the use of BPs in sensing devices.

Role of Dopamine D2 Receptors in the Consolidation of Amphetamine-Cue Memory in Conditioned Activity in Rats

The neurotransmitter dopamine (DA) plays an essential role in reward-related incentive learning, whereby neutral stimuli gain the ability to elicit approach and other responses. In an incentive learning paradigm called conditioned activity, animals receive a stimulant drug in a specific environment over the course of several days. When then placed in that environment drug-free, they generally display a conditioned hyperactive response. Modulating DA transmission at different time points during the paradigm has been shown to disrupt or enhance conditioning effects. For instance, blocking DA D2 receptors before sessions generally impedes the acquisition of conditioned activity. To date, no studies have examined the role of D2 receptors in the consolidation phase of conditioned activity; this phase occurs immediately after acquisition and involves the stabilization of memories for long-term storage. To investigate this possible role, I trained Wistar rats (N = 108) in the conditioned activity paradigm produced by amphetamine (2.0 mg/kg, intraperitoneally) to examine the effects of the D2 antagonist haloperidol (doses 0.10, 0.25, 0.50, 0.75, 1.0, & 2.0 mg/kg, intraperitoneally) administered 5 min after conditioning sessions. Two positive control groups received haloperidol 1 h before conditioning sessions (doses 1.0 mg/kg and 2.0 mg/kg). The results revealed that post-session haloperidol at all doses tested did not disrupt the consolidation of conditioned activity, while pre-session haloperidol at 2.0 mg/kg prevented acquisition, with the 1.0 mg/kg group trending toward a block. Additionally, post-session haloperidol did not diminish activity during conditioning days, unlike pre-session haloperidol. One possible reason for these findings is that the consolidation phase may have begun earlier than when haloperidol was administered, since the conditioned activity paradigm uses longer learning sessions than those generally used in consolidation studies. Future studies may test if conditioned activity can be achieved with shorter sessions; if so, haloperidol would then be re-tested at an earlier time point. D2 receptor second messenger systems may also be investigated in consolidation. Since drug-related incentive stimuli can evoke cravings in those with drug addiction, a better understanding of the mechanisms of incentive learning may lead to the development of solutions for these individuals.

Austerity: European democracies against the wall. CEPS Paperbacks. July 2013

The crisis in the eurozone has had a dramatic impact on the economic and social fabric of European countries. However important it may be, the economic dimension is only the symptom of a broader problem. The crisis is primarily political in nature. Lorenzo Bini Smaghi argues in this book that the crisis reflects the inability of western democracies to solve problems that have been building for over two decades. He finds that democratically elected officials are loathe to take unpopular decisions that could jeopardise their re-election. Emergency thus becomes the engine of political action, and the justification for corrective measures vis-à-vis the voters. As a consequence, the cure in the form of austerity, administered belatedly and under pressure from the markets, becomes even more painful and unpopular, giving rise to populist movements and endangering democracy itself.

Poor and under pressure: the social impact of Europe's fiscal consolidation. Bruegel Policy Contribution, Issue 2015/04, March 2015

Europe faces major challenges related to poverty, unemployment and polarisation between the south and the north, which impact adversely the current living conditions of many citizens, and also negatively impact medium- and long-term economic growth. Fiscal consolidation exaggerated social hardship. In vulnerable countries there was no alternative to fiscal consolidation, but in most EU countries and at aggregate EU level, consolidation was premature when the cyclical position of the economy was deteriorating. Spending on social protection was shielded relative to other spending categories, but public bank rescue costs were high. While the changes in the tax mix favoured job creation, the overall tax burden become more regressive. There is an increasing generational divide between the elderly and the young in terms of social indicators. Social spending on elderly people was favoured relative to spending on families, children and education. There is now a serious danger that a lost generation might develop in several member states. Forceful policies should include bold structural reforms, better use of the European economic governance framework, more demand promotion, and a revision of national tax/benefit systems for fair burden sharing between the wealthy and poor.

A case for adjusting fiscal consolidation in the eurozone. European Policy Brief No. 14, January 2013

Fiscal consolidation is essential to ensure the sustainability of eurozone countries’ public debt. However, as a principle, consolidation should not be pursued at a pace unnecessarily undermining growth in the short term. Repeated downward revisions of growth call for the use of the flexibility foreseen in the EU fiscal framework. The Commission should adapt the deadlines for fiscal correction to prevent excessive, pro-cyclical adjustment in 2013. In turn, adequate surveillance and coordination must ensure structural adjustments constitute the core of fiscal consolidation plans.

The Politics of Budget Consolidation in Britain and Germany: the Impact of Blame-Avoidance Opportunities. CES Germany & Europe Working Papers, No. 05.2, 2005

According to parts of the literature, blame avoidance opportunities, i.e. the necessity and applicability of blame avoidance strategies, may differ among countries according to the respective institutional set-ups and between governing parties according to their programmatic orientation. In countries with many veto actors, a strategy of "Institutional Cooperation" among these actors is expected to diffuse blame sufficiently to render other blame avoidance strategies obsolete. In contrast, governments in Westminster democracies should resort to the more unilateral strategies of presentation, policy design and timing. At the same time, parties of the left are expected to have an easier time implementing spending cuts while right parties are less vulnerable when proposing tax increases. Evidence from the politics of budget consolidation in Britain and Germany does not corroborate these hypotheses. Instead, it seems that party competition conditions the effects institutions and the partisan complexion of governments have on the politics of blame avoidance.