In vivo relevance for platelet glycoprotein Ib alpha residue Tyr276 in thrombus formation

Background: Platelet glycoprotein (GP) Ib-IX-V supports platelet adhesion on damaged vascular walls by binding to von Willebrand factor (VWF). For several decades it has been recognized that the alpha-subunit of GP (GPIb alpha) also binds thrombin but the physiological relevance, if any, of this interaction was unknown. Previous studies have shown that a sulfated tyrosine 276 (Tyr276) is essential for thrombin binding to GPIb alpha.Objectives: This study investigated the in vivo relevance of GPIb alpha residue Tyr276 in hemostasis and thrombosis.Methods: Transgenic mouse colonies expressing the normal human GPIb alpha subunit or a mutant human GPIb alpha containing a Phe substitution for Tyr276 (hTg(Y276F)) were generated. Both colonies were bred to mice devoid of murine GPIb alpha.Results: Surface-expressed GPIb alpha levels and platelet counts were similar in both colonies. hTg(Y276F) platelets were significantly impaired in binding alpha-thrombin but displayed normal binding to type I fibrillar collagen and human VWF in the presence of ristocetin. In vivo thrombus formation as a result of chemical damage (FeCl3) demonstrated that hTg(Y276F) mice have a delayed time to occlusion followed by unstable blood flow indicative of embolization. In models of laser-induced injury, thrombi developing in hTg(Y276F) animals were also less stable.Conclusions: The results demonstrate that GPIb alpha residue Tyr276 is physiologically important, supporting stable thrombus formation in vivo.

Climate Change Mitigation and Intergenerational Justice

Existing climate change mitigation policies are particularly concerned with the reconciliation of two seemingly conflicting aims: environmental protection and economic efficiency. The normative principles underlying these policies meanwhile focus on two central ideas: fair burden-sharing and agents' responsibility. However, both existing policy instruments and their supporting philosophical principles are highly problematic in terms of intergenerational justice and truly effective climate change mitigation. Three competing conceptions for allocating and distributing the burdens of climate change mitigation (cap-and-trade schemes, carbon emission taxes, and personal ecological space quotas) and their compatibility with principles of intra- and intergenerational justice are analysed and evaluated. None of the proposed instruments is able to satisfy the demands of effective mitigation and egalitarian justice on its own, which suggests that existing proposals for the distribution of emission rights and climate change-related costs need to be supported by a thicker account of intergenerational justice.

Reconsidering Resource Rights: The Case for a Basic Right to the Benefits of Life-Sustaining Ecosystem Services

In the presence of anthropogenic climate change, gross environmental degradation, and mass abject poverty, many political theorists currently debate issues such as people's right to water, the right to food, and the distribution of rights to natural resources more generally. However, thus far many theorists either focus (somewhat arbitrarily) only on one particular resource (e.g. water) or they treat all natural resources alike, meaning that many relevant distinctions within the group of natural resources are overlooked. Hence, the paper will start with an analysis of the various forms which natural resources can take and how this might influence one's conception of resource rights. In so doing, the paper argues that we have to carefully distinguish between the actual physical resources people might control and how we distribute these, and the life-sustaining benefits each and every person draws from sustainable and functioning ecosystems. Based on this distinction, the paper will argue for a right to the benefits of life-sustaining ecosystem services as a universal basic right every person has. Further distributive claims with respect to particular physical resources would thus be limited by the requirements of such a basic right.

D3.1 Benefits Analysis of the Initial Operational Cruiser-Feeder Concept

The REsearch on a CRuiser Enabled Air Transport Environment (RECREATE) project is considers the introduction and airworthiness of cruiser-feeder operations for civil aircraft. Cruiser-feeder operations are investigated as a promising pioneering idea for the air transport of the future. The soundness of the concept of cruiser-feeder operations for civil aircraft can be understood, taking air-to-air refueling operations as an example. For this example, a comprehensive estimate of the benefits can be made, which shows a fuel burn reduction potential and a CO2 emission reduction of 31% for a typical 6000 nautical miles flight with a payload of 250 passengers. This reduction potential is known to be large by any standard. The top level objective of the RECREATE project is to demonstrate on a preliminary design level that cruiser-feeder operations (as a concept to reduce fuel burn and CO2 emission levels) can be shown to comply with the airworthiness requirements for civil aircraft. The underlying Scientific and Technological (S&T) objectives are to determine and study airworthy operational concepts for cruiser-feeder operations, and to derive and quantify benefits in terms of CO2 emission reduction but also other benefits.

Work Package (WP) 3 has the objective to substantiate the assumed benefits of the cruiser/feeder operations through refined analysis and simulation. In this report, initial benefits evaluation of the initial RECREATE cruiser/feeder concepts is presented. The benefits analysis is conducted in delta mode, i.e. comparison is made with a baseline system. Since comparing different aircraft and air transport systems is never a trivial task, appropriate measures and metrics are defined and selected first. Non-dimensional parameters are defined and values for the baseline system derived.

The impact of cruiser/feeder operations such as air-to-air refueling are studied with respect to fuel-burn (or carbon-dioxide), noise and congestion. For this purpose, traffic simulations have been conducted.
Cruiser/feeder operations will have an impact on dispatch reliability as well. An initial assessment of the effect on dispatch reliability has been made and is reported.

Finally, a considerable effort has been made to create the infrastructure for economic delta analysis of the cruiser/feeder concept of operation. First results of the cost analysis have been obtained.

A Probe-Goal Approach to Agreement and Incorporation Restrictions in Southern Tiwa

Southern Tiwa (Tanoan) exhibits agreement with up to three arguments (ergative, absolutive, dative). This agreement is subject to certain restrictions resembling the Person-Case Constraint paradigm (Bonet 1991). Moreover, there is a correlation between agreement restrictions and conditions on (the obviation of) noun-incorporation in Southern Tiwa, as explicitly and elegantly captured by Rosen (1990) in terms of a heterogeneous feature hierarchy and rules of association. We attempt to recast Rosen’s central insights in terms of Anagnostopoulou’s probe-sharing model of Person-Case Constraint effects (Anagnostopoulou 2003, 2006), to show that the full range of Southern Tiwa agreement and (non-)incorporation restrictions can be given a single, unified analysis within the probe-goal-Agree framework of Chomsky (2001). In particular, we argue that Southern Tiwa’s triple-agreement system is characterized by (a) an independent class probe located on the heads T and v, and (b) a rule that allows this class probe to be deleted in the context of local-person T-agreement. The various restrictions on agreement and non-incorporation then reduce to a single source: failure of class-valuation with DP (as opposed to NP) arguments.