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  • 1
    Online Resource
    Online Resource
    Finding experts in online forums for enhancing knowledge sharing and accessibility
    Elsevier BV ; 2015
    In:  Computers in Human Behavior Vol. 51 ( 2015-10), p. 325-335
    Details
    In: Computers in Human Behavior, Elsevier BV, Vol. 51 ( 2015-10), p. 325-335
    Type of Medium: Online Resource
    ISSN: 0747-5632
    URL: Article
    DOI: 10.1016/j.chb.2015.04.055
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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    SSG: 5,2
    SSG: 7,11
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  • 2
    Online Resource
    Online Resource
    Applying learning behavioral Petri nets to the analysis of learning behavior in web-based learning environments
    Elsevier BV ; 2010
    In:  Information Sciences Vol. 180, No. 6 ( 2010-03), p. 995-1009
    Details
    In: Information Sciences, Elsevier BV, Vol. 180, No. 6 ( 2010-03), p. 995-1009
    Type of Medium: Online Resource
    ISSN: 0020-0255
    URL: Article
    DOI: 10.1016/j.ins.2009.11.022
    RVK:
    SA 5420
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
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    detail.hit.zdb_id: 1478990-5
    SSG: 24,1
    SSG: 7,11
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  • 3
    Online Resource
    Online Resource
    Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 41 ( 2016-10-11), p. 11549-11554
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 41 ( 2016-10-11), p. 11549-11554
    Abstract: Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score 〉 0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores 〉 0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1612368113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Heterodimeric complexes of Hop2 and Mnd1 function with Dmc1 to promote meiotic homolog juxtaposition and strand assimilation
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 29 ( 2004-07-20), p. 10572-10577
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 29 ( 2004-07-20), p. 10572-10577
    Abstract: Saccharomyces cerevisiae Hop2 and Mnd1 are abundant meiosisspecific chromosomal proteins, and mutations in the corresponding genes lead to defects in meiotic recombination and in homologous chromosome interactions during mid-prophase. Analysis of various double mutants suggests that HOP2 , MND1 , and DMC1 act in the same genetic pathway for the establishment of close juxtaposition between homologous meiotic chromosomes. Biochemical studies indicate that Hop2 and Mnd1 proteins form a stable heterodimer with a higher affinity for double-stranded than single-stranded DNA, and that this heterodimer stimulates the strand assimilation activity of Dmc1 in vitro . Together, the genetic and biochemical results suggest that Hop2, Mnd1, and Dmc1 are functionally interdependent during meiotic DNA recombination.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0404195101
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
    detail.hit.zdb_id: 209104-5
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  • 5
    Online Resource
    Online Resource
    Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 3 ( 2020-01-21), p. 1438-1446
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 3 ( 2020-01-21), p. 1438-1446
    Abstract: Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N - glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1908898117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 6
    Online Resource
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    TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 40 ( 2013-10), p. 16079-16084
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 40 ( 2013-10), p. 16079-16084
    Abstract: The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex, triggers caspase-1 activation and maturation of the proinflammatory cytokines IL-1β and IL-18 upon sensing a wide range of pathogen- and damage-associated molecules. Dysregulation of NLRP3 inflammasome activity contributes to the pathogenesis of many diseases, but its regulation remains poorly defined. Here we show that depletion of plasminogen activator inhibitor type 2 (PAI-2), a serine protease inhibitor, resulted in NLRP3- and ASC (apoptosis-associated Speck-like protein containing a C-terminal caspase recruitment domain)‐dependent caspase-1 activation and IL-1β secretion in macrophages upon Toll-like receptor 2 (TLR2) and TLR4 engagement. TLR2 or TLR4 agonist induced PAI-2 expression, which subsequently stabilized the autophagic protein Beclin 1 to promote autophagy, resulting in decreases in mitochondrial reactive oxygen species, NLRP3 protein level, and pro–IL-1β processing. Likewise, overexpressing Beclin 1 in PAI-2–deficient cells rescued the suppression of NLRP3 activation in response to LPS. Together, our data identify a tier of TLR signaling in controlling NLRP3 inflammasome activation and reveal a cell-autonomous mechanism which inversely regulates TLR- or Escherichia coli -induced mitochondrial dysfunction, oxidative stress, and IL-1β–driven inflammation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1306556110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
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    Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 19 ( 2013-05-07)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 19 ( 2013-05-07)
    Abstract: The overexpression of Aurora kinases in multiple tumors makes these kinases appealing targets for the development of anticancer therapies. This study identified two small molecules with a furanopyrimidine core, IBPR001 and IBPR002, that target Aurora kinases and induce a DFG conformation change at the ATP site of Aurora A. Our results demonstrate the high potency of the IBPR compounds in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice. Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fibers. This study used the IBPR compounds as well as MLN8237, a proven Aurora A inhibitor, as chemical probes to investigate the molecular role of HURP in mitotic spindle formation. These compounds effectively eliminated HURP phosphorylation, thereby revealing the coexistence and continuous cycling of HURP between unphosphorylated and phosphorylated forms that are associated, respectively, with microtubules emanating from centrosomes and kinetochores. Furthermore, these compounds demonstrate a spatial hierarchical preference for HURP in the attachment of microtubules extending from the mother to the daughter centrosome. The finding of inequality in the centrosomal microtubules revealed by these small molecules provides a versatile tool for the discovery of new cell-division molecules for the development of antitumor drugs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1220523110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 8
    Online Resource
    Online Resource
    A novel method for estimating the focal size of two confocal high-intensity focused ultrasound transducers
    Acoustical Society of America (ASA) ; 2005
    In:  The Journal of the Acoustical Society of America Vol. 117, No. 6 ( 2005-06-01), p. 3740-3749
    Details
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 117, No. 6 ( 2005-06-01), p. 3740-3749
    Abstract: Estimating the focal size and position of a high-intensity focused ultrasound (HIFU) transducer remains a challenge since traditional methods, such as hydrophone scanning or schlieren imaging, cannot tolerate high pressures, are directional, or provide low resolution. The difficulties increase when dealing with the complex beam pattern of a multielement HIFU transducer array, e.g., two transducers facing each other. In the present study we show a novel approach to the visualization of the HIFU focus by using shockwave-generated bubbles and a diagnostic B-mode scanner. Bubbles were generated and pushed by shock waves toward the HIFU beam, and were trapped in its pressure valleys. These trapped bubbles moved along the pressure valleys and thereby delineated the shape and size of the HIFU beam. The main and sidelobes of 1.1- and 3.5 MHz HIFU beams were clearly visible, and could be measured with a millimeter resolution. The combined foci could also be visualized by observing the generation of sustained inertial cavitation and enhanced scattering. The results of this study further demonstrate the possibility of reducing the inertial cavitation threshold by the local introduction of shock wave-generated bubbles, which might be useful when bubble generation and cavitation-related bioeffects are intended within a small region in vivo.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    URL: Article
    DOI: 10.1121/1.1904283
    RVK:
    EQ 1000
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2005
    detail.hit.zdb_id: 1461063-2
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  • 9
    Online Resource
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    Discovering unknown human and mouse transcription factor binding sites and their characteristics from ChIP-seq data
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 20 ( 2021-05-18)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 20 ( 2021-05-18)
    Abstract: Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin immunoprecipitation followed by sequencing) data. Applying it to the latest ENCODE ChIP-seq data for human and mouse, we found that using the irreproducible discovery rate as a quality-control criterion resulted in many experiments being unnecessarily discarded. By contrast, the number of motif occurrences in ChIP-seq peak regions provides a highly effective criterion, which is reliable even if supported by only one experimental replicate. In total, we obtained 2,058 motifs from 1,089 experiments for 354 human TFs and 163 motifs from 101 experiments for 34 mouse TFs. Among these motifs, 487 have not previously been reported. Mapping the canonical motifs to the human genome reveals a high TFBS density ±2 kb around transcription start sites (TSSs) with a peak at −50 bp. On average, a promoter contains 5.7 TFBSs. However, 70% of TFBSs are in introns (41%) and intergenic regions (29%), whereas only 12% are in promoters (−1 kb to +100 bp from TSSs). Notably, some TFs (e.g., CTCF, JUN, JUNB, and NFE2) have motifs enriched in intergenic regions, including enhancers. We inferred 142 cobinding TF pairs and 186 (including 115 completely) tethered binding TF pairs, indicating frequent interactions between TFs and a higher frequency of tethered binding than cobinding. This study provides a large number of previously undocumented motifs and insights into the biological and genomic features of TFBSs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2026754118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 10
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    Altered mismatch response precedes gray matter atrophy in subjective cognitive decline
    Wiley ; 2021
    In:  Psychophysiology Vol. 58, No. 6 ( 2021-06)
    Details
    In: Psychophysiology, Wiley, Vol. 58, No. 6 ( 2021-06)
    Abstract: This is the first study systematically investigating the magnetic mismatch negativity (MMNm) in individuals with and without subjective cognitive decline (SCD). We found that despite no structural atrophy, individuals with SCD showed reduced MMNm amplitudes particularly in the right inferior frontal gyrus compared to those without SCD. Our data suggest that self‐reported cognitive worsening is a reflection of objective alterations in brain function, which precedes gray matter atrophy.
    Type of Medium: Online Resource
    ISSN: 0048-5772 , 1469-8986
    URL: Issue
    URL: Article
    DOI: 10.1111/psyp.v58.6
    DOI: 10.1111/psyp.13820
    RVK:
    CL 1000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1484299-3
    SSG: 5,2
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