Between Differentiation and (Dis)Integration - Theoretical Explanations of a Post-Brexit European Union

The authors of this paper provide a critical analysis of the most prominent theoretical vehicles employed in studying differentiated integration in contemporary, post-Brexit Europe. They discuss the descriptive, explanatory, and interpretative potential of the selected theoretical approaches that are applied at the intersection of disintegration and European differentiation discourse. “The holy grail” of the theorising of the dynamic (and accelerating) processes of (dis)integration and differentiation remains undiscovered. Nevertheless, a constant search for theoretical explanation is needed in the in-depth analyses of the current state of the European Union

The Merits of a Decentralized Pollution-Monitoring System Based on Distributed Ledger Technology

Pollution-monitoring systems (PMSs) are used worldwide to sense environmental changes, such as air quality conditions or temperature increases, and to monitor compliance with regulations. However, organizations manage the environmental data collected by such PMSs in a centralized manner, which is why recorded environmental data are vulnerable to manipulation. Moreover, the analysis of pollution data often lacks transparency to outsiders, which may lead to wrong decisions regarding environmental regulations. To address these challenges, we propose a software design for PMSs based on distributed ledger technology (DLT) and the long-range (LoRa) protocol for flexible, transparent, and energy-efficient environment monitoring and data management. To design the PMS, we conducted a comprehensive requirements analysis for PMSs. We benchmarked different consensus mechanisms (e.g., BFT-SMaRt and Raft) and digital signature schemes (e.g., ECDSA and EdDSA) to adequately design the PMS and fulfill the identified requirements

Controlling Josephson transport by manipulation of Andreev levels in ballistic mesoscopic junctions

We discuss how to control dc Josephson current by influencing the structure and nonequilibrium population of Andreev levels via external electrostatic gates, external current injection and electromagnetic radiation. In particular we will consider the "giant" Josephson current in "long" SIS tunnel junctions and the regular and anomalous nonequilibrium Josephson currents in three terminal SNS junctions. We will briefly discuss applications to the Josephson field effect transistor (JOFET) and to the newly invented Josephson interference transistor (JOINT).Comment: 10 pages, 3 figures; contribution to a special volume of Superlattices and Microstructures journal (ed. P.F. Bagwell

Nitrous Oxide Fuels Blends: Research on premixed Monopropellants at the German Aerospace Center (DLR) since 2014

In 2014 DLR started research activities focused on premixed monopropellants consisting of nitrous oxide and hydrocarbons. Those propellants offer promising characteristics as they are non-toxic, deliver a high Isp consist of components with low cost and could simplify a propulsion system due to self-pressurized operation. Initially DLR chose a mixture of nitrous oxide (N2O) and ethene (C2H4). In the course of the project, a mixture of nitrous oxide and ethane (C2H6) was included to the research activities. The activities are part of DLRs Future Fuels project and divided into five main parts: 1) investigations of the combustion behavior of the propellant in a rocket combustor, 2) testing and developing of flame arresters, 3) development and reduction of reaction mechanisms, 4) numerical simulations of the combustion process and 5) basic miscibility investigations. The emphasis within the project is on the first three tasks, while the last two tasks are used to widen the knowledge about the propellants physical and combustion properties. The following paper will give a short summary of the activities carried out within the projects and focus on selected results regarding premixed propellants

The place of VEGF inhibition in the current management of renal cell carcinoma

Vascular endothelial growth factor (VEGF) is overexpressed in around 80% of patients with clear cell carcinoma of the kidney owing to the inactivation of von Hippel Lindau gene activity. VEGF stimulates angiogenesis and acts as an autocrine growth factor. A number of different agents are now available which target VEGF and its signalling pathways. A significant body of evidence has accumulated demonstrating that antagonism of VEGF and its downstream pathways is clinically useful in a significant proportion of patients with metastatic clear cell carcinoma of the kidney. Enough data is now available to recommend that patients with metastatic clear cell carcinoma of the kidney should at some point during the course of their disease be offered entry into a clinical trial enabling exposure to a targeted inhibitor of VEGF or its signalling pathways. Assuming early clinical trial data is substantiated by ongoing registration studies, efforts should be made to minimise the time taken between licensing and general availability of these active agents

Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment. Objective: To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2). Data Sources: For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013. Review/research methods: For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10–17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK. Results: For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) –0.74, 95% confidence interval (CI) –1.08 to –0.41; n = 75] and noradrenergic agents [clonidine (Dixarit®, Boehringer Ingelheim) and guanfacine: SMD –0.72, 95% CI –1.03 to –0.40; n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD –0.64, 95% CI –0.99 to –0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects. Limitations: The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions. Conclusions: Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal®, Janssen), clonidine and aripiprazole (Abilify®, Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications (‘apps’) and video consultation. Study registration: This study is registered as PROSPERO CRD42012002059

ILC2s—Trailblazers in the Host Response Against Intestinal Helminths

Group 2 innate lymphoid cells (ILC2s) were first discovered in experimental studies of intestinal helminth infection—and much of our current knowledge of ILC2 activation and function is based on the use of these models. It is perhaps not surprising therefore that these cells have also been found to play a key role in mediating protection against these large multicellular parasites. ILC2s have been intensively studied over the last decade, and are known to respond quickly and robustly to the presence of helminths—both by increasing in number and producing type 2 cytokines. These mediators function to activate and repair epithelial barriers, to recruit other innate cells such as eosinophils, and to help activate T helper 2 cells. More recent investigations have focused on the mechanisms by which the host senses helminth parasites to activate ILC2s. Such studies have identified novel stromal cell types as being involved in this process—including intestinal tuft cells and enteric neurons, which respond to the presence of helminths and activate ILC2s by producing IL-25 and Neuromedin, respectively. In the current review, we will outline the latest insights into ILC2 activation and discuss the requirement for—or redundancy of—ILC2s in providing protective immunity against intestinal helminth parasites