An allosteric switch controls the procoagulant and anticoagulant activities of thrombin.

Thrombin is an allosteric enzyme existing in two forms, slow and fast, that differ widely in their specificities toward synthetic and natural amide substrates. The two forms are significantly populated in vivo, and the allosteric equilibrium can be affected by the binding of effectors and natural substrates. The fast form is procoagulant because it cleaves fibrinogen with higher specificity; the slow form is anticoagulant because it cleaves protein C with higher specificity. Binding of thrombomodulin inhibits cleavage of fibrinogen by the fast form and promotes cleavage of protein C by the slow form. The allosteric properties of thrombin, which has targeted two distinct conformational states toward its two fundamental and competing roles in hemostasis, are paradigmatic of a molecular strategy that is likely to be exploited by other proteases in the blood coagulation cascade.

Differential tubulogenic and branching morphogenetic activities of growth factors: implications for epithelial tissue development.

At least two kidney epithelial cell lines, the Madin-Darby canine kidney (MDCK) and the murine inner medullary collecting duct line mIMCD-3, can be induced to form branching tubular structures when cultured with hepatocyte growth factor (HGF) plus serum in collagen I gels. In our studies, whereas MDCK cells remained unable to form tubules in the presence of serum alone, mIMCD-3 cells formed impressive branching tubular structures with apparent lumens, suggesting the existence of specific factors in serum that are tubulogenic for mIMCD-3 cells but not for MDCK cells. Since normal serum does not contain enough HGF to induce tubulogenesis, these factors appeared to be substances other than HGF. This was also suggested by another observation: when MDCK cells or mIMCD-3 cells were cocultured under serum-free conditions with the embryonic kidney, both cell types formed branching tubular structures similar to those induced by HGF; however, only in the case of MDCK cells could this be inhibited by neutralizing antibodies against HGF. Thus, the embryonic kidney produces growth factors other than HGF capable of inducing tubule formation in the mIMCD-3 cells. Of a number of growth factors examined, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to be tubulogenic for mIMCD-3 cells. Whereas only HGF was a potent tubulogenic factor for MDCK cells, HGF, TGF-alpha, and EGF were potent tubulogenic factors for mIMCD-3 cells. Nevertheless, there were marked differences in the capacity of these tubulogenic factors to induce tubulation as well as branching events in those tubules that did form (HGF >> TGF-alpha > EGF). Thus, at least three different growth factors can induce tubulogenesis and branching in a specific epithelial cell in vitro (though to different degrees), and different epithelial cells that are capable of forming branching tubular structures demonstrate vastly different responses to tubulogenic growth factors. The results are discussed in the context of branching morphogenesis during epithelial tissue development.

Analyzing the commercial activities of a street network by ranking their nodes: a case study in Murcia, Spain

Urban researchers and planners are often interested in understanding how economic activities are distributed in urban regions, what forces influence their special pattern and how urban structure and functions are mutually dependent. In this paper, we want to show how an algorithm for ranking the nodes in a network can be used to understand and visualize certain commercial activities of a city. The first part of the method consists of collecting real information about different types of commercial activities at each location in the urban network of the city of Murcia, Spain. Four clearly differentiated commercial activities are studied, such as restaurants and bars, shops, banks and supermarkets or department stores, but obviously we can study other. The information collected is then quantified by means of a data matrix, which is used as the basis for the implementation of a PageRank algorithm which produces a ranking of all the nodes in the network, according to their significance within it. Finally, we visualize the resulting classification using a colour scale that helps us to represent the business network.

The Developmental Activities of Elite Ice Hockey Players

The purpose of this study was to analyze the development of four 20 year-old elite hockey players through an in-depth examination of their sporting activities. The theoretical frameworkof deliberate practice (Ericsson, Krampe, & Tesch-Romer, 1993) and the notion of deliberate play (Côté, 1999) served as the theoretical foundations. Interviews were conducted to providea longitudinal and detailed account of each participant.s involvement in various sporting activities. The interviewer asked questions about the conditions and sporting activities for eachyear of development. The data obtained were validated through independent interviews conducted with three parents of three different athletes. The results were consistent with Côté.s(1999) three stages of development in sport: the sampling (age 6.12), specializing (age 13. 15), and investment (age 16+) years

Developmental Paths and Activities of Successful Sport Coaches

The purpose of this research report is to present an overview of an ongoing, international project designed to chart the developmental paths and activities of sport coaches. This brief report includes three sections: (a) conceptual framework used to guide the project, (b) project design and methodology, and (c) results from pilot studies with a sample of 15 successful coaches working in different sport contexts in the United States Unlike the findings for athletic profiles, where several trends across coaching contexts were evident, only one trend was found in how these diverse groups of coaches invested their time in coach developmental activities. In relation to other coaching activities very little time was devoted to formal coach education on an annual basis. The results reinforce the need to consider the coaching context when examining coach development and when designing coach development initiatives.

The autonomy of the EU legal order and the law-making activities of international organizations. Some examples regarding the Council most recent practice. Research Papers in Law 03/2012

[Introduction.] It is generally believed that while the principle of the autonomy of the EU legal order, in the sense of constitutional and institutional autonomy that is to say what concerns the autonomous decision-making of the EU, has been clearly strengthened by the most recent jurisprudence of the Court of Justice (eg. Moxplant3, Intertanko or the Kadi/Al Baraakat judgements or the Opinion 1/2009 of the CJEU etc.) as well as, in my opinion, in many aspects by the Treaty of Lisbon, it is still valid to add that the principle of a favourable approach, stemming from the Court jurisprudence, for the enhanced openness of the EU legal order to international law has remained equally important for the EU4. On the other hand, it should be also seen that in a globalized world, and following the increased role of the EU as an international actor, its indispensable and crucial role concerning the creation of world (legal) order in many policy fields ( for example let's think about the G20 issues, the global economic and financial crisis, the role of the EU in promoting and protecting human rights worldwide, the implementation of the multilateral or regional conventional law, developed in the framework the UN (e.g. in the field of agriculture or environment etc) or what concerns the Kyoto process on climate change or the conservation of marine biological resources at international level etc), it seems reasonable and justified to submit that the influence, for example, of the law-making activities of the main stakeholder international organizations in the mentioned policy-areas on the EU (especially on the development of its constantly evolving legal order) or vice-versa the influence of the EU law-making practice on these international organizations is significant, in many aspects mutually interdependent and more and more remarkable. This tendency of the 21st century doesn't mean, however, in my view, that the notion of the autonomy of the EU legal order would have been weakened by this increasing interaction between international law and EU law over the passed years. This contribution is going to demonstrate and prove these departuring points by giving some concrete examples from the most recent practice of the Council (all occuring either in the second half of 2009 or after the entry into force of the Lisbon Treaty), and which relate to two very important policy areas in the EU, namely the protection of human rights and the Common Fishery Policy.