Pan-European backcasting exercise, enriched with regional perspective, and including a list of short-term policy options

This deliverable reports on the results of the third and final pan-European stakeholder meeting and secondly, on the enrichment with a Pilot Area and regional perspective. The main emphasis is on backcasting as a means to arrive at long-term strategies and short-term (policy) actions

Liposomal Antioxidants for Protection against Oxidant-Induced Damage

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress

Channeling Effects in Direct Dark Matter Detectors

The channeling of the ion recoiling after a collision with a WIMP changes the ionization signal in direct detection experiments, producing a larger signal than otherwise expected. We give estimates of the fraction of channeled recoiling ions in NaI (Tl), Si and Ge crystals using analytic models produced since the 1960's and 70's to describe channeling and blocking effects. We find that the channeling fraction of recoiling lattice nuclei is smaller than that of ions that are injected into the crystal and that it is strongly temperature dependent.Comment: 8 pages, 12 figures, To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

BACKGROUND: Hypothermic perfusion (HP) of the liver is applied during total vascular exclusion (TVE) to reduce ischemic injury during liver resection. No studies have been performed comparing different perfusion solutions for HP. The aim of this experimental study was to compare Ringer-lactate solution (RL) with Celsior solution (Cs) for HP in a pig model of 60-min TVE. METHOD: Twenty pigs underwent 60-min TVE of the liver. Groups were TVE without HP (no-HP, n = 9), TVE with HP using RL (n = 6), and TVE with HP using Cs (n = 5). Blood and liver tissue samples were taken before TVE and during 24-h reperfusion. RESULTS: In the no-HP group, plasma aspartate aminotransferase values were significantly increased during reperfusion (p <0.05), while liver tissue pO(2) levels (p <0.01) were decreased when compared to the HP groups. After 24-h reperfusion, bile production and liver tissue glutathione content were significantly higher (p <0.05) in the Cs group (42.0 +/- 1.7 mL/h and 44.9 +/- 2.2 nmol/mg, respectively) as compared to the RL group (31.5 +/- 3.5 mL/h and 19.6 +/- 1.8 nmol/mg, respectively). CONCLUSION: The protective effect of HP during TVE was confirmed in this study. HP with Cs was more effective in reducing ischemic injury as compared to HP with R

Energy Investments under Climate Policy: A Comparison of Global Models

The levels of investment needed to mobilize an energy system transformation and mitigate climate change are not known with certainty. This paper aims to inform the ongoing dialogue and in so doing to guide public policy and strategic corporate decision making. Within the framework of the LIMITS integrated assessment model comparison exercise, we analyze a multi-IAM ensemble of long-term energy and greenhouse gas emissions scenarios. Our study provides insight into several critical but uncertain areas related to the future investment environment, for example in terms of where capital expenditures may need to flow regionally, into which sectors they might be concentrated, and what policies could be helpful in spurring these financial resources. We find that stringent climate policies consistent with a 2 degrees C climate change target would require a considerable upscaling of investments into low-carbon energy and energy efficiency, reaching approximately $45 trillion (range:$30-75 trillion) cumulative between 2010 and 2050, or about $1.1 trillion annually. This represents an increase of some$30 trillion ($10-55 trillion), or$0.8 trillion per year, beyond what investments might otherwise be in a reference scenario that assumes the continuation of present and planned emissions-reducing policies throughout the world. In other words, a substantial "clean-energy investment gap" of some $800 billion/yr exists -- notably on the same order of magnitude as present-day subsidies for fossil energy and electricity worldwide ($523 billion). Unless the gap is filled rather quickly, the 2 degrees C target could potentially become out of reach

Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating coronavirus outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses-including SARS-CoV, MERS-CoV, and SARS-CoV-2-is the papain-like protease (PLpro). PLpro cleaves part of the viral replicase polyproteins into non-structural protein subunits, which are essential to the viral replication cycle. Additionally, PLpro can cleave both ubiquitin and the ubiquitin-like protein ISG15 from host cell substrates as a mechanism to evade innate immune responses during infection. These roles make PLpro an attractive antiviral drug target. Here we demonstrate that ubiquitin variants (UbVs) can be selected from a phage-displayed library and used to specifically and potently block SARS-CoV-2 PLpro activity. A crystal structure of SARS-CoV-2 PLpro in complex with a representative UbV reveals a dimeric UbV bound to PLpro at a site distal to the catalytic site. Yet, the UbV inhibits the essential cleavage activities of the protease in vitro and in cells, and it reduces viral replication in cell culture by almost five orders of magnitude

IMAGE and MESSAGE Scenarios Limiting GHG Concentration to Low Levels

This report discusses the attainability of low greenhouse gas concentrations levels based on an analysis using two integrated assessment models (MESSAGE and IMAGE). Model runs were preformed which explored the feasibility of reaching radiative forcing levels in 2100 between 2.6 to 2.9 W/m2 above pre-industrial levels. Such low targets are necessary to limit global mean temperature increase to below 2oC compared to pre-industrial levels with high probability. The analysis examines the attainability of low targets systematically with respect to key uncertainties, including alternative baseline development pathways, availability of different technologies, emissions of bio-energy, and impacts of forestry and land use assumptions. A number of sensitivity tests were carried out to test the robustness of achieving low GHG concentration targets. The results from the two models are discussed in detail comprising energy profiles and emission pathways consistent with such low stabilization targets