Internationale verkeersongevallen en verzekering in Europees perspectief

Deze bundel staat in het teken van Europa. Onze bijdrage concentreert zich op de betekenis van “Europa” voor de positie van het (Nederlandse) slachtoffer dat personenschade heeft ge-leden. Wij beperken ons daarbij hoofdzakelijk tot het verkeersslachtoffer. Dat heeft een aantal redenen. In de eerste plaats is een beperking tot een deelterrein noodzakelijk in verband met de omvang van onze bijdrage. In de tweede plaats is het verkeersrecht een terrein waarop de Europese Unie (EU) zich al sinds het begin van de jaren ’70 van de vorige eeuw heeft gericht en waarop het aspect van enerzijds de Europese eenwording en anderzijds dat van de be-scherming van de zwakkere bij uitstek voorwerp van regelgeving is geworden

Running Backs in the NFL Draft and NFL Combine: Can Performance be Predicted?

Berri and Simmons (2009) investigate the relationship between the NFL Combine and the NFL Draft. They find that a quarterback’s performance in the Combine can have a significant impact on that player’s draft position. However, they find that no known aspect of a quarterback before they are drafted is an indicator of success in the NFL. I examine if these relationships exist for the Running Back position. I find similar results to Berri and Simmons: that performance in the Combine does have an effect on that player’s draft position, but that no aspect of a running back’s pre-draft characteristics can be seen as a sign of future NFL success

Barriers to Entry

Entry of firms into a market is an important economic mechanism that influences industry dynamics and contributes to allocative and dynamic efficiency. However, there are barriers that can prevent companies from entering a market, hampering the competitive process. Therefore, it is clear that barriers to entry are an important issue in competition policy. In this report, we studied a number of 37 different barriers with a special focus on the possible size effect of the barrier, the sustainability of the barrier, the way it can be measured and the relation with other barriers to entry.

Field-scale labelling and activity quantification of methane-oxidizing bacteria in a landfill-cover soil

Aerobic methane-oxidizing bacteria (MOB) play an important role in soils, mitigating emissions of the greenhouse gas methane (CH4) to the atmosphere. Here, we combined stable isotope probing on MOB-specific phospholipid fatty acids (PLFA-SIP) with field-based gas push-pull tests (GPPTs). This novel approach (SIP-GPPT) was tested in a landfill-cover soil at four locations with different MOB activity. Potential oxidation rates derived from regular- and SIP-GPPTs agreed well and ranged from 0.2 to 52.8 mmol CH4 (L soil air)−1 day−1. PLFA profiles of soil extracts mainly contained C14 to C18 fatty acids (FAs), with a dominance of C16 FAs. Uptake of 13C into MOB biomass during SIP-GPPTs was clearly indicated by increased δ13C values (up to c. 1500‰) of MOB-characteristic FAs. In addition, 13C incorporation increased with CH4 oxidation rates. In general, FAs C14:0, C16:1ω8, C16:1ω7 and C16:1ω6 (type I MOB) showed highest 13C incorporation, while substantial 13C incorporation into FAs C18:1ω8 and C18:1ω7 (type II MOB) was only observed at high-activity locations. Our findings demonstrate the applicability of the SIP-GPPT approach for in situ quantification of potential CH4 oxidation rates and simultaneous labelling of active MOB, suggesting a dominance of type I MOB over type II MOB in the CH4-oxidizing community in this landfill-cover soi

Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1

Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70S6K1-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin), it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target) and HIF-1α (a pVHL-target), implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition

Deciphering the function of DNGR-1 in cross-presentation through the characterisation of phagosomal compartments in cDC1

Induction of antigen specific cytotoxic CD8+ T lymphocyte (CTL) responses by dendritic cells (DCs) is essential for clearance of infected or malignantly transformed cells. Antigens derived from such cells are presented to naïve CD8+ T cells in the form of short antigenic peptides associated with major histocompatibility complex I (MHC I) on the DC surface. This process, called cross-presentation, often involves transfer of antigens from dying infected or malignantly transformed cells to DCs and is facilitated by innate receptors that sense dead cell-derived damage-associated molecular patterns (DAMPs). These receptors include the C-type lectin receptor DNGR-1, which allows DCs to detect the presence of dead or dying cells by binding to filamentous actin (F-actin) exposed by dead cell corpses. DNGR-1 promotes cross-presentation of dead cell-associated antigens but the mechanism involved is still poorly understood. The aim of my PhD project was to dissect the mechanism by which DNGR-1 facilitates cross-presentation of dead cell-associated antigens. I found it involved proteasomal degradation and was enhanced by inhibition of lysosomal proteases. Further, the cytoplasmic tail of DNGR-1 and, therefore likely DNGR-1 signalling, was essential to promote cross-presentation post cargo uptake. Since DNGR-1 was recruited to antigen-bearing phagosomes, I studied the characteristics of those DNGR-1+ phagosomes. Combined analysis of antigen degradation and staining for DNGR-1 and LAMP-2 revealed two distinct phagosome populations with varying degradative potential and MHC I recruitment: a DNGR-1+LAMP-2-MHC I+ that showed strikingly lower degradative potential, in contrast to DNGR-1-LAMP-2+MHC I- phagosomes. However, DNGR-1+ phagosomes eventually acquired LAMP-2+ resulting in an increase in antigen degradation. To test whether DNGR-1 ligand engagement was shaping the phagosomal proteome in cDC1s, I analysed FACS-purified DNGR-1+ and LAMP-2+ phagosome populations by mass spectrometry. A strong enrichment of the calcium pump SERCA1 and the autophagy initiator beclin-1 was observed in DNGR-1+ phagosomes containing DNGR-1 ligand. Preliminary experiments further revealed that the phagosomal lumen became accessible for cytosolic galectins in a DNGR-1-dependent manner suggesting that DNGR-1 might be involved in antigen to cytosol transfer. In summary, this thesis offers novel insights into the mechanisms by which dead cell antigens are cross-presented by cDC1 through the engagement of DNGR-1, which potentially regulates the stability of antigen-containing phagosomes and thus, might mediate the transfer of antigen from the phagosome into the cytosol

Multi-step self-guided pathways for shape-changing metamaterials

Multi-step pathways, constituted of a sequence of reconfigurations, are central to a wide variety of natural and man-made systems. Such pathways autonomously execute in self-guided processes such as protein folding and self-assembly, but require external control in macroscopic mechanical systems, provided by, e.g., actuators in robotics or manual folding in origami. Here we introduce shape-changing mechanical metamaterials, that exhibit self-guided multi-step pathways in response to global uniform compression. Their design combines strongly nonlinear mechanical elements with a multimodal architecture that allows for a sequence of topological reconfigurations, i.e., modifications of the topology caused by the formation of internal self-contacts. We realized such metamaterials by digital manufacturing, and show that the pathway and final configuration can be controlled by rational design of the nonlinear mechanical elements. We furthermore demonstrate that self-contacts suppress pathway errors. Finally, we demonstrate how hierarchical architectures allow to extend the number of distinct reconfiguration steps. Our work establishes general principles for designing mechanical pathways, opening new avenues for self-folding media, pluripotent materials, and pliable devices in, e.g., stretchable electronics and soft robotics.Comment: 16 pages, 3 main figures, 10 extended data figures. See https://youtu.be/8m1QfkMFL0I for an explanatory vide

Methane oxidation and emission in Lake Lugano (Southern Switzerland) : a lipid biomarker and isotopic approach

Methane is an important greenhouse gas in Earth's atmosphere. The sources of atmospheric methane are largely biogenic, being produced under anoxic conditions by methanogenic Archaea. Wetlands, which include lakes, are important contributors to the atmospheric methane budget, since they commonly feature anoxic sediments or bottom water. Methane oxidising bacteria at the interface between oxic and anoxic sediments and water limit the efflux of methane. Furthermore, in the oceans, methane is oxidised anaerobically by Archaea, in a process coupled to sulfate reduction. In freshwater environments, where sulfate concentrations are orders of magnitude lower, this process is not thermodynamically favourable, and archaeal anaerobic oxidation of methane is often absent. It has been proposed in certain lake environments, however, that anaerobic oxidation of methane does take place. One lake in which anaerobic oxidation of methane was proposed is the northern basin of Lake Lugano, southern Switzerland. Anaerobic oxidation of methane in this basin is explored in chapter 2 of this PhD thesis. Indeed we found methane concentration and carbon isotopic composition profiles characteristic of methane oxidation in the anoxic hypolimnion, more than 30 m below the interface between the oxic and anoxic waters. In addition, microbial biomass at these depths showed carbon isotope signatures of methane-derived carbon (d13C-values as low as -70‰ in C16:1 fatty acids), indicating that methane is used as a carbon source. However, no methane oxidation took place in incubation experiments under anoxic conditions. Addition of alternative potential electron acceptors did not stimulate methane oxidation, and methane oxidation was only observed in the presence of oxygen. Instead, we propose that episodic introduction of oxygenated water into the anoxic hypolimnion sustains a community of aerobic methanotrophs. Carbon derived from methane oxidation has been shown in several studies to constitute an important carbon input to aquatic ecosystems. In the studies reported in chapters 2 and 3, compound specific stable carbon isotope analysis of lipid biomarkers was used to trace methane-derived carbon through the ecosystems at redox interfaces and in the anoxic hypolimnion of Lake Lugano. In the monomictic southern basin (chapter 3), an anoxic benthic nepheloid layer develops during the period of water column stratification. This layer was found to be derived from microbial production in the hypolimnion. Methane oxidising bacteria constituted up to 30% of total microbial cell numbers in the nepheloid layer, and 77% to 96% of the organic carbon in this layer was methane-derived. High rates of aerobic methane oxidation at the top of the anoxic nepheloid layer led to an oxygen consumption that was greater than the downward diffusion, causing the anoxic nepheloid layer to expand. Bacterial aerobic methanotrophs migrate upwards through the water column with the interface between the oxic hypolimnion and the anoxic nepheloid layer. The extent of emission of methane to the atmosphere depends on the totality of sinks and sources in the lake basin. In both the northern and the southern basin of Lake Lugano, large amounts of methane are emitted from the sediments into the bottom water. However, consumption by aerobic methanotrophs at the oxic-anoxic redoxcline is near complete, and during stratified conditions, no methane escapes to the epilimnion. On the other hand, methane super-saturation in the surface water was observed throughout the year. Chapter 4 describes the results of three mapping campaigns of surface water methane concentrations in the northern basin of Lake Lugano, in spring and autumn. Additionally, methane concentration and carbon isotopic composition were measured on depth profiles down to 40 m depth in transects across the lake basin. Methane fluxes to the atmosphere were calculated from surface water concentration and wind speed. At a standardised wind speed of 1.6 m s-1 (average wind speed during the period from May until October) fluxes to the atmosphere were significantly higher in autumn (44 and 97 micromol m-2 d-1 in October 2011 and October 2012, respectively) than in spring (7 micromol m-2 d-1, May 2012). This difference is in part due to higher concentrations in autumn than in spring, and in part a result of a stronger dependence of the transfer velocity on buoyancy flux when the surface water cools. The source of methane in the surface water could not be determined with certainty. It is possible that internal waves at the thermocline induce friction at the sediment-water interface in the littoral zone, which leads to increased outgassing of sedimentary methane. However, the northern basin of Lake Lugano has steep shores along large parts of the basin, which offer little space for deposition of sediments, and the possibility of in situ production of methane in the water column must be considered

Preface

The University of Richmond Law Review is extremely pleased to present this special issue dedicated to Professor Akhil Reed Amar\u27s The Bill of Rights: Creation and Reconstruction. The purpose of the issue is to celebrate the groundbreaking nature of Professor Amar\u27s contemporary text by providing a collection of eleven scholarly commentaries in which some of the finest constitutional jurists in the United States react to the book. The commentators each offer a unique perspective on the dynamic text, utilizing legal, judicial, historical, philosophical, and even esoteric influences to analyze its contents. In an eloquent response to his academic peers, Continuing the Conversation, Professor Amar graciously addresses the individual commentaries by examining both praise and criticism alike, as proffered by each of the authors. The result is quite inviting to the reader; and the issue\u27s appeal is enhanced by the fact that the Law Review Editorial Board went to great lengths to preserve the particular writing styles of the individual authors