An uphill struggle? Towards coordinated EU engagement with China’s Belt and Road Initiative. EPC Policy Brief No. 48 November 2017

China’s 19th Party Congress unexpectedly amended the party’s constitution with a pledge to “pursue the Belt and Road Initiative”. This further elevates the status of president Xi’s heavily promoted foreign policy, which aims at creating trade and investment opportunities through the development of Eurasia’s continental and maritime infrastructure. As the implications of this policy are increasingly felt across Europe, following years of growing Chinese investments, so are the challenges it presents to Europe’s unity, prosperity and security. In light of these challenges a constructive engagement with China’s Belt and Road Initiative (BRI) constitutes an immense task for the European Union, whose position has been weakened by growing dissent among member states over the Union’s policy towards China

Draft Genome Sequences of Chlamydiales Bacterium STE3 and Neochlamydia sp. Strain AcF84, Endosymbionts of Acanthamoeba spp.

Chlamydiales bacterium STE3 and Neochlamydia sp. strain AcF84 are obligate intracellular symbionts of Acanthamoeba spp. isolated from the biofilm of a littoral cave wall and gills from striped tiger leaf fish, respectively. We report the draft genome sequences of these two environmental chlamydiae affiliated with the family Parachlamydiaceae

Ameliorative effect of IDS30, a stinging nettle leaf extract, on chronic colitis

Background and aims: Anti-TNF-α antibodies are very effective in the treatment of acute Crohn's disease, but are limited by the decline of their effectiveness after repeated applications. The stinging nettle leaf extract, IDS30, is an adjuvant remedy in rheumatic diseases dependent on a cytokine suppressive effect. We investigated the effect of IDS30 on disease activity of murine colitis in different models. Methods: C3H.IL-10−/− and BALB/c mice with colitis induced by dextran sodium sulphate (DSS) were treated with either IDS30 or water. Mice were monitored for clinical signs of colitis. Inflammation was scored histologically, and faecal IL-1β and mucosal cytokines were measured by ELISA. Mononuclear cell proliferation of spleen and Peyer's patches were quantified by 3H-thymidine. Results: Mice with chronic DSS colitis or IL-10−/− mice treated with IDS30 clinically and histologically revealed significantly (p<0.05) fewer signs of colitis than untreated animals. Furthermore, faecal IL-1β and mucosal TNF-α concentrations were significantly lower (p<0.05) in treated mice. Mononuclear cell proliferation after stimulation with lipopolysaccharide was significantly (p<0.001) reduced in mice treated with IDS30. Conclusions: The long-term use of IDS30 is effective in the prevention of chronic murine colitis. This effect seems to be due to a decrease in the Th1 response and may be a new therapeutic option for prolonging remission in inflammatory bowel diseas

The impacts of mining activities on the environment and the necessity for an environmental assessment strategy for such activity in South Africa

Mining activities disturb the earth’s geology and destabilise the geo-environment, with a consequent negative impact on sustainability. There is a close link between the mining sector, geology and urban development. A geo-environmental assessment (assessment of the spatial influence of geology on the environment), focusing on the regional geological character and setting, must therefore also lay the foundation for a long-term sustainable assessment of mining-related urban development. This must be done as a specialist study and be part of required environmental assessment on strategic level prior to development. Examples and historical cases of such developments indicate that this assessment must be based on the following three main aspects:•Characterisation of the underlying geology and mining-related structures: Specific geological environments and mining-related structures result in destabilisation and sinkhole development, as well as earth movement enhanced by mining activity, with a negative impact on the sustainability of mining-related urban development.•Characterisation of related natural resources: The physical character, long-term capacity, delineation and setting of all natural resources involved with mining activities affect the sustainability of related urban development. This includes water supply from groundwater resources, as well as the ore-body and natural resources needed to sustain the mining operation and urban development.•Characterisation of geological waste and pollutants: The disturbances of the geology during mining activities give rise to an unnatural interaction with the atmosphere. This results in acid mine drainage, contaminating water resources and pollution of the atmosphere with negative impact on sustainability.This article reviews the impacts of mining activities on the geo-environment and argues that the assessment thereof must be based on an integration of the legal required strategically environmental assessments, eco-efficient evaluations by the mining sector, and within the context of the global debate on sustainability

Requirements for an Open Digital Platform for Interdisciplinary Energy Research and Practice

Energy systems are changing rapidly and energy research is fundamental to enable and optimize this change involving academics, practitioners, and the public. Therefore, an open digital platform to share knowledge and experiences is crucial for the energy sector. We identify and discuss requirements from 36 semi-structured interviews with various stakeholders for a platform based on five essential elements. The competence element enables researchers and developers to find suitable partners for their research and practice projects, and the best practices element delivers ideas to structure cooperative energy research. The repository element helps to find available data and frameworks for energy systems’ simulation and optimizations. Frameworks and models are coupled by using the simulation element. Last, results and contents from the energy community can be published within the transparency element to reach various interested stakeholders. We discuss implications and recommendations as well as further research directions

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation

Background: Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions. Methods: Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O2) vs. normoxic conditions (21% O2). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi). Results: The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition. Conclusions: Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT0064175

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Treatment of chronic viral hepatitis in woodchucks by prolonged intrahepatic expression of interleukin-12

Chronic hepatitis B is a major cause of liver-related death worldwide. Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis B virus infection. Here, we tested the therapeutic potential of IL-12 gene therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), an infection that closely resembles chronic hepatitis B. The woodchucks were treated by intrahepatic injection of a helper-dependent adenoviral vector encoding IL-12 under the control of a liver-specific RU486-responsive promoter. All woodchucks with viral loads below 10(10) viral genomes (vg)/ml showed a marked and sustained reduction of viremia that was accompanied by a reduction in hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver histology. In contrast, none of the woodchucks with higher viremia levels responded to therapy. The antiviral effect was associated with the induction of T-cell immunity against viral antigens and a reduction of hepatic expression of Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the resistance to therapy in highly viremic woodchucks. These studies showed that lymphocytes from healthy woodchucks or from animals with low viremia levels produced gamma interferon (IFN-gamma) upon IL-12 stimulation, while lymphocytes from woodchucks with high viremia failed to upregulate IFN-gamma in response to IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat chronic hepadnavirus infection in woodchucks with viral loads below 10(10) vg/ml. Interestingly, this therapy is able to break immunological tolerance to viral antigens in chronic WHV carriers

Choosing the right model for unified flexibility modeling

Using aggregated flexibility from distributed small-scale power devices is an extensively discussed approach to meet the challenges in modern and increasingly stochastic energy systems. It is crucial to be able to model and map the flexibility of the respective power devices in a unified form to increase the value of the cumulative flexibility from different small-scale power devices by aggregation. In order to identify the most suitable approach for unified flexibility modeling we present a framework to evaluate and compare the advantages and disadvantages of already existing modeling approaches in different levels of detail. As an introduction to flexibility modeling and as a basis for the evaluation process we initially provide a comprehensive overview of the broad range of flexibility models described in scientific literature. Subsequently, five selected modeling approaches allowing the generation of a unified flexibility representation for different power devices are presented in detail. By using an evaluation metric we assess the suitability of the selected approaches for unified flexibility modeling and their applicability. To allow a more detailed performance analysis, the best evaluated models are implemented and simulations with different small-scale devices are performed. The results shown in this paper highlight the heterogeneity of modeling concepts deriving from the various interpretations of flexibility in scientific literature. Due to the varying complexity of the modeling approaches, different flexibility potentials are identified, necessitating a combination of approaches to capture the entire spectrum of the flexibility of different small-scale power devices. Furthermore, it is demonstrated that a complex model does not necessarily lead to the discovery of higher flexibility potentials, and recommendations are given on how to choose an appropriate model. © 2022, The Author(s)