133 research outputs found

    VDIP-TGV: Blind Image Deconvolution via Variational Deep Image Prior Empowered by Total Generalized Variation

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    Recovering clear images from blurry ones with an unknown blur kernel is a challenging problem. Deep image prior (DIP) proposes to use the deep network as a regularizer for a single image rather than as a supervised model, which achieves encouraging results in the nonblind deblurring problem. However, since the relationship between images and the network architectures is unclear, it is hard to find a suitable architecture to provide sufficient constraints on the estimated blur kernels and clean images. Also, DIP uses the sparse maximum a posteriori (MAP), which is insufficient to enforce the selection of the recovery image. Recently, variational deep image prior (VDIP) was proposed to impose constraints on both blur kernels and recovery images and take the standard deviation of the image into account during the optimization process by the variational principle. However, we empirically find that VDIP struggles with processing image details and tends to generate suboptimal results when the blur kernel is large. Therefore, we combine total generalized variational (TGV) regularization with VDIP in this paper to overcome these shortcomings of VDIP. TGV is a flexible regularization that utilizes the characteristics of partial derivatives of varying orders to regularize images at different scales, reducing oil painting artifacts while maintaining sharp edges. The proposed VDIP-TGV effectively recovers image edges and details by supplementing extra gradient information through TGV. Additionally, this model is solved by the alternating direction method of multipliers (ADMM), which effectively combines traditional algorithms and deep learning methods. Experiments show that our proposed VDIP-TGV surpasses various state-of-the-art models quantitatively and qualitatively.Comment: 13 pages, 5 figure

    Atrial Fibrillation Follow-up Investigation to Recover Memory and Learning Trial (AFFIRMING): Rationale and Design of a Multi-center, Double-blind, Randomized Controlled Trial

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    Background: People with atrial fibrillation (AF) have elevated risk of developing cognitive impairment. At present, there is a dearth of randomized controlled trials investigating cognitive impairment management in patients with AF. The Atrial Fibrillation Follow-up Investigation to Recover Memory and learning (AFFIRMING) study is aimed at evaluating the potential for computerized cognitive training to improve cognitive function in patients with AF. Methods: The study is a multi-center, double-blind, randomized controlled study using a 1:1 parallel design. A total of 200 patients with AF and mild cognitive decline without dementia are planned to be recruited. The intervention group will use the adaptive training software with changes in difficulty, whereas the positive control group will use basic training software with minimal or no variation in difficulty level. At the end of 12 weeks, the participants will be unblinded, and the positive control group will stop training. The intervention group will be rerandomized 1:1 to stop training or continue training. All participants will be followed up until 24 weeks. The primary endpoint is the proportion of the improvement of the global cognitive function at week 12 compared with baseline, using the Basic Cognitive Ability Test (BCAT)

    Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

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    <p>Abstract</p> <p>Background</p> <p>Celastrol is an active ingredient of the traditional Chinese medicinal plant <it>Tripterygium Wilfordii</it>, which exhibits significant antitumor activity in different cancer models <it>in vitro </it>and <it>in vivo</it>; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity.</p> <p>Methods</p> <p>The downregulation of heat shock protein 90 (HSP90) client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK), and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS) was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP) and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC) complexes.</p> <p>Results</p> <p>Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC), an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP). Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC. Moreover, the inhibition of MRC complex I activity preceded ROS accumulation in H1299 cells after celastrol treatment.</p> <p>Conclusion</p> <p>We identified ROS as the key intermediate for celastrol-induced cytotoxicity. JNK was activated by celastrol-induced ROS accumulation and then initiated mitochondrial-mediated apoptosis. Celastrol induced the downregulation of HSP90 client proteins through ROS accumulation and facilitated ROS accumulation by inhibiting MRC complex I activity. These results identify a novel target for celastrol-induced anticancer activity and define its mode of action.</p

    Detection of the Diffuse Supernova Neutrino Background with JUNO

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    As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

    Potential of Core-Collapse Supernova Neutrino Detection at JUNO

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    JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

    Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

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    Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30MM_{\odot} for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

    Functions of arabidopsis acyl-coenzyme A binding proteins in stress responses

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    In Arabidopsis thaliana, a gene family encodes acyl-CoA-binding proteins (ACBPs) conserved at the acyl-CoA-binding domain which facilitates the binding to acyl-CoA esters. These ACBPs, designated ACBP1 to ACBP6, range in size from 10.4 to 73.1 kD. Previous studies have shown that the the overexpression of ACBP1 or ACBP2 in Arabidopsis likely promotes repair of lipid membranes and result in enhanced tolerance to lead and cadmium, respectively. Microarray data (http://bar.utoronto.ca/) revealed that the expression of ACBP1 and ACBP2 is also regulated by other abiotic stresses, such as cold and drought, suggestive of their association with these environmental pressures. The aim of this study is to investigate and better understand the roles of ACBP1 and ACBP2 in different stress responses. It has been previously observed that the expression of both ACBP1 and ACBP4 is lead [Pb(II)]-inducible and recombinant ACBP1 and ACBP4 bind Pb(II) in vitro. In this study, ACBP1 and ACBP4 were overexpressed in Brassica juncea to test if these ACBPs could be extended for application in Pb(II) phytoremediation in transgenic B. juncea. On freezing (-12 to -8 °C) treatment, ACBP1-overexpressing Arabidopsis was freezing sensitive and accumulated more phosphatidic acid (PA), but less phosphatidylcholine (PC), in contrast to acbp1 mutant plants which were freezing tolerant and had reduced PA and elevated PC levels. Such changes in PC and PA were consistent with the expression of the mRNA encoding phospholipase D1 (PLD1), a major enzyme that promotes the hydrolysis of PC to PA. In contrast, the expression of phospholipase D (PLD), which plays a positive role in freezing tolerance, was up-regulated in acbp1 mutant plants and down-regulated in ACBP1-overexpressing plants. Reduced PLD1 expression and decreased hydrolysis of PC to PA may enhance membrane stability in the acbp1 mutant plants. Given that recombinant ACBP1 binds PA and acyl-CoA esters in vitro, the expression of PLD1 and PLD could be regulated by PA or acyl-CoAs maintained by ACBP1, if ACBP1 were to resemble the yeast 10-kD ACBP by its capability to modulate gene expression during stress responses. Interestingly, another membrane-associated ACBP, ACBP2, which shows high (76.9%) conservation in amino acid homology to ACBP1, did not appear to be affected by freezing treatment. Besides freezing stress, ACBP1, as well as ACBP2, have been observed to participate in abscisic acid (ABA) signaling. They both promote ABA signaling in seed germination and seedling development, while only ACBP2 is involved in the drought response. The overexpression of ACBP2 in Arabidopsis up-regulated reactive oxygen species (ROS) production culminating in reduction in stomatal aperture and water loss in guard cells, thereby enhancing drought tolerance. For tests in phytoremediation, B. juncea was selected for overexpression of ACBP1 and ACBP4 because it is fast-growing, has a higher biomass than Arabidopsis, and is known to be a good accumulator of Pb(II). However, results of Pb(II) treatment for two days showed that the overexpression of ACBP1 or ACBP4 in B. juncea did not significantly improve Pb(II) tolerance. Nevertheless, B. juncea overexpressing ACBP1 did accumulate Pb(II) in roots whereas ACBP4-overexpressing B. juncea lines accumulated Pb(II) in both shoots and roots. Given that B. juncea has a larger biomass than Arabidopsis, it is likely that the duration of Pb(II)-incubation tested in this study was not drastic enough for comparison, and the incubation time should be further extended for Pb(II) translocation. In addition, future studies on Arabidopsis should be conducted to better understand the mechanism of ACBP4-mediated Pb(II) accumulation using Arabidopsis acbp4 mutant and ACBP4-overexpressing plants.published_or_final_versionBiological SciencesDoctoralDoctor of Philosoph
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