Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Curio’s six lictors with laureled fasces (Cic. Att. 10.4.9) are best explained by his holding command in 49 BC not as Caesar’s legatus, but pro praetore with imperium nominally in his own right, granted (‘extra-constitutionally’) by Caesar directly, without vote of Senate and People.

Some humanist theologians within the French Reformed Church in the 17th century developed the notion that a disability of the intellect could exist in nature independently of any moral defect, freeing its possessors from any obligations of natural law. Sharpened by disputes with the church leadership, this notion began to suggest a species-type classification that threatened to override the importance of the boundary between elect and reprobate in the doctrine of predestination. This classification seems to look forward to the natural (...) history of mind that emerged later in the century. (shrink)

Les résultats de la physique quantique rendent manifeste une vérité que les philosophes sont en général mal disposés à reconnaître : c’est que le déterminisme n’est pas une affirmation sur la structure des choses, mais une méthode qui ne sert qu’à prédire le cours futur des événements. Les savants, en découvrant ses limites, ont donné aux philosophes et surtout aux logiciens une leçon inestimable sur la methode de la science et la nature de la eonnaissance.

Companies do have ethical responsibility and are not protected by limited liability from the consequences of their actions. A company's record and the preception of its ethics affect its reputation and ensure long term success or failure.The financial community has a history of placing moral considerations above legal or opportunistic expedients. But we are often exposed to moral dangers and the dangers of contamination are increasing. Deregulation and the technological revolution are sharpening ethical conflicts.

Liebe Frau Henry! Soeben bekomme ich Ihren Brief, Die Freude, die mir Ihre Ankündigung macht, veranlaßt mich, Ihnen sofort zu antworten. Sie wissen wohl, daß ich seit Jahren wünsche, Sie möchten Ihre philosophischen Arbeiten fortsetzen und möchten die dafür notwendige Muße finden. Ich weiß nicht, ob Sie wissen, daß ich Sie mehrfach für philosophische Lehrstühle, über deren Besetzung ich unter dem Gesichtspunkt der Naturphilosophie gefragt worden bin, vorgeschlagen habe.

In this paper a semantics for dynamic predicate logic is developed that uses sequence valued assignments. This semantics is compared with the usual relational semantics for dynamic predicate logic: it is shown that the most important intuitions of the usual semantics are preserved. Then it is shown that the refined semantics reflects out intuitions about information growth. Some other issues in dynamic semantics are formulated and discussed in terms of the new sequence semantics.