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In the burgeoning landscape of blockchain technologies, the quest for a robust and comprehensive evaluation framework remains an exigent challenge. This study introduces an unprecedented methodology that synergizes the common vulnerability scoring system (CVSS) and the weighting mechanism to evaluate blockchain platforms across the multiple dimensions of mainnet, fungible tokens, and non-fungible tokens, using miscellaneous criteria such as legal compliance and proprietary technology. CVSS is employed to perform a quantitative assessment of blockchain-specific vulnerabilities across various sub-factors, thereby establishing an empirical foundation. Subsequently, the weighting mechanism is used to effectively translating qualitative insights into quantifiable metrics. The introduction of this methodological framework is particularly timely and necessary considering the rapidly evolving landscape of blockchain technology. It promises to standardize the evaluation process, providing a robust foundation for future research, policy-making, and technological advancements in the blockchain domain. Consequently, our study not only fills a critical gap in the current literature but also paves the way for a more systematic and informed approach to blockchain assessment. This dual-tiered approach not only ensures a balanced evaluation, capturing both mechanistic intricacies and human subjectivity, but also renders a highly adaptable and scalable framework. The proposed methodology is anticipated to significantly contribute to the standardization of blockchain evaluation, thereby fostering informed decision-making among stakeholders and catalyzing advancements in the blockchain ecosystem.

Excessive medical waste is generated in various medical facilities, especially post-Covid. Recently, sterilization-based shredding systems are being widely used to treat medical waste; however, such systems are commonly over-designed, due to load variation among various treatment facilities. To overcome this challenge, a data-driven surrogate model framework is proposed to perform sensitivity analysis and design optimization based on different loading environments and capacity requirements. The stress estimation surrogate model was generated using the Latin hypercube sampling (LHS), which can represent the overall information of the design area with a limited sample. Furthermore, the data-driven model significantly reduced the computational time as increased numbers of samples were generated from the data-driven surrogate model, instead of finite element analysis (FEA). Two distinct design capacities of the shredding system were used for assessing the effectiveness of the present framework. The results demonstrated that surrogate model-based sensitivity analysis is an efficient approach to developing system designs based on various input and output conditions. The proposed approach mitigates the tremendous potential of the surrogate model, significantly reduces computational costs associated with sensitivity analysis, and yields promising accuracy for the optimization process. This method suggests a computationally efficient optimization method for different shredding capacities. Additionally, the proposed method does not remain at simply optimizing the existing system but provides optimization values for various capacity systems using the data of the existing design, therefore it can be applied to any mechanical system for designing an optimized and compact system.

The RV144 Thai phase III clinical trial’s canarypox–protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

Abstract This study examined the influence of the crystallinity of added nano-alumina on the sulfate resistance of ordinary Portland cement (OPC) paste. Two crystalline types of nano-aluminas (α-and γ-phase) were incorporated in cement pastes, which were exposed to sulfate solution. In the results, both paste samples having α- and γ-phase aluminas had accelerated compressive strength loss and increased length expansion compared to the sample without alumina addition. In particular, the rapidly decreased dynamic elastic modulus of the nano-alumina added samples postulates the greatly increased internal stress likely by the increased formation of volume expansive reaction products, such as ettringite, which was supported by the XRD and TG results. The greater ettringite formation in the nano-alumina added samples was likely due to reactive AH3 (=Al(OH)3) gel formation as the higher consumption degree of portlandite in the alumina added samples indirectly indicates the active AH3 gel formation, resulting in additional ettringite formation from the reaction of AH3 with Na2SO4 solution. A further degree of sulfate attack was observed in the γ-alumina added sample for the long-term Na2SO4 exposure (180 days) mainly due to the greater degree of gypsum formation inducing more internal expansive stress compared to the α-alumina added sample.

This study utilizes Thermal Infrared (TIR) imaging technology to detect hotspots in photovoltaic (PV) modules of solar power plants. Unmanned aerial vehicle (UAV)-based TIR imagery is crucial for efficiently analyzing fault detection in solar power plants. This research explores optimal operational parameters for generating high-quality TIR images using UAV technology. In addition to existing variables such as humidity, emissivity, height, wind speed, irradiance, and ambient temperature, newly considered variables including the angle of incidence between the target object and the thermal infrared camera are analyzed for their impact on TIR images. Based on the solar power plant’s tilt (20°) and the location coordinate data of the hotspot modules, the inner and outer products of the vectors were used to obtain the normal vector and angle of incidence of the solar power plant. It was discovered that the difference between measured TIR temperature data and Land Surface Temperature (LST) data varies with changes in the angle of incidence. The analysis presented in this study was conducted using multiple regression analysis to explore the relationships between dependent and independent variables. The Ordinary Least Squares (OLS) regression model employed was able to explain 63.6% of the variability in the dependent variable. Further, the use of the Condition Number (Cond. No.) and the Variance Inflation Factor (VIF) revealed that the multicollinearity among all variables was below 10, ensuring that the independence among variables was well-preserved while maintaining statistically significant correlations. Furthermore, a positive correlation was observed with the actual measured temperature values, while a negative correlation was observed between the TIR image data values and the angle of incidence. Moreover, it was found that an angle of incidence between 15° and 20° yields the closest similarity to LST temperature data. In conclusion, our research emphasizes the importance of adjusting the angle of incidence to 15–20° to enhance the accuracy of TIR imaging by mitigating overestimated TIR temperature values.

Based on the paradigm shift in modern warfare, ground forces conduct pilot operations of wireless unmanned maneuvering systems, such as tactical drones, in the form of manned and unmanned cooperative tactics after deploying the relevant systems in the battlefield. However, security considerations for relevant systems are limited to the scope of using only the existing end-to-end encryption and public key authentication modules, and no defense strategy to actively respond to specialized cyber-electronic warfare threats has been officially established. To drastically reduce both the potential attack surface and security vulnerabilities of drones employed in network-centric-warfare, a proactive defense technology that expires the effectiveness of attacks by avoiding invasive action at the target is expected to be essential. Accordingly, this paper proposes the concept of active moving-target-defense (MTD), an element of cyber deception that minimizes the rate of success of cyber-attacks while conversely maximizing both defense predominance and attack complexity asymmetrically, exclusive according to partially observable Markov decision process (POMDP)-based threat modeling that considers both the internal and external operation sequences of target drones. To optimally design the proposed drone-type MTD based on the Pareto frontier, we additionally advanced and simulated a drone-based defensive deception game framework (D3GF), which represents a general-sum combat framework reflecting decision logics such as the perfect Bayesian Nash equilibrium, stochastic Stackelberg, and partial signal game. This study was conducted to compare and calculate the efficiencies of the drone-type MTD’s deceptive defense, which had not been considered in prior studies, by unique environmental features inside and outside the drone. Furthermore, we conducted a detailed performance evaluation considering game metrics based on sensitivity analysis. Hereafter, the drone-type MTD will be extended into an actual active drone protection technology combining cyber flare-type avoidance strategies and cyber camouflage-type disarrangement strategies by expanding its optimization domain as a hypergame, while integrating it with drone decoy elements.

The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

This study presents a series of structured and adaptive processes aimed at tracking and verifying transactions recorded on the blockchain. Permissioned blockchains are employed across diverse enterprises for various purposes, including data recording, management, the utilization of blockchain services, and authentication. However, the processes of data tracking and transactions incur substantial resource and time expenditure. Furthermore, there is potential for information asymmetry within the blockchain ledger due to data breach attacks. Consequently, we propose a contract structured as a hash chain to mitigate resource and time consumption in the tracking and verification processes by organizing transaction hash values and content in a hash chain format based on cryptography. We generate a hash chain for the recorded transactions along the process line and expedite the tracking and verification process by navigating the relevant hash chain. This approach achieves faster and more accurate tracking procedures compared to conventional transaction tracking processes, simultaneously maintaining data symmetry within the blockchain ledger. We conduct a comparative analysis of a contract-based hash-chain-employing structure and two contracts related to tracking in terms of tracking time, CPU usage, and network traffic, among other metrics. The findings suggest that structuring transaction data in the form of a hash chain significantly enhances the efficiency and integrity of the data-tracking and verification processes. Consequently, in this study, we advocate for the adoption of contracts based on the hash chain format when leveraging the blockchain for tracking and verification purposes across various institutions.

Sepsis, characterized by an uncontrolled host inflammatory response to infections, remains a leading cause of death in critically ill patients worldwide. Sepsis-associated thrombocytopenia (SAT), a common disease in patients with sepsis, is an indicator of disease severity. Therefore, alleviating SAT is an important aspect of sepsis treatment; however, platelet transfusion is the only available treatment strategy for SAT. The pathogenesis of SAT involves increased platelet desialylation and activation. In this study, we investigated the effects of Myristica fragrans ethanol extract (MF) on sepsis and SAT. Desialylation and activation of platelets treated with sialidase and adenosine diphosphate (platelet agonist) were assessed using flow cytometry. The extract inhibited platelet desialylation and activation via inhibiting bacterial sialidase activity in washed platelets. Moreover, MF improved survival and reduced organ damage and inflammation in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. It also prevented platelet desialylation and activation via inhibiting circulating sialidase activity, while maintaining platelet count. Inhibition of platelet desialylation reduces hepatic Ashwell–Morell receptor-mediated platelet clearance, thereby reducing hepatic JAK2/STAT3 phosphorylation and thrombopoietin mRNA expression. This study lays a foundation for the development of plant-derived therapeutics for sepsis and SAT and provides insights into sialidase-inhibition-based sepsis treatment strategies.

ABSTRACT: The ride-hailing platform offers the business model of the on-demand business ecosystem in the era of the sharing economy. Platforms such as Uber, Lyft, and DiDi have become popular worldwide and established a strong position in urban transportation. This paper presents a case study analyzing the fierce competition between Uber and DiDi in the Chinese ride-hailing market. First, employing the canvas framework, we show the core characteristics of the business models of the two platforms. Our analysis and comparisons of the strategic positioning and implementation concerning the building blocks of canvas ascribe the success factors of DiDi and the causes of Uber’s failure. Although both Uber and DiDi provide similar service offerings for diverse market segments, Uber’s mismatches between its strategic focus on the premium segment and service operations proved to be a mistake. On the other hand, DiDi managed its business more efficiently by providing a wide range of service offerings while leveraging the two-sided market. As a result, DiDi has grown successfully as a one-stop transportation platform, which is well-suited to the Chinese market. This study provides meaningful insights into business model innovations in the sharing economy and implications for the evolution of future transportation platforms.

ABSTRACT HIV-1 cure strategies aiming to eliminate persistent infected cell reservoirs are hampered by a poor understanding of cells harboring viral DNA in vivo. We describe a novel method to identify, enumerate, and characterize in detail individual cells infected in vivo using a combination of single-cell multiplexed assays for integrated proviral DNA, quantitative viral and host gene expression, and quantitative surface protein expression without any in vitro manipulation. Latently infected CD4+ T cells, defined as harboring integrated provirus in the absence of spliced viral mRNA, were identified from macaque lymph nodes during acute, chronic, and combination antiretroviral therapy (cART)-suppressed simian immunodeficiency virus (SIV) infection. Latently infected CD4+ T cells were most abundant during acute SIV (~8% of memory CD4+ T cells) and persisted in chronic and cART-suppressed infection. Productively infected cells actively transcribing viral mRNA, by contrast, were much more labile and declined substantially between acute and chronic or cART-suppressed infection. Expression of most surface proteins and host genes was similar between latently infected cells and uninfected cells. Elevated FLIP mRNA and surface CD3 expression among latently infected cells suggest increased survival potential and capacity to respond to T cell receptor stimulation. These findings point to a large pool of latently infected CD4+ T cells established very early in acute infection and upregulated host factors that may facilitate their persistence in vivo, both of which pose potential challenges to eliminating HIV-1 reservoirs. IMPORTANCE Effective combination antiretroviral therapy controls HIV-1 infection but fails to eliminate latent viral reservoirs that give rise to viremia upon treatment interruption. Strategies to eradicate latently infected cells require a better understanding of their biology and distinguishing features to promote their elimination. Tools for studying these cells from patients are currently limited. Here, we developed a single-cell method to identify cells latently infected in vivo and to characterize these cells for expression of surface proteins and host genes without in vitro manipulation, capturing their in vivo state from SIV-infected macaques. Host factors involved in cell survival and proliferation were upregulated in latently infected cells, which were abundant in the earliest stages of acute infection. These studies provide insight into the basic biology of latently infected cells as well as potential mechanisms underlying the persistence of HIV-1/SIV reservoirs to inform development of novel HIV-1 cure strategies.

Countless endeavors have been undertaken to address the Byzantine Generals Problem, a generalization of the Two Generals Problem. The emergence of proof of work (PoW) for Bitcoin has led to various consensus algorithms diverging, and comparable existing consensus algorithms are being gradually utilized interchangeably, or only developed for each specific application domain. Our approach employs an evolutionary phylogeny method to classify blockchain consensus algorithms based on their historical development and current usage. To demonstrate the relatedness and lineage of distinct algorithms, as well as to support the recapitulation theory, which posits that the evolutionary history of its mainnets is mirrored in the development of an individual consensus algorithm, we present a taxonomy. We have created a comprehensive classification of past and present consensus algorithms that serves to organize this swift consensus algorithm evolution period. By recognizing similarities, we have compiled a list of different verified consensus algorithms and performed clustering on over 38 of these. Our new taxonomic tree presents five taxonomic ranks, including the evolutionary process and decision-making method, as a technique for analyzing correlation. Through the examination of the evolution and utilization of these algorithms, we have developed a systematic and hierarchical taxonomy that enables the grouping of consensus algorithms into distinct categories. The proposed method classifies various consensus algorithms according to taxonomic ranks and aims to reveal the direction of research on the application of blockchain consensus algorithms for each domain.

Current railroad customs clearance systems are problematic in that the movement of trains is occasionally restricted for extended periods during inspections to verify cargo integrity at customs clearance. Consequently, significant human and material resources are consumed to obtain customs clearance to the destination, considering different processes exist for cross-border trade. Therefore, we developed a cross-border blockchain-based non-stop customs clearance (NSCC) system to address these delays and reduce resource consumption for cross-border trains. The integrity, stability, and traceability of blockchain technology are used to construct a stable and reliable customs clearance system to address these problems. The proposed method connects diverse trade and customs clearance agreements in a single blockchain network, which ensures integrity and minimal resource consumption, and includes railroads, freight vehicles, and transit stations in addition to the current customs clearance system. The integrity and confidentiality of customs clearance data are protected using sequence diagrams and the blockchain to strengthen the resilience of the NSCC process against attacks; the blockchain-based NSCC system structurally verifies the attack resilience based on matching sequences. The results confirm that the blockchain-based NSCC system is time- and cost-efficient compared with the current customs clearance system and offers improved attack resilience.

Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

Surface coating approaches for silicon (Si) have demonstrated potential for use as anodes in lithium-ion batteries (LIBs) to address the large volume change and low conductivity of Si. However, the practical application of these approaches remains a challenge because they do not effectively accommodate the pulverization of Si during cycling or require complex processes. Herein, Si-embedded titanium oxynitride (Si-TiON) was proposed and successfully fabricated using a spray-drying process. TiON can be uniformly coated on the Si surface via self-assembly, which can enhance the Si utilization and electrode stability. This is because TiON exhibits high mechanical strength and electrical conductivity, allowing it to act as a rigid and electrically conductive matrix. As a result, the Si-TiON electrodes delivered an initial reversible capacity of 1663 mA h g−1 with remarkably enhanced capacity retention and rate performance.

The aim of this study is to synthesize phenethyl-conjugated chitosan oligosaccharide (COS) (abbreviated as ChitoPEITC) conjugates and then fabricate chlorin E6 (Ce6)-incorporated nanophotosensitizers for photodynamic therapy (PDT) of HCT-116 colon carcinoma cells. PEITC was conjugated with the amine group of COS. Ce6-incorporated nanophotosensitizers using ChitoPEITC (ChitoPEITC nanophotosensitizers) were fabricated by dialysis method. 1H nuclear magnetic resonance (NMR) spectra showed that specific peaks of COS and PEITC were observed at ChitoPEITC conjugates. Transmission electron microscope (TEM) confirmed that ChitoPEITC nanophotosensitizers have spherical shapes with small hydrodynamic diameters less than 200 nm. The higher PEITC contents in the ChitoPEITC copolymer resulted in a slower release rate of Ce6 from nanophotosensitizers. Furthermore, the higher Ce6 contents resulted in a slower release rate of Ce6. In cell culture study, ChitoPEITC nanophotosensitizers showed low toxicity against normal CCD986Sk human skin fibroblast cells and HCT-116 human colon carcinoma cells in the absence of light irradiation. ChitoPEITC nanophotosensitizers showed a significantly higher Ce6 uptake ratio than that of free Ce6. Under light irradiation, cellular reactive oxygen species (ROS) production of nanophotosensitizers was significantly higher than that of free Ce6. Especially, PEITC and/or ChitoPEITC themselves contributed to the production of cellular ROS regardless of light irradiation. ChitoPEITC nanophotosensitizers showed significantly higher PDT efficacy against HCT-116 cells than that of free Ce6. These results indicate that ChitoPEITC nanophotosensitizers have superior potential in Ce6 uptake, ROS production and PDT efficacy. In the HCT-116 cell-bearing mice tumor-xenograft model, ChitoPEITC nanophotosensitizers efficiently inhibited growth of tumor volume rather than free Ce6. In the animal imaging study, ChitoPEITC nanophotosensitizers were concentrated in the tumor tissue, i.e., fluorescence intensity in the tumor tissue was stronger than that of other tissues. We suggest that ChitoPEITC nanophotosensitizers are a promising candidate for the treatment of human colon cancer cells.

Antibodies that mediate non-neutralizing functions play an important role in the immune response to Ebola virus (EBOV) and are thought to impact disease outcome. EBOV has also been associated with long term sequelae in survivors, however, the extent to which antibodies that mediate non-neutralizing functions are associated with the development of these sequelae is unknown. Here, the presence of antibodies mediating different effector functions and how they relate to long-term sequelae two years after the 2007 Bundibugyo Ebola virus (BDBV) outbreak was investigated. The majority of survivors demonstrated robust antibody effector functional activity and demonstrated persistent polyfunctional antibody profiles to the EBOV glycoprotein (GP) two years after infection. These functions were strongly associated with the levels of GP-specific IgG1. The odds of developing hearing loss, one of the more common sequelae to BDBV was reduced when antibodies mediating antibody dependent cellular phagocytosis (ADCP), antibody dependent complement deposition (ADCD), or activating NK cells (ADNKA) were observed. In addition, hearing loss was associated with increased levels of several pro-inflammatory cytokines and levels of these pro-inflammatory cytokines were associated with lower ADCP. These results are indicating that a skewed antibody profile and persistent inflammation may contribute to long term outcome in survivors of BDBV infection

Purpose Watson for Oncology (WFO) is a computing system for considering treatment option with patients. The aim of this study is to determine the concordance rate of WFO and tumor board in treatment options of breast cancer. Methods One hundred and seventy breast cancer patients who were treated at Gachon University Gil Medical Center (GMC) from December 2016 to March 2018 were investigated. “Concordance” is defined that treatment provided by GMC tumor board and WFO-provided treatments (Recommend or For Consideration) were coincide. “Discordance” is defined that treatment provided by GMC tumor board and WFO-provided treatments (Not Recommended or Not Available) were coincide. Results In chemotherapy, of the total 170 patients, 23 patients were excluded, and the concordance rate was compared in 147 patients. Concordance rate was 93% (136/147). In the 11 patients who were discordant, seven patients complied with the treatment proposed by GMC tumor board due to insurance problems and age, and two patients did not follow the treatment proposed by WFO due to pregnancy and patient’s choice, and one patient chose a treatment determined by WFO, last one patient was not treated with chemotherapy because it was not considered to be clinically necessary. In radiotherapy, the overall agreement rate was as high as 99% (147/148). Conclusion Through this study, we found that many of the treatment proposals provided by WFO are highly reliable. Although the overall agreement is high in the radiotherapy regimen, the indication for radiotherapy by WFO is more aggressive and hypofractionated high dose intensity radiotherapy is growing trend by WFO.

In this study, the structural characteristics of malware distribution networks (MDNs) were examined and the network centrality of the relationships between websites containing malware, infection sites, intermediate connection sites, and initial connection sites were analyzed. The core malware sites within MDNs that contribute to the success of cyberattacks were identified, and the overall risk of the MDNs, which changes dynamically, was examined quantitatively to predict additional attacks. As such, real-time security events occurring in the information security systems of target organizations were collected and analyzed, and different types of security intelligence were assessed to recreate various MDNs. In addition, the risk levels of malicious URLs, IPs, etc. in MDNs were analyzed continuously over time, and a model suitable for predicting potential attack times was developed. The developed model identified the characteristics of potential future cyberattacks based on the analyzed initial MDN risk level, as well as the connectivity of and malware associated with the MDN, which change over time, thereby maintaining an average prediction accuracy of 94.9% over one week.

As the demand for mobile traffic is growing, radio frequency bandwidths often become insufficient for guaranteeing specific performance. Utilizing unlicensed 5 GHz broadband bandwidths, the LWA system enables the synergistic use of LTE and WiFi systems based on link aggregation techniques, without critical deterioration of service quality. This provides considerable benefits to the mobile operators when they successfully operate two networks and maintain an optimal balance in managing network resources. This study addresses balancing and fairness for newly emerging LWA systems. In particular, we develop a two-stage LWA access framework based on the Nash bargaining game. The framework further improves fairness and efficiency in the LTE-WiFi resource utilization by incorporating user segmentations on the basis of user characteristics, such as service contract and usage patterns. Extensive experiments using a network simulator with an NS-3 unlicensed band produce good performance in terms of fairness and efficiency. The proposed scheme demonstrates better outcomes compared to the existing methods while concurrently using radio resources in the LWA system in a fair manner. Moreover, our approach presents a simple and fast decision-making process and requires simple user profiles-contract status and traffic generation history. Therefore, the proposed scheme is far lighter and more flexible than traditional approaches that require extensive information exchanges between heterogeneous networks.

In inborn errors of metabolism, such as amino acid breakdown disorders, loss of function mutations in metabolic enzymes within the catabolism pathway lead to an accumulation of the catabolic intermediate that is the substrate of the mutated enzyme. In patients of such disorders, dietarily restricting the amino acid(s) to prevent the formation of these catabolic intermediates has a therapeutic or even entirely preventative effect. This demonstrates that the pathology is due to a toxic accumulation of enzyme substrates rather than the loss of downstream products. Here, we provide an overview of amino acid metabolic disorders from the perspective of the ‘toxic metabolites’ themselves, including their mechanism of toxicity and whether they are involved in the pathology of other disease contexts as well. In the research literature, there is often evidence that such metabolites play a contributing role in multiple other nonhereditary (and more common) disease conditions, and these studies can provide important mechanistic insights into understanding the metabolite-induced pathology of the inborn disorder. Furthermore, therapeutic strategies developed for the inborn disorder may be applicable to these nonhereditary disease conditions, as they involve the same toxic metabolite. We provide an in-depth illustration of this cross-informing concept in two metabolic disorders, methylmalonic acidemia and hyperammonemia, where the pathological metabolites methylmalonic acid and ammonia are implicated in other disease contexts, such as aging, neurodegeneration, and cancer, and thus there are opportunities to apply mechanistic or therapeutic insights from one disease context towards the other. Additionally, we expand our scope to other metabolic disorders, such as homocystinuria and nonketotic hyperglycinemia, to propose how these concepts can be applied broadly across different inborn errors of metabolism and various nonhereditary disease conditions.

There is an increased interest in designing cost-effective lightweight components to meet modern design requirements of improving cost and performance efficiency. This paper describes a significant effort to optimize the medical waste shredder blade through weight reduction by increasing material efficiency. The blade computer-aided design (CAD) model was produced through reverse engineering and converted to the finite element (FE) model to characterize von Mises stress and displacement. The obtained stress characteristics were introduced into the FE-SAFE for fatigue analysis. Furthermore, the FE model was analyzed through topological optimization using strain energy as the objective function while implementing the volume constraint. To obtain the optimal volume constraint for the blade model, several 3D numerical test cases were performed at various volume constraints. A significant weight reduction of 24.7% was observed for the 80% volume constraint (VC80). The FE analysis of optimal geometry indicated a 6 MPa decrease in the von Mises and a 14.5% increase in the fatigue life. Therefore, the proposed optimal design method demonstrated to be effective and easy to apply for the topology optimization of the shredder blade and has significantly decreased the structural weight without compromising the structural integrity and robustness.

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

Currently, in the field of military modernization, tactical networks using advanced unmanned aerial vehicle systems, such as drones, place an emphasis on proactively preventing operational limiting factors produced by cyber-electronic warfare threats and responding to them. This characteristic has recently been highlighted as a key concern in the functioning of modern network-based combat systems in research on combat effect analysis. In this paper, a novel discrete-event-system-specification-based cyber-electronic warfare M&S (D-CEWS) was first proposed as an integrated framework for analyzing communication effects and engagement effects on cyber-electronic warfare threats and related countermeasures that may occur within drones. Accordingly, for the first time, based on communication metrics in tactical ad hoc networks, an analysis was conducted on the engagement effect of blue forces by major wireless threats, such as multi-layered jamming, routing attacks, and network worms. In addition, the correlations and response logics between competitive agents were also analyzed in order to recognize the efficiency of mutual engagements between them based on the communication system incapacitation scenarios for diverse wireless threats. As a result, the damage effect by the cyber-electronic warfare threat, which could not be considered in the existing military M&S, could be calculated according to the PDR (packet delivery ratio) and related malicious pool rate change in the combat area, and the relevance with various threats by a quantifiable mission attribute given to swarming drones could also be additionally secured.

To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.

Nutrient utilization and energy metabolism are critical for the maintenance of cellular homeostasis. A mutation in the C9orf72 gene has been linked to the most common forms of neurodegenerative diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we have identified an evolutionarily conserved function of C9orf72 in the regulation of the transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes that is negatively modulated by mTORC1. Loss of the C. elegans orthologue of C9orf72, ALFA-1, causes the nuclear translocation of HLH-30/TFEB, leading to activation of lipolysis and premature lethality during starvation-induced developmental arrest in C. elegans. A similar conserved pathway exists in human cells, in which C9orf72 regulates mTOR and TFEB signaling. C9orf72 interacts with and dynamically regulates the level of Rag GTPases, which are responsible for the recruitment of mTOR and TFEB on the lysosome upon amino acid signals. These results have revealed previously unknown functions of C9orf72 in nutrient sensing and metabolic pathways and suggest that dysregulation of C9orf72 functions could compromise cellular fitness under conditions of nutrient stress.

Cell protrusion dynamics are heterogeneous at the subcellular level, but current analyses operate at the cellular or ensemble level. Here the authors develop a computational framework to quantify subcellular protrusion phenotypes and reveal the underlying actin regulator dynamics at the leading edge.

Natural killer (NK) cells are important for eliminating cells under stress or infected by virus, and may have a function in anti-HIV immunity. Here the authors show that different NK-activating stimuli induce distinct transcriptional fingerprints in human NK cells that are analogous to changes caused by HIV vaccination or chronic infection.

The aim of this study is to fabricate reactive oxygen species (ROS)-sensitive nanoparticles composed of succinyl β-cyclodextrin (bCDsu), memantine and thioketal linkages for application in Alzheimer’s disease, and to investigate the suppression of N-methyl-d-aspartate (NMDA) receptor 1 (NMDAR1) in cells. Thioketal diamine was attached to the carboxyl group of bCDsu to produce thioketal-decorated bCDsu conjugates (bCDsu-thioketal conjugates) and memantine was conjugated with thioketal dicarboxylic acid (memantine-thioketal carboxylic acid conjugates). Memantine-thioketal carboxylic acid conjugates were attached to bCDsu-thioketal conjugates to produce bCDsu-thioketal-memantine (bCDsuMema) conjugates. SH-SY5Y neuroblastoma cells and U87MG cells were used for NMDAR1 protein expression and cellular oxidative stress. Nanoparticles of bCDsuMema conjugates were prepared by means of a dialysis procedure. Nanoparticles of bCDsuMema conjugates had small particle sizes less than 100 nm and their morphology was found to be spherical in transmission electron microscopy observations (TEM). Nanoparticles of bCDsuMema conjugates responded to H2O2 and disintegrated or swelled in aqueous solution. Then, the nanoparticles rapidly released memantine according to the concentration of H2O2. In an in vivo animal imaging study, thioketal-decorated nanoparticles labelled with fluorescent dye such as chlorin e6 (Ce6) showed that the fluorescence intensity was stronger in the brain than in other organs, indicating that bCDsuMema nanoparticles can efficiently target the brain. When cells were exposed to H2O2, the viability of cells was time-dependently decreased. Memantine or bCDsuMema nanoparticles did not practically affect the viability of the cells. Furthermore, a western blot assay showed that the oxidative stress produced in cells using H2O2 increased the expression of NMDAR1 protein in both SH-SY5Y and U87MG cells. Memantine or bCDsuMema nanoparticles efficiently suppressed the NMDAR1 protein, which is deeply associated with Alzheimer’s disease. Fluorescence microscopy also showed that H2O2 treatment induced green fluorescence intensity, which represents intracellular ROS levels. Furthermore, H2O2 treatment increased the red fluorescence intensity, which represents the NMDAR1 protein, i.e., oxidative stress increases the expression of NMDAR1 protein level in both SH-SY5Y and U87MG cells. When memantine or bCDsuMema nanoparticles were treated in cells, the oxidative stress-mediated expression of NMDAR1 protein in cells was significantly decreased, indicating that bCDsuMema nanoparticles have the capacity to suppress NMDAR1 expression in brain cells, which has relevance in terms of applications in Alzheimer’s disease.

Illegally filmed images, the sharing of non-consensually filmed images over social media, and the secret recording and distribution of celebrity images are increasing. To catch distributors of illegally filmed images, many investigation techniques based on an analysis of the file attribute information of the original images have been introduced. As forensic science advances, various types of anti-forensic technologies are being produced, requiring investigators to open and analyze all videos from the suspect’s storage devices, raising the question of the invasion of privacy during the investigation. The suspect can even file a lawsuit, which makes issuing a warrant and conducting an investigation difficult. Thus, it is necessary to detect the original and manipulated images without needing to directly go through multiple videos. We propose an optimization analysis and detection method for extracting original and manipulated images from seized devices of suspects. In addition, to increase the detection rate of both original and manipulated images, we suggest a precise measurement approach for comparative thresholds. Thus, the proposed method is a new digital forensic methodology for comparing and identifying original and manipulated images accurately without the need for opening videos individually in a suspect’s mobile device.

This study aimed to alleviate the theoretical limitations of existing moving target defense (MTD) and decoy concepts and improve the efficiency of defensive deception technology within an organization. We present the concept of an open-source intelligence (OSINT)-based hierarchical social engineering decoy (HS-Decoy) strategy while considering the actual fingerprint of each organization. In addition, we propose a loosely proactive control-based MTD strategy that is based on the intended competitive exposure of OSINT between defenders and attackers. Existing MTDs and decoys are biased toward proactive prevention, in that they only perform structural mutation-based attack avoidance or induce static traps. They also have practical limitations, e.g., they do not consider security characterization of each organizational social engineering attack and related utilization plans, no quantitative deception modeling is performed for the attenuation of the attack surface through exposure to OSINT, and there is no operational plan for optimal MTD and decoy application within the organization. Through the applied deception concepts proposed here, the total attack efficiency was reduced by 287% compared to the existing MTD and decoys, while the artificial deception efficiency dominated by defenders was improved by 382%. In addition, the increase rate of deception overhead was also reduced by 174%, and an optimized deceptive trade-off was also presented. In order to enable an organization to utilize the OSINT concept, statistical error reduction, and MTD mutation cycle-based deceptive selectivity, it was introduced as a loose adaptive mutation rather than a preferential avoidance strategy, and an organization-specific optimization direction was introduced through a combination of HS-Decoy and LPC-MTD. In the future, in order to improve the operational reliability of the HS-Decoy and LPC-MTD-based combined model and standardize threat information for each organization, we intend to advance it into an international standard-based complex architecture and characterize it as game theory.

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal samples, and that this is tightly correlated with the increased expression of the xCT subunits SLC7A11 and SLC3A2. Erastin depletes levels of the antioxidant selenoproteins GPX4 and GPX1 in breast cancer cells by inhibiting xCT-dependent extracellular reduction which is required for selenium uptake and selenocysteine biosynthesis. Unexpectedly, while breast cancer cells are resistant compared to nontransformed cells against oxidative stress inducing drugs, at the same time they are hypersensitive to lipid peroxidation and ferroptosis induced by Erastin or Rsl-3, indicating that they are ‘addicted’ to the xCT/GPX4 axis. Our findings provide a strategic basis for targeting the anti-ferroptotic machinery of breast cancer cells depending on their xCT status, which can be further explored.

CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

Authentication algorithms in the form of cryptographic schemes, such as the Secure Hash Algorithm 1 (SHA-1) and the digital signature algorithm (DSA), specified in the current variable message format (VMF) military standard have numerous reliability-related limitations when applied to tactical data link (TDL) and multi-TDL networks (MTN). This is because TDL and MTN require maximum tactical security, communication integrity, and low network overhead based on many protocol header bits for rapid communication with limited network resources. The application of such authentication algorithms to TDL and MTN in a rapidly changing battlefield environment without reinforcement measures will lead to functional weaknesses and vulnerabilities when high-level digital-covert activities and deception tactics are implemented. Consequently, the existing VMF authentication scheme must be improved to secure transmission integrity, lower network transaction, and receive authentication tactical information in VMF-based combat network radio (CNR) networks. Therefore, in this study, a tactical wireless ad hoc network topology, similar to that of the existing CNRs, is considered, and a lightweight multi-factor hash chain-based authentication scheme that includes a time-based one-time password (T-OTP) for network overhead reduction and terminal authentication is proposed, coupled with exception handling. The proposed method enhances the confidentiality of tactical message exchanges and reduces unnecessary network transactions and transmission bits for authentication flows between real-time military terminals owned by squads, while ensuring robustness in limited battlefields. Based on these approaches, in the future, we intend to increase the authentication reliability between wireless terminals in the Korean variable message format (KVMF)-based CNR networks based on the Korean Army Corps network scenarios.

Event-based system (EBS) is prevalent in various systems including mobile cyber physical systems (MCPSs), Internet of Things (IoT) applications, mobile applications, and web applications, because of its particular communication model that uses implicit invocation and concurrency between components. However, an EBS’s non-determinism in event processing can introduce inherent security vulnerabilities into the system. Multiple types of attacks can incapacitate and damage a target EBS by exploiting this event-based communication model. To minimize the risk of security threats in EBSs, security efforts are required by determining the types of security flaws in the system, the relationship between the flaws, and feasible techniques for dealing with each flaw. However, existing security flaw taxonomies do not appropriately reflect the security issues that originate from an EBS’s characteristics. In this paper, we introduce a new taxonomy that defines and classifies the particular types of inherent security flaws in an EBS, which can serve as a basis for resolving its specific security problems. We also correlate our taxonomy with security attacks that can exploit each flaw and identify existing solutions that can be applied to preventing such attacks. We demonstrate that our taxonomy handles particular aspects of EBSs not covered by existing taxonomies.

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.

Insider threats that occur within organizations cause more serious damage than external threats. However, there are many factors that are difficult to determine, such as the definition, classification, and severity of security breaches; hence, it is necessary to analyze system logs and user behavior-based scenarios within organizations. The reality is that qualitative judgment criteria are different for everyone to apply, and there is no detailed verification procedure to compare them objectively. In this study, realistic insider threats were examined through the definition, classification, and correlation/association analysis of various human–machine logs of acts associated with security breaches that occur in an organization. In addition, a quantitative process and decision-making tool were developed for insider threats by establishing various internal information leakage scenarios. As a result, insider threats were assessed quantitatively and a decision-making process was completed that enabled case analysis based on several insider threat scenarios. This study will enable precise modeling of insider threats that occur in real organizations and will support an objective process and a decision-making system to establish a range of required information for security protection measures.

Highly dispersive molybdenum disulfide nanoflakes (MoS2 NFs), without any phase transition during the exfoliation process, are desirable for full utilization of their semiconductor properties in practical applications. Here, we demonstrate an innovate approach for fabricating MoS2 NFs by using hydrazine-assisted ball milling via the synergetic effect of chemical intercalation and mechanical exfoliation. The NFs obtained have a lateral size of 600–800 nm, a thickness less than 3 nm, and high crystallinity in the 2H semiconducting phase. They form a stable dispersion in various solvents, which will be helpful for many applications, due to the oxygen functional group. To investigate production of a two-dimensional (2D) photodetector, 2D semiconducting MoS2, MoS2–p-Si vertical devices were fabricated, and their optical properties were characterized. The photodiode exhibited consistent responses with excellent photo-switching characteristics with wavelengths of 850, 530, and 400 nm.

This study explored the possibility of using reverse osmosis (RO) reject water as a mixing water for producing cementitious bricks using calcium sulfoaluminate (CSA) cement along with gypsum, and it investigated the changes in the properties of CSA cement pastes when RO reject water was used. The results were compared with those obtained using purified water and seawater. Overall, the use of RO reject water improved the cement paste’s strength. Given that the use of RO reject water very slightly affected ettringite formation but more significantly influenced the Al2O3-Fe2O3-mono (AFm) phases (i.e., monosulfate, kuzelite, and Friedel’s salt) and amorphous aluminum hydroxide (AH3), the strength improvement was likely mainly due to the formation of Friedel’s salt rather than ettringite formation. This study also demonstrated that the use of RO reject water for brick production satisfied the Korean Standards (KS) F 4004 and toxicity characteristic leaching procedure (TCLP); thus, it is recommended to use RO reject water as a mixing water to produce CSA cement bricks for use in construction.

Most recent cyberattacks have employed new and diverse malware. Various static and dynamic analysis methods are being introduced to detect and defend against these attacks. The malware that is detected by these methods includes advanced present threat (APT) attacks, which allow additional intervention by attackers. Such malware presents a variety of threats (DNS, C&C, Malicious IP, etc.) This threat information used to defend against variants of malicious attacks. However, the intelligence that is detected in this manner is used in the blocking policies of information-security systems. Consequently, it is difficult for staff who perform Computer Emergence Response Team security control to determine the extent to which cyberattacks such as malware are a potential threat. Additionally, it is difficult to use this intelligence to establish long-term defense strategies for specific APT attacks or implement intelligent internal security systems. Therefore, a decision-making model that identifies threat sources and malicious activities (MAs) that occur during the static and dynamic analysis of various types of collected malware and performs machine learning based on a quantitative analysis of these threat sources and activities is proposed herein. This model estimates malware risk indices (MRIs) in detail using an analytic hierarchy process to analyze malware and the probabilities of MAs. The analysis results were significant, as the consistency index of the estimated MRI values for 51300 types of malware, which were collected during a specific control period, was maintained at

Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state.

This study explores the combined effect of NaCl and gypsum on the strength of the CaO-activated ground-granulated blast furnace slag (GGBFS) binder system. In the CaO-activated GGBFS system, the incorporation of NaCl without gypsum did not improve the strength of the system. However, with the presence of gypsum, the use of NaCl yielded significantly greater strength than the use of either gypsum or NaCl alone. The presence of NaCl largely increases the solubility of gypsum in a solution, leading to a higher concentration of sulfate ions, which is essential for generating more and faster formations of ettringite in a fresh mixture of paste. The significant strength enhancement of gypsum was likely due to the accelerated and increased formation of ettringite, accompanied by more efficient filling of pores in the system.

We consider a dominant platform provider operating both legacy and new platforms that connects users with suppliers in a two-sided market context. In addition to the typical indirect network effects in the two-sided market, backward compatibility works on the new platform. Thus, users joining the new one can also enjoy the services provided by suppliers using the legacy platform. Users and suppliers are linearly differentiated between two platforms as in the Hotelling model and play a subscription game of choosing one platform at the lower level. The suppliers in the new platform may suffer from congestion, which can be alleviated by platform provider’s investment on the new one. The platform provider also determines price margins for the supplier sides. Our equilibrium (eq.) analysis in the subscription game identifies an interior eq. (coexistence of both platforms in both sides). Though the backward compatibility plays a stabilizing role for the interior eq., its stability is fragile due to the network effects. Rather, some boundary eq.’s, where at least one side tips to the legacy or the new platform, are more likely to be stable. The backward compatibility is a key factor that characterizes the stable boundary eq.’s. The upper stage game is led by the platform provider, which tries to maneuver the system toward one of the stable boundary eq.’s using price margins and investment. The platform provider prefers an all-new boundary eq. when the indirect network effect and the maximum price margin for the new platform are large; thus, it puts a significant investment in the new one. With a small indirect network effect for suppliers, however, the platform provider does not invest in the new platform and choose a separate boundary eq. where two sides split into different platforms. Whether the user side completely tips to the new one (completely separated eq.) or not (partially separated eq.) depends on the backward compatibility. The relative advantage of the all-new eq. over the separate eq.’s in terms of social welfare from both sides depends on the backward compatibility as well as the indirect network effects for the new platform.

ObjectivesThis research was conducted to identify both the users' service requirements on health information websites (HIWs) and the key functional elements for running HIWs. With the quality function deployment framework, the derived service attributes (SAs) are mapped into the suppliers' functional characteristics (FCs) to derive the most critical FCs for the users' satisfaction.MethodsUsing the survey data from 228 respondents, the SAs, FCs and their relationships were analyzed using various multivariate statistical methods such as principal component factor analysis, discriminant analysis, correlation analysis, etc. Simple and compound FC priorities were derived by matrix calculation.ResultsNine factors of SAs and five key features of FCs were identified, and these served as the basis for the house of quality model. Based on the compound FC priorities, the functional elements pertaining to security and privacy, and usage support should receive top priority in the course of enhancing HIWs.ConclusionsThe quality function deployment framework can improve the FCs of the HIWs in an effective, structured manner, and it can also be utilized for critical success factors together with their strategic implications for enhancing the service quality of HIWs. Therefore, website managers could efficiently improve website operations by considering this study's results.

The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF), a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF) prolyl hydroxylase-2 (PHD-2) was tested by an in vitro von Hippel–Lindau protein (VHL) binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM) assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α), and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1.

Embryonic stem (ES) cells have many of the characteristics of an optimal cell source for cell-replacement therapy. Although the usefulness of the in vitro generation of dopamine (DA)-neural precursors from ES cells has been widely discussed, functional recovery in animal models of Parkinson’s disease is not fully understood. In 6-hydroxydopamine-lesioned rats, apomorphine markedly induced contralateral rotation. Apomorphine-induced rotation was significantly reduced by transplantation of neuron-like cells that had differentiated from mouse ES cells using nicotinamide, but not L-lysine. In addition, methamphetamine-induced ipsilateral rotation was significantly reduced. On the other hand, picrotoxin did not inhibit apomorphine-induced rotational asymmetry. Fluoxetine alone and fenfluramine alone induced slight contralateral rotation and rotation in both directions, respectively, and these effects were similar in transplanted rats. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers. In contrast, immunoreactivities for γ-aminobutyric acid (GABA) and serotonin (5-HT) neurons were not changed. These results suggest that improvement of rotational behavior may be induced predominantly by transplantation of nicotinamide-treated ES cell-derived DA neurons, rather than by changes in the activities of GABA or 5-HT neural systems, in hemiparkinsonian rats. Keywords:: mouse embryonic stem cell, dopaminergic differentiation, transplantation, rat striatum, Parkinson’s disease