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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.  相似文献   
3.
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.  相似文献   
4.
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.  相似文献   
5.
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.  相似文献   
6.
A retention model for ionizable compounds in micellar liquid chromatography is derived and verified. The use of the model for the prediction of retention is illustrated and appropriate optimization strategies for the separation of ionizable compounds in Micellar Liquid Chromatography are discussed.  相似文献   
7.
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.  相似文献   
8.
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.  相似文献   
9.
Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome.  相似文献   
10.
Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar KD values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as 1H,15N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.  相似文献   
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