Optimal claim behaviour for third-party liability insurances with perfect information

In this paper we analyse the optimal claim behaviour of a policy holder having a third-party liability insurance in which one is allowed to decide at the end of an insurance year which damages occurred during that year should be claimed. This analysis can only be carried out in detail in case the damages are negative exponentially distributed. Moreover, we present some computational results using an existing bonus—malus system and a horizon of 10 and 25 years and compare these results with similar computations for a corresponding third-party liability insurance in which the policy holder has to decide within a limited time period after the accident to claim or not to claim.Markov decision processes;optimal critical claim size;order statistics

Optimal claim behaviour for third-party liability insurances with perfect information

In this paper we analyse the optimal claim behaviour of a policy holder having a third-party liability insurance in which one is allowed to decide at the end of an insurance year which damages occurred during that year should be claimed. This analysis can only be carried out in detail in case the damages are negative exponentially distributed. Moreover, we present some computational results using an existing bonus—malus system and a horizon of 10 and 25 years and compare these results with similar computations for a corresponding third-party liability insurance in which the policy holder has to decide within a limited time period after the accident to claim or not to claim

Biodiesel production using blue-green cyanobacterium Synechococcus elongatus PCC 7942

Due to concerns about global climate change and diminishing supplies of petroleum, there is a need to develop a clean sustainable alternative. The two main alternative fuels are bioethanol and biodiesel. Production of these biofuels using cyanobacteria is a new promising development. I describe the initial rational engineering of S. elongatus PCC 7942 for the production of biodiesel precursors. Three strains were constructed Se:T, Se:∆A and Se:∆A+T. These were subsequently characterized with regard to their intracellular and extracellular fatty acid (FA) profile, intracellular hydrocarbon profile and effect on growth. This provided a comprehensive picture of early effects caused by the introduced mutations. I describe further rational optimization of free FA production by overexpressing the native acetyl-CoA carboxylase (ACCase) from S. elongatus PCC 7942. Introduction of the ACCase in wild type S. elongatus PCC 7942 alone did not cause an increase in intracellular FAs. However, in strain Se:∆A+T, there was a significant increase in the amount of extracellular FAs. I describe the initial inverse metabolic engineering of S. elongatus PCC 7942 for the production of biodiesel precursors. Our results suggest that the GTP-binding protein Era is a promising target to further rational engineering to improve the production of biofuel precursors.The research described in this thesis took place as part of the project “Groene diesel uit blauwwieren” and was financially supported by the Dutch Ministry of Economic Affairs (EOSLT 07039)Microbial Biotechnolog

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

SummaryHypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons

GTP-binding protein Era: a novel gene target for biofuel production

Background: Biodiesel production using cyanobacteria is a promising alternative to fossil fuels. In this study we created a transposon library of Synechococcus elongatus PCC 7942 in order to identify novel gene targets for enhanced fatty acid and hydrocarbon production. The transposon library was subsequently screened for desirable traits using macro- and microscopic observations as well as staining with the lipophilic dye Nile Red. Results: Based on the screening results, we selected a single mutant, which has an insertion in the gene encoding for the GTP-binding protein Era. We subsequently verified the phenotype-genotype relation by overexpression, reintroducing and complementing the mutation. Overexpression of era caused a reduction in the cell size in the late exponential phase of growth and an increase in the total amount of intracellular fatty acids. Reintroduction of the inactivated transposon caused a significant increase in the cellular length as well as changes in the amounts of individual hydrocarbons and fatty acids. Ectopic complementation of this mutation fully restored the hydrocarbon production profile to that of wild-type and partially restored the fatty acid production. Moreover, the cellular size was significantly smaller than that of the inactivated transposon mutant. Conclusions: The GTP-binding protein Era has never been studied in cyanobacteria and proved to be an essential gene for S. elongatus PCC 7942. We also found that this protein is important for hydrocarbon and fatty acid metabolism as well as determination of the cell size in PCC 7942. Our results suggest that the GTP-binding protein Era can be used as a novel target for further improvement of biofuel precursors production

The discovery of novel LPMO families with a new Hidden Markov model

Microbial Biotechnolog

Programming of central and peripheral insulin resistance by low birthweight and postnatal catch-up growth in male mice.

AIMS: Intra-uterine growth restriction (IUGR) followed by accelerated postnatal growth is associated with an increased risk of obesity and type 2 diabetes. We aimed to determine central and peripheral insulin sensitivity in mice that underwent IUGR followed by postnatal catch-up growth and investigate potential molecular mechanisms underpinning their physiology. METHODS: We used a C57BL/6J mouse model of maternal diet-induced IUGR (maternal diet, 8% protein) followed by cross-fostering to a normal nutrition dam (maternal diet, 20% protein) and litter size manipulation to cause accelerated postnatal catch-up growth. We performed intracerebroventricular insulin injection and hyperinsulinaemic-euglycaemic clamp studies to examine the effect of this early nutritional manipulation on central and peripheral insulin resistance. Furthermore, we performed quantitative real-time PCR and western blotting to examine the expression of key insulin-signalling components in discrete regions of the hypothalamus. RESULTS: IUGR followed by accelerated postnatal growth caused impaired glucose tolerance and peripheral insulin resistance. In addition, these 'recuperated' animals were resistant to the anorectic effects of central insulin administration. This central insulin resistance was associated with reduced protein levels of the p110β subunit of phosphoinositide 3-kinase (PI3K) and increased serine phosphorylation of IRS-1 in the arcuate nucleus (ARC) of the hypothalamus. Expression of the gene encoding protein tyrosine phosphatase 1B (PTP1B; Ptpn1) was also increased specifically in this region of the hypothalamus. CONCLUSIONS/INTERPRETATION: Mice that undergo IUGR followed by catch-up growth display peripheral and central insulin resistance in adulthood. Recuperated offspring show changes in expression/phosphorylation of components of the insulin signalling pathway in the ARC. These defects may contribute to the resistance to the anorectic effects of central insulin, as well as the impaired glucose homeostasis seen in these animals