Once the shovel hits the ground : Evaluating the management of complex implementation processes of public-private partnership infrastructure projects with qualitative comparative analysis

Much attention is being paid to the planning of public-private partnership (PPP) infrastructure projects. The subsequent implementation phase – when the contract has been signed and the project ‘starts rolling’ – has received less attention. However, sound agreements and good intentions in project planning can easily fail in project implementation. Implementing PPP infrastructure projects is complex, but what does this complexity entail? How are projects managed, and how do public and private partners cooperate in implementation? What are effective management strategies to achieve satisfactory outcomes? This is the fi rst set of questions addressed in this thesis. Importantly, the complexity of PPP infrastructure development imposes requirements on the evaluation methods that can be applied for studying these questions. Evaluation methods that ignore complexity do not create a realistic understanding of PPP implementation processes, with the consequence that evaluations tell us little about what works and what does not, in which contexts, and why. This hampers learning from evaluations. What are the requirements for a complexity-informed evaluation method? And how does qualitative comparative analysis (QCA) meet these requirements? This is the second set of questions addressed in this thesis

The non-fibrillating n-terminal of α-synuclein binds and co-fibrillates with heparin

The intrinsically disordered protein α-synuclein (aSN) is, in its fibrillated state, the main component of Lewy bodies-hallmarks of Parkinson's disease. Additional Lewy body components include glycosaminoglycans, including heparan sulfate proteoglycans. In humans, heparan sulfate has, in an age-dependent manner, shown increased levels of sulfation. Heparin, a highly sulfated glycosaminoglycan, is a relevant mimic for mature heparan sulfate and has been shown to influence aSN fibrillation. Here, we decompose the underlying properties of the interaction between heparin and aSN and the effect of heparin on fibrillation. Via the isolation of the first 61 residues of aSN, which lacked intrinsic fibrillation propensity, fibrillation could be induced by heparin, and access to the initial steps in fibrillation was possible. Here, structural changes with shifts from disorder via type I β-turns to β-sheets were revealed, correlating with an increase in the aSN1-61/heparin molar ratio. Fluorescence microscopy revealed that heparin and aSN1-61 co-exist in the final fibrils. We conclude that heparin can induce the fibrillation of aSN1-61, through binding to the N-terminal with an affinity that is higher in the truncated form of aSN. It does so by specifically modulating the structure of aSN via the formation of type I β-turn structures likely critical for triggering aSN fibrillation

Formation of covalent di-tyrosine dimers in recombinant α-synuclein

Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein \u3b1-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further associated with mitochondrial dysfunction and formation of reactive oxygen species. Oxidative stress causes chemical modification of native \u3b1-synuclein, plausibly further influencing misfolding events. Here, we present evidence for the spontaneous formation of covalent di-tyrosine \u3b1-synuclein dimers in standard recombinant protein preparations, induced without extrinsic oxidative or nitrative agents. The dimers exhibit no secondary structure but advanced SAXS studies reveal an increased structural definition, resulting in a more hydrophobic micro-environment than the highly disordered monomer. Accordingly, monomers and dimers follow distinct fibrillation pathways

How (in)accurate are demand forecasts in public works projects? The case of transportation.

his article presents results from the first statistically significant study of traffic forecasts in transportation infrastructure projects. The sample used is the largest of its kind, covering 210 projects in 14 nations worth U.S.$59 billion. The study shows with very high statistical significance that forecasters generally do a poor job of estimating the demand for transportation infrastructure projects. For 9 out of 10 rail projects, passenger forecasts are overestimated; the average overestima-tion is 106%. For half of all road projects, the difference between actual and forecasted traffic is more than ±20%. The result is substantial financial risks, which are typically ignored or downplayed by planners and decision makers to the detriment of social and economic welfare. Our data also show that forecasts have not become more accurate over the 30-year period studied, despite claims to the contrary by forecasters. The causes of inaccuracy in forecasts are different for rail and road projects, with political causes playing a larger role for rail than for road. The cure is transparency, accountability, and new forecasting methods. The challenge is to change the governance structures for forecasting and project development. Our article shows how planners may help achieve this