77 research outputs found

    The Cytotoxicity and Mode of Action of 2,3,4-Trisubstituted Pyrroles and Related Derivatives in Human Tmolt4 Leukemia Cells

    Get PDF
    4-Carbechoxy-l-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybcnzoyl)-3-(4-methoxyphcnyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g. human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase a, RNA polymerases, nucleoside kinase and ribonucleoside reductase

    The MUSE-Wide survey: Three-dimensional clustering analysis of Lyman-α\alpha emitters at 3.3<z<63.3<z<6

    Get PDF
    We present an analysis of the spatial clustering of 695 Lyα\alpha-emitting galaxies (LAE) in the MUSE-Wide survey. All objects have spectroscopically confirmed redshifts in the range 3.3<z<63.3<z<6. We employ the K-estimator of Adelberger et al. (2005), adapted and optimized for our sample. We also explore the standard two-point correlation function approach, which is however less suited for a pencil-beam survey such as ours. The results from both approaches are consistent. We parametrize the clustering properties by, (i) modelling the clustering signal with a power law (PL), and (ii) adopting a Halo Occupation Distribution (HOD) model. Applying HOD modeling, we infer a large-scale bias of bHOD=2.80−0.38+0.38b_{\rm{HOD}}=2.80^{+0.38}_{-0.38} at a median redshift of the number of galaxy pairs ⟹zpair⟩≃3.82\langle z_{\rm pair}\rangle\simeq3.82, while the PL analysis results in bPL=3.03−0.52+1.51b_{\rm{PL}}=3.03^{+1.51}_{-0.52} (r0=3.60−0.90+3.10  h−1r_0=3.60^{+3.10}_{-0.90}\;h^{-1}Mpc and Îł=1.30−0.45+0.36\gamma=1.30^{+0.36}_{-0.45}). The implied typical dark matter halo (DMH) mass is log⁥(MDMH/[h−1M⊙])=11.34−0.27+0.23\log(M_{\rm{DMH}}/[h^{-1}\rm{M}_\odot])=11.34^{+0.23}_{-0.27}. We study possible dependencies of the clustering signal on object properties by bisecting the sample into disjoint subsets, considering Lyα\alpha luminosity, UV absolute magnitude, Lyα\alpha equivalent width, and redshift as variables. We find a suggestive trend of more luminous Lyα\alpha emitters residing in more massive DMHs than their lower Lyα\alpha luminosity counterparts. We also compare our results to mock LAE catalogs based on a semi-analytic model of galaxy formation and find a stronger clustering signal than in our observed sample. By adopting a galaxy-conserving model we estimate that the LAEs in the MUSE-Wide survey will typically evolve into galaxies hosted by halos of log⁥(MDMH/[h−1M⊙])≈13.5\log(M_{\rm{DMH}}/[h^{-1}\rm{M}_\odot])\approx13.5 at redshift zero, suggesting that we observe the ancestors of present-day galaxy groups.Comment: Accepted for publication in A&A. 22 pages, 20 figures, 4 table

    Phage Display in the Quest for New Selective Recognition Elements for Biosensors

    Get PDF
    Phages are bacterial viruses that have gained a significant role in biotechnology owing to their widely studied biology and many advantageous characteristics. Perhaps the best-known application of phages is phage display that refers to the expression of foreign peptides or proteins outside the phage virion as a fusion with one of the phage coat proteins. In 2018, one half of the Nobel prize in chemistry was awarded jointly to George P. Smith and Sir Gregory P. Winter "for the phage display of peptides and antibodies." The outstanding technology has evolved and developed considerably since its first description in 1985, and today phage display is commonly used in a wide variety of disciplines, including drug discovery, enzyme optimization, biomolecular interaction studies, as well as biosensor development. A cornerstone of all biosensors, regardless of the sensor platform or transduction scheme used, is a sensitive and selective bioreceptor, or a recognition element, that can provide specific binding to the target analyte. Many environmentally or pharmacologically interesting target analytes might not have naturally appropriate binding partners for biosensor development, but phage display can facilitate the production of novel receptors beyond known biomolecular interactions, or against toxic or nonimmunogenic targets, making the technology a valuable tool in the quest of new recognition elements for biosensor development.This study was supported by the Ministry of Economy and Competitiveness (Ministerio de Ciencia, InnovaciĂłn y Universidades RTI2018-096410-B-C21). R.P. acknowledges UCM for a predoctoral grant and R.B. the PI17CIII/00045 grant from the AES-ISCIII program.S

    Discovery of the luminous X-ray ignition eRASSt J234402.9−-352640; I. Tidal disruption event or a rapid increase in accretion in an active galactic nucleus?

    Full text link
    In November 2020, a new, bright object, eRASSt J234402.9−-352640, was discovered in the second all-sky survey of SRG/eROSITA. The object brightened by a factor of at least 150 in 0.2--2.0 keV flux compared to an upper limit found six months previous, reaching an observed peak of 1.76−0.24+0.03×10−111.76_{-0.24}^{+0.03} \times 10^{-11} erg cm−2^{-2} s−1^{-1}. The X-ray ignition is associated with a galaxy at z=0.10z=0.10, making the peak luminosity log10(L0.2−2keV/[erg s−1])_{10}(L_{\rm 0.2-2keV}/[\textrm{erg s}^{-1}])=44.7±0.144.7\pm0.1. Around the time of the rise in X-ray flux, the nucleus of the galaxy brightened by approximately 3 mag. in optical photometry, after correcting for the host. We present data from Swift, XMM-Newton, and NICER, which reveal a very soft spectrum as well as strong 0.2--2.0 keV flux variability on multiple timescales. Optical spectra taken in the weeks after the ignition event show a blue continuum with broad, asymmetric Balmer emission lines, and high-ionisation ([OIII]λλ\lambda\lambda4959,5007) and low-ionisation ([NII]λ\lambda6585, [SII]λλ\lambda\lambda6716,6731) narrow emission lines. Following the peak in the optical light curve, the X-ray, UV, and optical photometry all show a rapid decline. The X-ray light curve shows a decrease in luminosity of ∌\sim0.45 over 33 days and the UV shows a drop of ∌\sim0.35. eRASSt J234402.9−-352640 also shows a brightening in the mid-infrared, likely powered by a dust echo of the luminous ignition. We find no evidence in Fermi-LAT Îł\gamma-ray data for jet-like emission. The event displays characteristics of a tidal disruption event (TDE) as well as of an active galactic nucleus (AGN), complicating its classification. Based on the softness of the X-ray spectrum, the presence of high-ionisation optical emission lines, and the likely infrared echo, we find that a TDE within a turned-off AGN best matches our observations.Comment: 25 pages, 17 figures, 9 tables, Accepted for publication in A&

    The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

    Get PDF
    The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

    Black hole accretion and host galaxies of obscured quasars in XMM-COSMOS

    Get PDF
    We explore the connection between black hole growth at the center of obscured quasars selected from the XMM-COSMOS survey and the physical properties of their host galaxies. We study a bolometric regime ( 8 x 10^45 erg/s) where several theoretical models invoke major galaxy mergers as the main fueling channel for black hole accretion. We confirm that obscured quasars mainly reside in massive galaxies (Mstar>10^10 Msun) and that the fraction of galaxies hosting such powerful quasars monotonically increases with the stellar mass. We stress the limitation of the use of rest-frame color-magnitude diagrams as a diagnostic tool for studying galaxy evolution and inferring the influence that AGN activity can have on such a process. We instead use the correlation between star-formation rate and stellar mass found for star-forming galaxies to discuss the physical properties of the hosts. We find that at z ~1, ~62% of Type-2 QSOs hosts are actively forming stars and that their rates are comparable to those measured for normal star-forming galaxies. The fraction of star-forming hosts increases with redshift: ~71% at z ~2, and 100% at z ~3. We also find that the the evolution from z ~1 to z ~3 of the specific star-formation rate of the Type-2 QSO hosts is in excellent agreement with that measured for star-forming galaxies. From the morphological analysis, we conclude that most of the objects are bulge-dominated galaxies, and that only a few of them exhibit signs of recent mergers or disks. Finally, bulge-dominated galaxies tend to host Type-2 QSOs with low Eddington ratios (lambda<0.1), while disk-dominated or merging galaxies have at their centers BHs accreting at high Eddington ratios (lambda > 0.1).Comment: Accepted by A&A. 20 pages, 16 figures, 2 tables. A version with higher resolution figures and SED fits of Appendix A is available at http://www.eso.org/~vmainier/QSO2/qso2.pd

    The eROSITA Final Equatorial Depth Survey (eFEDS) X-ray catalogue

    Get PDF
    Context. The eROSITA X-ray telescope on board the Spectrum-Roentgen-Gamma (SRG) observatory combines a large field of view and a large collecting area in the energy range between similar to 0.2 and similar to 8.0 keV. This gives the telescope the capability to perform uniform scanning observations of large sky areas. Aims. SRG/eROSITA performed scanning observations of the similar to 140 square degree eROSITA Final Equatorial Depth Survey field (the eFEDS field) as part of its performance verification phase ahead of the planned four years of all-sky scanning operations. The observing time of eFEDS was chosen to slightly exceed the depth expected in an equatorial field after the completion of the all-sky survey. While verifying the capability of eROSITA to perform large-area uniform surveys and serving as a test and training dataset to establish calibration and data analysis procedures, the eFEDS survey also constitutes the largest contiguous soft X-ray survey at this depth to date, supporting a range of early eROSITA survey science investigations. Here we (i) present a catalogue of detected X-ray sources in the eFEDS field providing information about source positions and extent, as well as fluxes in multiple energy bands, and (ii) document the suite of tools and procedures developed for eROSITA data processing and analysis, which were validated and optimised by the eFEDS work. Methods. The data were fed through a standard data processing pipeline, which applies X-ray event calibration and provides a set of standard calibrated data products. A multi-stage source detection procedure, building in part on experience from XMM-Newton, was optimised and calibrated by performing realistic simulations of the eROSITA eFEDS observations. Source fluxes were computed in multiple standard energy bands by forced point source fitting and aperture photometry. We cross-matched the eROSITA eFEDS source catalogue with previous XMM-ATLAS observations, which confirmed the excellent agreement of the eROSITA and XMM-ATLAS source fluxes. Astrometric corrections were performed by cross-matching the eROSITA source positions with an optical reference catalogue of quasars. Results. We present a primary catalogue of 27 910 X-ray sources (542 of which are significantly spatially extended) detected in the 0.2-2.3 keV energy range with detection likelihoods >= 6, corresponding to a (point source) flux limit of 6.5 x 10(-15) erg cm(-2 )s(-1) in the 0.5-2.0 keV energy band (80% completeness). A supplementary catalogue contains 4774 low-significance source candidates with detection likelihoods between 5 and 6. In addition, a hard-band sample of 246 sources detected in the energy range 2.3-5.0 keV above a detection likelihood of 10 is provided. In an appendix, we finally describe the dedicated data analysis software package, the eROSITA calibration database, and the standard calibrated data products.Peer reviewe

    The Use of Phage-Displayed Peptide Libraries to Develop Tumor-Targeting Drugs

    Get PDF
    Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by the size of the molecules and non-specific uptake by the reticuloendothelial system. Peptides are much smaller molecules that can specifically target cancer cells and as such may alleviate complications with antibody therapy. Although many endogenous and exogenous peptides have been developed into clinical therapeutics, only a subset of these consists of cancer-targeting peptides. Combinatorial biological libraries such as bacteriophage-displayed peptide libraries are a resource of potential ligands for various cancer-related molecular targets. Target-binding peptides can be affinity selected from complex mixtures of billions of displayed peptides on phage and further enriched through the biopanning process. Various cancer-specific ligands have been isolated by in vitro, in vivo, and ex vivo screening methods. As several peptides derived from phage-displayed peptide library screenings have been developed into therapeutics in current clinical trials, which validates peptide-targeting potential, the use of phage display to identify cancer-targeting therapeutics should be further exploited

    The angular clustering of infrared-selected obscured and unobscured quasars

    Get PDF
    This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2014 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Recent studies of luminous infrared-selected active galactic nuclei (AGN) suggest that the reddest, most obscured objects display a higher angular clustering amplitude, and thus reside in higher mass darkmatter haloes. This is a direct contradiction to the prediction of the simplest unification-by-orientation models of AGN and quasars. However, clustering measurements depend strongly on the 'mask' that removes low-quality data and describes the sky and selection function.We find that applying a robust, conservative mask to WISE-selected quasars yields a weaker but still significant difference in the bias between obscured and unobscured quasars. These findings are consistent with results from previous Spitzer surveys, and removes any scale dependence of the bias. For obscured quasars with =0.99, we measure a bias of bq = 2.67 ± 0.16, corresponding to a halo mass of log(Mh/M⊙h-1) = 13.3 ± 0.1, while for unobscured sources with = 1.04 we find bq = 2.04 ± 0.17 with a halo mass log(Mh/M⊙h-1) = 12.8 ± 0.1. This improved measurement indicates that WISE-selected obscured quasars reside in haloes only a few times more massive than the haloes of their unobscured counterparts, a reduction in the factor of ∌10 larger halo mass as has been previously reported using WISE-selected samples. Additionally, an abundance matching analysis yields lifetimes for both obscured and unobscured quasar phases on the order of a few 100 Myr (∌1 per cent of the Hubble time) - however, the obscured phase lasts roughly twice as long, in tension with many model predictions.Peer reviewe
    • 

    corecore