50 research outputs found
Direct cellular delivery of human proteasomes to delay tau aggregation
No full textThe 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated
proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been
suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial
to prevent the accumulation of protein aggregates. Here we show that purified proteasomes
can be directly transported into cells through mesoporous silica nanoparticle-mediated
endocytosis. Proteasomes that are loaded onto nanoparticles through non-covalent
interactions between polyhistidine tags and nickel ions fully retain their proteolytic activity.
Cells treated with exogenous proteasomes are more efficient in degrading overexpressed
human tau than endogenous proteasomal substrates, resulting in decreased levels of tau
aggregates. Moreover, exogenous proteasome delivery significantly promotes cell survival
against proteotoxic stress caused by tau and reactive oxygen species. These data demonstrate
that increasing cellular proteasome activity through the direct delivery of purified
proteasomes may be an effective strategy for reducing cellular levels of proteotoxic proteins.135371sciescopu
Highly efficient gene silencing and bioimaging based on fluorescent carbon dots in vitro and in vivo
No full textSmall interfering RNA (siRNA) is an attractive therapeutic candidate for sequencespecific gene silencing to treat incurable diseases using small molecule drugs. However, its efficient intracellular delivery has remained a challenge. Here, we have developed a highly biocompatible fluorescent carbon dot (CD), and demonstrate a functional siRNA delivery system that induces efficient gene knockdown in vitro and in vivo. We found that CD nanoparticles (NPs) enhance the cellular uptake of siRNA, via endocytosis in tumor cells, with low cytotoxicity and unexpected immune responses. Real-time study of fluorescence imaging in live cells shows that CD NPs favorably localize in cytoplasm and successfully release siRNA within 12 h. Moreover, we demonstrate that CD NP-mediated siRNA delivery significantly silences green fluorescence protein (GFP) expression and inhibits tumor growth in a breast cancer cell xenograft mouse model of tumor-specific therapy. We have developed a multifunctional siRNA delivery vehicle enabling simultaneous bioimaging and efficient downregulation of gene expression, that shows excellent potential for gene therapy.close
Sterically Controlled Excited-State Intramolecular Proton Transfer Dynamics in Solution
No full text© 2019 American Chemical Society.Excited-state intramolecular proton transfer (ESIPT) is a fundamental ultrafast photochemical process. Although it has been intensively studied for the development of novel photonic devices such as organic light-emitting diodes, the relation between ESIPT reaction and intramolecular charge transfer (ICT) is still a subject of debate. Furthermore, the effects of the molecular geometry and of the substituent on ESIPT and ICT processes are still unclear. To address these issues, we synthesized a set of four compounds designed to control the electron density distribution of the proton-donating (PD) group and the steric hindrance between the PD and the adjacent phenyl groups: three 2-(1-phenyl-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol derivatives, PIPP-Xs (X = H, F, and OMe), and 2-(1-phenyl-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)naphthalen-2-ol (PIPN). We then investigated their ESIPT and ICT dynamics as well as the related structural changes using femtosecond transient absorption spectroscopy and theoretical calculations. Although the four compounds commonly exhibit a dual emission originating from the excited enol (E*) and keto (K*) tautomers, their emission properties, such as emission maxima and lifetimes, are systematically modulated by substitution at the para-position of the PD group. The experimental and time-dependent density functional theory calculation results showed that the substitution of an electron-withdrawing group at the para-position of the PD group and the planarity between the PD and proton-accepting (PA) groups play important roles in inducing an efficient ESIPT characterized by increased emission of the K∗ tautomer. On the other hand, the photoexcitation for PIPP-Xs induces the formation of cis-K*, which is the most stable structure, whereas in PIPN the E∗ tautomer generated by the photoexcitation is rapidly converted to two species, cis-K∗ and per-K∗ with time constants of <0.2 and 0.5 ps, respectively. Furthermore, the per-K∗ state of PIPN has a charge transfer characteristic, suggesting intramolecular charge migration induced by the formation of per-K∗ state. This distinctive dynamics of PIPN is due to its pretwisted structure between PD and PA groups. The results provided in this study demonstrate that the molecular geometry plays an important role in the ESIPT and ICT processes11sciescopu
Cooperative protein structural dynamics of homodimeric hemoglobin linked to water cluster at subunit interface revealed by time-resolved X-ray solution scattering
No full textHomodimeric hemoglobin (HbI) consisting of two subunits is a good model system for investigating the allosteric structural transition as it exhibits cooperativity in ligand binding. In this work, as an effort to extend our previous study on wild-type and F97Y mutant HbI, we investigate structural dynamics of a mutant HbI in solution to examine the role of well-organized interfacial water cluster, which has been known to mediate intersubunit communication in HbI. In the T72V mutant of HbI, the interfacial water cluster in the T state is perturbed due to the lack of Thr72, resulting in two less interfacial water molecules than in wild-type HbI. By performing picosecond time-resolved X-ray solution scattering experiment and kinetic analysis on the T72V mutant, we identify three structurally distinct intermediates (I1, I2, and I3) and show that the kinetics of the T72V mutant are well described by the same kinetic model used for wild-type and F97Y HbI, which involves biphasic kinetics, geminate recombination, and bimolecular CO recombination. The optimized kinetic model shows that the R-T transition and bimolecular CO recombination are faster in the T72V mutant than in the wild type. From structural analysis using species-associated difference scattering curves for the intermediates, we find that the T-like deoxy I3 intermediate in solution has a different structure from deoxy HbI in crystal. In addition, we extract detailed structural parameters of the intermediates such as E-F distance, intersubunit rotation angle, and heme-heme distance. By comparing the structures of protein intermediates in wild-type HbI and the T72V mutant, we reveal how the perturbation in the interfacial water cluster affects the kinetics and structures of reaction intermediates of HbI. © 2016 Author(s)1571sciescopu
New Frontiers of Laser Welding Technology
No full textWith the advances in power sources and optic technologies, high-power laser welding has been utilized in many applications such as automotive, battery manufacturing, and electronic industries [...
All-Sky 1 km MODIS Land Surface Temperature Reconstruction Considering Cloud Effects Based on Machine Learning
No full textOpen AccessArticle
All-Sky 1 km MODIS Land Surface Temperature Reconstruction Considering Cloud Effects Based on Machine Learning
by Dongjin ChoORCID,Dukwon Bae,Cheolhee YooORCID,Jungho Im *ORCID,Yeonsu LeeORCID andSiwoo LeeORCID
Department of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Anand Inamdar
Remote Sens. 2022, 14(8), 1815; https://doi.org/10.3390/rs14081815
Received: 9 February 2022 / Revised: 5 April 2022 / Accepted: 7 April 2022 / Published: 9 April 2022
(This article belongs to the Special Issue Land Surface Temperature Estimation Using Remote Sensing)
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Abstract
A high spatio-temporal resolution land surface temperature (LST) is necessary for various research fields because LST plays a crucial role in the energy exchange between the atmosphere and the ground surface. The moderate-resolution imaging spectroradiometer (MODIS) LST has been widely used, but it is not available under cloudy conditions. This study proposed a novel approach for reconstructing all-sky 1 km MODIS LST in South Korea during the summer seasons using various data sources, considering the cloud effects on LST. In South Korea, a Local Data Assimilation and Prediction System (LDAPS) with a relatively high spatial resolution of 1.5 km has been operated since 2013. The LDAPS model???s analysis data, binary MODIS cloud cover, and auxiliary data were used as input variables, while MODIS LST and cloudy-sky in situ LST were used together as target variables based on the light gradient boosting machine (LightGBM) approach. As a result of spatial five-fold cross-validation using MODIS LST, the proposed model had a coefficient of determination (R2) of 0.89???0.91 with a root mean square error (RMSE) of 1.11???1.39 ??C during the daytime, and an R2 of 0.96???0.97 with an RMSE of 0.59???0.60 ??C at nighttime. In addition, the reconstructed LST under the cloud was evaluated using leave-one-station-out cross-validation (LOSOCV) using 22 weather stations. From the LOSOCV results under cloudy conditions, the proposed LightGBM model had an R2 of 0.55???0.63 with an RMSE of 2.41???3.00 ??C during the daytime, and an R2 of 0.70???0.74 with an RMSE of 1.31???1.36 ??C at nighttime. These results indicated that the reconstructed LST has higher accuracy than the LDAPS model. This study also demonstrated that cloud cover information improved the cloudy-sky LST estimation accuracy by adequately reflecting the heterogeneity of the relationship between LST and input variables under clear and cloudy skies. The reconstructed all-sky LST can be used in a variety of research applications including weather monitoring and forecasting
Improving I/O Performance in Smart TVs
No full textAbstract-To use the XML file, it must be converted into a tree structure form in smart TV application. However, when the application is terminated, tree are eliminated in process address space. When application is restarted, XML file need to be converted to tree again in order to execute application. This study presents a Fast I/O technique that enables restarting a application without data conversion process by adding persistency in tree in a smart TV environment. Fast I/O technique provides an object, in which the tree are saved adding persistency in process address space. The data structure gains persistency by saving the tree in an object and reusing it without data conversion when restarting the application. Fast I/O technique was applied in the web browser to parse HTML and skip the process of composing a tree. Running time was reduced up to 61% in the test environment, consisting of CPU, memory, and an SSD
In vitro development of mouse parthenogenetic embryos: Effect of temperature before oocyte activation
No full textThis study was conducted to establish the optimal temperature condition before oocyte activation in B6D2 F1 mouse. In experiment 1, two embryo culture media (CZB vs KSOM) were evaluated for the development of activated mouse oocytes. Parthenogenetic embryos cultured in KSOM showed better blastocyst development than ones cultured in CZB(56.2% vs 81.0%, p<0.01). Two-hour of pre-incubation before activation significantly reduced the number of hatched blastocysts in KSOM (22.0% versus 8.8%, p<0.05). In experiment 2, recovered oocytes were pre-incubated at different temperature conditions before activation. The experimental groups were divided by 5 as follows. Group A: pre-incubation for 120 min at 37℃, Group B: pre-incubation at 37℃ for 90 min then at 25℃ for 30 min, Group C: pre-incubation at 37℃ for 60 min then at 25℃ for 60 min, Group D: pre-incubation at 37℃ for 30 min then at 25℃ for 90 min, and Group E: pre-incubation at 25℃ for 120 min before activation. Group A (67.6%) and B (66.7%) showed better development to the blastocyst stage than other groups (Group C: 50.0%, Group D: 49.2%, Group E: 33.3%, p<0.05). The present study indicates that the temperature before activation affects the development of B6D2 F1 mouse parthenogenetic oocytes and exposure to room temperature should be limited to 30-min when the oocytes are left in HEPES-buffered medium for micromanipulation
