This paper is motivated by the success of YouTube, which is attractive to content creators as well as corporations for its potential to rapidly disseminate digital content. The networked structure of ...interactions on YouTube and the tremendous variation in the success of videos posted online lends itself to an inquiry of the role of social influence. Using a unique data set of video information and user information collected from YouTube, we find that social interactions are influential not only in determining which videos become successful but also on the magnitude of that impact. We also find evidence for a number of mechanisms by which social influence is transmitted, such as (i) a preference for conformity and homophily and (ii) the role of social networks in guiding opinion formation and directing product search and discovery. Econometrically, the problem in identifying social influence is that individuals' choices depend in great part upon the choices of other individuals, referred to as the
reflection problem
. Another problem in identification is to distinguish between social contagion and user heterogeneity in the diffusion process. Our results are in sharp contrast to earlier models of diffusion, such as the Bass model, that do not distinguish between different social processes that are responsible for the process of diffusion. Our results are robust to potential self-selection according to user tastes, temporal heterogeneity and the reflection problem. Implications for researchers and managers are discussed.
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•The estimated meperidine consumption rate was about 8.2 times higher than in 2013•Approximately 10.6% of the obese population of South Korea are regular drug users•Ephedrine imports ...are 3.5 times higher than the estimated consumption rate•Anti-obesity drug and zolpidem consumption rates were estimated for the first time
Drug abuse trends in South Korea were assessed by estimating the consumption rates of drugs that may be abused or misused by performing wastewater-based drug epidemiology. Of the 29 target compounds, 10 were found in samples from three wastewater treatment plants. Ephedrine had the highest mean estimated consumption rate, 574.1 mg d−1 (1000 people)−1. The anti-obesity drugs phendimetrazine and phentermine had the second and fifth highest mean estimated consumption rates, 182.9 and 113.1 mg d−1 (1000 people)−1, respectively. The zolpidem consumption rate was 65.8 mg d−1 (1000 people)−1. Methamphetamine was the only illicit drug detected in wastewater, and the estimated consumption rates (14.9–28.6 mg d−1 (1000 people)−1) were similar to consumption rates found in previous Korean studies (not detected to 45.8 mg d−1 (1000 people)−1). The mean estimated meperidine and cis-tramadol (opioid) consumption rates were 120 and 27.5 mg d−1 (1000 people)−1, respectively, and were 8.2 and 1.7 times higher, respectively, than the consumption rates found in 2013. Methylphenidate was detected in the influent and effluent samples at mean concentrations of 2.7 and 2.6 ng L−1, respectively, but the methylphenidate consumption rate could not be estimated because of the low excretion rate for humans (<1%).
RAS proteins play critical roles in various cellular processes, including growth and transformation. RAS proteins are subjected to protein stability regulation via the Wnt/β‐catenin pathway, and ...glycogen synthase kinase 3 beta (GSK3β) is a key player for the phosphorylation‐dependent RAS degradation through proteasomes. GSK3β‐mediated RAS degradation does not occur in cells that express a nondegradable mutant (MT) β‐catenin. Here, we show that β‐catenin directly interacts with RAS at the α‐interface region that contains the GSK3β phosphorylation sites, threonine 144 and threonine 148 residues. Exposure of these sites by prior β‐catenin degradation is required for RAS degradation. The introduction of a peptide that blocks the β‐catenin‐RAS interaction by binding to β‐catenin rescues the GSK3β‐mediated RAS degradation in colorectal cancer (CRC) cells that express MT β‐catenin. The coregulation of β‐catenin and RAS stabilities by the modulation of their interaction provides a mechanism for Wnt/β‐catenin and RAS‐ERK pathway cross‐talk and the synergistic transformation of CRC by both APC and KRAS mutations.
Synopsis
GSK3β promotes phosphorylation‐ and polyubiquitination‐dependent proteasomal RAS degradation. β‐Catenin directly interacts with RAS, thereby preventing GSK3β‐dependent phosphorylation and degradation, defining the basis for the synergistic effect of β‐catenin and RAS on cancer growth.
β‐Catenin directly interacts with RAS at the α‐interface that contains GSK3β phosphorylation sites.
β‐Catenin degradation is required for subsequent GSK3β‐mediated RAS degradation.
Targeting both β‐catenin and RAS for degradation is a potential approach against colorectal cancer.
GSK3β promotes phosphorylation‐ and polyubiquitination‐dependent proteasomal RAS degradation. β‐Catenin directly interacts with RAS, thereby preventing GSK3β‐dependent phosphorylation and degradation, defining the basis for the synergistic effect of β‐catenin and RAS on cancer growth.
•Organophosphate ester (OPE) removal in DWTPs was studied.•Seasonal variations occurred for DWTPs treating river water but not reservoir water.•Advanced processes (activated carbon/ozonation) removed ...around 50% of total OPEs.•Activated carbon removed 84% and 49% of TCIPP and TCEP (chlorinated OPEs).•The hazard quotient varied according to water sources and treatment process.
In this study, the fate of organophosphate esters (OPEs) in conventional and advanced drinking water treatment plants (DWTPs) was investigated in field scale. In addition, the risk of OPEs by drinking water was assessed. The average total OPE concentrations in raw and treated water were lower in the rainy season (94.3 and 57.1 ng/L, respectively) than dry season (163 and 84.2 ng/L, respectively). Advanced DWTPs showed better removal efficiencies of major OPEs rather than those in conventional DWTPs. The average removal rates for two chlorinated OPEs, including tris(2-chloroethyl)phosphate (TCEP) and tris(1-chloro-2-propyl)phosphate (TCIPP), were negative (TCEP: −87%, TCIPP: −41%) for a conventional DWTP but positive (TCEP: 46%, TCIPP: 49%) for advanced DWTPs using granular activated carbon filtration. The average removal rates for advanced DWTPs were statistically higher for the alkyl/aryl OPEs, tri-n-butyl phosphate (TNBP: 67%) and tris(2-butoxyethyl) phosphate (TBOEP: 63%), than those for the conventional DWTPs (TNBP: 21%, TBOEP: 25%). The hazardous quotient (HQ) of major OPEs were lower for advanced DWTPs and water irrigated from upstream sties/reservoir compared to that of conventional DWTPs and water irrigated from downstream sites. We believe that this is the first comparison of OPE removal efficiencies achieved in conventional and advanced DWTPs.
Plasmonic coupling-based electromagnetic field localization and enhancement are becoming increasingly important in chemistry, nanoscience, materials science, physics, and engineering over the past ...decade, generating a number of new concepts and applications. Among the plasmonically coupled nanostructures, metal nanostructures with nanogaps have been of special interest due to their ultrastrong electromagnetic fields and controllable optical properties that can be useful for a variety of signal enhancements such as surface-enhanced Raman scattering (SERS). The Raman scattering process is highly inefficient, with a very small cross-section, and Raman signals are often poorly reproducible, meaning that very strong, controllable SERS is needed to obtain reliable Raman signals with metallic nanostructures and thus open up new avenues for a variety of Raman-based applications. More specifically, plasmonically coupled metallic nanostructures with ultrasmall (∼1 nm or smaller) nanogaps can generate very strong and tunable electromagnetic fields that can generate strong SERS signals from Raman dyes in the gap, and plasmonic nanogap-enhanced Raman scattering can be defined as Raman signal enhancement from plasmonic nanogap particles with ∼1 nm gaps. However, these promising nanostructures with extraordinarily strong optical signals have shown limited use for practical applications, largely due to the lack of design principles, high-yield synthetic strategies with nanometer-level structural control and reproducibility, and systematic, reliable single-molecule/single-particle-level studies on their optical properties. All these are extremely important challenges because even small changes (<1 nm) in the structure of the coupled plasmonic nanogaps can significantly affect the plasmon mode and signal intensity. In this Account, we examine and summarize recent breakthroughs and advances in plasmonic nanogap-enhanced Raman scattering with metal nanogap particles with respect to the design and synthesis of plasmonic nanogap structures, as well as ultrasensitive and quantitative Raman signal detection using these structures. The applications and prospects of plasmonic nanogap particle-based SERS are also discussed. In particular, reliable synthetic and measurement strategies for plasmonically coupled nanostructures with ∼1 nm gap, in which both the nanogap size and the position of a Raman-active molecule in the gap can be controlled with nanometer/sub-nanometer-level precision, can address important issues regarding the synthesis and optical properties of plasmonic nanostructures, including structural and signal reproducibility. Further, single-molecule/single-particle-level studies on the plasmonic properties of these nanogap structures revealed that these particles can generate ultrastrong, quantifiable Raman signals in a highly reproducible manner.
Flexible supercapacitors are promising energy storage devices for emerging wearable electronics. However, due to the poor mechanical strength, complicated device manufacturing process, and ...unsatisfactory low-temperature tolerance, their overall performance for practical applications is hindered. Herein, we report a hydrogen bonding-reinforced, dual-crosslinked poly(vinyl alcohol), acrylic acid, and H2SO4 (PVA-AA-S) hydrogel electrolyte for all-in-one flexible supercapacitors. The PVA-AA-S hydrogel demonstrates excellent compressive/tensile properties and high ionic conductivity. It tolerates compressive stress of 0.53 MPa and is stretchable up to 500%. The hydrogel-based all-in-one supercapacitor shows promising electrochemical performance under various harsh conditions. The device energy density and power density reach up to 14.2 μWh cm–2 and 0.94 mW cm–2, respectively. Furthermore, it retains nearly 80% capacitance after being stored at −35 °C for 23 days. The excellent performance of the hydrogel electrolyte originates from its abundant strong hydrogen bonding between polymer chains and water molecules.
The pairwise maximum entropy model (MEM) for resting state functional MRI (rsfMRI) has been used to generate energy landscape of brain states and to explore nonlinear brain state dynamics. Researches ...using MEM, however, has mostly been restricted to fixed‐effect group‐level analyses, using concatenated time series across individuals, due to the need for large samples in the parameter estimation of MEM. To mitigate the small sample problem in analyzing energy landscapes for individuals, we propose a Bayesian estimation of individual MEM using variational Bayes approximation (BMEM). We evaluated the performances of BMEM with respect to sample sizes and prior information using simulation. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data, particularly utilizing the empirical priors derived from group data. We then analyzed individual rsfMRI of the Human Connectome Project to show the usefulness of MEM in differentiating individuals and in exploring neural correlates for human behavior. MEM and its energy landscape properties showed high subject specificity comparable to that of functional connectivity. Canonical correlation analysis identified canonical variables for MEM highly associated with cognitive scores. Inter‐individual variations of cognitive scores were also reflected in energy landscape properties such as energies, occupation times, and basin sizes at local minima. We conclude that BMEM provides an efficient method to characterize dynamic properties of individuals using energy landscape analysis of individual brain states.
We propose a Bayesian maximum entropy model estimation (BMEM) to characterize nonlinear brain state dynamics in each individual. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data. BMEM and its energy landscape properties showed high subject specificity.
In Mycobacterium smegmatis, the transcriptional activity of the alternative sigma factor SigF is posttranslationally regulated by the partner switching system consisting of SigF, the anti-SigF RsbW1, ...and three anti-SigF antagonists (RsfA, RsfB, and RsbW3). We previously demonstrated that expression of the SigF regulon is strongly induced in the Δaa3 mutant of M. smegmatis lacking the aa3 cytochrome c oxidase, the major terminal oxidase in the respiratory electron transport chain. Here, we identified and characterized the RsfSR two-component system involved in regulating the phosphorylation state of the major anti-SigF antagonist RsfB. RsfS (MSMEG_6130) is a histidine kinase with the cyclase/histidine kinase–associated sensing extracellular 3 domain at its N terminus, and RsfR (MSMEG_6131) is a receiver domain–containing protein phosphatase 2C–type phosphatase that can dephosphorylate phosphorylated RsfB. We demonstrated that phosphorylation of RsfR on Asp74 by RsfS reduces the phosphatase activity of RsfR toward phosphorylated RsfB and that the cellular abundance of the active unphosphorylated RsfB is increased in the Δaa3 mutant relative to the WT strain. We also demonstrated that the RsfSR two-component system is required for induction of the SigF regulon under respiration-inhibitory conditions such as inactivation of the cytochrome bcc1 complex and aa3 cytochrome c oxidase, as well as hypoxia, electron donor-limiting, high ionic strength, and low pH conditions. Collectively, our results reveal a key regulatory element involved in regulating the SigF signaling system by monitoring the state of the respiratory electron transport chain.
Mitigating preventable readmissions, where patients are readmitted for the same primary diagnosis within 30 days, poses a significant challenge to the delivery of high-quality healthcare. Toward this ...end, we develop a novel, predictive analytics model, termed as the beta geometric Erlang-2 (BG/EG) hurdle model, which predicts the propensity, frequency, and timing of readmissions of patients diagnosed with congestive heart failure (CHF). This unified model enables us to answer three key questions related to the use of predictive analytics methods for patient readmissions: whether a readmission will occur, how often readmissions will occur, and when a readmission will occur. We test our model using a unique data set that tracks patient demographic, clinical, and administrative data across 67 hospitals in North Texas over a four-year period. We show that our model provides superior predictive performance compared to extant models such as the logit, BG/NBD hurdle, and EG hurdle models. Our model also allows us to study the association between hospital usage of health information technologies (IT) and readmission risk. We find that health IT usage, patient demographics, visit characteristics, payer type, and hospital characteristics, are significantly associated with patient readmission risk. We also observe that implementation of cardiology information systems is associated with a reduction in the propensity and frequency of future readmissions, whereas administrative IT systems are correlated with a lower frequency of future readmissions. Our results indicate that patient profiles derived from our model can serve as building blocks for a predictive analytics system to identify CHF patients with high readmission risk.
With advances in the design, synthesis and analysis of various metallic nanoparticles and substrates, surface‐enhanced Raman scattering (SERS) with plasmonic nanostructures has been extensively ...studied, and numerous SERS applications have been demonstrated in various applications including biomedical applications; however, the mechanism of SERS is not completely understood yet, and many challenges, including structural and spectral reproducibility, exist to achieve quantitative SERS analysis for practical and reliable use of SERS. Since SERS signal reproducibility mainly stems from structural reproducibility of targeted nanostructures, single‐particle SERS analysis is highly beneficial in understanding SERS signals generated from different plasmonic nanostructures and provides analytical insights that cannot be obtained with ensemble‐average spectrum‐based analysis. Single‐particle analysis is typically composed of single‐particle images and spectra, and the statistical results show the single‐particle SERS enhancement factor distribution of SERS signals and precise structure‐spectrum relationship. In particular, studying and evaluating single‐molecule SERS results require single‐particle analysis to fully understand how single‐particle images and spectra are correlated with how the position, orientation and resonance of a Raman dye affect single‐molecule SERS signals from individual nanoparticles, and this is often correlated with computational simulation results. In this mini‐review, we introduce key issues for quantitative SERS and present the fundamental SERS features obtained by single‐particle analysis, focused on plasmonic nanogap structures since these structures offer the very strong electromagnetic field‐based SERS signals with high controllability in structure and signal. We categorized the nanogap particle‐based SERS platforms into two different classes – plasmonic nanogap strctures with an intergap (the gap between two structures; intergap nanoparticles) and plasmonic nanogap structures with an intragap (the gap formed inside a single particle; intragap nanoparticles). Finally, we discuss the challenges and perspectives in designing and synthesizing nanogap structures that deliver strong, reproducible, and reliable SERS signals for the quantitative SERS analysis.
Surface‐enhanced Raman scattering (SERS) with plasmonic gap nanoparticles provides an intense optical signal with a high reliability, but several issues remain for realization of the quantitative SERS with respect to design, synthesis, measurement and applications of SERS nanogap structures. This review focuses on the fundamentals and advances in quantitative SERS with plasmonic gap nanostructures mainly based on single‐particle anlaysis, and also discusses critical issues, challenges, and perspectives for the quantitative SERS with nanoparticles.
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