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  • 1
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    Genome-wide analysis of LXR{alpha} activation reveals new transcriptional networks in human atherosclerotic foam cells (2013)
    Oxford University Press
    Details
    Publication Date: 2013-04-02
    Description: Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2 -gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Bispecific digoxigenin-binding antibodies for targeted payload delivery [Applied Biological Sciences] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-05-18
    Description: Bispecific antibodies that bind cell-surface targets as well as digoxigenin (Dig) were generated for targeted payload delivery. Targeting moieties are IgGs that bind the tumor antigens Her2, IGF1R, CD22, or LeY. A Dig-binding single-chain Fv was attached in disulfide-stabilized form to C termini of CH3 domains of targeting antibodies. Bispecific molecules were expressed in mammalian cells and purified in the same manner as unmodified IgGs. They are stable without aggregation propensity and retain binding specificity/affinity to cell-surface antigens and Dig. Digoxigeninylated payloads were generated that retain full functionality and can be complexed to bispecific antibodies in a defined 2∶1 ratio. Payloads include small compounds (Dig-Cy5, Dig-Doxorubicin) and proteins (Dig-GFP). Complexed payloads are targeted by the bispecifics to cancer cells and because these complexes are stable in serum, they can be applied for targeted delivery. Because Dig bispecifics also effectively capture digoxigeninylated compounds under physiological conditions, separate administration of uncharged Dig bispecifics followed by application of Dig payload is sufficient to achieve antibody-mediated targeting in vitro and in vivo.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Electrical detection of electron-spin-echo envelope modulations in thin-film silicon solar cells (2011)
    American Physical Society (APS)
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    Publication Date: 2011-11-15
    Description: Author(s): M. Fehr, J. Behrends, S. Haas, B. Rech, K. Lips, and A. Schnegg [Phys. Rev. B 84, 193202] Published Mon Nov 14, 2011
    Keywords: Semiconductors I: bulk
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 4
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    Driven dipole oscillations and the lowest-energy excitations of strongly interacting lattice bosons in a harmonic trap (2014)
    American Physical Society (APS)
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    Publication Date: 2014-04-01
    Description: Author(s): K. He, J. Brown, S. Haas, and M. Rigol We show that the analysis of the time evolution of the occupation of site and momentum modes of harmonically trapped lattice hard-core bosons, under driven dipole oscillations, allows one to determine the energy of the lowest one-particle excitations of the system in equilibrium. The analytic soluti... [Phys. Rev. A 89, 033634] Published Mon Mar 31, 2014
    Keywords: Matter waves and collective properties of cold atoms and molecules
    Print ISSN: 1050-2947
    Electronic ISSN: 1094-1622
    Topics: Physics
    Published by American Physical Society (APS)
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  • 5
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    Coherent control of non-Markovian photon-resonator dynamics (2014)
    American Physical Society (APS)
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    Publication Date: 2014-08-26
    Description: Author(s): A. F. J. Levi, L. Campos Venuti, T. Albash, and S. Haas We study the unitary time evolution of photons interacting with a dielectric resonator using coherent control pulses. We show that non-Markovianity of transient photon dynamics in the resonator subsystem may be controlled to within a photon-resonator transit time. In general, appropriate use of cohe... [Phys. Rev. A 90, 022119] Published Mon Aug 25, 2014
    Keywords: Fundamental concepts
    Print ISSN: 1050-2947
    Electronic ISSN: 1094-1622
    Topics: Physics
    Published by American Physical Society (APS)
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  • 6
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    Phase diagram of electron-doped dichalcogenides (2014)
    American Physical Society (APS)
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    Publication Date: 2014-12-02
    Description: Author(s): M. Rösner, S. Haas, and T. O. Wehling Using first-principle calculations, we examine the sequence of phases in electron-doped dichalcogenides, such as recently realized in field-gated MoS 2 . Upon increasing the electron-doping level, we observe a succession of semiconducting, metallic, superconducting, and charge density wave regimes, i.... [Phys. Rev. B 90, 245105] Published Mon Dec 01, 2014
    Keywords: Electronic structure and strongly correlated systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 7
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    Interaction of relativistic short proton bunches with space charge limited electron clouds (2014)
    American Physical Society (APS)
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    Publication Date: 2014-12-04
    Description: Author(s): F. B. Petrov, O. Boine-Frankenheim, and O. S. Haas The electron cloud buildup and interaction with a train of relativistic, short proton bunches is studied using particle-in-cell codes. The simulation models describe the electron generation at the beam pipe wall as well as the wakefield behind the bunches. The study focuses on the space charge limit... [Phys. Rev. ST Accel. Beams 17, 121001] Published Wed Dec 03, 2014
    Keywords: High-Energy Accelerators and Colliders
    Electronic ISSN: 1098-4402
    Topics: Physics
    Published by American Physical Society (APS)
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  • 8
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    Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-03
    Description: RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3'-CH 2 -CO-NH-5' amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P–OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5'-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Long-range structure in ribonuclease P RNA (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-11-08
    Description: Phylogenetic-comparative and mutational analyses were used to elucidate the structure of the catalytically active RNA component of eubacterial ribonuclease P (RNase P). In addition to the refinement and extension of known structural elements, the analyses revealed a long-range interaction that results in a second pseudoknot in the RNA. This feature strongly constrains the three-dimensional structure of RNase P RNA near the active site. Some RNase P RNAs lack this structure but contain a unique, possibly compensating, structural domain. This suggests that different RNA structures located at different positions in the sequence may have equivalent architectural functions in RNase P RNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haas, E S -- Morse, D P -- Brown, J W -- Schmidt, F J -- Pace, N R -- GM34527/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Nov 8;254(5033):853-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington 47405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1719634" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis/enzymology/genetics ; Base Composition ; Base Sequence ; Biological Evolution ; Endoribonucleases/*genetics ; Escherichia coli/enzymology/genetics ; *Escherichia coli Proteins ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Nucleic Acid Conformation ; RNA, Bacterial/*genetics ; RNA, Catalytic/*genetics ; Ribonuclease P
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-07-05
    Description: The functional complexity of the human transcriptome is not yet fully elucidated. We report a high-throughput sequence of the human transcriptome from a human embryonic kidney and a B cell line. We used shotgun sequencing of transcripts to generate randomly distributed reads. Of these, 50% mapped to unique genomic locations, of which 80% corresponded to known exons. We found that 66% of the polyadenylated transcriptome mapped to known genes and 34% to nonannotated genomic regions. On the basis of known transcripts, RNA-Seq can detect 25% more genes than can microarrays. A global survey of messenger RNA splicing events identified 94,241 splice junctions (4096 of which were previously unidentified) and showed that exon skipping is the most prevalent form of alternative splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sultan, Marc -- Schulz, Marcel H -- Richard, Hugues -- Magen, Alon -- Klingenhoff, Andreas -- Scherf, Matthias -- Seifert, Martin -- Borodina, Tatjana -- Soldatov, Aleksey -- Parkhomchuk, Dmitri -- Schmidt, Dominic -- O'Keeffe, Sean -- Haas, Stefan -- Vingron, Martin -- Lehrach, Hans -- Yaspo, Marie-Laure -- New York, N.Y. -- Science. 2008 Aug 15;321(5891):956-60. doi: 10.1126/science.1160342. Epub 2008 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18599741" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Cell Line ; Cell Line, Tumor ; Computational Biology ; DNA, Complementary ; DNA, Intergenic ; Exons ; *Gene Expression Profiling ; *Genome, Human ; Humans ; Introns ; Oligonucleotide Array Sequence Analysis ; RNA Polymerase II/metabolism ; *RNA Splice Sites ; RNA, Messenger/*genetics ; *Sequence Analysis, RNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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