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GC1126A, a novel ADAMTS13 mutein, evades autoantibodies in immune-mediated thrombotic thrombocytopenic purpura
No full textImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening blood disorder characterized by the formation of blood clots in small blood vessels. It is caused by antibodies targeting the A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13), which plays a role in cleaving von Willebrand factor. Most patients with iTTP have autoantibodies against specific domains of the ADAMTS13 protein, particularly the cysteine-rich and spacer domains. This study aimed to identify ADAMTS13 muteins that are resistant to autoantibodies and maintain their enzymatic activity. A panel of muteins was generated using rational and random mutagenesis methods and screened for autoantibody binding and ADAMTS13 activity. The selected muteins were assessed for pharmacodynamic biomarkers and pharmacokinetic profiles in the iTTP-mimic and wild-type mice, respectively. GC1126A was the most effective variant for escaping autoantibodies and had a longer half-life than the wild-type ADAMTS13 fragment (MDTCS). In the iTTP-mimic mouse model, GC1126A treatment significantly improved platelet counts, lactate dehydrogenase levels, and ADAMTS13 residual activity. In addition, GC1126A outperformed recombinant human wild-type ADAMTS13 (rh WT-ADAMTS13) and caplacizumab in terms of platelet recovery and sustained effectiveness. Results from the ex vivo study using plasma from patients with iTTP showed that GC1126A exhibited higher residual activity than rh WT-ADAMTS13, particularly in patients with high autoantibody titers. These findings suggest that GC1126A could be a promising new treatment option for patients with iTTP.Y
Unveiling Key Descriptors of Ionomer Materials for Enhanced Electrochemical CO2 Reduction
No full textPolymeric ionomers near the catalyst surface of CO2 reduction reaction (CO2RR) electrodes affect their efficiency; however, their multifaceted properties complicate structure-activity relationship elucidation. Here, we synthesized polycarbazole-based anion-exchange (QPC) ionomers bearing varying functionalized side chains to explore this relationship. Comprehensive analysis in physicochemical properties, electrochemical activity, and operando ATR-SEIRAS revealed that functional group modification significantly influenced the intrinsic ionomer properties, thereby affecting the Ag catalyst properties, microenvironments of interfacial water structures, and reaction kinetics of the protonation step for CO2RR and the hydrogen evolution reaction (HER). Notably, the QPC-trimethyl phosphonium (TMP) ionomer induced favorable interfacial water structures, having a high proportion of strong H-bonded water with low Stark tuning slopes, which inhibit HER and promote CO2RR. A high CO Faradaic efficiency (>90%) was maintained using QPC-TMP in a membrane electrode assembly, even under varying CO2 concentrations (100-15%) and elevated temperatures (28-72 degrees C). These findings suggest that the catalytic environment can be optimized by fine-tuning the ionomer structure, contributing to the advancement of high-performance CO2RR ionomers.N
Advancements in surface plasmon resonance sensors for real-time detection of chemical analytes: sensing materials and applications
No full textChemicals are being used in various fields with the development of industry, but the importance of human safety from chemical exposure is becoming increasingly evident. Traditional detection methods, which analyze analytes through preprocessing, have limitations in real-time applications. In contrast, LSPR and SPR sensors, which can rapidly and accurately detect chemicals in real time, are among the most reliable methods for protecting against chemical threats. LSPR and SPR sensors detect minute interactions between sensing materials and chemicals through changes in absorbance and refractive index, enabling the accurate detection of even the smallest changes. To maximize the performance of LSPR and SPR sensors capable of real-time detection and apply them across various fields, ongoing research has focused on innovative materials, fabrication techniques, and nanostructures. The future perspectives on sensing materials for real-time detection technologies used by LSPR and SPR sensors are discussed. This review presents guidelines for selecting sensing materials for use in LSPR and SPR sensors in real-time applications.Y
Levelling up learning in higher education: Gamification of in-video components to supercharge student learning and achievement in video-based learning
No full textAbstract: Despite the rapid growth of video-based learning in higher education, students face challenges in sustaining their full attention on video lectures. While gamification has been used to engage students, there have been few attempts to gamify in-video learning. The study aimed to create a gamified instructional video and examine the effects on learning. We identified gamification principles that can be incorporated to gamify in-video components. An experiment conducted for validation purposes involved 48 undergraduate and graduate students. The results revealed that the participants who learned from the gamified instruction video (ie, experimental group, n = 23) had higher levels of necessary cognitive load required for accomplishing the given tasks than the participants who learned from a conventional video (ie, control group, n = 25). Although there was no significant difference in situational interest, the experimental group also exhibited better achievement, higher levels of intrinsic motivation, and learning satisfaction than the control group. Interview results revealed that the experimental group had a positive learning experience and clarified how the gamification strategies contributed to the outcomes. We discuss the implications of this study for research and practice. Practitioner notes What is already known about this topic Video-based learning (VBL) is recognized for its ability to accommodate students with diverse educational needs, and higher education has paid attention to its accessibility. During VBL, students face challenges in sustaining their full attention on video lectures unless they are highly motivated to learn. Moreover, students lack access to receive real-time guidance and feedback. What this paper adds We created a gamified VBL environment by embedding game elements into an instructional video. The experimental results indicated that the gamified video did not significantly increase learners' situational interest but enhanced necessary cognitive load, intrinsic motivation, learning satisfaction, and academic achievement. Interview findings supported these results, revealing that the gamified video effectively reduced unnecessary cognitive load while increasing cognitive efforts toward achieving learning objectives, thereby fostering engaging learning experiences. Implications for practice and/or policy Our attempts to create gamified instructional videos demonstrated how to enhance video lectures through gamification strategies and offered guidance for the design of gamified instructional videos. We also contributed to the exploration of gamification strategies in education and the potential of relatively underexplored gamification elements.N
Efficacy of furanone in reducing the bacterial contamination and marginal bone loss of dental implants
No full textIn two-piece dental implants, gaps at the implant-abutment interface (IAI) allow bacterial contamination, contributing to peri-implantitis and marginal bone loss (MBL). This study investigates the clinical efficacy of (5Z)-4-bromo-5-(bromomethylene)-2(5 H)-furanone (furanone), a quorum sensing inhibitor, for mitigating bacterial contamination and MBL around dental implants. Dental implants with dog's bacteria and various concentrations of furanone were incubated anaerobically for 7 days to evaluate the anti-bacterial effect of furanone, and bacterial quantification was performed in vitro. The mandibular premolars and molars of three mongrel dogs were extracted three months before implant placement. After the implant fixture was placed, furanone and/or bacteria were added to the inner space of the fixture and connected with a healing abutment. The MBL was assessed by soft X-ray microscopy after 0, 2, 4, 8, and 16 weeks of implant placement. Furanone (20 and 30 mM) significantly inhibited bacterial growth at the IAI in vitro. The MBL at the IAI by bacterial contamination was reduced with furanone (20 mM) in vivo. Bacterial contamination at the IAI causes a substantial MBL, which can be effectively mitigated by furanone, thereby highlighting its potential as an antibacterial agent for reducing MBL for the long-term survival of the dental implants.Y
The Impact of Seoul-Yangyang Expressway on Local Economy
No full text본 연구는 성향 점수 매칭-이중차분법을 이용하여 서울양양고속도로 동홍천-양양 구간 개통의 효과를 분석하였다. 서울양양고속도로 개통으로 강원 북부 지역 전반에서 1인당 지방세는 17.2%, 사업체 수는 2.5%, 종사자 수는 5.6% 증가하고, 이러한 긍정적 효과는 내륙 지역보다 해안 지역에서 더 큰 것으로 추정되었다. 구체적으로 제조업 부문에 대한 파급효과는 내륙 지역을 중심으로 발생한 데 반해, 관광 관련 서비스업에서의 효과는 해안 지역에 편중되어 있었다. 그러나 제조업 비중이 작고 서비스업 비중이 큰 강원 지역의 특성으로 인해 전반적인 고속도로 효과는 해안 지역에서 더 크고 유의하게 나타났다고 할 수 있다.N
Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration
No full textIn regenerative medicine, extracellular vesicles (EVs) possess the potential to repair injured cells by delivering modulatory factors. However, the therapeutic effect of EVs in large-scale tissue defects, which are subject to prolonged timelines for tissue architecture and functional restoration, remains poorly understood. In this study, we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin (GelTA) that can be in-situ crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers (hiPSCmyofibers) and hiPSC-muscle precursor cells. This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix. Secreted EVs from the hiPSC-myofibers contain specific microRNAs, potentially improving myogenesis and angiogenesis. Herein, we demonstrate increased myogenic markers and fusion/differentiation indexes through the combinatory effects of EVs and integrin-mediated adhesions in the 3D matrix. Furthermore, we observe a unique impact of EVs, which aid in maintaining the viability and phenotype of myofibers under harsh environments. The hybrid hydrogel in-situ crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains. Later, we confirmed a combinational effect, whereby muscle tissue regeneration and functional restoration were improved, via an in vivo murine volumetric muscle loss model.Y
Price-Fixing Cartels and Firm Innovation
No full textThis paper examines the relationship between price-fixing cartels and firm innovation using a data set encompassing all 461 cartel cases and 1,818 firms identified in the United States in the years 1975-2016. A difference-in-differences estimation reveals a positive relationship between collusion and innovation. Colluding firms exhibited increases of 28% in patent filings, 20% in top-quality patents, and 16% in research and development investment. Innovation breadth also expanded by 16%, suggesting that firms explored new technological areas. Once cartels were dissolved, innovation activities reverted to precollusion levels. The effect varied across industries and was more pronounced in fastgrowing and patent-intensive industries, underscoring the importance of technological opportunities. Further, the umbrella pricing effect that also benefits noncolluding competitors offers a unique opportunity to unpack mechanisms. Results reveal that the extra financial resources account for at least a quarter of the effect with stronger cartels exhibiting more pronounced effects. Specifically, firms that relied more on internal financing before collusion and that generated higher revenues during collusion showed a greater effect; no evidence was found of capital reallocation within firms. As much as the remaining three quarters of the effect can be attributed to managerial expectations of future profitability. These findings offer insights for managers and policymakers aiming to foster novel innovation although careful interpretation is required given the heterogeneous effects.N
Attribute-based Subsidy Can Affect Consumers BEV Purchase Decision
No full textWe examine the effectiveness of government financial subsidies on battery electric vehicle (BEV) purchasing behavior using a discrete choice model. By optimizing a representative consumers decision-making model, we demonstrate that the effectiveness of financial subsidies depend on the price elasticity of BEV demand. By analyzing a dataset of individual consumers BEV purchase records, we validate our theoretical argument that financial subsidies can encourage consumers to choose eco-friendly BEV models when demand is price elastic. Our findings reveal that South Korean central government subsidies, tailored to the environmental characteristics of EVs, positively influence the sales of eco-friendly BEV models in a price-elastic market. Our results imply that governments should carefully design subsidy policies based on the price elasticity of BEV model demand to maximize their environmental impact
Sterilizable vertical n-type organic electrochemical transistors for skin-conformal ECG monitoring
No full textThe development of stable, high-performance epidermal biosignal monitoring devices is critical for advancing wearable healthcare technologies. Here, we present a novel electrochemical transistor-based biosignal sensor utilizing a 4-terminal vertical Corbino configuration and an n-doped poly(benzodifurandione) (n-PBDF) polymer. The 4-terminal device configuration effectively reduces the parasitic resistance, enabling a high transconductance of 374 mS at a low operational voltage, and one of the highest reported mu C* values of 1787 F cm- 1 V- 1 s-1 for n-type OECTs. In addition, this device achieves exceptional operational stability, maintaining consistent performance over extended periods, and demonstrates a superior shelf-life stability under ambient conditions. Furthermore, the sensor exhibits robust sterilization capabilities, withstanding both UV and thermal sterilization processes without performance degradation. Mechanical flexibility, a key requirement for on-skin applications, is ensured by the intrinsic properties of the n-PBDF polymer and the ultra-thin device architecture. The combination of these features makes this device an ideal candidate for monitoring of biosignals such as electrocardiograms, addressing practical challenges in wearable biosensing technologies.N