De gebiedsontwikkelaar:onderzoeksrapport

Onderzoek in opdracht van het Kenniscentrum NoorderRuimte. Het praktijkdoel is het opzetten van een kennisnetwerk en het onderzoeken naar het huidige onderwijsaanbod op het gebied van gebiedsontwikkeling en te onderzoeken in hoeverre dit aansluit op het vak van gebiedsontwikkelaar. Met dit onderzoek wordt het fundament gelegd om met vervolgonderzoek verder aan het praktijkdoel te kunnen werken. De centrale vraag van dit onderzoek luidt: Wat zijn de kenmerken van de sociale en de fysieke taken van de gebiedsontwikkelaar

Tyrosine hydroxylase phosphorylation is under the control of serine 40

Tyrosine hydroxylase catalyzes the initial and rate-limiting step in the biosynthesis of the neurotransmitter dopamine. The phosphorylation state of Ser40 and Ser31 is believed to exert a direct effect on the enzymatic activity of tyrosine hydroxylase. Interestingly, some studies report that Ser31 phosphorylation affects Ser40 phosphorylation, while Ser40 phosphorylation has no effect on Ser31 phosphorylation, a process named hierarchical phosphorylation. Here, we provide a detailed investigation into the signal transduction mechanisms regulating Ser40 and Ser31 phosphorylation in dopaminergic mouse MN9D and Neuro2A cells. We find that cyclic nucleotide signaling drives Ser40 phosphorylation, and that Ser31 phosphorylation is strongly regulated by ERK signaling. Inhibition of ERK1/2 with UO126 or PD98059 reduced Ser31 phosphorylation, but surprisingly had no effect on Ser40 phosphorylation, contradicting a role for Ser31 in the regulation of Ser40. Moreover, to elucidate a possible hierarchical mechanism controlling tyrosine hydroxylase phosphorylation, we introduced tyrosine hydroxylase variants in Neuro2A mouse neuroblastoma cells that mimic either phosphorylated or unphosphorylated serine residues. When we introduced a Ser40Ala tyrosine hydroxylase variant, Ser31 phosphorylation was completely absent. Additionally, neither the tyrosine hydroxylase variant Ser31Asp, nor the variant Ser31Ala had any significant effect on basal Ser40 phosphorylation levels. These results suggest that tyrosine hydroxylase is not controlled by hierarchical phosphorylation in the sense that first Ser31 has to be phosphorylated and subsequently Ser40, but, conversely, that Ser40 phosphorylation is essential for Ser31 phosphorylation. Overall our study suggests that Ser40 is the crucial residue to target so as to modulate tyrosine hydroxylase activity

Numerical analysis of image based high-throughput zebrafish infection screens: matching meaning with data

Computer Systems, Imagery and Medi

Linking Unserved Energy to Weather Regimes

The integration of renewable energy sources into power systems is expected to increase significantly in the coming decades. This can result in critical situations related to the strong variability in space and time of weather patterns. During these critical situations the power system experiences a structural shortage of energy across multiple time steps and regions, leading to Energy Not Served (ENS) events. Our research explores the relationship between six weather regimes that describe the large scale atmospheric flow and ENS events in Europe by simulating future power systems. Our results indicate that most regions have a specific weather regime that leads to the highest number of ENS events. However, ENS events can still occur during any weather regime, but with a lower probability. In particular, our findings show that ENS events in western and central European countries often coincide with either the positive Scandinavian Blocking (SB+), characterised by cold air penetrating Europe under calm weather conditions from north-eastern regions, or North Atlantic Oscillation (NAO+) weather regime, characterised by westerly flow and cold air in the southern half of Europe. Additionally, we found that the relative impact of one of these regimes reaches a peak 10 days before ENS events in these countries. In Scandinavian and Baltic countries, on the other hand, our results indicate that the relative prevalence of the negative Atlantic Ridge (AR-) weather regime is higher during and leading up to the ENS event.Comment: Rogier H. Wuijts and Laurens P. Stoop contributed equally to this wor

The influence of weather regimes on European renewable energy production and demand

The growing share of variable renewable energy increases the meteorological sensitivity of power systems. This study investigates if large-scale weather regimes capture the influence of meteorological variability on the European energy sector. For each weather regime, the associated changes to wintertime -mean and extreme- wind and solar power production, temperature-driven energy demand and energy shortfall (residual load) are explored. Days with a blocked circulation pattern, i.e. the Scandinavian Blocking and NAO negative regimes, on average have lower than normal renewable power production, higher than normal energy demand and therefore, higher than normal energy shortfall. These average effects hide large variability of energy parameters within each weather regime. Though the risk of extreme high energy shortfall events increases in the two blocked regimes (by a factor of 2.0 and 1.5, respectively), it is shown that such events occur in all regimes. Extreme high energy shortfall events are the result of rare circulation types and smaller-scale features, rather than extreme magnitudes of common large-scale circulation types. In fact, these events resemble each other more strongly than their respective weather regime mean pattern. For (sub-)seasonal forecasting applications weather regimes may be of use for the energy sector. At shorter lead times or for more detailed system analyses, their ineffectiveness at characterising extreme events limits their potential

The Climatological Renewable Energy Deviation Index

Here we propose an index to quantify and analyse the impact of climatological variability on the energy system at different timescales. We define the Climatological Renewable Energy Deviation Index (CREDI) as the cumulative anomaly of a renewable resource with respect to its climate over a specific time period of interest. We analyse the index at decadal, annual and (sub-)seasonal timescales using the forthcoming Pan-European Climate Database and consider the starting point and window of analysis for its use at those timescales. The CREDI is meant as an analytical tool for researchers and stakeholders to help them quantify, understand, and explain, the impact of the variability of weather on the energy system across timescales. Improved understanding translates to better assessments of how renewable resources, and the associated risks for energy security, may fare in current and future climatological settings. The practical use of the index is in resource planning. For example transmission system operators may be able to adjust short-term planning to reduce adequacy issues before they occur or combine the index with storyline event selection for improved assessments of climate change related risks

Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet

Objective: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of ‘metabolic’ OA.Design: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets.Results: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups.Conclusions: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development