The LAB@FUTURE Project - Moving Towards the Future of E-Learning

This paper presents Lab@Future, an advanced e-learning platform that uses novel Information and Communication Technologies to support and expand laboratory teaching practices. For this purpose, Lab@Future uses real and computer-generated objects that are interfaced using mechatronic systems, augmented reality, mobile technologies and 3D multi user environments. The main aim is to develop and demonstrate technological support for practical experiments in the following focused subjects namely: Fluid Dynamics - Science subject in Germany, Geometry - Mathematics subject in Austria, History and Environmental Awareness – Arts and Humanities subjects in Greece and Slovenia. In order to pedagogically enhance the design and functional aspects of this e-learning technology, we are investigating the dialogical operationalisation of learning theories so as to leverage our understanding of teaching and learning practices in the targeted context of deployment

Understanding brønsted-acid catalyzed monomolecular reactions of Alkanes in Zeolite Pores by combining insights from experiment and theory

Acidic zeolites are effective catalysts for the cracking of large hydrocarbon molecules into lower molecular weight products required for transportation fuels. However, the ways in which the zeolite structure affects the catalytic activity at BrOnsted protons are not fully understood. One way to characterize the influence of the zeolite structure on the catalysis is to study alkane cracking and dehydrogenation at very low conversion, conditions for which the kinetics are well defined. To understand the effects of zeolite structure on the measured rate coefficient (k(app)), it is necessary to identify the equilibrium constant for adsorption into the reactant state (Kads-H+) and the intrinsic rate coefficient of the reaction (k(int)) at reaction temperatures, since k(app) is proportional to the product of Kads-H+ and k(int). We show that Kads-H+ cannot be calculated from experimental adsorption data collected near ambient temperature, but can, however, be estimated accurately from configurational-bias Monte Carlo (CBMC) simulations. Using monomolecular cracking and dehydrogenation of C-3-C-6 alkanes as an example, we review recent efforts aimed at elucidating the influence of the acid site location and the zeolite framework structure on the observed values of k(app) and its components, Kads-H+ and k(int)

Ethene dimerization on zeolite-hosted Ni ions : reversible mobilization of the active site

The active site in ethene oligomerization catalyzed by Ni-zeolites is proposed to be a mobile Ni(II) complex, based on density functional theory-based molecular dynamics (DFT-MD) simulations corroborated by continuous-flow experiments on Ni-SSZ-24 zeolite. The results of the simulations at operating conditions show that ethene molecules reversibly mobilize the active site as they exchange with the zeolite as ligands on Ni during reaction. Microkinetic modeling was conducted on the basis of free-energy profiles derived with DFT-MD for oligomerization on these mobile [(ethene)(2)-Ni-alkyl](+) species. The model reproduces the experimentally observed high selectivity to dimerization and indicates that the mechanism is consistent with the observed second-order rate dependence on ethene pressure

Population structure of multidrug resistant Klebsiella oxytoca within hospitals across the UK and Ireland identifies sharing of virulence and resistance genes with K. pneumoniae.

Klebsiella oxytoca, a member of the Enterobacteriaceae, is a gram-negative pathogenic bacterium of environmental origin, which can cause infection in healthcare settings. Outbreaks of multidrug-resistant K. oxytoca infection have been increasingly reported in hospitalized patients. Despite the growing importance of this pathogen, there is limited knowledge about the population structure and epidemiology of antimicrobial resistant K. oxytoca. We investigated the population structure and genomic basis of antimicrobial resistance of 41 multidrug resistant K. oxytoca isolates recovered from bloodstream infections across the UK and Ireland. Our results show that K. oxytoca has a highly diverse population, which is composed of several distinct clades, and we identified one recent expansion of a clone within our dataset. Although the K. oxytoca genomes are clearly distinct from the genomes of a global collection of Klebsiella pneumoniae complex, pre-dominantly composed of K. pneumoniae, we found evidence for sharing of core genes through recombination, as well as the exchange of accessory antimicrobial resistance and virulence factor genes between the species. Our findings also suggest that the different K. oxytoca clades have acquired antimicrobial resistance and virulence factor genes independently. This highlights the clinical and therapeutic importance of genetic flexibility in K. oxytoca and the relevance of this in its role as an opportunistic pathogen

Metabolic Activity and mRNA Levels of Human Cardiac CYP450s Involved in Drug Metabolism

Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68) of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7), samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects

Impact on erosive runoff and costs for local communities of agricultural-soil-use-change scenarios: the case of Pays de Caux (France)

Theme 1. WS 1.3. Understanding agricultural structural changes to support inclusive policy dialogueRecurring mudflows in the silty areas of North-West Europe and particularly in Pays de Caux (France) result in significant costs for local communities. These flows result from erosion processes which occur on agricultural land located upstream of urban areas. Farming practices depend on changes in external factors (prices, regulatory system) that may lead to an increase in erosion and mudflows issues. Public-action programs can limit the possible damage of these changes but any strengthening of these policies (compensation for farmers) induces costs for the community. Our goal is to examine the economic feasibility of action programs designed to counter some agricultural scenarios driven by changing external factors. To do so, we compared the cost of compensating farmers with the local populations’ willingness to pay (WTP). We built scenarios of changes in farming systems with a 2015 horizon at the scale of the Pays de Caux, 2007 being the initial situation. We chose two scenarios of the disappearance of dairy farming, since local stakeholders were concerned with the future of local livestock farming and particularly by trends of declining dairy farming. One scenario (StopMilk) did not include any public-action program, the other one (StopMilkEnv) involved a program based on the funding of environmental-friendly cultivation techniques . These scenarios were assessed at the small watershed scale (7 km²) in terms of both changes in farming systems and effects on runoff. Finally, the economic evaluation of additional costs of StopMilkEnv was extrapolated at the level of the Austreberthe watershed syndicate1 (214 km²). Our results show that StopMilk leads to a significant increase in runoff, whereas the local public-action program proposed with StopMilkEnv reduces runoff below the 2007 level. The willingness to pay of the residents of the Austreberthe watershed for a 5 years program was around €395,000/year and a comparison with the cost of the environmental-friendly cultivation techniques revealed that the funding of such practices would be possible but would require borrowing by the community

Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: Implications for laminitis

Equine laminitis, a disease of the lamellar structure of the horse’s hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Tolllike receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-�), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-� and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-�, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However, inflammation may have a role to play in the later stages (e.g., repair or remodelling) of the disease

Barrieren grenzüberschreitender Unternehmenskooperationen in deutschen Grenzregionen - das Beispiel der deutsch-niederländischen Euregio

Grenzüberschreitende Kooperationen sind für viele Unternehmen in Grenzregionen von großer Bedeutung, um neue Absatzmärkte und Ressourcen zu erschließen, neues Wissen zu generieren, Kostenvorteile zu nutzen und sich strategisch zu positionieren. Zudem entstehen grenzüberschreitende Unternehmenskooperationen in EU-Grenzregionen oftmals auch zur Förderung der regionalen Entwicklung. Jedoch zeigt sich, dass bei diesen Kooperationen spezifische Hürden bestehen, die bislang kaum untersucht wurden. Ziel dieses Beitrags ist es, am Beispiel der deutsch-niederländische Grenzregion – Euregio ‒, die hemmenden Faktoren grenzüberschreitender Unternehmenskooperationen zu erfassen und zu analysieren sowie Handlungsempfehlungen zur Überwindung dieser Barrieren herauszuarbeiten. Die Ergebnisse verdeutlichen, dass fünf wesentliche Hemmnisse beim Aufbau und bei der Aufrechterhaltung von grenzüberschreitenden Unternehmenskooperationen in der Euregio bestehen: rechtliche und bürokratische Hürden, kulturelle Unterschiede und Sprachbarrieren, mangelnde Nachhaltigkeit von Förderprojekten, geringe personelle und zeitliche Ressourcen sowie Informations- und Beratungsdefizite. Der Beitrag erweitert durch die Analyse der hemmenden Faktoren die wirtschafts- und sozialwissenschaftliche Forschung zu grenzüberschreitenden Unternehmenskooperationen in deutschen Grenzregionen.In EU border regions, cross-border business cooperation is of great importance for many companies. It opens opportunities to exploit new markets and resources, generate knowledge, exploit cost advantages, and for companies to position themselves strategically. Cross-border cooperation is also often seen as a way to promote regional development. However, it has become apparent that there are specific obstacles to this form of cooperation that have, up to now, hardly been investigated. The aim of this paper is therefore, to identify and analyse the factors inhibiting cross-border business cooperation, using the example of the German-Dutch Euregio, and to develop recommendations for action to overcome these barriers. The results show that there are five main obstacles to establishing and maintaining cross-border business cooperation in the Euregio: legal and bureaucratic hurdles, cultural differences and language barriers, lack of sustainability of funding of projects, lack of human and time resources, and lack of information and advice. By analysing the inhibiting factors, this contribution expands economic and social science research on cross-border business cooperation in German border regions

Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in <i>Staphylococcus aureus</i>

Abstract Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing a S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiological relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo