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

The role of lysine palmitoylation/myristoylation in the function of the TEAD transcription factors

The TEAD transcription factors are the most downstream elements of the Hippo pathway. Their transcriptional activity is modulated by different regulator proteins and by the palmitoylation/myristoylation of a specific cysteine residue. In this report, we show that a conserved lysine present in these transcription factors can also be acylated, probably following the intramolecular transfer of the acyl moiety from the cysteine. Using Scalloped (Sd), the Drosophila homolog of human TEAD, as a model, we designed a mutant protein (Glu352Gln Sd ) that is predominantly acylated on the lysine (Lys350 Sd ). This protein binds in vitro to the three Sd regulators-Yki, Vg and Tgi-with a similar affinity as the wild type Sd, but it has a significantly higher thermal stability than Sd acylated on the cysteine. This mutant was also introduced in the endogenous locus of the sd gene in Drosophila using CRISPR/Cas9. Homozygous mutants reach adulthood, do not present obvious morphological defects and the mutant protein has both the same level of expression and localization as wild type Sd. This reveals that this mutant protein is both functional and able to control cell growth in a similar fashion as wild type Sd. Therefore, enhancing the lysine acylation of Sd has no detrimental effect on the Hippo pathway. However, we did observe a slight but significant increase of wing size in flies homozygous for the mutant protein suggesting that a higher acylation of the lysine affects the activity of the Hippo pathway. Altogether, our findings indicate that TEAD/Sd can be acylated either on a cysteine or on a lysine, and suggest that these two different forms may have similar properties in cells

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

LC-MALDI MS and MS/MS--an efficient tool in proteome analysis.

Liquid chromatography-matrix-assisted laser desorption/ionization mass spectrometry represents a sensitive, hyphenated MS- and MS/MS-technique with a broad range of applications in all areas ofproteome analysis. Whereas a number of interface types have been developed for coupling MALDI MS and liquid chromatography, in this chapter selected on-line and off-line types and techniques will be discussed with respect to their individual properties and performance. The technique is especially attractive in off-line mode where LC-separation and MS analyses are decoupled and each step can be performed at its individual optimum. Different speed of chromatographic separation and achievement of S/N criteria in MS or MS/MS mode can be optimized independently by individual adjustment of specific operating parameters. This flexibility makes LC-MALDI MS attractive for the analysis of peptide mixtures from low to medium complexity. Using sequential MS analysis of parallel LC runs (multiplexing), even highly complex samples can be handled. Quantitation at the MS and MS/MS level can be accomplished by a variety of labeling techniques, where the predominant formation of singly charged ions in MALDI alleviates the assignment of isotopomers. After discussing the level of complementarity between LC-MALDI and LC-ESI MS, selected applications of LC-MALDI MS are presented. Examples of membrane protein analysis applying 1D SDS PAGE are discussed in detail as well as applications in protein interaction analysis. These application examples clearly show that in all respects LC-MALDI MS and MS/MS are flexible and sensitive techniques which can be adapted to a wide range of different workflows

Proteomics: From Protein Identification to Biological function

The term 'proteome' describes the expressed protein complement of a genome. The largely invariant genome of an individual or organism determines its potential for gene- and protein expression but does not specify which proteins are expressed in the various types of cells in an organism or individual or their level or extent of post-translational modification. Furthermore, the proteomes of cells are directly affected by environmental factors, such as stress or drug treatment, or by aging and disease. This review briefly describes a selection of the main technologies applied by proteome sciences and their applications to study complex biological problems

Phosphorylation disrupts the central helix in Op18/stathmin and suppresses binding to tubulin

Protein phosphorylation represents a ubiquitous control mechanism in living cells. The structural prerequisites and consequences of this important post-translational modification, however, are poorly understood. Oncoprotein 18/stathmin (Op18) is a globally disordered phosphoprotein that is involved in the regulation of the microtubule (MT) filament system. Here we document that phosphorylation of Ser63, which is located within a helix initiation site in Op18, disrupts the transiently formed amphipathic helix. The phosphoryl group reduces tubulin binding 10-fold and suppresses the MT polymerization inhibition activity of Op18’s C-terminal domain. Op18 represents an example where phosphorylation occurs within a regular secondary structural element. Together, our findings have implications for the prediction of phosphorylation sites and give insights into the molecular behavior of a globally disordered protein

Additional file 1: of Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition

is a figure showing BYL719 resistance in PIK3CA mutant breast cancer cells. A BYL719 resistance is reversible. BYL719 dose-response of parental and resistant lines (on or off BYL719 for 2 weeks) after 3 days of treatment. Cell numbers were evaluated using the sulforhodamide B assay. GI50 values were calculated using GraphPad Prism 6 software. Data are mean ± SEM (n >2). B pS6/S6 ratios in cells treated with DMSO or BYL719 (IC90) for 24 hours. Data are mean of pS6/S6 ratio ± SEM (n >3, *P <0.01). Immunoblots from three independent experiments have been quantified using the ImageJ software. (PDF 117 kb