Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2018-07-20
    Description: Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor B activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
    Keywords: Cell Biology, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-10-17
    Description: Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different developmental times. Drosophila neuroblasts produce long, stereotyped lineages of neurons. We searched for factors that could regulate neural temporal fate by RNA-sequencing lineage-specific neuroblasts at various developmental times. We found that two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low and low-to-high temporal gradients with lineage-specific temporal dynamics. Imp and Syp promote early and late fates, respectively, in both a slowly progressing and a rapidly changing lineage. Imp and Syp control neuronal fates in the mushroom body lineages by regulating the temporal transcription factor Chinmo translation. Together, the opposing Imp/Syp gradients encode stem cell age, specifying multiple cell fates within a lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Zhiyong -- Yang, Ching-Po -- Sugino, Ken -- Fu, Chi-Cheng -- Liu, Ling-Yu -- Yao, Xiaohao -- Lee, Luke P -- Lee, Tzumin -- R01-GM084947/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):317-20. doi: 10.1126/science.aad1886.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. ; Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. Departments of Bioengineering, Electrical Engineering, and Computer Science, and Biophysics Graduate Program, University of California Berkeley, 408C Stanley Hall, Berkeley, CA, USA. ; Departments of Bioengineering, Electrical Engineering, and Computer Science, and Biophysics Graduate Program, University of California Berkeley, 408C Stanley Hall, Berkeley, CA, USA. ; Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. leet@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472907" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; Drosophila Proteins/genetics/metabolism/*physiology ; Drosophila melanogaster/genetics/*growth & development ; Mushroom Bodies/cytology/growth & development ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/*cytology ; Neurogenesis/genetics/*physiology ; Neurons/*cytology ; RNA-Binding Proteins/genetics/*physiology ; Sequence Analysis, RNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2018-08-09
    Description: Safety assessments are a crucial first step in preventing coal and gas outburst accidents. The main purpose of this study was to create a new accident prevention technique using a novel safety assessment method based on fault tree basic event importance, grey relational analysis and the bow tie model. The innovation of the proposed method lies in generating the composite importance of a basic event from the fundamental importance via grey relational analysis; bow tie analysis serves to reveal the most critical basic event. First, the minimal cut sets and minimal path sets of a coal and gas outburst accident are determined by fault tree analysis. The role of minimal cut and path sets is determined and the coal and gas outburst occurrence frequency is calculated accordingly. Second, the structure, probability, critical and Fussell–Vesely importance ranked basic events differently due to different aspects of the basic events as investigated. We establish a composite importance to represent single basic events and achieved new ranking results by grey relational analysis. Third, the critical basic event low permeability coefficient is analysed via bow tie model and safety measures are defined which prevent the dangerous consequences of a low permeability coefficient. An actual coal and gas outburst accident is used as a case study to test the feasibility and effectiveness of the proposed method.
    Keywords: power and energy systems, energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-10-25
    Description: Sand casting operations, though commonplace, pose a significant threat of explosion accidents. This paper presents a novel sand casting safety assessment technique based on fault tree analysis, Heinrich accident triangle, hazard and operability–layer of protection analysis (HAZOP–LOPA) and bow tie model components. Minimal cut sets and minimal path sets are first determined based on fault tree analysis, then the frequency of sand casting explosion accidents is calculated based on the Heinrich accident triangle. Third, the risk level of venting quality can be reduced by adopting HAZOP–LOPA; the residual risk level of venting quality remains excessive even after adopting two independent protective layers. The bow tie model is then adopted to determine the causes and consequences of venting quality. Five preventative measures are imposed to enhance the venting quality of foundry sand accompanied by 16 mitigative safety measures. Our results indicate that the risk attributable to low foundry sand venting quality can be minimized via bow tie analysis.
    Keywords: mechanical engineering
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-07-19
    Description: Safe production is the foundation of the normal operations of petrochemical enterprises, and it helps maintain social stability. The main purpose of this study is to prevent petrochemical enterprise accidents by proposing a composite safety assessment approach based on the cloud model, preliminary hazard analysis–layer of protection analysis (PHA–LOPA) and the bow-tie model. First, the petrochemical enterprise and its relevant indicators were evaluated based on the cloud model. Second, the quantitative effect of the uncertainty transformation on the evaluation result of the cloud model was further analysed. This mainly includes the error analysis of the numerical characteristics under the conditions of few samples and small values. Third, the critical indicators such as shock and noise can be weakened and prevented by corresponding safety measures based on PHA–LOPA and the bow-tie model. After adopting two independent protection layers, the risk levels of shock and noise decrease from 3 to 2. Then, shock and noise were analysed in depth with the bow-tie model, and the causes and consequences were identified. Moreover, corresponding safety measures were taken to prevent accidents. The case study validated the validity and feasibility of the composite safety assessment approach proposed here.
    Keywords: energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-01-06
    Description: The origin of the pseudogap region below a temperature T * is at the heart of the mysteries of cuprate high-temperature superconductors. Unusual properties of the pseudogap phase, such as broken time-reversal and inversion symmetry are observed in several symmetry-sensitive experiments: polarized neutron diffraction, optical birefringence, dichroic angle-resolved photoemission spectroscopy, second harmonic generation, and polar Kerr effect. These properties suggest that the pseudogap region is a genuine thermodynamic phase and are predicted by theories invoking ordered loop currents or other forms of intra-unit-cell (IUC) magnetic order. However, muon spin rotation (μSR) and nuclear magnetic resonance (NMR) experiments do not see the static local fields expected for magnetic order, leaving room for skepticism. The magnetic resonance probes have much longer time scales, however, over which local fields could be averaged by fluctuations. The observable effect of the fluctuations in magnetic resonance is then dynamic relaxation. We have measured dynamic muon spin relaxation rates in single crystals of YBa 2 Cu 3 O y (6.72 〈 y 〈 6.95) and have discovered "slow" fluctuating magnetic fields with magnitudes and fluctuation rates of the expected orders of magnitude that set in consistently at temperatures T mag T *. The absence of any static field (to which μSR would be linearly sensitive) is consistent with the finite correlation length from neutron diffraction. Equally important, these fluctuations exhibit the critical slowing down at T mag expected near a time-reversal symmetry breaking transition. Our results explain the absence of static magnetism and provide support for the existence of IUC magnetic order in the pseudogap phase.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...