58 research outputs found

    A chalcone derivative reactivates latent HIV-1 transcription through activating P-TEFb and promoting Tat-SEC interaction on viral promoter.

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    The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency. Amt-87 works by activating the human transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elongation complex (SEC) used by the viral encoded Tat protein to activate HIV transcription. Amt-87 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive 7SK snRNP, and inducing the formation of the Tat-SEC complex at the viral promoter. Together, our data reveal chalcones as a promising category of compounds that should be further explored to identify effective LRAs for targeted reversal of HIV latency

    The MALATANG Survey : The L GAS-L IR Correlation on Sub-kiloparsec Scale in Six Nearby Star-forming Galaxies as Traced by HCN J = 4 → 3 and HCO + J = 4 → 3

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    This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. The Version of Record is available online at https://doi.org/10.3847/1538-4357/aac512.We present HCN J = 4→3 and HCO+ J = 4→3 maps of six nearby star-forming galaxies, NGC 253, NGC 1068, IC 342, M82, M83, and NGC 6946, obtained with the James Clerk Maxwell Telescope as part of the MALATANG survey. All galaxies were mapped in the central 2×2 region at 14 (FWHM) resolution (corresponding to linear scales of ∼0.2-1.0 kpc). The LIR-Ldense relation, where the dense gas is traced by the HCN J = 4→3 and the HCO+ J = 4→3 emission, measured in our sample of spatially resolved galaxies is found to follow the linear correlation established globally in galaxies within the scatter. We find that the luminosity ratio, LIR/Ldense, shows systematic variations with LIR within individual spatially resolved galaxies, whereas the galaxy-integrated ratios vary little. A rising trend is also found between LIR/Ldense ratio and the warm-dust temperature gauged by the 70 μm/100 μm flux ratio. We find that the luminosity ratios of IR/HCN (4-3) and IR/HCO+ (4-3), which can be taken as a proxy for the star formation efficiency (SFE) in the dense molecular gas (SFE dense), appear to be nearly independent of the dense gas fraction ( f dense) for our sample of galaxies. The SFE of the total molecular gas (SFEmol) is found to increase substantially with f dense when combining our data with those on local (ultra)luminous infrared galaxies and high-z quasars. The mean LHCN(4-3) LHCO+(4-3) line ratio measured for the six targeted galaxies is 0.9±0.6. No significant correlation is found for the L'HCN(4-3) L'HCO+(4-3) ratio with the star formation rate as traced by L IR, nor with the warm-dust temperature, for the different populations of galaxies.Peer reviewe

    Experimental measurement-based quantum computing beyond the cluster-state model

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    The paradigm of measurement-based quantum computation opens new experimental avenues to realize a quantum computer and deepens our understanding of quantum physics. Measurement-based quantum computation starts from a highly entangled universal resource state. For years, clusters states have been the only known universal resources. Surprisingly, a novel framework namely quantum computation in correlation space has opened new routes to implement measurement-based quantum computation based on quantum states possessing entanglement properties different from cluster states. Here we report an experimental demonstration of every building block of such a model. With a four-qubit and a six-qubit state as distinct from cluster states, we have realized a universal set of single-qubit rotations, two-qubit entangling gates and further Deutsch's algorithm. Besides being of fundamental interest, our experiment proves in-principle the feasibility of universal measurement-based quantum computation without using cluster states, which represents a new approach towards the realization of a quantum computer.Comment: 26 pages, final version, comments welcom

    Off-line evaluation of indoor positioning systems in different scenarios: the experiences from IPIN 2020 competition

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    Every year, for ten years now, the IPIN competition has aimed at evaluating real-world indoor localisation systems by testing them in a realistic environment, with realistic movement, using the EvAAL framework. The competition provided a unique overview of the state-of-the-art of systems, technologies, and methods for indoor positioning and navigation purposes. Through fair comparison of the performance achieved by each system, the competition was able to identify the most promising approaches and to pinpoint the most critical working conditions. In 2020, the competition included 5 diverse off-site off-site Tracks, each resembling real use cases and challenges for indoor positioning. The results in terms of participation and accuracy of the proposed systems have been encouraging. The best performing competitors obtained a third quartile of error of 1 m for the Smartphone Track and 0.5 m for the Foot-mounted IMU Track. While not running on physical systems, but only as algorithms, these results represent impressive achievements.Track 3 organizers were supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska Curie Grant 813278 (A-WEAR: A network for dynamic WEarable Applications with pRivacy constraints), MICROCEBUS (MICINN, ref. RTI2018-095168-B-C55, MCIU/AEI/FEDER UE), INSIGNIA (MICINN ref. PTQ2018-009981), and REPNIN+ (MICINN, ref. TEC2017-90808-REDT). We would like to thanks the UJI’s Library managers and employees for their support while collecting the required datasets for Track 3. Track 5 organizers were supported by JST-OPERA Program, Japan, under Grant JPMJOP1612. Track 7 organizers were supported by the Bavarian Ministry for Economic Affairs, Infrastructure, Transport and Technology through the Center for Analytics-Data-Applications (ADA-Center) within the framework of “BAYERN DIGITAL II. ” Team UMinho (Track 3) was supported by FCT—Fundação para a Ciência e Tecnologia within the R&D Units Project Scope under Grant UIDB/00319/2020, and the Ph.D. Fellowship under Grant PD/BD/137401/2018. Team YAI (Track 3) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 109-2221-E-197-026. Team Indora (Track 3) was supported in part by the Slovak Grant Agency, Ministry of Education and Academy of Science, Slovakia, under Grant 1/0177/21, and in part by the Slovak Research and Development Agency under Contract APVV-15-0091. Team TJU (Track 3) was supported in part by the National Natural Science Foundation of China under Grant 61771338 and in part by the Tianjin Research Funding under Grant 18ZXRHSY00190. Team Next-Newbie Reckoners (Track 3) were supported by the Singapore Government through the Industry Alignment Fund—Industry Collaboration Projects Grant. This research was conducted at Singtel Cognitive and Artificial Intelligence Lab for Enterprises (SCALE@NTU), which is a collaboration between Singapore Telecommunications Limited (Singtel) and Nanyang Technological University (NTU). Team KawaguchiLab (Track 5) was supported by JSPS KAKENHI under Grant JP17H01762. Team WHU&AutoNavi (Track 6) was supported by the National Key Research and Development Program of China under Grant 2016YFB0502202. Team YAI (Tracks 6 and 7) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 110-2634-F-155-001

    Off-Line Evaluation of Indoor Positioning Systems in Different Scenarios: The Experiences From IPIN 2020 Competition

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    Every year, for ten years now, the IPIN competition has aimed at evaluating real-world indoor localisation systems by testing them in a realistic environment, with realistic movement, using the EvAAL framework. The competition provided a unique overview of the state-of-the-art of systems, technologies, and methods for indoor positioning and navigation purposes. Through fair comparison of the performance achieved by each system, the competition was able to identify the most promising approaches and to pinpoint the most critical working conditions. In 2020, the competition included 5 diverse off-site off-site Tracks, each resembling real use cases and challenges for indoor positioning. The results in terms of participation and accuracy of the proposed systems have been encouraging. The best performing competitors obtained a third quartile of error of 1 m for the Smartphone Track and 0.5 m for the Foot-mounted IMU Track. While not running on physical systems, but only as algorithms, these results represent impressive achievements.Track 3 organizers were supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska Curie Grant 813278 (A-WEAR: A network for dynamic WEarable Applications with pRivacy constraints), MICROCEBUS (MICINN, ref. RTI2018-095168-B-C55, MCIU/AEI/FEDER UE), INSIGNIA (MICINN ref. PTQ2018-009981), and REPNIN+ (MICINN, ref. TEC2017-90808-REDT). We would like to thanks the UJI’s Library managers and employees for their support while collecting the required datasets for Track 3. Track 5 organizers were supported by JST-OPERA Program, Japan, under Grant JPMJOP1612. Track 7 organizers were supported by the Bavarian Ministry for Economic Affairs, Infrastructure, Transport and Technology through the Center for Analytics-Data-Applications (ADA-Center) within the framework of “BAYERN DIGITAL II. ” Team UMinho (Track 3) was supported by FCT—Fundação para a Ciência e Tecnologia within the R&D Units Project Scope under Grant UIDB/00319/2020, and the Ph.D. Fellowship under Grant PD/BD/137401/2018. Team YAI (Track 3) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 109-2221-E-197-026. Team Indora (Track 3) was supported in part by the Slovak Grant Agency, Ministry of Education and Academy of Science, Slovakia, under Grant 1/0177/21, and in part by the Slovak Research and Development Agency under Contract APVV-15-0091. Team TJU (Track 3) was supported in part by the National Natural Science Foundation of China under Grant 61771338 and in part by the Tianjin Research Funding under Grant 18ZXRHSY00190. Team Next-Newbie Reckoners (Track 3) were supported by the Singapore Government through the Industry Alignment Fund—Industry Collaboration Projects Grant. This research was conducted at Singtel Cognitive and Artificial Intelligence Lab for Enterprises (SCALE@NTU), which is a collaboration between Singapore Telecommunications Limited (Singtel) and Nanyang Technological University (NTU). Team KawaguchiLab (Track 5) was supported by JSPS KAKENHI under Grant JP17H01762. Team WHU&AutoNavi (Track 6) was supported by the National Key Research and Development Program of China under Grant 2016YFB0502202. Team YAI (Tracks 6 and 7) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 110-2634-F-155-001.Peer reviewe

    Fracture Evaluation and Dynamic Stress Concentration of Granite Specimens Containing Elliptic Cavity under Dynamic Loading

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    The Split-Hopkinson pressure bar (SHPB) was used to determine the fracture characteristics of a long bar rock specimen with an elliptical cavity under different axial ratios and dip angles. A high speed camera was applied to record the fracturing process of the granite specimen around the cavity. The experimental results showed that the fracture characteristics around the elliptical cavity were closely related to the axial ratio and dip angle. A three-dimensional numerical model was established using LS-DYNA to quantitatively analyze the dynamic stress state around the cavity. The numerical results indicate that the dip angle and axial ratio of the elliptical cavity significantly affected the dynamic stress concentration factor (DSCF), then affected the rock failure. The location of higher DSCF led to a higher possibility of spalling failure. The maximum DSCF remarkably decreased with a decreasing dip angle and increased the axial ratio. In the dynamic loading propagate process, the stress concentration distribution around the cavity formed by a compression stress wave had a certain damaging effect on the destruction of rock around the cavity, and the stress concentration generated by the tensile stress wave was the main factor of the rock fracture, which was most notable in the peak area of the stress concentration

    Protostane and Fusidane Triterpenes: A Mini-Review

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    Protostane triterpenes belong to a group of tetracyclic triterpene that exhibit unique structural characteristics. Their natural distribution is primarily limited to the genus Alisma of the Alismataceae family, but they have also been occasionally found in other plant genera such as Lobelia, Garcinia, and Leucas. To date, there are 59 known protostane structures. Many of them have been reported to possess biological properties such as improving lipotropism, hepatoprotection, anti-viral activity against hepatitis B and HIV-I virus, anti-cancer activity, as well as reversal of multidrug resistance in cancer cells. On the other hand, fusidanes are fungal products characterized by 29-nor protostane structures. They possess antibiotic properties against staphylococci, including the methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid is a representative member which has found clinical applications. This review covers plant sources of the protostanes, their structure elucidation, characteristic structural and spectral properties, as well as biological activities. The fungal sources, structural features, biological activities of fusidanes are also covered in this review. Additionally, the biogenesis of these two types of triterpenes is discussed and a refined pathway is proposed

    Protostane and Fusidane Triterpenes: A Mini-Review

    No full text
    Protostane triterpenes belong to a group of tetracyclic triterpene that exhibit unique structural characteristics. Their natural distribution is primarily limited to the genus Alisma of the Alismataceae family, but they have also been occasionally found in other plant genera such as Lobelia, Garcinia, and Leucas. To date, there are 59 known protostane structures. Many of them have been reported to possess biological properties such as improving lipotropism, hepatoprotection, anti-viral activity against hepatitis B and HIV-I virus, anti-cancer activity, as well as reversal of multidrug resistance in cancer cells. On the other hand, fusidanes are fungal products characterized by 29-nor protostane structures. They possess antibiotic properties against staphylococci, including the methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid is a representative member which has found clinical applications. This review covers plant sources of the protostanes, their structure elucidation, characteristic structural and spectral properties, as well as biological activities. The fungal sources, structural features, biological activities of fusidanes are also covered in this review. Additionally, the biogenesis of these two types of triterpenes is discussed and a refined pathway is proposed

    Dizziness, nausea and progressive lethargy for two months, with mental behavior abnormality for one month

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    DOI: 10.3969/j.issn.1672-6731.2018.02.01
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