Authority and Interest in the Theory of Right

I suggest a new role for authority and interest in the theory of right: Rights can be explicated as sets of prohibitions, permissions and commands, and they must be justified by interests. I argue as follows: (1) The two dominant theories of right—“Will Theory” and “Interest Theory”—have certain standard problems. (2) These problems are systematic: Will Theory’s criterion of the ability to enforce a duty is either false or empty outside of its original legal context, whereas Interest Theory includes in the definition of a right what actually belongs to the justification of the practice within which that right is assigned. (3) I recast the connection between authority, interests and rights in a way that avoids each theory’s standard problem. (4) The resulting theory also has three further advantages: It analyzes rights in terms of very basic and familiar concepts; it mirrors the understanding of rights in actual public discourse, and it is compatible with a wide selection of moral theories. Since its core is about a specific use of modal auxiliary verbs, I call this new theory the “Modal Theory of Right.

Cross-border cooperation: the meaning of cognitive and normative expectations for the emergence of Global research and development cooperation

Drawing on Niklas Luhmann's theory of social systems, we analyse the importance of different styles of expectation (cognitive and normative) for global research and development. In our study, we find that contrary to Luhmann's prediction in 1971, the normative expectation style still plays a vital role for the cooperative deals under examination. The second result of our study is that non-state mechanismus such as reputation, resource-dependency and trust are highly important for the stabilization of normative expectations in global business transactions. The role of the state-based legal system is reduced to stabilizing few, albeit crucial, normative expectations. --

Interest, Instructional Strategies, and the Creation of Group Space

Research on small-group work and on whole class discussions has shown specific benefits for student learning. At the same time, research on interest stresses the generation of situational interest when particular learning conditions are met. This qualitative study explores whether the type of instructional strategy (small group vs. whole class discussion) influences triggering of situational interest about theoretical and practice-oriented pedagogical topics among preservice science teachers (N = 44). Triggering of interest was identified by participation rate, degree of comfort during interactions, and quality of arguments. Results show that whole class discussions of theoretical topics shifted towards practical teaching issues, while small groups sustained the theoretical nature of a topic. Both interaction patterns imply triggering of situational interest. But the small group interaction patterns indicate the collective construction of a “triple problem-solving space”, in which content, social/relational, and interest were balanced from the start; the whole class discussions needed first to renegotiate the content

Anscombe on the Sources of Normativity

Anscombe is usually seen as a critic of “Modern Moral Philosophy.” I attempt a systematic reconstruction and a defense of Anscombe’s positive theory. Anscombe’s metaethics is a hybrid of social constructivism and Aristotelian naturalism. Her three main claims are the following: (1) We cannot trace all duties back to one moral principle; there is more than one source of normativity. (2) Whether I have a certain duty will often be determined by the social practices of my community. For instance, duties imposed by other people’s rights are socially constructed. (3) Whether something constitutes a good, however, will often be determined by human nature—which is not socially constructed

Widerspruchsvolle und ambivalente Strukturwandlugen bei noch nicht völlig absehbarer Trendrichtung

Als ein wesentliches Element der Gesundheitsreform wird am 1. Januar 2009 ein Gesundheitsfonds zur Finanzierung der Gesetzlichen Krankenversicherung eingeführt. Derzeit werden wichtige Weichen für die Gesundheitsreform gestellt. Wie ist es zu der Entscheidung für einen Gesundheitsfonds gekommen? Welche Probleme können durch die Gesundheitsreform gelöst werden und welche werden neu geschaffen? Wird der Wettbewerb im Krankenversicherungssystem gestärkt? Welche Anreiz- und Budget-Wirkungen hat die Honorarreform? In welche Richtung zeigen die Strukturwandlungen im Sozialversicherungssystem

Cross-border cooperation: the meaning of cognitive and normative expectations for the emergence of Global research and development cooperation

Drawing on Niklas Luhmann's theory of social systems, we analyse the importance of different styles of expectation (cognitive and normative) for global research and development. In our study, we find that contrary to Luhmann's prediction in 1971, the normative expectation style still plays a vital role for the cooperative deals under examination. The second result of our study is that non-state mechanismus such as reputation, resource-dependency and trust are highly important for the stabilization of normative expectations in global business transactions. The role of the state-based legal system is reduced to stabilizing few, albeit crucial, normative expectations

G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation

Platelet G i protein Gα i2 is an essential mediator of thrombo-inflammatory organ damage in mice

Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury following ischemia and reperfusion. Important regulators of platelet function are G proteins controlled by seven transmembrane receptors. The Gi protein Gα(i2) mediates platelet activation in vitro, but its in vivo role in hemostasis, arterial thrombosis, and postischemic infarct progression remains to be determined. Here we show that mice lacking Gα(i2) exhibit prolonged tail-bleeding times and markedly impaired thrombus formation and stability in different models of arterial thrombosis. We thus generated mice selectively lacking Gα(i2) in megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to those in global Gα(i2)-deficient mice. To examine the impact of platelet Gα(i2) in postischemic thrombo-inflammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to experimental models of cerebral and myocardial ischemia/reperfusion injury. In the model of transient middle cerebral artery occlusion stroke Gna(i2)(fl/fl)/PF4-Cre mice developed significantly smaller brain infarcts and fewer neurological deficits than littermate controls. Following myocardial ischemia, Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which correlated with diminished formation of the ADP-dependent platelet neutrophil complex. In conclusion, our data provide definitive evidence that platelet Gα(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo.Fil: Devanathan, Vasudharani. University of Tübingen; AlemaniaFil: Hagedorn, Ina. University Hospital; AlemaniaFil: Köhler, David. University of Tübingen; AlemaniaFil: Pexa, Katja. Universitat Dusseldorf; AlemaniaFil: Cherpokova, Deya. University Hospital; AlemaniaFil: Kraft, Peter. Universität Würzburg; AlemaniaFil: Singh, Madhurendra. Universitat Dusseldorf; AlemaniaFil: Rosenberger, Peter. University of Tübingen; AlemaniaFil: Stoll, Guido. Universität Würzburg; AlemaniaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Research Triangle Park; AlemaniaFil: Piekorz, Roland P.. Universitat Dusseldorf; AlemaniaFil: Beer-Hammer, Sandra. University of Tübingen; AlemaniaFil: Nieswandt, Bernhard. University Hospital; AlemaniaFil: Nürnberg, Bernd. University of Tübingen; Alemani

CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo

Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) is a surface glycoprotein expressed on various blood cells, epithelial cells, and vascular cells. CEACAM1 possesses adhesive and signaling properties mediated by its intrinsic immunorecep-tor tyrosine-based inhibitory motifs that recruit SHP-1 protein-tyrosine phosphatase. In this study, we demonstrate that CEACAM1 is expressed on the surface and in intracellular pools of platelets. In addition, CEACAM1 serves to negatively regulate signaling of platelets by collagen through the glycoprotein VI (GPVI)/Fc receptor (FcR)-?-chain. ceacam1 -/- platelets displayed enhanced type I collagen and GPVI-selective ligand, collagen-related peptide (CRP), CRP-mediated platelet aggregation, enhanced platelet adhesion on type I collagen, and elevated CRP-mediated alpha and dense granule secretion. Platelets derived from ceacam1-/- mice form larger thrombi when perfused over a collagen matrix under arterial flow compared with wild-type mice. Furthermore, using intravital microscopy to ferric chloride-injured mesenteric arterioles, we show that thrombi formed in vivo in ceacam1-/- mice were larger and were more stable than those in wild-type mice. GPVI depletion using monoclonal antibody JAQ1 treatment of ceacam1-/- mice showed a reversal in the more stable thrombus growth phenotype. ceacam1-/- mice were more susceptible to type I collagen-induced pulmonary thromboembolism than wild-type mice. Thus, CEACAM1 acts as a negative regulator of platelet-collagen interactions and of thrombus growth involving the collagen GPVI receptor in vitro and in vivo

G_13 is an essential mediator of platelet activation in hemostasis and thrombosis

Platelet activation at sites of vascular injury is essential for primary hemostasis, but also underlies arterial thrombosis leading to myocardial infarction or stroke. Platelet activators such as adenosine diphosphate, thrombin or thromboxane A_2 (TXA_2) activate receptors that are coupled to heterotrimeric G proteins. Activation of platelets through these receptors involves signaling through G_q, G_i and G_z (refs. 4, 5, 6). However, the role and relative importance of G12 and G13, which are activated by various platelet stimuli, are unclear. Here we show that lack of Galpha_13, but not Galpha_12, severely reduced the potency of thrombin, TXA2 and collagen to induce platelet shape changes and aggregation in vitro. These defects were accompanied by reduced activation of RhoA and inability to form stable platelet thrombi under high shear stress ex vivo. Galpha_13 deficiency in platelets resulted in a severe defect in primary hemostasis and complete protection against arterial thrombosis in vivo. We conclude that G_13-mediated signaling processes are required for normal hemostasis and thrombosis and may serve as a new target for antiplatelet drugs