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1.
  • Campbell, Peter J., et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - 1476-4687. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes.
2.
  • Chen, Mei-Qin, et al. (författare)
  • Arabidopsis NMD3 is required for nuclear export of 60S ribosomal subunits and affects secondary cell wall thickening
  • 2012
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 7:4, s. 35904-35904
  • Tidskriftsartikel (refereegranskat)abstract
    • NMD3 is required for nuclear export of the 60S ribosomal subunit in yeast and vertebrate cells, but no corresponding function of NMD3 has been reported in plants. Here we report that Arabidopsis thaliana NMD3 (AtNMD3) showed a similar function in the nuclear export of the 60S ribosomal subunit. Interference with AtNMD3 function by overexpressing a truncated dominant negative form of the protein lacking the nuclear export signal sequence caused retainment of the 60S ribosomal subunits in the nuclei. More interestingly, the transgenic Arabidopsis with dominant negative interference of AtNMD3 function showed a striking failure of secondary cell wall thickening, consistent with the altered expression of related genes and composition of cell wall components. Observation of a significant decrease of rough endoplasmic reticulum (RER) in the differentiating interfascicular fiber cells of the transgenic plant stems suggested a link between the defective nuclear export of 60S ribosomal subunits and the abnormal formation of the secondary cell wall. These findings not only clarified the evolutionary conservation of NMD3 functions in the nuclear export of 60S ribosomal subunits in yeast, animals and plants, but also revealed a new facet of the regulatory mechanism underlying secondary cell wall thickening in Arabidopsis. This new facet is that the nuclear export of 60S ribosomal subunits and the formation of RER may play regulatory roles in coordinating protein synthesis in cytoplasm and transcription in nuclei.
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3.
  • Zhu, Zhen-Long, et al. (författare)
  • Cytoplasmic expression of p33(ING1b) is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma.
  • 2013
  • Ingår i: Oncology letters. - 1792-1074. ; 5:1, s. 161-166
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>p33(ING1b), a newly discovered candidate tumor suppressor gene and a nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33(ING1b) has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies. Since little is known about the clinicopathological significance of p33(ING1b) in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC. p33(ING1b) expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33(ING1b) protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P&lt;0.0001). Furthermore, the cases with lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P=0.001). The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P&lt;0.0001) in ESCC, and the cases positive for both proteins had a high lymph node metastasis rate (P=0.001). In conclusion, p33(ING1b) cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the tumorigenesis and metastasis of ESCC.</p>
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4.
  • Zhu, Zhen-Long, et al. (författare)
  • PINCH expression and its clinicopathological significance in gastric adenocarcinoma
  • 2012
  • Ingår i: Disease Markers. - IOS Press. - 0278-0240 .- 1875-8630. ; 33:4, s. 171-178
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma. less thanbrgreater than less thanbrgreater thanPatients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n = 30) and gastric adenocarcinoma (n = 73), from gastric cancer patients. less thanbrgreater than less thanbrgreater thanResults: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X-2 = 9.711, p = 0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X-2 = 11.151, p = 0.001). PINCH expression was not correlated with patients gender, age, tumour size, differentiation and invasion depth (p andgt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma.</p>
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5.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.</p>
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6.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.</p>
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7.
  • Kristan, Matej, et al. (författare)
  • The Visual Object Tracking VOT2015 challenge results
  • 2015
  • Ingår i: Proceedings 2015 IEEE International Conference on Computer Vision Workshops ICCVW 2015. - IEEE. - 978-0-7695-5720-5 ; s. 564-586
  • Konferensbidrag (refereegranskat)abstract
    • <p>The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website(1).</p>
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8.
  • Luo, Zhong-Zhen, et al. (författare)
  • PbGa2MSe6 (M = Si, Ge) : Two Exceptional Infrared Nonlinear Optical Crystals
  • 2015
  • Ingår i: Chemistry of Materials. - 0897-4756 .- 1520-5002. ; 27:3, s. 914-922
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Two noncentrosymmetric (NCS) quaternary selenides, PbGa2SiSe6 (&lt;bold&gt;1&lt;/bold&gt;) and PbGa2GeSe6 (&lt;bold&gt;2&lt;/bold&gt;), with second-order nonlinear optical (NLO) responses, were synthesized by a conventional high-temperature solid-state reaction method. Compounds &lt;bold&gt;1&lt;/bold&gt; and &lt;bold&gt;2&lt;/bold&gt; are constructed by three NCS chromophores, [PbSe4], [GaSe4], and [Ga/SiSe4] or [Ga/GeSe4], with the covalent interactions between the X and Se atoms (X = Pb, Ga, Ga/Si, or Ga/Ge). They crystallize in the polar space groups Cc and Fdd2, respectively. Inspiringly, compound &lt;bold&gt;2&lt;/bold&gt; is phase-matchable (PM) and shows high laser-induced damage threshold (LIDT) of 3.7 x AgGaS2 and wide transparent region (0.6325 mu m) in the mid-infrared (MIR) region. Most importantly, it presents extraordinary strong second harmonic generation (SHG) at 2.05 mu m radiation of about 12 x AgGaS2 at the particle size of 2545 mu m, which represents the strongest SHG among PM chalcogenides to date. The calculated major SHG tensor elements of compounds &lt;bold&gt;1&lt;/bold&gt; and &lt;bold&gt;2&lt;/bold&gt; are d31 = 224.7 and d12 = 222.1 pm/V, respectively, while the calculated d36 of AgGaS2 is only 21.2 pm/V.</p>
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9.
  • Mahajan, Anubha, et al. (författare)
  • Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
  • 2014
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 46:3, s. 234-234
  • Tidskriftsartikel (refereegranskat)abstract
    • To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
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10.
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