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1.
Adv Sci (Weinh) ; : e2103433, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34761571

RESUMO

Lithium metal batteries (LMBs) show several limitations, such as high flammability and Li dendrite growth. All-solid-state LMBs (ASSLMBs) are promising alternatives to conventional liquid electrolyte (LE)-based LMBs. However, it is challenging to prepare a solid electrolyte with both high ionic conductivity and low electrode-electrolyte interfacial resistance. In this study, to overcome these problems, a solid composite electrolyte (SCE) consisting of Li6.25 La3 Zr2 Al0.25 O12 and polyvinylidene fluoride-co-hexafluoropropylene is used, which has attracted considerable attention in recent years as a solid-state electrolyte. To operate LMBs without an LE, optimization of the electrode-solid-electrolyte interface is crucial. To achieve this, physical and chemical treatments are performed, i.e., direct growth of each layer by drop casting and thermal evaporation, and plasma treatment before the Li evaporation process, respectively. The optimized ASSLMB (amorphous V2 O5- x (1 µm)/SCE (30 µm)/Li film (10 µm)) has a high discharge capacity of 136.13 mAh g-1 (at 50 °C and 5 C), which is 90% of that of an LMB with an LE. It also shows good cycling performance (>99%) over 1000 cycles. Thus, the proposed design minimizes the electrode-solid-electrolyte interfacial resistance, and is expected to be suitable for integration with existing commercial processes.

2.
Nanomaterials (Basel) ; 11(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34685132

RESUMO

Sodium-ion batteries (SIBs) have been increasingly studied due to sodium (Na) being an inexpensive ionic resource (Na) and their battery chemistry being similar to that of current lithium-ion batteries (LIBs). However, SIBs have faced substantial challenges in developing high-performance anode materials that can reversibly store Na+ in the host structure. To address these challenges, molybdenum sulfide (MoS2)-based active materials have been considered as promising anodes, owing to the two-dimensional layered structure of MoS2 for stably (de)inserting Na+. Nevertheless, intrinsic issues of MoS2-such as low electronic conductivity and the loss of active S elements after a conversion reaction-have limited the viability of MoS2 in practical SIBs. Here, we report MoS2 embedded in carbon nanofibers encapsulated with a reduced graphene oxide (MoS2@CNFs@rGO) composite for SIB anodes. The MoS2@CNFs@rGO delivered a high capacity of 345.8 mAh g-1 at a current density of 100 mA g-1 for 90 cycles. The CNFs and rGO were synergistically taken into account for providing rapid pathways for electrons and preventing the dissolution of S sources during repetitive conversion reactions. This work offers a new point of view to realize MoS2-based anode materials in practical SIBs.

3.
ACS Appl Mater Interfaces ; 13(36): 43123-43133, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472836

RESUMO

Inorganic materials such as SiOx and SiNx are commonly used as dielectric layers in thin-film transistors (TFTs), but recent advancements in TFT devices, such as inclusion in flexible electronics, require the development of novel types of dielectric layers. In this study, CVD-deposited poly(p-xylylene) (PPx)-based polymers were evaluated as alternative dielectric layers. CVD-deposited PPx can produce thin, conformal, and pinhole-free polymer layers on various surfaces, including oxides and metals, without interfacial defects. Three types of commercial polymers were successfully deposited on various substrates and exhibited stable dielectric properties under frequency and voltage sweeps. Additionally, TFTs with PPx as a dielectric material and an oxide semiconductor exhibited excellent device performance; a mobility as high as 22.72 cm2/(V s), which is the highest value among organic gate dielectric TFTs, to the best of our knowledge. Because of the low-temperature deposition process and its unprecedented mechanical flexibility, TFTs with CVD-deposited PPx were successfully fabricated on a flexible plastic substrate, exhibiting excellent durability over 10000 bending cycles. Finally, a custom-synthesized functionalized PPx was introduced into top-gated TFTs, demonstrating the possibility for expanding this concept to a wide range of chemistries with tunable gate dielectric layers.

4.
Nat Commun ; 12(1): 4298, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262033

RESUMO

Single-phase multiferroic materials that allow the coexistence of ferroelectric and magnetic ordering above room temperature are highly desirable, motivating an ongoing search for mechanisms for unconventional ferroelectricity in magnetic oxides. Here, we report an antisite defect mechanism for room temperature ferroelectricity in epitaxial thin films of yttrium orthoferrite, YFeO3, a perovskite-structured canted antiferromagnet. A combination of piezoresponse force microscopy, atomically resolved elemental mapping with aberration corrected scanning transmission electron microscopy and density functional theory calculations reveals that the presence of YFe antisite defects facilitates a non-centrosymmetric distortion promoting ferroelectricity. This mechanism is predicted to work analogously for other rare earth orthoferrites, with a dependence of the polarization on the radius of the rare earth cation. Our work uncovers the distinctive role of antisite defects in providing a mechanism for ferroelectricity in a range of magnetic orthoferrites and further augments the functionality of this family of complex oxides for multiferroic applications.

5.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206601

RESUMO

To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H]2+ ions than [M+H]+ ions, making doubly charged ions more suitable for trace analysis.


Assuntos
Butirilcolinesterase/sangue , Agentes Neurotóxicos , Organofosfatos , Plasma , Biomarcadores/sangue , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/toxicidade , Humanos , Agentes Neurotóxicos/farmacocinética , Agentes Neurotóxicos/toxicidade , Organofosfatos/farmacocinética , Organofosfatos/toxicidade
6.
Nutrients ; 13(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807703

RESUMO

During adolescence, healthy eating habits are important, and regular meal intake has an especially positive effect on future health. However, the rate of skipping breakfast has gradually increased. Therefore, this study was conducted to evaluate the positive effects of a rice-based breakfast in Korean adolescents who usually skip breakfast. In this open parallel-group, randomized controlled trial, 105 middle and high school students aged 12-18 years who habitually skipped breakfast were recruited. They were randomly divided into three groups: the rice meal group (RMG, n = 35), wheat meal group (WMG, n = 35), and general meal group (GMG, n = 35). The RMG and WMG received a rice-based breakfast and wheat-based breakfast, respectively, for 12 weeks. After a 12-week intervention, the body fat mass (p < 0.05) and body mass index (p < 0.05) in the RMG were significantly lower than those in the other two groups, and the stress score was also significantly lower in the RMG (p < 0.05). Moreover, after the intervention, in the RMG only, compared to baseline levels, the relative theta (RT) wave activity significantly decreased in eight electrode sites, and the relative alpha (RA) wave activity increased significantly. Eating a rice-based breakfast has positive effects on body fat accumulation and cognitive function in Korean adolescents. Furthermore, a rice-based breakfast plan that is preferred by adolescents should be developed to assist them in developing healthy eating habits.


Assuntos
Desjejum/fisiologia , Desjejum/psicologia , Dieta Saudável/métodos , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Oryza , Adolescente , Ritmo alfa , Índice de Massa Corporal , Criança , Cognição , Feminino , Humanos , Masculino , República da Coreia , Estudantes/psicologia , Ritmo Teta , Triticum
7.
Molecules ; 26(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670472

RESUMO

As a first step toward studying the properties of Novichok (ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)), we investigated its degradation products and fragmentation pathways in aqueous solution at different pH levels by liquid chromatography-tandem mass spectrometry. A234 was synthesized in our laboratory and characterized by nuclear magnetic resonance spectroscopy. Three sets of aqueous samples were prepared at different pH levels. A stock solution of A234 was prepared in acetonitrile at a concentration of 1 mg/mL and stored at -20 °C until use. Aqueous samples (0.1 mg/mL) were prepared by diluting the stock solution with deionized water. The acidic aqueous sample (pH = 3.5) and basic aqueous sample (pH = 9.4) were prepared using 0.01 M acetic acid and 0.01 M potassium carbonate, respectively. The analysis of the fragmentation patterns and degradation pathways of A234 showed that the same degradation products were formed at all pH levels. However, the hydrolysis rate of A234 was fastest under acidic conditions. In all three conditions, the fragmentation pattern and the major degradation product of A234 were determined. This information will be applicable to studies regarding the decontamination of Novichok and the trace analysis of its degradation products in various environmental matrices.


Assuntos
Agentes Neurotóxicos/análise , Organofosfatos/análise , Espectrometria de Massas em Tandem/métodos , Água/química , Cromatografia Líquida , Concentração de Íons de Hidrogênio , Organofosfatos/química , Soluções , Fatores de Tempo
8.
ACS Nano ; 15(3): 4561-4575, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33629830

RESUMO

In accordance with the fourth industrial revolution (4IR), thin-film all-solid-state batteries (TF-ASSBs) are being revived as the most promising energy source to power small electronic devices. However, current TF-ASSBs still suffer from the perpetual necessity of high-performance battery components. While every component, a series of a TF solid electrolyte (i.e., lithium phosphorus oxynitride (LiPON)) and electrodes (cathode and Li metal anode), has been considered vital, the lack of understanding of and ability to ameliorate the cathode (or anode)-electrolyte interface (CEI) (or AEI) has impeded the development of TF-ASSBs. In this work, we suggest an ensemble design of TF-ASSBs using LiPON (500 nm), an amorphous TF-V2O5-x cathode with oxygen vacancies (Ovacancy), a thin evaporated Li anode (evp-Li) with a thickness of 1 µm, and an artificial ultrathin Al2O3 layer between evp-Li and LiPON. Well-defined Ovacancy sites, such as O(II)vacancy and O(III)vacancy, in amorphous TF-V2O5-x not only allow isotropic Li+ diffusion at the CEI but also enhance both the ionic and electronic conductivities. For the AEI, we employed protective Al2O3, which was specially sputtered using the facing target sputtering (FTS) method to form a homogeneous layer without damage from plasma. In regard to the contact with evp-Li, interfacial stability, electrochemical impedance, and battery performance, the nanometric Al2O3 layers (1 nm) were optimized at different temperatures (40, 60, and 80 °C). The TF-ASSB cell containing Al2O3 (1 nm) delivers a high specific capacity of 474.01 mAh cm-3 under 60 °C at 2 C for the 400th cycle, and it achieves a long lifespan as well as ultrafast rate capability levels, even at 100 C; these results were comparable to those of TF Li-ion battery cells using a liquid electrolyte. We demonstrated the reaction mechanism at the AEI utilizing time-of-flight secondary ion mass spectrometry (TOF-SIMS) and molecular dynamics (MD) simulations for a better understanding. Our design provides a signpost for future research on the rational structure of TF-LIBs.

9.
Membranes (Basel) ; 11(1)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430261

RESUMO

The development of highly porous and thin separator is a great challenge for lithium-ion batteries (LIBs). However, the inevitable safety issues always caused by poor mechanical integrity and internal short circuits of the thin separator must be addressed before this type of separator can be applied to lithium-ion batteries. Here, we developed a novel multilayer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) membrane with a highly porous and lamellar structure, through a combination of evaporation-induced phase separation and selective solvent etching methods. The developed membrane is capable of a greater amount of electrolyte uptake and excellent electrolyte retention resulting from its superior electrolyte wettability and highly porous structure, thereby offering better electrochemical performance compared to that of a commercial polyolefin separator (Celgard). Moreover, benefiting from the layered configuration, the tensile strength of the membrane can reach 13.5 MPa, which is close to the mechanical strength of the Celgard type along the transversal direction. The elaborate design of the multilayered structure allows the fabrication of a new class of thin separators with significant improvements in the mechanical and electrochemical performance. Given safer operation, the developed multilayer membrane may become a preferable separator required for high-power and high-energy storage devices.

10.
J Nanosci Nanotechnol ; 21(3): 1815-1819, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404454

RESUMO

Nanoscale carbon materials have a broad range of applications in the field of surface and material sciences. Each vibration mode of a Raman and Fourier transform infrared (FT-IR) spectra corresponds to a specific frequency of a bond in the core and surface of the crystal, thus it is highly sensitive to morphology, implying that every band is sensitive to the orientation of the bonds and the atomic weight at either end of the bond. Accordingly, in this study we apply transmission electron microscope (TEM), Raman spectroscopies, and model calculations to study the relative content of carbon-carbon (C-C) bonds to the anhydrous and weakly aggregated elementary nanoscale carbon particles of detonation nanodiamonds. One point of the Raman bands at approximately 1300 cm-1 established that there are highly uniform C-C bonds in a tetrahedral crystal field environment not unlike that of diamonds. Another point at approximately 1600 cm-1 would be a hexagonal graphene-like sheet. By analyzing the relative content of carbon bonds using the area of intensity of the Raman peaks and a simulation of crystal morphology, we suggest that the number of graphene surface layers would be monolayers in nanodiamonds, comprising two kinds of C-C bonds, one being sp3 bonds of diamond in the core and the other being sp2 bonds of graphene on the surface.

11.
Cyberpsychol Behav Soc Netw ; 24(1): 41-47, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33325791

RESUMO

Effects of violent video games on aggression remain contentious despite decades of empirical investigations. Using eight-wave panel data collected from 662 South Korean adolescents (grades 4, 7, and 10) for a 4-year period (number of observations = 5,296), the current research critically tested competing hypotheses concerning the relations between violent video games and aggression. In so doing, we directly compared the results from dynamic fixed-effects (FE) regression with those from conventional contemporaneous FE regression to observe if different statistical models yield different outcomes. Consistent with the catharsis hypothesis, the dynamic FE model showed that violent (vs. nonviolent) game playing significantly lowered both verbal and physical aggression among heavy players, with no corresponding effect of the game type for light players. By contrast, results from the contemporaneous FE model lent support to the stimulation hypothesis, with violent game playing leading to increased physical aggression as well as verbal aggression among heavy players. Violent game playing did not significantly affect anger and hostility, but overall game time did, although in opposite directions depending on the statistical model. Specifically, the dynamic FE model indicated a significant reduction of the negative emotions as a result of increased game playing, whereas the contemporaneous FE model showed a significant increase in both emotions. Methodological implications and directions for future research are discussed.


Assuntos
Comportamento do Adolescente/psicologia , Agressão/psicologia , Catarse , Modelos Psicológicos , Jogos de Vídeo/psicologia , Violência/psicologia , Adolescente , Criança , Emoções , Feminino , Humanos , Estudos Longitudinais , Masculino , Análise de Regressão , República da Coreia
12.
J Exp Med ; 218(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315086

RESUMO

ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction.


Assuntos
Dano ao DNA/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Rim/patologia , Rim/fisiopatologia , Mutação/genética , Alelos , Substituição de Aminoácidos , Sequência de Bases , Linhagem Celular , Citoplasma/metabolismo , Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/metabolismo , Endonucleases/deficiência , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Luz , Fígado/patologia , Fígado/fisiopatologia , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto/genética , Estabilidade Proteica , Irmãos
13.
Food Sci Anim Resour ; 40(2): 274-285, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32161922

RESUMO

In this study, ovalbumin (OVA) hydrolysates were prepared using various proteolytic enzymes and the anti-inflammatory activities of the hydrolysates were determined. Also, the potential application of OVA as a functional food material was discussed. The effect of OVA hydrolysates on the inhibition of nitric oxide (NO) production was evaluated via the Griess reaction, and their effects on the expression of inducible NO synthase (inducible nitric oxide synthase, iNOS) were assessed using the quantitative real-time PCR and Western blotting. To determine the mechanism by which OVA hydrolysates activate macrophages, pathways associated with the mitogen-activated protein kinase (MAPK) signaling were evaluated. When the OVA hydrolysates were added to RAW 264.7 cells without lipopolysaccharide (LPS) stimulation, they did not affect the production of NO. However, both the OVA-Protex 6L hydrolysate (OHPT) and OVA-trypsin hydrolysate (OHT) inhibited NO production dose-dependently in LPS- stimulated RAW 264.7 cells. Especially, OHT showed a strong NO-inhibitory activity (62.35% at 2 mg/mL) and suppressed iNOS production and the mRNA expression for iNOS (p<0.05). Also, OHT treatment decreased the phosphorylation levels of Jun amino-terminal kinases (JNK) and extracellular signal-regulated kinases (ERK) in the MAPK signaling pathway. These findings suggested that OVA hydrolysates could be used as an anti-inflammatory agent that prevent the overproduction of NO.

14.
Nucleic Acids Res ; 48(6): 3328-3342, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32002546

RESUMO

Monoubiquitination of the Fanconi anemia complementation group D2 (FANCD2) protein by the FA core ubiquitin ligase complex is the central event in the FA pathway. FANCA and FANCG play major roles in the nuclear localization of the FA core complex. Mutations of these two genes are the most frequently observed genetic alterations in FA patients, and most point mutations in FANCA are clustered in the C-terminal domain (CTD). To understand the basis of the FA-associated FANCA mutations, we determined the cryo-electron microscopy (EM) structures of Xenopus laevis FANCA alone at 3.35 Å and 3.46 Å resolution and two distinct FANCA-FANCG complexes at 4.59 and 4.84 Å resolution, respectively. The FANCA CTD adopts an arc-shaped solenoid structure that forms a pseudo-symmetric dimer through its outer surface. FA- and cancer-associated point mutations are widely distributed over the CTD. The two different complex structures capture independent interactions of FANCG with either FANCA C-terminal HEAT repeats, or the N-terminal region. We show that mutations that disturb either of these two interactions prevent the nuclear localization of FANCA, thereby leading to an FA pathway defect. The structure provides insights into the function of FANCA CTD, and provides a framework for understanding FA- and cancer-associated mutations.


Assuntos
Proteína do Grupo de Complementação A da Anemia de Fanconi/ultraestrutura , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/ultraestrutura , Proteína do Grupo de Complementação G da Anemia de Fanconi/ultraestrutura , Anemia de Fanconi/genética , Animais , Núcleo Celular/genética , Núcleo Celular/ultraestrutura , Microscopia Crioeletrônica , Cristalografia por Raios X , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/ultraestrutura , Anemia de Fanconi/patologia , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação G da Anemia de Fanconi/química , Humanos , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Mutação , Ligação Proteica/genética , Conformação Proteica , Xenopus laevis/genética
15.
Sci Rep ; 10(1): 719, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959828

RESUMO

Si doping was used to significantly improve the bias stability of ZnON thin-film transistors. Si 3 W (~1%) doped ZnON TFTs showed a saturation mobility of 19.70 cm2/Vs along with remarkable improvements in the threshold voltage shift for negative gate bias stress (NBS) within 1.69 V. The effects of Si doping were interpreted by the experimental correlation between device performance and physical analysis, as well as by the theoretical calculation. Si doping induces the reduction of N-related defects by increasing stoichiometric Zn3N2, and decreasing nonstoichiometric ZnxNy. In addition, Si doping reduces the band edge states below the conduction band. According to density functional theory (DFT) calculations, Si, when it substitutes for Zn, acts as a carrier suppressor in the ZnON matrix.

16.
ACS Appl Mater Interfaces ; 12(3): 3719-3726, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31889442

RESUMO

The trade-off between performance and stability in amorphous oxide semiconductor-based thin-film transistors (TFTs) has been a critical challenge, meaning that it is difficult to simultaneously achieve high mobility and stability under bias and light stresses. Here, an amorphous mixture of two indium-free BaSnO3 and ZnSnO3 compounds, a-(Zn,Ba)SnO3, is proposed as a feasible strategy to achieve high mobility and stability at the same time. The choice of BaSnO3 as a counterpart to ZnSnO3, a well-known In-free candidate in amorphous oxide semiconductors, is to improve structural order and oxygen stoichiometry due to the large heat of formation and to preserve electron mobility due to the same kind of octahedral Sn-O network. Our first-principles calculations indeed show that compared to pure a-ZnSnO3, BaSnO3 plays a crucial role in restoring structural order in both stoichiometric and O-deficient supercells without seriously damaging the conduction band minimum. The resulting features of a-(Zn,Ba)SnO3 reduce O-deficiency and the valence band tail states, which are known to be critically associated with instability. It is experimentally demonstrated that a-(Zn,Ba)SnO3-based TFTs simultaneously exhibit high mobility (>20 cm2 V-1 s-1) and remarkable stability against negative bias illumination stress (ΔVth: <0.9 V). Our results suggest that a-(Zn,Ba)SnO3 would be a strong In-free candidate for next-generation TFT display, replacing the conventional a-InGaZnO4.

17.
Nucleic Acids Res ; 48(4): 2173-2188, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31925419

RESUMO

The XPA protein functions together with the single-stranded DNA (ssDNA) binding protein RPA as the central scaffold to ensure proper positioning of repair factors in multi-protein nucleotide excision repair (NER) machinery. We previously determined the structure of a short motif in the disordered XPA N-terminus bound to the RPA32C domain. However, a second contact between the XPA DNA-binding domain (XPA DBD) and the RPA70AB tandem ssDNA-binding domains, which is likely to influence the orientation of XPA and RPA on the damaged DNA substrate, remains poorly characterized. NMR was used to map the binding interfaces of XPA DBD and RPA70AB. Combining NMR and X-ray scattering data with comprehensive docking and refinement revealed how XPA DBD and RPA70AB orient on model NER DNA substrates. The structural model enabled design of XPA mutations that inhibit the interaction with RPA70AB. These mutations decreased activity in cell-based NER assays, demonstrating the functional importance of XPA DBD-RPA70AB interaction. Our results inform ongoing controversy about where XPA is bound within the NER bubble, provide structural insights into the molecular basis for malfunction of disease-associated XPA missense mutations, and contribute to understanding of the structure and mechanical action of the NER machinery.


Assuntos
Reparo do DNA/genética , Modelos Moleculares , Proteína de Replicação A/química , Proteína de Xeroderma Pigmentoso Grupo A/química , DNA/química , DNA/genética , Dano ao DNA/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Humanos , Espectroscopia de Ressonância Magnética , Ligação Proteica/genética , Proteína de Replicação A/genética , Proteína de Xeroderma Pigmentoso Grupo A/genética
18.
IEEE Trans Med Imaging ; 39(2): 526-533, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31380749

RESUMO

Dynamic in vivo biodistribution of gold nanoparticles (GNPs) in living mice was first successfully acquired by a pinhole X-ray fluorescence (XRF) imaging system using polychromatic X-rays. The system consisted of fan-beam X-rays to stimulate GNPs and a 2D cadmium zinc telluride (CZT) gamma camera to collect K-shell XRF photons emitted from the GNPs. 2D XRF images of kidney slices of three Balb/C mice were obtained within 2 minutes of irradiation per slice. 40 mg of GNPs suspended in a 0.2 mL phosphate-buffered saline was injected into the mice via a tail vein. The mice were scanned over a 60 min period after the injection of GNPs in order to acquire a dynamic biodistribution of GNPs. The concentrations of GNPs measured by the CZT gamma camera were then validated by inductively coupled plasma atomic emission spectroscopy and ex vivo L-shell XRF measurements using a silicon drift detector. The GNP concentrations in the right-side kidneys were 1.58% by weight (wt%) at T =0 min and 0.77 wt% at T=60 min after the injection. This investigation showed a dramatically reduced scan time and imaging dose. Hence, we conclude that dynamic in vivo XRF imaging of GNPs is technically feasible in a benchtop system. The developed pinhole XRF imaging system can be a potential molecular imaging modality for metal nanoparticles to emerge as a radiosensitizer and a drug-delivery agent.


Assuntos
Ouro/farmacocinética , Nanopartículas Metálicas/química , Imagem Molecular/métodos , Imagem Óptica/métodos , Espectrometria por Raios X/métodos , Animais , Feminino , Ouro/química , Rim/diagnóstico por imagem , Rim/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Imagens de Fantasmas , Distribuição Tecidual
19.
Adv Mater ; 31(43): e1903738, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31517407

RESUMO

Lattice defects typically reduce lattice thermal conductivity, which has been widely exploited in applications such as thermoelectric energy conversion. Here, an anomalous dependence of the lattice thermal conductivity on point defects is demonstrated in epitaxial WO3 thin films. Depending on the substrate, the lattice of epitaxial WO3 expands or contracts as protons are intercalated by electrolyte gating or oxygen vacancies are introduced by adjusting growth conditions. Surprisingly, the observed lattice volume, instead of the defect concentration, plays the dominant role in determining the thermal conductivity. In particular, the thermal conductivity increases significantly with proton intercalation, which is contrary to the expectation that point defects typically lower the lattice thermal conductivity. The thermal conductivity can be dynamically varied by a factor of ≈1.7 via electrolyte gating, and tuned over a larger range, from 7.8 to 1.1 W m-1 K-1 , by adjusting the oxygen pressure during film growth. The electrolyte-gating-induced changes in thermal conductivity and lattice dimensions are reversible through multiple cycles. These findings not only expand the basic understanding of thermal transport in complex oxides, but also provide a path to dynamically control the thermal conductivity.

20.
Nucleic Acids Res ; 47(16): 8337-8347, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31372632

RESUMO

DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome.


Assuntos
Enzimas Reparadoras do DNA/química , Reparo do DNA , DNA Viral/química , Proteínas de Ligação a DNA/química , DNA/química , Dímeros de Pirimidina/química , Bacteriófago lambda/química , Bacteriófago lambda/genética , Sítios de Ligação , DNA/genética , DNA/metabolismo , Dano ao DNA , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , DNA Viral/genética , DNA Viral/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Difusão , Humanos , Cinética , Modelos Moleculares , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Concentração Osmolar , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Dímeros de Pirimidina/metabolismo , Imagem Individual de Molécula
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