Activation of Ca2+ signaling in neutrophils by the mast cell-released immunophilin FKBP12.

The immunophilins of the FK506-binding protein (FKBP) family are intracellular proteins that bind the immunosuppresants FK506 and rapamycin. In this study we show that HMC-1 mast cells sensitized with IgE release FKBP12 upon stimulation with anti-IgE. The release is rapid and not affected by actinomycin D or cycloheximide, suggesting that it is due to exocytosis from a storage compartment. FKBP12 from HMC-1 mast cells exhibits biological activity. When applied extracellularly to human neutrophils, it induces transient changes in the intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ release from intracellular stores. Inhibition of [Ca2+]i changes by ruthenium red and ryanodine indicates that ryanodine receptor/Ca2+ release channels are involved in FKBP12-induced Ca2+ signaling. Neutrophil activation by mast cell-derived FKBP12 is prevented by complexing FKBP12 with FK506 or rapamycin. These results demonstrate that extracellular FKBP12 functions as a cytokine in cell-to-cell communication. They further suggest a pathophysiological role for FKBP12 as a mediator in immediate or type I hypersensitivity and may have implications for novel therapeutic strategies in the treatment of allergic disorders with FK506 and rapamycin.

Constraining the GRB-Magnetar Model by Means of the Galactic Pulsar Population

A large fraction of Gamma-ray bursts (GRBs) displays an X-ray plateau phase within <105 s from the prompt emission, proposed to be powered by the spin-down energy of a rapidly spinning newly born magnetar. In this work we use the properties of the Galactic neutron star population to constrain the GRB-magnetar scenario. We re-analyze the X-ray plateaus of all Swift GRBs with known redshift, between 2005 January and 2014 August. From the derived initial magnetic field distribution for the possible magnetars left behind by the GRBs, we study the evolution and properties of a simulated GRB-magnetar population using numerical simulations of magnetic field evolution, coupled with Monte Carlo simulations of Pulsar Population Synthesis in our Galaxy. We find that if the GRB X-ray plateaus are powered by the rotational energy of a newly formed magnetar, the current observational properties of the Galactic magnetar population are not compatible with being formed within the GRB scenario (regardless of the GRB type or rate at z = 0). Direct consequences would be that we should allow the existence of magnetars and "super-magnetars" having different progenitors, and that Type Ib/c SNe related to Long GRBs form systematically neutron stars with higher initial magnetic fields. We put an upper limit of ≤16 "super-magnetars" formed by a GRB in our Galaxy in the past Myr (at 99% c.l.). This limit is somewhat smaller than what is roughly expected from Long GRB rates, although the very large uncertainties do not allow us to draw strong conclusion in this respect.

Solidarity and cohesion. CHALLENGE EUROPE Issue 22. Challenges and new beginnings: Priorities for the EU's new leadership, September 2014

In the past five years, the concept of solidarity has quietly lost much of its traction in the public discourse in Europe. Widely used at the time of the creation of the single market, the emergence of the common currency and during the EU's big bang enlargement of 2004-2007, it has recently become a more confused organising principle. The European system has been affected by growing levels of distrust, which has much to do with the way in which the euro zone crisis was tackled. In spite of massive resources having been mobilised to support countries in need, mutual accusations and discord have become ever more present in the EU's policy-making process.

Economic Implications of Enlargement. Bruges European Economic Policy (BEEP) Briefing 1/2002

The Eastern enlargement is about to be decided by the European Council. As expected, the “end game “ of the negotiations and assessments is heavily biased by a narrow perspective on net transfers, on income compensations to Central European farmers and on the psychological politics of a single “big bang “. None of these three so-called key items of the end game are of much relevance to appreciate the significance of enlargement. Net transfers have little to do with the costs and benefits of club membership for countries which pay, and can lead to addiction and lethargy rather than extra growth if market integration, macro-economic stability and domestic reforms are not taken serious (as the case of Greece before 1997 has demonstrated). Income compensations for Eastern farmers are crucial for this pressure group, and symbolically of some importance in domestic politics because of the perversity that rich farmers get more, but their absence is likely to serve the public interest in candidate countries far better. And being part of the big bang, as against getting in one or three years later, has assumed a dramatic meaning during this end game, far beyond its true proportions. This hectic European theatre tends to obscure what enlargement is mainly about, now that the stability and values have been secured for the peoples from Central Europe. In a guaranteed setting of peace, freedom and security, enlargement is about greater prosperity.

Contributo do médico dentista nas ciências forenses

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Disruptive Marketing Strategy - ribaltare i classici modelli di approccio al mercato

Viviamo in un epoca di cambiamenti. Continuamente, giorno dopo giorno, il vecchio scompare per fare spazio al nuovo. La tecnologia permea sempre più in ogni aspetto della vita, conquistando le nostre abitudini, cambiando il nostro modo di vedere il mondo, e, in maniera inevitabile, il nostro modo di agire. L’essere umano ha da sempre cercato di concepire cose che ancora non ci sono, per cambiare la realtà e modellarla a suo piacimento. Si parte, quindi, da qualcosa che fin dalla nascita è dentro ognuno di noi, un desiderio che arde nell'animo umano, che si alimenta grazie al soffio dell’immaginazione e che non c’è modo di spegnere. L’innovazione porta novità. Resistere al cambiamento non è sempre facile, e se si cerca di ostacolarlo esso ti travolgerà. “Affrontare il cambiamento è come scalare una colata di fango giù per una collina” - esordisce in “The Innovator Dilemma”, Clayton M. Christensen - “Bisogna affrontare qualsiasi cosa per rimanere su di essa, e non appena ci si ferma per prendere fiato si viene seppelliti”. Si intuisce come il cambiamento tecnologico non solo sia di fondamentale evidenza nella vita di ognuno, ma come esso abbia cambiato e stia cambiando il modo di fare business. In questo umile lavoro si è voluto analizzare come certi tipi di innovazione abbiano il potere di cambiare tutto un sistema di riferimento sul quale prima l’impresa faceva affidamento. Sono le Disruptive Innovation – le innovazioni dirompenti – quelle innovazioni che ribaltano un modello di business, il modo di vedere un prodotto, la logica dietro a certe operations aziendali, che seppur sembrassero solide, si sgretolano scontrandosi con innovazioni così forti. Vi è poi una domanda critica a cui si è cercato di rispondere. Si può fare Disruptive Marketing? Alcuni esempi virtuosi ci mostrano come si possa attuare una strategia di questo genere, e come si possa “comprendere, creare, comunicare e distribuire valore” in modo innovativo.

Das weisse Haus; Roman.

Translation of Det hvide hus.

Praxis medica systematice exposita selectis diarii nosocomii Fredericiani illustrata /

Mode of access: Internet.

Materialien zur Kunde des älteren englischen Dramas.

Editor: W. Bang.

Gesammelte Werke : in vier Bänden /

Mode of access: Internet.

Laws relating to agriculture,

p. 464-536: Bureau of Animal Industry act and amendments; Meat importation act ... Infectious disease of livestock and poultry ... Bang's disease or tubercular cattle.

Measures against animal tuberculosis in Denmark. Report submitted to the International Congress on Tuberculosis, Washington, 1908.

Mode of access: Internet.

Every man out of his humor : reprinted from Holme's quarto of 1600 /

Mode of access: Internet.

Geological report to the ... General Assembly of the State of Tennessee, made ...

1st report never published by the state; an extract from it is given in the Transactions of the Geological Society of Pennsylvania, v. 1, p. 240-243. A brief summary of the 2d report was published in the Tennessee House journal for 1833, p. 303-305. A 10th report was presented to the House in 1850 and printed, but no copy of it can now be found.--cf. L.C. Glenn, in American geologist, v. 35, no. 2, p. 82-89.

Odense amt : beskrevet efter opfordring af det Kgl. Landhuusholdnings-selskab.

Mode of access: Internet.