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  • 1
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    Catching jetted tidal disruption events early in millimetre (2016)
    Oxford University Press
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    Publication Date: 2016-07-20
    Description: Relativistic jets can form from at least some tidal disruption events (TDEs) of (sub-)stellar objects around supermassive black holes. We detect the millimetre (MM) emission of IGR J12580+0134 – the nearest TDE known in the galaxy NGC 4845 at the distance of only 17 Mpc, based on Planck all-sky survey data. The data show significant flux jumps after the event, followed by substantial declines, in all six high-frequency Planck bands from 100 to 857 GHz. We further show that the evolution of the MM flux densities is well consistent with our model prediction from an off-axis jet, as was initially suggested from radio and X-ray observations. This detection represents the second TDE with MM detections; the other is Sw J1644+57, an on-axis jetted TDE at redshift of 0.35. Using the on- and off-axis jet models developed for these two TDEs as templates, we estimate the detection potential of similar events with the Large Millimeter Telescope (LMT) and the Atacama Large Millimeter/submillimeter Array (ALMA). Assuming an exposure of 1 h, we find that the LMT (ALMA) can detect jetted TDEs up to redshifts z ~ 1 (2), for a typical disrupted star mass of ~1 M . The detection rates of on- and off-axis TDEs can be as high as ~0.6 (13) and 10 (220) yr –1 , respectively, for the LMT (ALMA). We briefly discuss how such observations, together with follow-up radio monitoring, may lead to major advances in understanding the jetted TDEs themselves and the ambient environment of the circumnuclear medium.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 2
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    Yeast cell-based analysis of human lactate dehydrogenase isoforms (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Human lactate dehydrogenase (LDH) has attracted attention as a potential target for cancer therapy and contraception. In this study, we reconstituted human lactic acid fermentation in Saccharomyces cerevisiae , with the goal of constructing a yeast cell-based LDH assay system. pdc null mutant yeast (mutated in the endogenous pyruvate decarboxylase genes) are unable to perform alcoholic fermentation; when grown in the presence of an electron transport chain inhibitor, pdc null strains exhibit a growth defect. We found that introduction of the human gene encoding LDHA complemented the pdc growth defect; this complementation depended on LDHA catalytic activity. Similarly, introduction of the human LDHC complemented the pdc growth defect, even though LDHC did not generate lactate at the levels seen with LDHA. In contrast, the human LDHB did not complement the yeast pdc null mutant, although LDHB did generate lactate in yeast cells. Expression of LDHB as a red fluorescent protein (RFP) fusion yielded blebs in yeast, whereas LDHA-RFP and LDHC-RFP fusion proteins exhibited cytosolic distribution. Thus, LDHB exhibits several unique features when expressed in yeast cells. Because yeast cells are amenable to genetic analysis and cell-based high-throughput screening, our pdc /LDH strains are expected to be of use for versatile analyses of human LDH.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of The Japanese Biochemical Society (JBS).
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  • 3
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    Finding optimal interaction interface alignments between biological complexes (2015)
    Oxford University Press
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    Publication Date: 2015-06-14
    Description: Motivation: Biological molecules perform their functions through interactions with other molecules. Structure alignment of interaction interfaces between biological complexes is an indispensable step in detecting their structural similarities, which are key s to understanding their evolutionary histories and functions. Although various structure alignment methods have been developed to successfully access the similarities of protein structures or certain types of interaction interfaces, existing alignment tools cannot directly align arbitrary types of interfaces formed by protein, DNA or RNA molecules. Specifically, they require a ‘ blackbox preprocessing ’ to standardize interface types and chain identifiers. Yet their performance is limited and sometimes unsatisfactory. Results: Here we introduce a novel method, PROSTA-inter, that automatically determines and aligns interaction interfaces between two arbitrary types of complex structures. Our method uses sequentially remote fragments to search for the optimal superimposition. The optimal residue matching problem is then formulated as a maximum weighted bipartite matching problem to detect the optimal sequence order-independent alignment. Benchmark evaluation on all non-redundant protein – DNA complexes in PDB shows significant performance improvement of our method over TM-align and iAlign (with the ‘ blackbox preprocessing ’ ). Two case studies where our method discovers, for the first time, structural similarities between two pairs of functionally related protein – DNA complexes are presented. We further demonstrate the power of our method on detecting structural similarities between a protein – protein complex and a protein – RNA complex, which is biologically known as a protein – RNA mimicry case. Availability and implementation: The PROSTA-inter web-server is publicly available at http://www.cbrc.kaust.edu.sa/prosta/ . Contact: xin.gao@kaust.edu.sa
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    Evolview v2: an online visualization and management tool for customized and annotated phylogenetic trees (2016)
    Oxford University Press
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    Publication Date: 2016-07-06
    Description: Evolview is an online visualization and management tool for customized and annotated phylogenetic trees. It allows users to visualize phylogenetic trees in various formats, customize the trees through built-in functions and user-supplied datasets and export the customization results to publication-ready figures. Its ‘dataset system’ contains not only the data to be visualized on the tree, but also ‘modifiers’ that control various aspects of the graphical annotation. Evolview is a single-page application (like Gmail); its carefully designed interface allows users to upload, visualize, manipulate and manage trees and datasets all in a single webpage. Developments since the last public release include a modern dataset editor with keyword highlighting functionality, seven newly added types of annotation datasets, collaboration support that allows users to share their trees and datasets and various improvements of the web interface and performance. In addition, we included eleven new ‘Demo’ trees to demonstrate the basic functionalities of Evolview, and five new ‘Showcase’ trees inspired by publications to showcase the power of Evolview in producing publication-ready figures. Evolview is freely available at: http://www.evolgenius.info/evolview/ .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Current helicity and magnetic field anisotropy in solar active regions (2015)
    Oxford University Press
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    Publication Date: 2015-10-15
    Description: The electric current helicity density $\displaystyle \chi =\langle \epsilon _{ijk}b_i{\scriptstyle\frac{\mathrm{\partial} b_k}{\mathrm{\partial} x_j}}\rangle$ contains six terms, where b i are components of the magnetic field. Due to the observational limitations, only four of the above six terms can be inferred from solar photospheric vector magnetograms. By comparing the results for simulation we distinguished the statistical difference of above six terms for isotropic and anisotropic cases. We estimated the relative degree of anisotropy for three typical active regions and found that it is of order 0.8 which means the assumption of local isotropy for the observable current helicity density terms is generally not satisfied for solar active regions. Upon studies of the statistical properties of the anisotropy of magnetic field of solar active regions with latitudes and with evolution in the solar cycle, we conclude that the consistency of that assumption of local homogeneity and isotropy requires further analysis in the light of our findings.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells (2015)
    Oxford University Press
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    Publication Date: 2015-06-24
    Description: The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Differentially expressed glycosylated patterns of {alpha}-1-antitrypsin as serum biomarkers for the diagnosis of lung cancer (2015)
    Oxford University Press
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    Publication Date: 2015-01-30
    Description: Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Cluster gas fraction as a test of gravity (2015)
    Oxford University Press
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    Publication Date: 2015-12-13
    Description: We propose a new cosmological test of gravity, by using the observed mass fraction of X-ray-emitting gas in massive galaxy clusters. The cluster gas fraction, believed to be a fair sample of the average baryon fraction in the Universe, is a well-understood observable, which has previously mainly been used to constrain background cosmology. In some modified gravity models, such as f ( R ) gravity, gas temperature in a massive cluster is determined by the effective mass (the mass that would have produced the same gravitational effect assuming standard gravity as the cluster actually does in f ( R ) gravity) of that cluster, which can be larger than its true mass. On the other hand, X-ray luminosity is determined by the true gas density, which in both modified gravity and -cold-dark-matter models depends mainly on b / m and hence the true total cluster mass. As a result, the standard practice of combining gas temperatures and X-ray surface brightnesses of clusters to infer their gas fractions can, in modified gravity models, lead to a larger – in f ( R ) gravity this can be 1/3 larger – value of b / m than that inferred from other observations such as the cosmic microwave background. Our quick calculation shows that the Hu–Sawicki n  = 1 f ( R ) model with $|\bar{f}_{R0}|=5\times 10^{-5}$ is in tension with the gas fraction data of the 42 clusters analysed by Allen et al. We also discuss the implications for other modified gravity models.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis (2014)
    Oxford University Press
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    Publication Date: 2014-01-11
    Description: Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is a promising vehicle due to its long-lasting gene expression and low toxicity. However, ALS afflicts broad areas of the central nervous system (CNS). A lack of practical means to spread rAAV broadly has hindered its application in treatment of ALS. To overcome this barrier, we injected several rAAV serotypes into the cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9 transduced cells throughout the length of the spinal cord following a single intrathecal injection and in the broad forebrain following a single injection into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10 robustly transduced motor neurons throughout the spinal cord in a non-human primate. These results suggested a therapeutic potential of this vector for ALS. To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant SOD1 expression and slowed the disease progression. Our results demonstrate the potential of rAAVs for delivering gene therapy to treat ALS and other diseases that afflict broad areas of the CNS.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    ChemMapper: a versatile web server for exploring pharmacology and chemical structure association based on molecular 3D similarity method (2013)
    Oxford University Press
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    Publication Date: 2013-07-06
    Description: : ChemMapper is an online platform to predict polypharmacology effect and mode of action for small molecules based on 3D similarity computation. ChemMapper collects 〉350 000 chemical structures with bioactivities and associated target annotations (as well as 〉3 000 000 non-annotated compounds for virtual screening). Taking the user-provided chemical structure as the query, the top most similar compounds in terms of 3D similarity are returned with associated pharmacology annotations. ChemMapper is designed to provide versatile services in a variety of chemogenomics, drug repurposing, polypharmacology, novel bioactive compounds identification and scaffold hopping studies. Availability: http://lilab.ecust.edu.cn/chemmapper/ . Contact: xfliu@ecust.edu.cn or hlli@ecust.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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