A modernised ECT reflecting EU values and objectives: a multilateral framework promoting energy investment in a sustainable way?

In recent years, the Energy Charter Treaty has come under immense scrutiny and criticism for allegedly protecting the fossil fuel industry and undercutting sovereignty. As a key stakeholder in the modernisation process, the EU has been determined to reform the investment protection standards and the investor–state dispute settlement mechanism to include new provisions on sustainable development and climate change. However, after three years of protracted negotiations, the proposed reform of the Energy Charter Treaty needs to appropriately address the escalating global challenges regarding climate action and sustainable development. With member states such as Poland, Spain and the Netherlands announcing their intention to withdraw, the future of the Charter is hanging in the balance. This article focuses on the modernisation of the Energy Charter Treaty and whether the reformed Charter is fit for purpose, from an EU perspective, to address the impacts of climate change. In the absence of meeting core EU objectives and alignment with the Paris Agreement, this article questions whether the EU can deviate from the only multilateral framework in the energy sector to address the EU’s climate policy goals. The extent to which the Charter is capable of a new lease of life, moving from the ashes of the Cold War as an instrument facilitating investment protection to a green treaty promoting sustainable development and climate change, remains to be seen

On the Efficiency of Atomic Multi-reader, Multi-writer Distributed Memory

This paper considers quorum-replicated, multi-writer, multi-reader (MWMR) implementations of surviv-able atomic registers in a distributed message-passing system with processors prone to failures. Previous implementations in such settings invariably required two rounds of communication between readers/writers and replica owners. Hence the question arises whether it is possible to have single round read and/or write operations in this setting. As a first step, we present an algorithm, called CWFR, that allows the classic two round write operations, while supporting single round read operations. Since multiple write operations may be concurrent with a read operation, this algorithm involves an iterative (local) discovery of the latest completed write operation. This algorithm precipitates the question of whether fast (single round) writes may co-exist with fast reads. We thus devise a second algorithm, called SFW, that exploits a new technique called server side ordering (SSO), which –unlike previous approaches – places partial responsibility for the ordering of write operations on the replica owners (the servers). With SSO, fast write operations are introduced for the very first time in the MWMR setting. While this is possible, we show that under certain conditions the MWMR model imposes in-herent limitations on any quorum-based fast write implementation of a safe read/write register and potentiall

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

__Background:__ Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma. __Methods:__ To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined. __Results:__ Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells. __Conclusion:__ These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma

Pharma-nutrition interface: The gap is narrowing

The interaction between pharmacology and nutrition science is on the rise. Nutritional status is considered one of the important determinants of health and disease and several diseases of our time have a clear link with lifestyle factors including the diet. There is also increasing realization that a continuum between health and disease often exists without strict boundaries. Understanding the subtle interactions between genes, environment and homeostatic processes is the key in finding effective ways to prevent, treat or manage disease. Both pharmacologists and nutritionists are recognizing that most of the low hanging fruit has been picked, and that the one disease–one target–one drug (or nutrient) concept will provide fewer successes than it did in the past. Instead, complex multi-factorial diseases require multi-pathway understanding and multi-targeting approaches which will often result in compound combinations. Therapeutic synergy between foods and drugs does not necessarily mean that both have the same primary target. There are also examples of nutritional products that effectively contribute to the therapeutic regimen by improving the patients' general condition or by reducing side-effects of drugs. Examples of conditions and diseases that are highlighted in this review include the metabolic syndrome with its co-morbidities, immune-related diseases and HIV. With the aging population there are other fields emerging, including CNS-related diseases and cancer, where we will likely see an increased synergy between the two disciplines that seemed to have lost contact since the times of Hippocrate

Endothelial activation and induction of monocyte adhesion by nontransferrin-bound iron present in human sera.

Contains fulltext : 49413.pdf (publisher's version ) (Closed access)Nontransferrin-bound iron (NTBI) has been detected in iron overload diseases. This form of iron may exert pro-oxidant effects and modulate cellular function and inflammatory response. The present study has aimed to investigate the effects of serum NTBI on monocyte adherence to endothelium. Measured by a recently developed high-throughput fluorescence-based assay, serum NTBI was found to be higher in both homozygotes of HFE C282Y mutation of hereditary hemochromatosis (7.9+/-0.6 microM, n=9, P<0.001) and heterozygotes (4.0+/-0.5 microM, n=8, P<0.001), compared with controls (1.6+/-0.2 microM, n=21). The effects of these sera on monocyte adhesion and endothelial activation were examined. Adhesion of normal human monocytes to C282Y homozygote- and heterozygote-serum-treated human umbilical vein endothelial cells was higher (25.0+/-0.9 and 22.1+/-0.7%, respectively) compared with controls (17.6+/-0.5%, both P<0.001). For the three groups combined, the expression of adhesion molecules, ICAM-1, VCAM-1, and E-selectin, was positively correlated to NTBI levels but not to the inflammatory marker C-reactive protein. Furthermore, accumulation of intracellular labile iron and oxidative radicals within the cells due to NTBI was evidenced. Finally, counteraction of NTBI-induced endothelial activation was observed using iron chelators. These findings therefore identify a physiological function of NTBI in monocyte-endothelial interactions that may also contribute to the development of atherosclerosis and neurodegenerative diseases

Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infection.

Contains fulltext : 50778.pdf (publisher's version ) (Closed access)BACKGROUND: Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. MATERIALS AND METHODS: Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. RESULTS: An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. CONCLUSIONS: Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis

Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women.

Contains fulltext : 49568.pdf (publisher's version ) (Closed access)BACKGROUND: Epidemiological studies aimed at correlating coronary heart disease (CHD) with serum ferritin levels have thus far yielded inconsistent results. We hypothesized that a labile iron component associated with non-transferrin-bound iron (NTBI) that appears in individuals with overt or cryptic iron overload might be more suitable for establishing correlations with CHD. METHODS AND RESULTS: We investigated the relation of NTBI, serum iron, transferrin saturation, and serum ferritin with risk of CHD and acute myocardial infarction (AMI). The cohort used comprised a population-based sample of 11 471 postmenopausal women aged 49 to 70 years at enrollment in 1993 to 1997. During a median follow-up of 4.3 years (quartile limits Q1 to Q3: 3.3 to 5.4), 185 CHD events were identified, including 66 AMI events. We conducted a case-cohort study using all CHD cases and a random sample from the baseline cohort (n=1134). A weighted Cox proportional hazards model was used to estimate hazard ratios for tertiles of iron variables in relation to CHD and AMI. Adjusted hazard ratios of women in the highest NTBI tertile (range 0.38 to 3.51) compared with the lowest (range -2.06 to -0.32) were 0.84 (95% confidence interval 0.61 to 1.16) for CHD and 0.47 (95% confidence interval 0.31 to 0.71) for AMI. The results were similar for serum iron, transferrin saturation, and serum ferritin. CONCLUSIONS: Our results show no excess risk of CHD or AMI within the highest NTBI tertile compared with the lowest but rather seem to demonstrate a decreased risk. Additional studies are warranted to confirm our findings

Formal Verification of Consensus Algorithms Tolerating Malicious Faults

Abstract. Consensus is the paradigmatic problem in fault-tolerant distributed computing: it requires network nodes that communicate by message passing to agree on common value even in the presence of (benign or malicious) faults. Several algorithms for solving Consensus exist, but few of them have been rigorously verified, much less so formally. The Heard-Of model proposes a simple, unifying framework for defining distributed algorithms in the presence of communication faults. Algorithms proceed in communication-closed rounds, and assumptions on the faults tolerated by the algorithm are stated abstractly in the form of communication predicates. Extending previous work on the case of benign faults, our approach relies on the fact that properties such as Consensus can be verified over a coarse-grained, round-based representation of executions. We have encoded the Heard-Of model in the interactive proof assistant Isabelle/HOL and have used this encoding to formally verify three Consensus algorithms based on synchronous and asynchronous assumptions. Our proofs give some new insights into the correctness of the algorithms, in particular with respect to transient faults.

Rambo: a robust, reconfigurable atomic memory service for dynamic networks

n this paper, we present Rambo, an algorithm for emulating a read/write distributed shared memory in a dynamic, rapidly changing environment. Rambo provides a highly reliable, highly available service, even as participants join, leave, and fail. In fact, the entire set of participants may change during an execution, as the initial devices depart and are replaced by a new set of devices. Even so, Rambo ensures that data stored in the distributed shared memory remains available and consistent. There are two basic techniques used by Rambo to tolerate dynamic changes. Over short intervals of time, replication suffices to provide fault-tolerance. While some devices may fail and leave, the data remains available at other replicas. Over longer intervals of time, Rambo copes with changing participants via reconfiguration, which incorporates newly joined devices while excluding devices that have departed or failed. The main novelty of Rambo lies in the combination of an efficient reconfiguration mechanism with a quorum-based replication strategy for read/write shared memory. The Rambo algorithm can tolerate a wide variety of aberrant behavior, including lost and delayed messages, participants with unsynchronized clocks, and, more generally, arbitrary asynchrony. Despite such behavior, Rambo guarantees that its data is stored consistency. We analyze the performance of Rambo during periods when the system is relatively well-behaved: messages are delivered in a timely fashion, reconfiguration is not too frequent, etc. We show that in these circumstances, read and write operations are efficient, completing in at most eight message delays.National Science Foundation (U.S.) (ITR Grant CCR-0121277)National Science Foundation (U.S.) (9804665)National Science Foundation (U.S.) (9984778)National Science Foundation (U.S.) (9988304)National Science Foundation (U.S.) (0311368