The Standard Model of particle physics elegantly describes the fundamental constituents of matter and their interactions. The electroweak gauge and top-quark Yukawa couplings can be directly probed in the associated ...

Studying past climate states is important to understand climate changes and climate variability on centennial to orbital timescales, to analyze the reaction of the Earth system to large-scale changes in external forcings, ...

Pulsars, highly magnetised rapidly-rotating neutron stars, have proved themselves to be incredible tools for exploring many aspects of fundamental physics and astrophysics. More opportunities for building new theories and ...

The discovery of the Higgs boson by the ATLAS and CMS collaborations at the Large Hadron Collider was a major success in particle physics. Even though studies of the Higgs boson suggest that its properties are in agreement with the Standard Model (SM) expectations, there are still many open questions connected to the physics of the Higgs sector. New physics extensions of the SM attempt to answer these questions. Many new physics models predict heavy resonances which decay into final states with a SM Higgs boson. In this thesis a search for a heavy resonance V′ decaying via a W or Z boson and a Higgs boson into a final state with leptons and b-quark jets with the ATLAS detector is presented. One of the main challenges in this analysis is the reconstruction of Higgs bosons with a high Lorentz-boost decaying into b-quark jets. In this thesis, reconstruction algorithms for boosted H → b<span style="text-decoration:overline">b</span><span style="text-decoration:overline"></span> decays are discussed, laying emphasis on the identification of b-jets (b-tagging) in boosted topologies. A new method for a data-based double-b-tagging calibration using gluon splitting (g→ b<span style="text-decoration:overline">b</span><span style="text-decoration:overline"></span>) events is presented for the first time for the ATLAS experiment....

In the present work, the phosphorylation profile of the chloroplast-localized Calcium Sensing Receptor (CAS) from A. thaliana was investigated and it could be shown that CAS is a target of multiple protein kinases acting differentially on several residues. Phosphoproteomics followed up by biochemical kinase assays strongly indicated that CAS is part of a phosphorylation network involving the important state transistion kinases STN7 and STN8 as well as, at least, one other calcium-regulated protein kinase. The role of light and calcium behind the activation of CAS phosphorylation was investigated in vitro in more detail and revealed that, at least under normal growth light conditions, STN7 might be the major kinase acting on CAS.<br /> The analysis was extended at the level of individual residues by studying the phylogenetic conservation of experimentally described phosphoresidues of the A. thaliana CAS isoform and by conducting in vitro assays using recombinant CAS fragments carrying mutations at selected positions. These analyses confirmed the relevance of the previously described phosphorylation site Thr-380, but also showed that other residues, in particular Thr-376, are possible targets.<br /> A spectrometric analysis of cas mutant plants revealed that CAS is very likely involved in the processes of photoacclimation to high light, as evidenced by a persistent strong excitation of PSI under this condition. The analysis of the phosphorylation status of several known thylakoid phosphoproteins in the cas mutant further suggested a potential defect in the dephosphorylation of the important light harvesting protein LHCII under high irradiance, suggesting a possible role for CAS in mediating the activity of the TAP38 phosphatase.<br /> In addition to the post-translational modification of CAS, a potential involvement of CAS in the circadian network of the chloroplast was explored. RT-PCR analyses revealed that the transcription of the CAS follows a regular diurnal rhythm, with the highest levels of its transcript levels found at the end of the night and lowest levels at the end of the day. Interestingly, the levels of the CAS protein appear to follow an opposite, 12 hours shifted rhythm, suggesting a physiological requirement for higher abundance of CAS during the day. In light of these results, a possible working model is discussed that integrates the evidences on the phosphorylation profiles and the diurnal regulation with a suggested involvement of CAS in photoacclimation responses....

Tau, a microtubule associated protein, forms abnormal aggregates in many neurodegenerative diseases such as Alzheimer disease (AD). There is an urgent need for disease-modifying therapies of AD and related tauopathies. Inhibiting the aggregation of tau and the accumulation of neurofibrillary tangles (NFTs) could be helpful in combating tau pathology. Recent studies show that tau induced toxicity is mainly due to the presence of oligomers of tau rather than the monomers and fibrillar aggregates (Kaniyappan et al., 2017, Flach et al., 2012, Lasagna-Reeves et al., 2010). <br /> To combat the toxicity of tau oligomers we developed antibodies against the purified low-n tau oligomers (dimers to hexamers) of Tau^RDΔK, the strongly aggregating repeat domain of tau. Monoclonal antibodies were tested by various biochemical and biophysical methods for their specificity to bind to the toxic oligomers. Some antibodies show specificity to aggregates of tau while others detect all forms of tau. Antibodies 2B10 and 6H1, described as representative examples, bind to tau oligomers with high specificity as judged by dotblot, dynamic light scattering (DLS) and immunofluorescence analysis. As these antibodies are dependent on tau conformations, they appear non-specific in denaturing methods like western blotting. 2B10 and 6H1 antibodies are able to inhibit the tau aggregation up to ~90% in vitro (Tau^RDΔK, hTau^P301L), as judged by the Thioflavin S fluorescence assay which is sensitive to ß-structure. In the presence of antibodies tau protein forms only up to low-n oligomers as judged by light scattering and atomic force microscopy (AFM). The choice of the pH of the column elution buffer of the antibodies plays a key role in determining the activity of the antibodies, as antibodies eluted at low pH have a higher activity compared to the same antibodies eluted at high pH. <br /> The ability of antibodies to inhibit the aggregation of tau was tested in an N2a cell model of tau pathology which expresses the pro-aggregant tau repeat domain Tau^RDΔK. Antibodies were added to the extracellular medium, without or with protein transfection reagent (Xfect) which stimulates cellular uptake. In this assay, 2B10 antibody failed to inhibit tau aggregation (ThS signal) and failed to prevent aggregation induced apoptosis (Annexin V signal). By contrast, in the split-luciferase complementation assay the antibody 2B10, applied extracellularly, was able to prevent the dimerization/oligomerization of tau. Surprisingly this antibody has only a relatively low affinity to tau but is still very active in inhibiting tau aggregation in vitro. Antibodies added extracellularly were taken up by the cells and sorted into lysosomes. Their inhibitory effect can be explained by the fact that the internalized antibody recruits the toxic tau protein or oligomers to the lysosomes for degradation. In summary, a subset of antibodies raised against the purified low-n oligomers of Tau^RDΔK are able to inhibit tau aggregation both in vitro and in a cell model of tau pathology....

Pulsars are rapidly rotating, highly magnetised neutron stars which emit electromagnetic radiation from their magnetic poles in the form of highly collimated beams. Pulsars are known as a powerful tool to probe the ...

In this work the calculation of the ρ resonance's decay parameters with N_f = 2+1+1 flavour lattice QCD is presented. The calculation is performed based on gauge configuration ensembles produced by the ETM collaboration which were generated with three different lattice spacing values and pion masses ranging from 230 MeV to 500 MeV. The calculation of resonance parameters with Lattice QCD requires correlation functions of all relevant decay channels in multiple moving reference frames. In this work operators resembling a ρ meson as well as a p⁺p system are used. The boost to moving frames breaks rotational symmetry and thereby causes a level splitting. Operators which transform like basis states of the reduced symmetry groups' irreducible representations are constructed to determine each energy level individually. Aided by the stochastic Laplacian Heaviside method correlation functions are calculated for all lattice momenta up to (0, 0, 2) and all irreducible representations that emerge. <br /> From these correlation functions energy levels are determined under consideration of systematic error sources. Most notably the effect of thermal pollutions and bias from fit range selection are taken into account. By applying the Lüscher method the energy spectra are translated into phase shift curves on each ensemble separately. From a Breit-Wigner fit to the phase shift curves the ρ meson mass and width on all ensembles are determined. The results are fed into a combined fit of mass and width and extrapolated to the chiral and continuum limit. <br /> The main result of this thesis are the continuum extrapolated values of M_ρ and Γ_ρ at the physical point which were determined to <center> M_ρ = 769(19) MeV and Γ_ρ = 129(7) MeV. </center> <br /> Lattice artefacts could not be resolved within the statistical uncertainties of this work. While the ρ meson mass is in very good agreement with experiment the corresponding decay width differs by about two standard deviations from its experimental counterpart....

Lattice quantum chromodynamics (QCD) is a powerful tool to calculate the dynamics of low-energy, non-perturbative QCD. It has made great strides in numerically evaluating hadronic observables by simulating the interactions ...

Für eine umfassende forensisch-toxikologische Interpretation von Substanznachweisen in biologischen Matrizes bedarf es einer fundierten Datenlage. Neben pharmakologischen bzw. toxikologischen Eigenschaften der Substanzen ...