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  • 1
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    Clustering properties of g-selected galaxies at z ~ 0.8 (2016)
    Oxford University Press
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    Publikationsdatum: 2016-07-21
    Beschreibung: Current and future large redshift surveys, as the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey (SDSS-IV/eBOSS) or the Dark Energy Spectroscopic Instrument (DESI), will use emission-line galaxies (ELGs) to probe cosmological models by mapping the large-scale structure of the Universe in the redshift range 0.6 〈 z 〈 1.7. With current data, we explore the halo–galaxy connection by measuring three clustering properties of g -selected ELGs as matter tracers in the redshift range 0.6 〈 z 〈 1: (i) the redshift-space two-point correlation function using spectroscopic redshifts from the BOSS ELG sample and VIPERS; (ii) the angular two-point correlation function on the footprint of the CFHT-LS; (iii) the galaxy–galaxy lensing signal around the ELGs using the CFHTLenS. We interpret these observations by mapping them on to the latest high-resolution MultiDark Planck N -body simulation, using a novel (Sub)Halo-Abundance Matching technique that accounts for the ELG incompleteness. ELGs at z ~ 0.8 live in haloes of (1 ± 0.5) x 10 12 h –1 M and 22.5 ± 2.5 per cent of them are satellites belonging to a larger halo. The halo occupation distribution of ELGs indicates that we are sampling the galaxies in which stars form in the most efficient way, according to their stellar-to-halo mass ratio.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    Inhibiting the stringent response blocks Mycobacterium tuberculosis entry into quiescence and reduces persistence (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉The stringent response enables 〈i〉Mycobacterium tuberculosis〈/i〉 (〈i〉Mtb〈/i〉) to shut down its replication and metabolism under various stresses. Here we show that 〈i〉Mtb〈/i〉 lacking the stringent response enzyme Rel〈sub〉Mtb〈/sub〉 was unable to slow its replication rate during nutrient starvation. Metabolomics analysis revealed that the nutrient-starved 〈i〉rel〈sub〉Mtb〈/sub〉〈/i〉-deficient strain had increased metabolism similar to that of exponentially growing wild-type bacteria in nutrient-rich broth, consistent with an inability to enter quiescence. Deficiency of 〈i〉rel〈sub〉Mtb〈/sub〉〈/i〉 increased the susceptibility of mutant bacteria to killing by isoniazid during nutrient starvation and in the lungs of chronically infected mice. We screened a pharmaceutical library of over 2 million compounds for inhibitors of Rel〈sub〉Mtb〈/sub〉 and showed that the lead compound X9 was able to directly kill nutrient-starved 〈i〉M. tuberculosis〈/i〉 and enhanced the killing activity of isoniazid. Inhibition of Rel〈sub〉Mtb〈/sub〉 is a promising approach to target 〈i〉M. tuberculosis〈/i〉 persisters, with the potential to shorten the duration of TB treatment.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    Bayesian redshift-space distortions correction from galaxy redshift surveys (2016)
    Oxford University Press
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    Publikationsdatum: 2016-01-29
    Beschreibung: We present a Bayesian reconstruction method which maps a galaxy distribution from redshift- to real-space inferring the distances of the individual galaxies. The method is based on sampling density fields assuming a lognormal prior with a likelihood modelling non-linear stochastic bias. Coherent redshift-space distortions are corrected in a Gibbs-sampling procedure by moving the galaxies from redshift- to real-space according to the peculiar motions derived from the recovered density field using linear theory. The virialized distortions are corrected by sampling candidate real-space positions along the line of sight, which are compatible with the bulk flow corrected redshift-space position adding a random dispersion term in high-density collapsed regions (defined by the eigenvalues of the Hessian). This approach presents an alternative method to estimate the distances to galaxies using the three-dimensional spatial information, and assuming isotropy. Hence the number of applications is very broad. In this work, we show the potential of this method to constrain the growth rate up to k  ~ 0.3 h  Mpc –1 . Furthermore it could be useful to correct for photometric redshift errors, and to obtain improved baryon acoustic oscillations (BAO) reconstructions.
    Print ISSN: 1745-3925
    Digitale ISSN: 1745-3933
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog [Pharmacology] (2011)
    National Academy of Sciences
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    Publikationsdatum: 2011-05-18
    Beschreibung: The capsaicin receptor TRPV1 is the principal transduction channel for nociception. Excessive TRPV1 activation causes pathological pain. Ideal pain mangement requires selective inhibition of hyperactive pain-sensing neurons, but sparing normal nociception. We sought to determine whether it is possible to use activity-dependent TRPV1 agonists to identify nerves with excessive TRPV1 activity, as well as exploit the TRPV1 pore to deliver charged anesthetics for neuronal silencing. We synthesized a series of permanently charged capsaicinoids and found that one, cap-ET, efficaciously evoked TRPV1-dependent entry of Ca2+ or the large cationic dye YO-PRO-1 comparably to capsaicin, but far smaller electrical currents. Cap-ET–induced YO-PRO-1 transport required permeation of both the agonist and the dye through the TRPV1 pore and could be enhanced by kinase activation or oxidative covalent modification. Moreover, cap-ET reduced capsaicin-induced currents by a voltage-dependent block of the pore. A low dose of cap-ET elicited entry of permanently charged Na+ channel blockers to effectively suppress Na+ currents in sensory neurons presensitized with oxidative chemicals. These results implicate therapeutic potential of these unique TRPV1 agonists exhibiting activity-dependent ion transport but of minimal pain-producing risks.
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Molecular basis of T cell inactivation by CTLA-4 (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 1998-12-18
    Beschreibung: CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, K M -- Chuang, E -- Griffin, M -- Khattri, R -- Hong, D K -- Zhang, W -- Straus, D -- Samelson, L E -- Thompson, C B -- Bluestone, J A -- P01 AI35294-6/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute for Cancer Research, and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856951" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Abatacept ; Animals ; Antigens, CD ; Antigens, Differentiation/*metabolism ; CTLA-4 Antigen ; Cell Line ; Cells, Cultured ; Humans ; *Immunoconjugates ; Intracellular Signaling Peptides and Proteins ; *Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/metabolism ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred BALB C ; Models, Immunological ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; SH2 Domain-Containing Protein Tyrosine Phosphatases ; *Signal Transduction ; T-Lymphocytes/*immunology ; Transfection ; src Homology Domains
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS) (2013)
    Oxford University Press
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    Publikationsdatum: 2013-07-26
    Beschreibung: We report a novel gene for a parkinsonian disorder. X-linked parkinsonism with spasticity (XPDS) presents either as typical adult onset Parkinson's disease or earlier onset spasticity followed by parkinsonism. We previously mapped the XPDS gene to a 28 Mb region on Xp11.2–X13.3. Exome sequencing of one affected individual identified five rare variants in this region, of which none was missense, nonsense or frame shift. Using patient-derived cells, we tested the effect of these variants on expression/splicing of the relevant genes. A synonymous variant in ATP6AP2 , c.345C〉T (p.S115S), markedly increased exon 4 skipping, resulting in the overexpression of a minor splice isoform that produces a protein with internal deletion of 32 amino acids in up to 50% of the total pool, with concomitant reduction of isoforms containing exon 4. ATP6AP2 is an essential accessory component of the vacuolar ATPase required for lysosomal degradative functions and autophagy, a pathway frequently affected in Parkinson's disease. Reduction of the full-size ATP6AP2 transcript in XPDS cells and decreased level of ATP6AP2 protein in XPDS brain may compromise V-ATPase function, as seen with siRNA knockdown in HEK293 cells, and may ultimately be responsible for the pathology. Another synonymous mutation in the same exon, c.321C〉T (p.D107D), has a similar molecular defect of exon inclusion and causes X-linked mental retardation Hedera type (MRXSH). Mutations in XPDS and MRXSH alter binding sites for different splicing factors, which may explain the marked differences in age of onset and manifestations.
    Print ISSN: 0964-6906
    Digitale ISSN: 1460-2083
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Building a better understanding of the massive high-redshift BOSS CMASS galaxies as tools for cosmology (2016)
    Oxford University Press
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    Publikationsdatum: 2016-08-21
    Beschreibung: We explore the massive bluer star-forming population of the Sloan Digital Sky Survey (SDSS) III/BOSS CMASS DR11 galaxies at z  〉 0.55 to quantify their differences, in terms of redshift-space distortions and large-scale bias, with respect to the luminous red galaxy sample. We perform a qualitative analysis to understand the significance of these differences and whether we can model and reproduce them in mock catalogues. Specifically, we measure galaxy clustering in CMASS on small and intermediate scales (0.1 r 50 h –1  Mpc) by computing the two-point correlation function – both projected and redshift-space – of these galaxies, and a new statistic, (), able to separate the coherent and dispersed redshift-space distortion contributions and the large-scale bias. We interpret our clustering measurements by adopting a Halo Occupation Distribution (HOD) scheme that maps them on to high-resolution N -body cosmological simulations to produce suitable mock galaxy catalogues. The traditional HOD prescription can be applied to the red and the blue samples, independently, but this approach is unphysical since it allows the same mock galaxies to be either red or blue. To overcome this ambiguity, we modify the standard formulation and infer the red and the blue models by splitting the full mock catalogue into two complementary and non-overlapping submocks. This separation is performed by constraining the HOD with the observed CMASS red and blue galaxy fractions and produces reliable and accurate models.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model (2014)
    Oxford University Press
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    Publikationsdatum: 2014-02-08
    Beschreibung: Arrhythmogenic right ventricular cardiomyopathy (ARVC) termed a ‘disease of the desmosome’ is an inherited cardiomyopathy that recently underwent reclassification owing to the identification of left-dominant and biventricular disease forms. Homozygous loss-of-function mutations in the desmosomal component, desmoplakin, are found in patients exhibiting a biventricular form of ARVC; however, no models recapitulate the postnatal hallmarks of the disease as seen in these patients. To gain insights into the homozygous loss-of-function effects of desmoplakin in the heart, we generated cardiomyocyte-specific desmoplakin-deficient mice (DSP-cKO) using ventricular myosin light chain-2-Cre mice. Homozygous DSP-cKO mice are viable but display early ultrastructural defects in desmosomal integrity leading to a cardiomyopathy reminiscent of a biventricular form of ARVC, which includes cell death and fibro-fatty replacement within the ventricle leading to biventricular dysfunction, failure and premature death. DSP-cKO mice also exhibited ventricular arrhythmias that are exacerbated with exercise and catecholamine stimulation. Furthermore, DSP-cKO hearts exhibited right ventricular conduction defects associated with loss of connexin 40 expression and electrical wavefront propagation defects associated with loss of connexin 43 expression. Dose-dependent assessment of the effects of loss of desmoplakin in neonatal ventricular cardiomyocytes revealed primary loss of connexin 43 levels, phosphorylation and function independent of the molecular dissociation of the mechanical junction complex and fibro-fatty manifestation associated with ARVC, suggesting a role for desmoplakin as a primary stabilizer of connexin integrity. In summary, we provide evidence for a novel mouse model, which is reminiscent of the postnatal onset of ARVC while highlighting mechanisms underlying a biventricular form of human ARVC.
    Print ISSN: 0964-6906
    Digitale ISSN: 1460-2083
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
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  • 9
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    Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants (2003)
    National Academy of Sciences
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    Publikationsdatum: 2003-04-17
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
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  • 10
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    χ2 test for feature detection (1993)
    Elsevier
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    Publikationsdatum: 1993-11-01
    Print ISSN: 0031-3203
    Digitale ISSN: 1873-5142
    Thema: Informatik
    Publiziert von Elsevier
    Standort Signatur Erwartet Verfügbarkeit
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