Het RandstadRail-project: Lightrail, Zware opgave. Onafhankelijk onderzoek Randstadrail Haagse deel

Onderzoeksopdracht en onderzoekvragen: Doel van het onderzoek was het tot stand brengen van een rapport, op basis waarvan de verantwoordelijk bestuurder verantwoording kan afleggen aan het Algemeen Bestuur van Haaglanden en lessen getrokken kunnen worden voor de aanpak van toekomstige grote infrastructuurprojecten. De volgende vragen stonden in het onderzoek centraal: - Wat was de feitelijke gang van zaken rond de gebeurtenissen en incidenten die zich bij de bouw en indienstneming van RandstadRail voordeden? - Welke rol speelde de organisatie en aansturing van het project op strategisch en bestuurlijke niveau daarbij in de periode vanaf 2001? - In hoeverre voldeden deze aan de eisen die daar, gegeven (toentertijd) geldende normen betreffende adequaat bestuur en management, aan gesteld dienen te worden? - Welke lessen kunnen hieruit geleerd worden ten aanzie

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning

Sustainable development goals as accountability mechanism? A case study of Dutch infrastructure agencies

The UN sustainable development goals (SDGs) were adopted by the United Nations as a “universal call to action to end poverty, protect the planet, and ensure that by 2030 all people enjoy peace and prosperity.” These goals prove to have a strong appeal to managers in both public and private sectors. Despite the popularity of the goals, little is known about the consequences (intended and unintended, desired and undesired) of organisations adopting SDGs in their management practices. Therefore, our research question is: “What is the potential role of SDGs as an accountability mechanism?” The following article will study how organisations responsible for technological infrastructures in the Netherlands use the SDGs as an accountability mechanism. To do this, the authors will first provide an overview of the SDGs and how we conceptualize accountability. We will then present our case study methodology before looking at a single case study based on interviews with employees from three organizations running infrastructure in the Netherlands. Based on this case study, we will provide a broader analysis of the key tensions that are becoming apparent when using the SDGs as an accountability mechanism. In conclusion, we will argue that the SDGs may provide a valuable tool to make organizations more accountable to societal needs, however further shifts are needed in the way the accountability mechanisms are designed in order to ensure meaningful accountability.Organisation & Governanc

Dreaming of the Travelers’ Experience in 2040: Exploring Governance Strategies and Their Consequences for Personal Mobility Systems

The boundaries between collective and individual transport are fading. Current solutions for payment and planning of trips are suboptimal for journeys that span across individual, collective and shared transport modalities. The discussion around these innovations often tends towards public authorities needing to strengthen their integrating role, or towards the private companies developing key innovations. We argue that focusing on only one of these perspectives, either integration or innovation, is likely to lead to what we call ‘subtopias’. Furthermore, we discuss and resolve the conflict between the two roles based on four different scenarios, ranging from nightmare to utopian dream. Our claim is that a balance is needed between, rather than a prevalence for private and public, for integrated and innovative mobility services to manifest themselves. As we see it, authorities will need to direct, harmonize and coordinate specific elements of personal mobility systems in order to be able to facilitate a seamless multi-modal mobility experience for travelers

Topogenesis of microbody enzymes: a sequence comparison of the genes for the glycosomal (microbody) and cytosolic phosphoglycerate kinases of Trypanosoma brucei.

To determine how microbody enzymes enter microbodies, we are studying the genes for cytosolic and glycosomal (microbody) isoenzymes in Trypanosoma brucei. We have found three genes (A, B and C) coding for phosphoglycerate kinase (PGK) in a tandem array in T. brucei. Gene B codes for the cytosolic and gene C for the glycosomal isoenzyme. Genes B and C are 95% homologous, and the predicted protein sequences share approximately 45% amino acid homology with other eukaryote PGKs. The microbody isoenzyme differs from the cytosolic form and other PGKs in two respects: a high positive charge and a carboxy-terminal extension of 20 amino acids. Our results show that few alterations are required to redirect a protein from cytosol to microbody. From a comparison of our results with the unpublished data for three other glycosomal glycolytic enzymes we infer that the high positive charge represents the major topogenic signal for uptake of proteins into glycosomes