Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Taking on a wider view: public value interests of construction clients in a changing construction industry

For financial and strategic reasons, public and semi-public construction clients increasingly depend on private parties to carry out public service delivery. They subcontract operational responsibilities to private parties while remaining socio-politically responsible for ensuring public values. Public administration literature mainly addresses the importance of procedural and performance values in safeguarding public values. However, safeguarding the quality of the built environment also requires a focus on product values. In this study, we aim to increase the understanding of the meaning and significance of public values in the daily practice of public construction clients and identify the challenges they face in commissioning these seemingly opposing values. A set of semi-structured interviews with the public administrators of a variety of public and semi-public construction client organizations in the Netherlands shows that both internal and external factors influence the collaborative practices between clients and contractors. This causes a value shift from an emphasis on procedural values to managing performance and product values, indicating that clients need to take on a wider view on public values. Six main public value dilemmas were found that complicate the task of developing an open, transparent and sustainable long-term client–contractor relationship. The current contractual system, however, lacks the flexibility to facilitate this product-based value view in construction.     

Acetaldehyde in Mineral Water Stored in Polyethylene Terephthalate (PET) Bottles: Odour Threshold and Quantification

The use of PET bottles for packaging soft drinks and mineral waters is still growing world wide. The production process for these bottles is improving constantly. These improvements are focussed on bottles with better barrier properties, higher inertness and higher heat stability. One of the factors determining the quality of PET bottles is the release of acetaldehyde into the product during storage. A literature survey was conducted on the odour and taste detection threshold of acetaldehyde in water. A method is described to rapidly determine the concentration of acetaldehyde in water up to a level of 1 μg/l. This method was used to determine the concentration of acetaldehyde in mineral water during storage in PET bottles. In still water no acetaldehyde could be found, whereas the concentration of acetaldehyde in carbonated mineral water increased steadily upon storage. Model experiments were performed to find an explanation.     

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease’s etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer’s patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.     

Measuring Progress on Climate Change Adaptation Policy by Dutch Water Boards

The Netherlands is particularly vulnerable for the impacts of climate change on the water system. Regional water authorities, or water boards, are given an important role to design and implement specific adaptation policies and measures to manage these impacts. From the early 2000s onwards water boards are starting to adapt to climate change impacts, yet no systematic assessments exist to assess whether or not progress is being made and what explains similarities and differences across water boards. This paper aims to address these critical questions by analyzing the progress of all Dutch water boards for the period 2005–2016. We systematically collected and analyzed three consecutive water management plans for all 23 water boards in the Netherlands. We use content analysis methods to analyze progress by looking into their vulnerability and three levels of adaptation: recognition, groundwork and adaptation action. The results show that over time the number of reported climate change adaptation initiatives by the water boards is increasing, but most climate change adaptation is still at the recognition or groundwork level. Our findings reveal a diversity of efforts to adapt to climate change among Dutch water boards. We conclude that while (inter)national water and climate change adaptation policies have called for more adaptation action at regional levels, the unequal progress across the Netherlands suggests that existing ‘soft’ policy measures to push for adaptation might not be sufficient to ensure progress on adaptation across all water boards.     

Bioinspired pressure actuated adhesive system

We developed a dry synthetic adhesive system inspired by gecko feet adhesion that can switch reversibly from adhesion to non-adhesion with applied pressure as external stimulus. Micropatterned polydimethylsiloxane (PDMS) surfaces with pillars of 30 μm length and 10 μm diameter were fabricated using photolithography and moulding. Adhesion properties were determined with a flat probe as a function of preload. For low and moderate applied compressive preloads, measured adhesion was 7.5 times greater than on flat controls whereas for high applied preloads adhesion dropped to very low values. In situ imaging shows that the increased preload caused the pillars to deform by bending and/or buckling and to lose their adhesive contact. The elasticity of PDMS aids the pillar recovery to the upright position upon removal of preload enabling repeatability of the switch.     

What governs the transition to a sustainable hydrogen economy? Articulating the relationship between technologies and political institutions

There is a lack of integrated knowledge on the transition to a sustainable energy system. The paper focuses on the relationship between technologies and institutions in the field of hydrogen from the perspective of political theory. The paper unfolds four paradigms of governance: ‘Governance by policy networking’, Governance by government’, ‘Governance by corporate business’, and ‘Governance by challenge’, and looks into the major line of argument in support of these paradigms and into their possible bias with respect to hydrogen options. Each of these paradigms reveals an institutional bias in that it articulates specific opportunities for collaboration and competition in order to stimulate the transition to a sustainable hydrogen economy. The paper makes the observation that there is a compelling need to reframe fashionable discourse such as the necessary shift from government to governance or from government to market. Instead, specific questions with respect to the impact of guiding policy frameworks on innovation will highlight that neither ‘neutral’ nor ‘optimal’ frameworks for policy making exist, where competing hydrogen options are at stake. The identification of paradigms of governance maybe considered a methodological device for (participator) policy analysis.     

IV. Yeast sequencing reports. New open reading frames,one of which is similar to the nifV gene of Azotobacter vinelandii,Found on a 12·5 kbp fragment of chromosome IV of Saccharomyces cerevisiae

The nucleotide sequence of a 12·5 kbp segment of the left arm of chromosome IV is described. Five open reading frames (ORFs) longer than 100 amino acids were detected, all of which are completely confined to the 12·5 kbp region. Two ORFs (D1271 and D1286) correspond to previously sequenced genes (PPH22 and VMA1 or TFP1, respectively). ORF D1298 shows the characteristics of α-isopropylmalate and homocitrate synthase genes and is similar to the nifV gene of Azotobacter vinelandii. Two more ORFs have no apparent homologue in the data libraries. Conversely, two smaller ORFs of 25 and 85 amino acids encoding the ribosomal protein YL41A and an ATPase inhibitor, respectively, were detected. Although a substantial part of the 12·5 kbp fragment apparently lacks protein-coding characteristics, no other elements, such as tRNA genes or transposons, were found. The nucleotide sequence data reported in this paper will appear in the EMBL, GenBank and DDBJ Nucleotide Sequence Databases under the Accession Number X83276.     

Reduced decoder complexity and latency in pixel-domain Wyner–Ziv video coders

In some video coding applications, it is desirable to reduce the complexity of the video encoder at the expense of a more complex decoder. Wyner–Ziv (WZ) video coding is a new paradigm that aims to achieve this. To allocate a proper number of bits to each frame, most WZ video coding algorithms use a feedback channel, which allows the decoder to request additional bits when needed. However, due to these multiple bit requests, the complexity and the latency of WZ video decoders increase massively. To overcome these problems, in this paper we propose a rate allocation (RA) algorithm for pixel-domain WZ video coders. This algorithm estimates at the encoder the number of bits needed for the decoding of every frame while still keeping the encoder complexity low. Experimental results show that, by using our RA algorithm, the number of bit requests over the feedback channel—and hence, the decoder complexity and the latency—are significantly reduced. Meanwhile, a very near-to-optimal rate-distortion performance is maintained. This work has been partially supported by the Spanish Ministry of Education and Science and the European Commission (FEDER) under grant TEC2005-07751-C02-01. A. Pižurica is a postdoctoral research fellow of FWO, Flanders.