How are results represented and modified? : remarks on Jäger & Blutner's anti-decomposition

The paper investigates a recent proposal to resultativity by G. Jäger and R. Blutner (J&B). J&B say that the representation of result states of accomplishments by means of CAUSE and BECOME is not correct and should not be done in the syntax in terms of decomposition. They develop an axiomatic approach where each accomplishment/achievement is related to its result by a particular axiom. Modification of the result by "again" makes use of these axioms and the restitutive/resultative ambiguity is a matter of lexical ambiguity or polysemy. They argue that the classical decomposition theory cannot treat the restitutive reading of "A Delaware settled in New Jersey again" (there had been Delawares in New Jersey but not this particular one; and those earlier Delawares never moved to New Jersey but were borne there). I discuss (and dispute) these data and compare the two theories. J&B's contains an OT-part dealing with the disambiguating role of stress. While the decomposition theory cannot deal with the data mentioned, it can integrate the OT-part of J&B's theory

Delineating the DNA damage response using systems biology approaches

Cellular responses to DNA damage are highly variable and strongly depend on the cellular and organismic context. Studying the DNA damage response is crucial for a better understanding of cancer formation and ageing as well as genotoxic stress-induced cancer therapy. To do justice to the multifaceted cellular changes, elicited by DNA damage, use of high-throughput techniques and integration with bioinformatics tools is of great value. This thesis summarizes recent advances in the field of systems biology studies of the DNA damage response and furthermore shows integrated approaches of the study of DNA damage response signaling networks in embryonic stem and cancer cells. By integration of transcriptional changes and the phosphorylation and metabolic response of cisplatin-treated embryonic stem cells, with RNAi-based knockdown screens we identify novel DNA damage response signaling networks, linking process such as Wnt signaling, translation arrest or altered metabolic pathways to the cellular response to DNA damage. Furthermore, genes, whose knockdown sensitizes embryonic stem cells to DNA damage-induced killing, are tested in cancer cells of varying genetic backgrounds identifying a small subset of genes, which represent potential drug targets for sensitization of cancer cells. Altogether, our systems approach for studying the DNA damage response identifies novel DNA damage-induced signaling networks and molecules, which modulate survival in the presence of DNA damage, potentially providing new targets for therapeutic intervention or biomarker discovery.Research was supported by the Netherlands Genomics Initiative /Netherlands Organization for Scientific Research (NWO): nr 050-060-510. Support for thesis printing came from Havelland Stiftung, Berlin.UBL - phd migration 201

Annex 1 - Glossary

This glossary defines some specific terms as the Lead Authors intend them to be interpreted in the context of this report

Global gyrokinetic simulations of ITG turbulence in the configuration space of the Wendelstein 7-X stellarator

We study the effect of turbulent transport in different magnetic configurations of the Weldenstein 7-X stellarator. In particular, we performed direct numerical simulations with the global gyrokinetic code GENE-3D, modeling the behavior of Ion Temperature Gradient turbulence in the Standard, High-Mirror, and Low-Mirror configurations of W7-X. We found that the Low-Mirror configuration produces more transport than both the High-Mirror and the Standard configurations. By comparison with radially local simulations, we have demonstrated the importance of performing global nonlinear simulations to predict the turbulent fluxes quantitatively

Overview of core impurity transport in the first divertor operation of Wendelstein 7-X

The impurity transport at Wendelstein 7-X during its most recent campaign is characterized and documented for a variety of different plasma scenarios. An overview of its dependence on several quantities is given, which allows identification of transport regimes and the major driver for impurity transport. Beyond this, a comparison with the impurity behavior in other fusion devices is now possible. In contrast to other stellarators, no density dependence of the impurity transport has been found. Additionally, the influence of the turbulence contribution to the overall transport is reflected in the dependence on various parameters, e.g. turbulent diffusion and density fluctuation amplitudes. With this database approach, one can now also apply scaling laws to make extrapolations about the impurity confinement in future plasma scenarios

Benchmarking common quantification strategies for large-scale phosphoproteomics

Quantitative phosphoproteomics has become a standard method in molecular and cell biology. Here, the authors compare performance and parameters of phosphoproteome quantification by LFQ, SILAC, and MS2-/MS3-based TMT and introduce a TMT-adapted algorithm for calculating phosphorylation site stoichiometry

Does simvastatin stimulate bone formation in vivo?

BACKGROUND: Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS) to the known anabolic effects of PTH in an established model of ovariectomized (OVX) Swiss-Webster mice. METHODS: Mice were ovariectomized at 12 weeks of age (T0), remained untreated for 5 weeks to allow development of osteopenia (T5), followed by treatment for 8 weeks (T13). Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT). Liquid chromatography/mass spectrometry (LC/MS) was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH) in the mouse serum. RESULTS: Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day) compared to the OVX-vehicle treated group (p < 0.001). However, the same comparison for the SVS-treated group (10 mg/kg/day administered by gavage) showed no significant difference (p = NS). LC/MS detected SVS and SVS-OH in mouse serum 20 minutes after gavage of 100 mg SVS. A serum osteocalcin assay (OC) demonstrated that neither bone formation nor osteoblast activity is significantly enhanced by SVS treatment in this in vivo study. CONCLUSIONS: While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo