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  • 11
    Publication Date: 2011-06-28
    Description: Evolutionary studies necessary to dissect diverse biological processes have been limited by the lack of reverse genetic approaches in most organisms with sequenced genomes. We established a broadly applicable strategy using zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) for targeted disruption of endogenous genes and cis-acting regulatory elements in diverged nematode species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489282/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Andrew J -- Lo, Te-Wen -- Zeitler, Bryan -- Pickle, Catherine S -- Ralston, Edward J -- Lee, Andrew H -- Amora, Rainier -- Miller, Jeffrey C -- Leung, Elo -- Meng, Xiangdong -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Meyer, Barbara J -- GM30702/GM/NIGMS NIH HHS/ -- R01 GM030702/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 15;333(6040):307. doi: 10.1126/science.1207773. Epub 2011 Jun 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI), Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700836" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis/*genetics ; Caenorhabditis elegans/*genetics ; Deoxyribonucleases, Type II Site-Specific/genetics/*metabolism ; Gene Targeting ; Genes, Helminth ; *Genetic Techniques ; *Genome, Helminth ; INDEL Mutation ; Mutagenesis ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/chemistry ; Transgenes ; *Zinc Fingers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2015-11-28
    Description: The tidal disruption of a star by a supermassive black hole leads to a short-lived thermal flare. Despite extensive searches, radio follow-up observations of known thermal stellar tidal disruption flares (TDFs) have not yet produced a conclusive detection. We present a detection of variable radio emission from a thermal TDF, which we interpret as originating from a newly launched jet. The multiwavelength properties of the source present a natural analogy with accretion-state changes of stellar mass black holes, which suggests that all TDFs could be accompanied by a jet. In the rest frame of the TDF, our radio observations are an order of magnitude more sensitive than nearly all previous upper limits, explaining how these jets, if common, could thus far have escaped detection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Velzen, S -- Anderson, G E -- Stone, N C -- Fraser, M -- Wevers, T -- Metzger, B D -- Jonker, P G -- van der Horst, A J -- Staley, T D -- Mendez, A J -- Miller-Jones, J C A -- Hodgkin, S T -- Campbell, H C -- Fender, R P -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):62-5. doi: 10.1126/science.aad1182. Epub 2015 Nov 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, MD 21218, USA. sjoert@jhu.edu. ; Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH, UK. International Centre for Radio Astronomy Research, Curtin University, GPO Box U1987, Perth WA 6845, Australia. ; Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027, USA. ; Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA, UK. ; Department of Astrophysics, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, Netherlands. ; Department of Astrophysics, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, Netherlands. SRON, Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht, Netherlands. ; Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052, USA. ; Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH, UK. ; Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, MD 21218, USA. ; International Centre for Radio Astronomy Research, Curtin University, GPO Box U1987, Perth WA 6845, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612833" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 13
    Publication Date: 2017-09-08
    Description: Here, we present and characterize the spontaneous X-linked recessive mutation casper , which causes oculocutaneous albinism in threespine sticklebacks ( Gasterosteus aculeatus ). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19) near the stickleback ortholog of Hermansky-Pudlak syndrome 5 ( Hps5 ). casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5 , predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 14
    Publication Date: 1982-10-15
    Description: A linear photodiode array has been used as the photodetector element in a new ultraviolet-visible detection system for high-performance liquid chromatography. This array allows simultaneous acquisition of light intensity data at all wavelengths between 190 and 600 nanometers. By use of a computer network concept in the electronics, this detection system can process eight different chromatographic signals simultaneously in real time and acquire spectra manually or automatically. Detector response times are variable and can be as low as 0.040 second, and bandwidth selection is variable from 4 to 400 nanometers. These characteristics permit fast chromatographic techniques and user-selectable signal-to-noise ratio enhancement. Spectra can be acquired in 10 milliseconds, permitting qualitative characterization at several different points on a single peak without destroying chromatographic signal integrity. Examples illustrate applications in fast high-performance liquid chromatography peak purity determination, and postanalysis data reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, J C -- George, S A -- Willis, B G -- New York, N.Y. -- Science. 1982 Oct 15;218(4569):241-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17838610" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2018-03-30
    Description: Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo–electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB.
    Keywords: Biochemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 16
    Publication Date: 2019
    Description: 〈p〉The integrated stress response (ISR) tunes the rate of protein synthesis. Control is exerted by phosphorylation of the general translation initiation factor eIF2. eIF2 is a guanosine triphosphatase that becomes activated by eIF2B, a two-fold symmetric and heterodecameric complex that functions as eIF2’s dedicated nucleotide exchange factor. Phosphorylation converts eIF2 from a substrate into an inhibitor of eIF2B. We report cryo–electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state. The structures reveal that the eIF2B decamer is a static platform upon which one or two flexible eIF2 trimers bind and align with eIF2B’s bipartite catalytic centers to catalyze nucleotide exchange. Phosphorylation refolds eIF2α, allowing it to contact eIF2B at a different interface and, we surmise, thereby sequestering it into a nonproductive complex.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 17
    Publication Date: 2015-10-30
    Description: SN 2006gy was the most luminous supernova (SN) ever observed at the time of its discovery and the first of the newly defined class of superluminous supernovae (SLSNe). The extraordinary energetics of SN 2006gy and all SLSNe (〉10 51  erg) require either atypically large explosion energies (e.g. pair-instability explosion) or the efficient conversion of kinetic into radiative energy (e.g. shock interaction). The mass-loss characteristics can therefore offer important clues regarding the progenitor system. For the case of SN 2006gy, both a scattered and thermal light echo from circumstellar material (CSM) have been reported at later epochs (day ~800), ruling out the likelihood of a pair-instability event and leading to constraints on the characteristics of the CSM. Owing to the proximity of the SN to the bright host-galaxy nucleus, continued monitoring of the light echo has not been trivial, requiring the high resolution offered by the Hubble Space Telescope (HST) or ground-based adaptive optics (AO). Here, we report detections of SN 2006gy using HST and Keck AO at ~3000 d post-explosion and consider the emission mechanism for the very late-time light curve. While the optical light curve and optical spectral energy distribution are consistent with a continued scattered-light echo, a thermal echo is insufficient to power the K '-band emission by day 3000. Instead, we present evidence for late-time infrared emission from dust that is radiatively heated by CSM interaction within an extremely dense dust shell, and we consider the implications on the CSM characteristics and progenitor system.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 18
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of agricultural and food chemistry 3 (1955), S. 151-155 
    ISSN: 1520-5118
    Source: ACS Legacy Archives
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
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  • 19
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 168 (1951), S. 838-838 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Recently we have prepared a routine for testing on the Edsac the primality of numbers of the form kP + 1, with P as defined above, and have found ten values of k that give prime numbers. The largest of these gives the present (June 7) largest known prime, namely,934(212' 1) + 1. J. C. P. MILLER ...
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  • 20
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Dissolved paramagnetic ions generally provide an efficient mechanism for the relaxation of nuclear spins in solution, a phenomenon called the nuclear magnetic resonance-paramagnetic relaxation enhancement (NMR-PRE). Metal ions with electron spins S≥1 exhibit rich NMR relaxation phenomena originating in the properties of the zero-field splitting (zfs) interaction, which vanishes for spin-〈fraction SHAPE="CASE"〉12 ions but which is nonzero for S≥1 ions in site symmetry lower than cubic. For S≥1 ions in the vicinity of the zfs-limit, i.e., at magnetic-field strengths low enough that the zfs energy exceeds the Zeeman energy, the NMR-PRE depends strongly on the detailed structure of the electron spin energy levels as well as on the spatial quantization of the spin motion. It is shown theoretically and experimentally that the NMR-PRE produced by integer spins can be influenced strongly by the small intradoublet zero-field splittings, i.e., the splittings between the components of the non-Kramers doublets, which are produced by noncylindrical components of the crystal field potential. These small splittings produce relatively low-frequency oscillations in the dipolar field associated with 〈Sz(circumflex)〉 (the spin component along the molecule-fixed z(circumflex) axis). These motions decouple the nuclear spin from the electron spin, thereby depressing, in some cases very strongly, the NMR-PRE. The presence of a relatively small Zeeman field, comparable in magnitude to the intradoublet spacing but small compared to the larger interdoublet zfs splittings, causes a major change in the spin wave functions which has profound effects on the motions of the electron spin. When the Zeeman energy exceeds the small zfs splitting, the oscillatory motion of 〈Sz(circumflex)〉 damps out, with the result that the electron spin couples more effectively to the nuclear spin, providing a more efficient NMR relaxation pathway. NMR-PRE data are presented for the S=1 complex Ni(II)(o-pda)2Cl2 (o-pda=ortho-phenylenediamine) which confirm the importance of the splitting of the mS=±1 non-Kramers doublet on the NMR relaxation efficiency. The zfs E-parameter was measured from the NMR data to be |E|=0.26 cm−1. The S=2 spin system, Mn(III)-tetraphenylporphyrin sulfonate, exhibits a related phenomenon which arises from the effects of a small zfs splitting, Δε±2, of the mS=±2 non-Kramers doublet that is caused by a fourfold rotational component of the crystal field potential. The splitting Δε±2 was measured from NMR data to be 0.20 cm−1. © 1998 American Institute of Physics.
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