A proteomic atlas of senescence-associated secretomes for aging biomarker development.

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the "SASP Atlas," a comprehensive proteomic database of soluble proteins and exosomal cargo SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo

Symmetry and disorder of the vitreous vortex lattice in an overdoped BaFe_{2-x}Co_xAs_2 superconductor: Indication for strong single-vortex pinning

The disordered flux line lattice in single crystals of the slightly overdoped aFe_{2-x}Co_xAs_2 (x = 0.19, Tc = 23 K) superconductor is studied by magnetization measurements, small-angle neutron scattering (SANS), and magnetic force microscopy (MFM). In the whole range of magnetic fields up to 9 T, vortex pinning precludes the formation of an ordered Abrikosov lattice. Instead, a vitreous vortex phase (vortex glass) with a short-range hexagonal order is observed. Statistical processing of MFM datasets lets us directly measure its radial and angular distribution functions and extract the radial correlation length \zeta. In contrast to predictions of the collective pinning model, no increase in the correlated volume with the applied field is observed. Instead, we find that \zeta decreases as 1.3*R1 ~ H^(-1/2) over four decades of the applied magnetic field, where R1 is the radius of the first coordination shell of the vortex lattice. Such universal scaling of \zeta implies that the vortex pinning in iron arsenides remains strong even in the absence of static magnetism. This result is consistent with all the real- and reciprocal-space vortex-lattice measurements in overdoped as-grown aFe_{2-x}Co_xAs_2 published to date and is thus sample-independent. The failure of the collective pinning model suggests that the vortices remain in the single-vortex pinning limit even in high magnetic fields up to 9 T.Comment: 11 pages, 6 figure

Symmetry and disorder of the vitreous vortex lattice in an overdoped BaFe_{2-x}Co_xAs_2 superconductor: Indication for strong single-vortex pinning

The disordered flux line lattice in single crystals of the slightly overdoped aFe_{2-x}Co_xAs_2 (x = 0.19, Tc = 23 K) superconductor is studied by magnetization measurements, small-angle neutron scattering (SANS), and magnetic force microscopy (MFM). In the whole range of magnetic fields up to 9 T, vortex pinning precludes the formation of an ordered Abrikosov lattice. Instead, a vitreous vortex phase (vortex glass) with a short-range hexagonal order is observed. Statistical processing of MFM datasets lets us directly measure its radial and angular distribution functions and extract the radial correlation length \zeta. In contrast to predictions of the collective pinning model, no increase in the correlated volume with the applied field is observed. Instead, we find that \zeta decreases as 1.3*R1 ~ H^(-1/2) over four decades of the applied magnetic field, where R1 is the radius of the first coordination shell of the vortex lattice. Such universal scaling of \zeta implies that the vortex pinning in iron arsenides remains strong even in the absence of static magnetism. This result is consistent with all the real- and reciprocal-space vortex-lattice measurements in overdoped as-grown aFe_{2-x}Co_xAs_2 published to date and is thus sample-independent. The failure of the collective pinning model suggests that the vortices remain in the single-vortex pinning limit even in high magnetic fields up to 9 T.Comment: 11 pages, 6 figure

SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells

Cellular senescence irreversibly arrests cell proliferation, accompanied by a multi-component senescence-associated secretory phenotype (SASP) that participates in several age-related diseases. Using stable isotope labeling with amino acids (SILACs) and cultured cells, we identify 343 SASP proteins that senescent human fibroblasts secrete at 2-fold or higher levels compared with quiescent cell counterparts. Bioinformatic analysis reveals that 44 of these proteins participate in hemostasis, a process not previously linked with cellular senescence. We validated the expression of some of these SASP factors in cultured cells and in vivo. Mice treated with the chemotherapeutic agent doxorubicin, which induces widespread cellular senescence in vivo, show increased blood clotting. Conversely, selective removal of senescent cells using transgenic p16-3MR mice showed that clearing senescent cells attenuates the increased clotting caused by doxorubicin. Our study provides an in-depth, unbiased analysis of the SASP and unveils a function for cellular senescence in hemostasis

Untersuchungen am Rotations-Schwingungsspektrum des Schwefeldioxid mittels Diodenlaserspektrometrie

SIGLEAvailable from TIB Hannover: DW 3059 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

A pumping lemma for output languages of macro tree transducers

The concept of macro tree transducer is a formal model for studying properties of syntax-directed translations and of functional languages which are based on primitive recursion. In this paper, for output languages of producing and nondeleting macro tree transducers, we introduce and prove a pumping lemma. We apply this pumping lemma to gain two results: (1) there is no producing and nondeleting macro tree transducer which computes the set of all monadic trees with double exponential height as output and (2) there are hierarchies of producing and nondeleting macro tree transducers with respect to their number of functions. (orig.)Available from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Neue Messverfahren im Bohrkopf zur Erfassung des Vollschnittmaschinenvortriebs und Konsolidierung der Streckenstoesse im Bohrkopfbereich

SIGLEAvailable from TIB Hannover: FR 5486+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Charles W. Eliot, president of Harvard University (May 19, 1869-May 19, 1909)

"This essay was originally written for the Deutsche rundschau of Berlin." - Note.Introduction.- I. The University at the time of Eliot's inauguration.- II. The College under Eliot's administration.- III. The professional schools under Eliot's administration.- IV. Eliot's educational philosophy.- V. Eliot's social philosophy (The ideals of American democracy).- VI. Eliot's life, public activities, personality.Mode of access: Internet

Neue Messverfahren im Bohrkopf zur Erfassung des Vollschnittmaschinenvortriebs und Konsolidierung der Streckenstoesse im Bohrkopfbereich

SIGLEAvailable from TIB Hannover: FR 5486+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman