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Unveiling crystal orientation-dependent interface property in composite cathodes for solid-state batteries by in situ microscopic probe
No full textA critical bottleneck toward all-solid-state batteries lies in how the solid(electrode)-solid(electrolyte) interface is fabricated and maintained over repeated cycles. Conventional composite cathodes, with crystallographically distinct electrode/electrolyte interfaces of random particles, create complexities with varying (electro)chemical compatibilities. To address this, we employ an epitaxial model system where the crystal orientations of cathode and solid electrolyte are precisely controlled, and probe the interfaces in real-time during co-sintering by in situ electron microscopy. The interfacial reaction is highly dependent on crystal orientation/alignment, especially the availability of open ion channels. Interfaces bearing open ion paths of NCM are more susceptible to interdiffusion, but stabilize with the early formed passivation layer. Conversely, interfaces with closed ion pathway exhibit stability at intermediate temperatures, but deteriorate rapidly at high temperature due to oxygen evolution, increasing interfacial resistance. The elucidation of these distinct interfacial behaviors emphasizes the need for decoupling collective interfacial properties to enable rational design in solid-state batteries.Y
Fabrication and evaluation of chitosan-coated nanostructured lipid carriers for co-delivery of paclitaxel and PD-L1 siRNA
No full textThis study aimed to develop a nanostructured lipid carrier (NLC) capable of co-delivering paclitaxel (PTX) and programmed death-ligand 1 (PD-L1) small interfering RNA (siRNA) to enhance PTX bioavailability and bolster immunity through PD-L1 knockdown. We prepared a PTX-loaded NLC (P-NLC) and coated it with positively charged chitosan (Chi) to create P-NLC-Chi, which was subsequently conjugated to siRNA (P-NLC-Chi-siRNA). The P-NLC-Chi formulation was optimized using the Box-Behnken design. P-NLC-Chi measured 123.8 +/- 0.52 nm (zeta potential, 22.71 +/- 0.49 mV). By verifying the gel retardation assay and observing changes in the zeta potential, the optimal binding ratio of NLC to PD-L1 siRNA was identified as 50:1. The P-NLC-Chi-siRNA particle size was 181.97 +/- 0.67 nm, with a zeta potential of 18.66 +/- 0.23 mV. siRNA stability was observed in serum over a 24-h period. Enhanced cytotoxicity and intracellular uptake of the complex were evident in breast cancer cells and breast cancer-resistant cells (MCF-7 and MCF-7/ADR cells, respectively). Evaluation of P-glycoproteinmediated efflux demonstrated that NLC mitigated drug efflux in MCF-7/ADR cells. Subcutaneous injection of PNLC-Chi-siRNA into tumor-bearing BALB/c nude mice injected with MCF-7/ADR cells revealed a reduction in tumor size. In vitro and in vivo experiments indicated a significant reduction in PD-L1 mRNA expression levels. Additionally, an in vivo study revealed tumor-specific CD4 + and CD8 + T cell responses within the tumor tissue following the injection of P-NLC-Chi-siRNA. Our findings suggest that Chi-coated NLC for the co-delivery of PTX and PD-L1 siRNA has great potential as an innovative delivery system for chemoimmunotherapy.N
Accurate prediction of protein-ligand interactions by combining physical energy functions and graph-neural networks
No full textWe introduce an advanced model for predicting protein-ligand interactions. Our approach combines the strengths of graph neural networks with physics-based scoring methods. Existing structure-based machine-learning models for protein-ligand binding prediction often fall short in practical virtual screening scenarios, hindered by the intricacies of binding poses, the chemical diversity of drug-like molecules, and the scarcity of crystallographic data for protein-ligand complexes. To overcome the limitations of existing machine learning-based prediction models, we propose a novel approach that fuses three independent neural network models. One classification model is designed to perform binary prediction of a given protein-ligand complex pose. The other two regression models are trained to predict the binding affinity and root-mean-square deviation of a ligand conformation from an input complex structure. We trained the model to account for both deviations in experimental and predicted binding affinities and pose prediction uncertainties. By effectively integrating the outputs of the triplet neural networks with a physics-based scoring function, our model showed a significantly improved performance in hit identification. The benchmark results with three independent decoy sets demonstrate that our model outperformed existing models in forward screening. Our model achieved top 1% enrichment factors of 32.7 and 23.1 with the CASF2016 and DUD-E benchmark sets, respectively. The benchmark results using the LIT-PCBA set further confirmed its higher average enrichment factors, emphasizing the model's efficiency and generalizability. The model's efficiency was further validated by identifying 23 active compounds from 63 candidates in experimental screening for autotaxin inhibitors, demonstrating its practical applicability in hit discovery.Scientific contributionOur work introduces a novel training strategy for a protein-ligand binding affinity prediction model by integrating the outputs of three independent sub-models and utilizing expertly crafted decoy sets. The model showcases exceptional performance across multiple benchmarks. The high enrichment factors in the LIT-PCBA benchmark demonstrate its potential to accelerate hit discovery.Y
Synergistic effect of periodontitis and C-reactive protein levels on mortality: NHANES 2001-2004
No full textPeriodontitis is associated with elevated C-reactive protein (CRP) levels. Although the coexistence of periodontitis and elevated CRP levels may heighten the risk of mortality, previous studies have not confirmed their synergistic effect. Understanding this interaction is crucial for identifying potential interventions to reduce mortality risk in individuals with periodontitis. This study aimed to assess the synergistic effects of periodontitis and elevated CRP levels on mortality in 7,938 adult individuals who participated in the National Health and Nutrition Examination Study 2001-2004. The association of periodontitis status and CRP levels with mortality was assessed using a survey-weighted Cox model. The interactive effect was estimated; the synergistic effect of CRP levels and periodontitis status on mortality was assessed using the relative excess risk due to interaction (RERI). Periodontitis was diagnosed in 1,065 (13.4%) participants. Compared with the participants without periodontitis and possessing CRP levels of <= 0.5 mg/dL, those with periodontitis (hazard ratio [HR], 1.38) or CRP levels of > 0.5 mg/dL (HR 1.23) had higher HRs. The participants with both periodontitis and CRP levels of > 0.5 mg/dL had the highest HR of 2.01. The additive scale interactive effect of the periodontal status and CRP levels, measured using RERI 0.41 (-0.07, 0.95), was positive and nearly significant in the total population. The synergy between the periodontal status and CRP levels was more prominent in the participants aged >= 60 years than that in younger individuals. Periodontitis with high CRP levels may indicate a high mortality rate, indicating the importance of active monitoring and intensive management of periodontitis and inflammatory markers.Y
Succession of Samhyeonyukgak in Gyeonggi Province in the second half of the 20th century
No full text경기 삼현육각은 1950년대에 이미 순수 기악곡으로서 모음곡 형태의 연속적으로 연주는 형태가 시도되었다. 1958년에 녹음된 경기 삼현육각의 악곡구성은 거상악으로 연주되었던 대풍류 계열의 음악과 무용 반주 음악으로 연주되었던 음악들의 조합으로 이루어졌으나, 느린 악곡에서 점차 빨라진 뒤 중간 속도의 허튼타령으로 돌아가서 긴장을 풀며 끝내도록 재구성되었다. 그러나 1960년대에 지영희에 의해 거상악, 행진음악, 무용반주음악의 용도별로 삼현육각 악곡이 제시되면서 이러한 구분에 의한 악곡구성이 주로 전승되었다. 반면 줄타기 등과 같이 다른 용도로 연주되던 삼현육각 악곡구성 등은 주목을 받지 못했고, 그 전승 역시 단절된 것으로 보인다. 선율적인 면에서는 1950년대 녹음된 경기 삼현육각의 [삼현도드리], [염불도드리]가 오늘날까지 그대로 전승되어 오고 있다고 할 수 있겠다. 이들 악곡은 관악영산회상에 속하는 곡으로 향제 삼현 육각 중 경기 삼현육각의 악곡으로만 확인되고 있다. 즉, 향제 삼현육각으로서 변주되거나 변형될 요소가 적었던 것이라고도 볼 수 있겠다. 반면에 [긴염불]은 1950년대 음원과 1969년 지영희 피리 교본, 2006년 녹음 자료는 동일하게 연주했지만, 1960년대, 1980년대에 다르게 연주하는 음원 자료 도 확인되고 있다.
The composition of the music of Gyeonggi Samhyeonyukgak recorded in 1958 consisted of a combination of Daepungryu music played as Geosangak and music played as dance accompaniment music, but after gradually accelerating from the slow music, it was reconstructed to return to the mid-speed. However, in the 1960s, as Samhyeonyukgak music was presented by Ji Young-hee for each purpose of Geosangak, marching music, and dance accompaniment music, the composition of the music based on this classification was mainly transmitted. In this process, the composition of Samhyeonyukgak music, which was played for other purposes such as Jultagi, did not receive attention, and the transmission also seems to have been cut off. On the other hand, in terms of melody, it can be said that Samhyundodri and Yeombuldodri of Samhyeonyukgak in Gyeonggi Province recorded in the 1950s have been handed down to this day. These songs belong to the Gwanak Youngsan Hoesang and are identified only as those of Gyeonggi Samhyeonyukgak among the Hyangje Samhyeonyukgak. In other words, it can be said that there were few elements to be changed or transformed as a Hyangje Samhyeonyukgak. On the other hand, Ginyeombul had the same sound source as the 1950s sound source, the 1969 Ji Young-hees Piri textbook, and the 2006 recording material, but sound source materials that were played differently in the 1960s and 1980s are also being confirmed
대체 나랑 무슨 상관인데?
No full text원제와 출처: Rodrigo Baño, ¿Y a mí qué me importa?, Análisis del Año 2023, Santiago: Departamento de Sociología, Universidad de Chile, 2024, pp. 7-29.2019년 10월 소위 폭발(Estallido)로 정점에 이른 칠레의 거센 사회적 동원들 이후, 개헌 프로세스를 통해 이 갈등을 제도적으로 해소하려는 노력이 있었다. 좌파가 이 프로세스를 장악했지만 2022년 국민투표에서 신헌법이 부결됐다. 이후 2차 개헌 프로세스에 착수했다. 이번에는 우파가 헤게모니를 장악했으나 이들이 만든 신헌법 역시 2023년 국민투표에서 부결됐다.
이 선거 결과들과 기타 비교 가능한 다른 선거들에 대한 분석은 광범위한 정치무관심(apoliticismo)에 관한 몇 가지 고찰을 위한 토대이다. 이 정치무관심은 갈등 처리를 위한 제도화된 메커니즘인 민주주의 체제의 기능을 크게 저해하고 있는 듯하다
Dual reality of public security as a push factor for emigration in Honduras: Deteriorating subjective perceptions of public security and significant threat to minors
No full text본 논문은 해외 이주의 배출요인으로서 온두라스의 치안 불안을 재조명하고 두 현상 간에
작용하는 주요 메커니즘을 설명하고자 한다. 본 논문은 다음과 같은 연구 문제를 제기한다. 2010
년대 온두라스의 해외 이주 추이와 치안 상황의 변화는 어떠한 상관관계를 가지고 있는가? 두 변
수 간의 관계를 설명하는 주요한 인과적 메커니즘은 무엇인가? 이에 본 논문은 온두라스 해외 이
주에 대한 실태 확인과 동시에, 치안에 대한 객관적 지수와 주관적 인식의 괴리를 파악함으로써 온
두라스 치안의 이중적 현실을 조명한다. 나아가 치안의 이중적 현실의 기저에서 해외 이주를 강화
하는 메커니즘으로 미성년자에 미치는 치안 불안의 악영향을 주목한다. 본 논문의 분석 시기는 극
단적인 국경의 차단 및 경계 강화로 공식적, 비공식적 해외 이주가 모두 비정상적으로 통제된
COVID-19 발생 직전인 2019년까지로 제한한다. 본 논문은 2010년대 온두라스의 해외 이주가
객관적 치안 지수의 변화에 모순된 주관적 치안 인식에 의해 견인되었다고 주장한다. 치안 악화라
는 통념과 달리 온두라스의 객관적 치안 지수는 전반적인 개선을 나타낸 반면, 치안에 대한 주관적
인식은 악화일로를 거듭했고 해외 이주라는 이주 행위자의 결정에 더욱 실질적인 요인으로 작용했
다는 것이다. 본 논문은 또한 온두라스 해외 이주를 심화시킨 치안에 대한 주관적 인식 악화의 기
저에 미성년자에 대한 사회적 폭력, 특히 조직범죄 집단에 의한 직간접적인 폭력이 주요 메커니즘
으로 크게 작용하였다고 주장한다.
This paper examines Honduran unstable public security as a source
of emigration and attempts to explain the main mechanism between the two
phenomena. This paper raises the following research questions. What is the
relationship between emigration trend and public security conditions in Honduras
in the 2010s? What is the main causal mechanism behind such relationship
between the two variables? To answer the questions, this paper verifies the actual
trend of emigration in Honduras and sheds light on the dual reality of Honduran
public security by identifying the gap between the objective indicators and the
subjective perceptions of public security. Furthermore, it pays attention to the
negative effects of unstable public security on minors as the mechanism to
strengthen emigration under the dual reality of public security. The analysis of this
paper is limited up to the year of 2019, just before the outbreak of COVID-19, when
both formal and informal international migrations were abnormally restricted due
to extreme border closure and surveillance. This paper argues that Honduran
emigration in the 2010s was driven by the subjective perceptions of public security,
which are contradictory to the changes of objective security indicators. Unlike the
common belief in deteriorating public security, the objective indicators of public
security in Honduras showed an overall improvement. In contrast, the subjective
perceptions of public security continued to worsen and functioned as the more
practical factor for emigration decision. This paper also argues that social violence
against minors, especially direct and indirect violence by organized crime groups,
served as the major mechanism underlying the worsening subjective perceptions
of public security that intensified Honduran emigration
Polyketide Origin of the Indole Ring during the Biosynthesis of Indole Alkaloid Coprisidins
No full textCoprisidins, a new class of indole alkaloids, feature a 1,4-naphthoquinone moiety attached to C-3 of 2-oxindole. Heterologous expression of a type II polyketide synthase-containing gene cluster resulted in the generation of three coprisidins. Gene disruption and isotope feeding studies suggested that the 2-oxindole moieties of coprisidins originate from a tetracyclic aromatic polyketide through oxidative rearrangements. This represents a novel biosynthetic route for the synthesis of indole rings in nature.N