First-principles, atomistic thermodynamics for oxidation catalysis

Present knowledge of the function of materials is largely based on studies (experimental and theoretical) that are performed at low temperatures and ultra-low pressures. However, the majority of everyday applications, like e.g. catalysis, operate at atmospheric pressures and temperatures at or higher than 300 K. Here we employ ab initio, atomistic thermodynamics to construct a phase diagram of surface structures in the (T,p)-space from ultra-high vacuum to technically-relevant pressures and temperatures. We emphasize the value of such phase diagrams as well as the importance of the reaction kinetics that may be crucial e.g. close to phase boundaries.Comment: 4 pages including 2 figure files. Submitted to Phys. Rev. Lett. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

A method to correct differential nonlinearities in subranging analog-to-digital converters used for digital gamma-ray spectroscopy

The influence on $\gamma$-ray spectra of differential nonlinearities (DNL) in subranging, pipelined analog-to-digital converts (ADCs) used for digital $\gamma$-ray spectroscopy was investigated. The influence of the DNL error on the $\gamma$-ray spectra, depending on the input count-rate and the dynamic range has been investigated systematically. It turned out, that the DNL becomes more significant in $\gamma$-ray spectra with larger dynamic range of the spectroscopy system. An event-by-event offline correction algorithm was developed and tested extensively. This correction algorithm works especially well for high dynamic ranges

Jahn-Teller stabilization of a "polar" metal oxide surface: Fe3O4(001)

Using ab initio thermodynamics we compile a phase diagram for the surface of Fe3O4(001) as a function of temperature and oxygen pressures. A hitherto ignored polar termination with octahedral iron and oxygen forming a wave-like structure along the [110]-direction is identified as the lowest energy configuration over a broad range of oxygen gas-phase conditions. This novel geometry is confirmed in a x-ray diffraction analysis. The stabilization of the Fe3O4(001)-surface goes together with dramatic changes in the electronic and magnetic properties, e.g., a halfmetal-to-metal transition.Comment: 4 pages, 4 figure

Mol. Cell. Proteomics

Post-translational modification of proteins by ubiquitin is a fundamentally important regulatory mechanism. However, proteome-wide analysis of endogenous ubiquitylation remains a challenging task, and almost always has relied on cells expressing affinity tagged ubiquitin. Here we combine single-step immunoenrichment of ubiquitylated peptides with peptide fractionation and high-resolution mass spectrometry to investigate endogenous ubiquitylation sites. We precisely map 11,054 endogenous putative ubiquitylation sites (diglycine-modified lysines) on 4,273 human proteins. The presented data set covers 67% of the known ubiquitylation sites and contains 10,254 novel sites on proteins with diverse cellular functions including cell signaling, receptor endocytosis, DNA replication, DNA damage repair, and cell cycle progression. Our method enables site-specific quantification of ubiquitylation in response to cellular perturbations and is applicable to any cell type or tissue. Global quantification of ubiquitylation in cells treated with the proteasome inhibitor MG-132 discovers sites that are involved in proteasomal degradation, and suggests a nonproteasomal function for almost half of all sites. Surprisingly, ubiquitylation of about 15% of sites decreased more than twofold within four hours of MG-132 treatment, showing that inhibition of proteasomal function can dramatically reduce ubiquitylation on many sites with non-proteasomal functions. Comparison of ubiquitylation sites with acetylation sites reveals an extensive overlap between the lysine residues targeted by these two modifications. However, the crosstalk between these two post-translational modifications is significantly less frequent on sites that show increased ubiquitylation upon proteasome inhibition. Taken together, we report the largest site-specific ubiquitylation dataset in human cells, and for the first time demonstrate proteome-wide, site-specific quantification of endogenous putative ubiquitylation sites

Scaling of Gene Expression with Transcription-Factor Fugacity

The proteins associated with gene regulation are often shared between multiple pathways simultaneously. By way of contrast, models in regulatory biology often assume these pathways act independently. We demonstrate a framework for calculating the change in gene expression for the interacting case by decoupling repressor occupancy across the cell from the gene of interest by way of a chemical potential. The details of the interacting regulatory architecture are encompassed in an effective concentration, and thus, a single scaling function describes a collection of gene expression data from diverse regulatory situations and collapses it onto a single master curve

Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo

The Transcription Factor Titration Effect Dictates Level of Gene Expression

Models of transcription are often built around a picture of RNA polymerase and transcription factors (TFs) acting on a single copy of a promoter. However, most TFs are shared between multiple genes with varying binding affinities. Beyond that, genes often exist at high copy number—in multiple identical copies on the chromosome or on plasmids or viral vectors with copy numbers in the hundreds. Using a thermodynamic model, we characterize the interplay between TF copy number and the demand for that TF. We demonstrate the parameter-free predictive power of this model as a function of the copy number of the TF and the number and affinities of the available specific binding sites; such predictive control is important for the understanding of transcription and the desire to quantitatively design the output of genetic circuits. Finally, we use these experiments to dynamically measure plasmid copy number through the cell cycle

Analysis of OPM potentials for multiplet states of 3d transition metal atoms

We apply the optimized effective potential method (OPM) to the multiplet energies of the 3d$^n$ transition metal atoms, where the orbital dependence of the energy functional with respect to orbital wave function is the single-configuration HF form. We find that the calculated OPM exchange potential can be represented by the following two forms. Firstly, the difference between OPM exchange potentials of the multiplet states can be approximated by the linear combination of the potentials derived from the Slater integrals $F^2({\rm 3d,3d})$ and $F^4({\rm 3d,3d})$ for the average energy of the configuration. Secondly, the OPM exchange potential can be expressed as the linear combination of the OPM exchange potentials of the single determinants.Comment: 15 pages, 6 figures, to be published in J. Phys.

Adlayer core-level shifts of random metal overlayers on transition-metal substrates

We calculate the difference of the ionization energies of a core-electron of a surface alloy, i.e., a B-atom in a A_(1-x) B_x overlayer on a fcc-B(001)-substrate, and a core-electron of the clean fcc-B(001) surface using density-functional-theory. We analyze the initial-state contributions and the screening effects induced by the core hole, and study the influence of the alloy composition for a number of noble metal-transition metal systems. Data are presented for Cu_(1-x)Pd_x/Pd(001), Ag_(1-x) Pd_x/Pd(001), Pd_(1-x) Cu_x/Cu(001), and Pd_(1-x) Ag_x/Ag(001), changing x from 0 to 100 %. Our analysis clearly indicates the importance of final-state screening effects for the interpretation of measured core-level shifts. Calculated deviations from the initial-state trends are explained in terms of the change of inter- and intra-atomic screening upon alloying. A possible role of alloying on the chemical reactivity of metal surfaces is discussed.Comment: 4 pages, 2 figures, Phys. Rev. Letters, to appear in Feb. 199