A novel genome-wide approach to identify in vivo targets of Notch signalling

The Notch signalling pathway regulates many developmental processes in metazoan embryos and adults such as cell proliferation, stem cell maintenance, cell fate specification and apoptosis. Despite the importance of this pathway, few targets have been identified, with the Hes (Hairy and Enhancer-of-split) protein family being the best-characterised group of downstream effectors. I have established transgenic mice carrying Biotin Acceptor Peptide (BAP)- tagged versions of Notch1. The tagged protein is fully functional and is biotinylated after crossing to mice expressing the biotinylase from E. coli. Biotinylation was confirmed in a range of different tissues. However, streptavidin chromatin pull-down (bioChIP) experiments from these tissues showed no significant enrichment of known Notch1 target sequences. A possible explanation could be the indirect and transient nature of the interaction between Notch, its DNA binding partner CSL and the promoter of the target gene. A transgenic mouse line expressing a BAP-tagged version of the transcription factor Hes7, a downstream effector of Notch signalling and key regulator of somitogenesis, was similarly generated. Although the tagged Hes7 protein is functional and gets biotinylated in cell culture assays, the transgenic mice exhibit a severe somite/skeletal phenotype indicating that the tagged allele is hypomorphic. A detailed analysis of the phenotype revealed differential axial requirements for Hes7

Gundlach oscillations and Coulomb blockade of Co nano-islands on MgO/Mo(100) investigated by scanning tunneling spectroscopy at 300 K

Ultrathin MgO films on Mo(100) with a thickness up to 12 ML are studied by scanning tunneling microscopy and spectroscopy at room temperature. The spatial variation of the work function within the MgO film is mapped by field emission resonance states (Gundlach oscillations) using dz/dU spectroscopy. We found circular spots with significantly reduced work function (DeltaPhi=0.6 eV), which are assigned to charged defects within the MgO film. On top of the MgO films, small Co cluster are deposited with an average contact area of 4 nm^2. These islands exhibit Coulomb oscillations in dI/dU spectra at room temperature. Good agreement with orthodox theory is achieved showing variations of the background charge Q_0 for islands at different positions, which are in accordance with the work function differences determined by the Gundlach oscillations.Comment: 7 pages, 3 figure

Temperature-dependent change of the fractal dimension of Cu dendrites on Cu(111)

We investigate the shape of monatomic high Cu islands on a Cu(111) surface by variable-temperature scanning tunneling microscopy between 110 K and 240 K. Low temperature dendrites evolve towards more compact shapes at increasing temperature; finally reaching the equilibrium shape of a hexagon with rounded corners. Time-lapsed imaging at increasing temperature reveals the onset of shape change to be at ≈170 K, corresponding to the onset of edge and corner diffusion of atoms along the island's borders. Despite a substantial variation for individual islands at each temperature, the mean fractal dimension increases monotonously between 170 K up to 240 K, from the smallest to the largest values feasible for islands grown on surfaces. © 2020 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft

Probing electron-electron interaction in quantum Hall systems with scanning tunneling spectroscopy

Using low-temperature scanning tunneling spectroscopy applied to the Cs-induced two-dimensional electron system (2DES) on p-type InSb(110), we probe electron-electron interaction effects in the quantum Hall regime. The 2DES is decoupled from p-doped bulk states and exhibits spreading resistance within the insulating quantum Hall phases. In quantitative agreement with calculations we find an exchange enhancement of the spin splitting. Moreover, we observe that both the spatially averaged as well as the local density of states feature a characteristic Coulomb gap at the Fermi level. These results show that electron-electron interaction effects can be probed down to a resolution below all relevant length scales.Comment: supplementary movie in ancillary file

Glass Model, Hubbard Model and High-Temperature Superconductivity

In this paper we revisit the glass model describing the macroscopic behavior of the High-Temperature superconductors. We link the glass model at the microscopic level to the striped phase phenomenon, recently discussed widely. The size of the striped phase domains is consistent with earlier predictions of the glass model when it was introduced for High-Temperature Superconductivity in 1987. In an additional step we use the Hubbard model to describe the microscopic mechanism for d-wave pairing within these finite size stripes. We discuss the implications for superconducting correlations of Hubbard model, which are much higher for stripes than for squares, for finite size scaling, and for the new view of the glass model picture.Comment: 7 pages, 7 figures (included), LaTex using Revtex, accepted by Int. J. Mod. Phys.

Bistability and oscillatory motion of natural nano-membranes appearing within monolayer graphene on silicon dioxide

The recently found material graphene is a truly two-dimensional crystal and exhibits, in addition, an extreme mechanical strength. This in combination with the high electron mobility favours graphene for electromechanical investigations down to the quantum limit. Here, we show that a monolayer of graphene on SiO2 provides natural, ultra-small membranes of diameters down to 3 nm, which are caused by the intrinsic rippling of the material. Some of these nano-membranes can be switched hysteretically between two vertical positions using the electric field of the tip of a scanning tunnelling microscope (STM). They can also be forced to oscillatory motion by a low frequency ac-field. Using the mechanical constants determined previously, we estimate a high resonance frequency up to 0.4 THz. This might be favorable for quantum-electromechanics and is prospective for single atom mass spectrometers.Comment: 9 pages, 4 figure

International market exposure to sovereign ESG

We quantify equity and bond market sensitivity to sovereign ESG scores and their variations which, theoretically, is equivalent to evaluating the demand for ESG at the global scale. We do so by estimating a longitudinal model, at the issue level, that captures exposures to sovereign ESG factors for both equity and fixed income indices. In spite of the surging interest in ESG investing, our results do not support a strong impact of ESG factors on the returns of international markets, implying that the demand for ESG at the country level is not a significant driver of prices. Nevertheless, we document a strong association between GDP growth and ESG scores at the country level

Multiple sequence alignment based on set covers

We introduce a new heuristic for the multiple alignment of a set of sequences. The heuristic is based on a set cover of the residue alphabet of the sequences, and also on the determination of a significant set of blocks comprising subsequences of the sequences to be aligned. These blocks are obtained with the aid of a new data structure, called a suffix-set tree, which is constructed from the input sequences with the guidance of the residue-alphabet set cover and generalizes the well-known suffix tree of the sequence set. We provide performance results on selected BAliBASE amino-acid sequences and compare them with those yielded by some prominent approaches