Die Rolle des Four-and-a-half-LIM-only-Protein 2 (FHL2) in der Gelenkzerstörung bei Rheumatoider Arthritis

Die Rheumatoide Arthritis (RA) zeichnet sich durch schweren Inflammation und Gelenkzerstörung aus. Aktivierte synovialen Fibroblasten (RASF) haften an der Knorpelmatrix der Gelenke und sezernieren erhöhte Mengen Matrix-zerstörender Enzymen. Eine der zentralen Fragen in der RA ist, wie diese Aktivierung der RASF induziert wird. Die vorliegende Arbeit beschreibt, FHL2 als einen anti-arthritischen Faktor, der im synovialen Gewebe im Verlauf der RA transient exprimiert wird und in frühen, vorwiegend inflammatorischen Phasen hochreguliert ist. proinflammatorische Zytokine hemmen FHL2 und es kommt zur Expression von Matrix-zerstörenden Proteasen. Somit scheint Verhältnis der proinflammatorischen zu den profibrotischen Zytokinen entscheidend zu sein, ob es zu einer Heilung kommt, oder ob die RA in die chronische Phase übergeht. Die Menge des FHL2-Proteins in synovialen Fibroblasten ist an dieser Stelle entscheidend für die Richtung, in die sich die Entzündung in den Gelenken entwickelt

REPROCESSING OF POWER REACTOR FUELS. Quarterly Progress Report No. 9 for October 1, 1959 to January 1, 1960

Pressure and mechanical vibration are effective in maintaining continuous anodic dissolution in HHO/sub 3/ of stainless steel contained in an electrolytically inert anode basket. Zirconium metal can be electrolytically disintegrated in HNO/sub 2/ by the same technique: in this case 85% of the zirconium precipitates as ZrO/sub 2/ and only 15% remains in solution. When Zr- 10% U alloy is electrolytically disintegrated in HNO/sub 3/, 60 to 80% of the zirconium precipitates as ZrO/sub 2/, carrying 10% or more of the uranium. The constituents of a charge of PRDC elements, zirconium and U- Mo alloy. were dissolved in a two-step process with HNO/sub 3/ and HF. The rate of dissolution of irradiated PRDC fuel is one to two times that of unirradiated fuel. (For preceding period see DP-439.) (auth

Distributing the burdens of climate change

Global climate change raises many questions for environmental political theorists. This article focuses on the question of identifying the agents that should bear the financial burden of preventing dangerous climate change. Identifying in a fair way the agents that should take the lead in climate mitigation and adaptation, as well as the precise burdens that these parties must bear, will be a key aspect of the next generation of global climate policies. After a critical review of a number of rival approaches to burden sharing, the paper argues that only a principled and philosophically robust reconciliation of three approaches to burden sharing (‘contribution to problem’, ‘ability to pay’ and ‘beneficiary pays’) can generate a satisfactory mix of theoretical coherence and practical application

Chiral symmetry restoration and axial vector renormalization for Wilson fermions

Lattice gauge theories with Wilson fermions break chiral symmetry. In the U(1) axial vector current this manifests itself in the anomaly. On the other hand it is generally expected that the axial vector flavour mixing current is non-anomalous. We give a short, but strict proof of this to all orders of perturbation theory, and show that chiral symmetry restauration implies a unique multiplicative renormalization constant for the current. This constant is determined entirely from an irrelevant operator in the Ward identity. The basic ingredients going into the proof are the lattice Ward identity, charge conjugation symmetry and the power counting theorem. We compute the renormalization constant to one loop order. It is largely independent of the particular lattice realization of the current.Comment: 11 pages, Latex2

Sharing the effort of the European Green Deal among countries

In implementing the European Green Deal to align with the Paris Agreement, the EU has raised its climate ambition and in 2022 is negotiating the distribution of increased mitigation effort among Member States. Such partitioning of targets among subsidiary entities is becoming a major challenge for implementation of climate policies around the globe. We contrast the 2021 European Commission proposal - an allocation based on a singular country attribute - with transparent and reproducible methods based on three ethical principles. We go beyond traditional effort-sharing literature and explore allocations representing an aggregated least regret compromise between different EU country perspectives on a fair allocation. While the 2021 proposal represents a nuanced compromise for many countries, for others a further redistribution could be considered equitable. Whereas we apply our approach within the setting of the EU negotiations, the framework can easily be adapted to inform debates worldwide on sharing mitigation effort among subsidiary entities

Effort Sharing among EU Member States: Green Deal Emission Reduction Targets for 2030 (Short Version)

After having agreed in the European Council of December 2019 on transforming the European Union to climate neutrality by 2050, the next step requires adjusting the 2030 targets on climate and energy accordingly. This Research Brief focuses on the effort sharing (ES) sector, which covers all greenhouse gas (GHG) emissions that are neither included in the EU Emissions Trading Scheme (EU ETS) nor covered under “land use and land use change”1. Starting from the Effort Sharing Decision of 2018, this Brief frames the issue in the broader context of global emission budgets that are compatible with the Paris Agreement climate targets and considers criteria for allocating the respective EU budget among the EU-27. The Research Brief (full version) is available upon request: [email protected]

Membrane-Protein Interactions in a Generic Coarse-Grained Model for Lipid Bilayers

We study membrane-protein interactions and membrane-mediated protein-protein interactions by Monte Carlo simulations of a generic coarse-grained model for lipid bilayers with cylindrical hydrophobic inclusions. The strength of the hydrophobic force and the hydrophobic thickness of the proteins are systematically varied. The results are compared with analytical predictions of two popular analytical theories: The Landau-de Gennes theory and the elastic theory. The elastic theory provides an excellent description of the fluctuation spectra of pure membranes and successfully reproduces the deformation profiles of membranes around single proteins. However, its prediction for the potential of mean force between proteins is not compatible with the simulation data for large distances. The simulations show that the lipid-mediated interactions are governed by five competing factors: Direct interactions, lipid-induced depletion interactions, lipid bridging, lipid packing, and a smooth long-range contribution. The mechanisms leading to "hydrophobic mismatch" interactions are critically analyzed.Comment: 16 pages, 8 figures, accepted for publication in Biophysical Journa

Foliations of Isonergy Surfaces and Singularities of Curves

It is well known that changes in the Liouville foliations of the isoenergy surfaces of an integrable system imply that the bifurcation set has singularities at the corresponding energy level. We formulate certain genericity assumptions for two degrees of freedom integrable systems and we prove the opposite statement: the essential critical points of the bifurcation set appear only if the Liouville foliations of the isoenergy surfaces change at the corresponding energy levels. Along the proof, we give full classification of the structure of the isoenergy surfaces near the critical set under our genericity assumptions and we give their complete list using Fomenko graphs. This may be viewed as a step towards completing the Smale program for relating the energy surfaces foliation structure to singularities of the momentum mappings for non-degenerate integrable two degrees of freedom systems.Comment: 30 pages, 19 figure

Long-term risk of adverse outcomes according to atrial fibrillation type.

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE