We derive the optimal underwriting method and the quantitative initial public offering (IPO) pricing rule that this method implies in a market with informational frictions consisting of fully ...rational banks, issuers, and investors. In an efficient IPO market, an issuer’s expected initial return will be determined entirely by the combination of this pricing rule and issuer fundamentals. Applying this rule, we find that we can explain the quantitative magnitude of the principal aspects of the time-series and cross-sectional variation in IPO average initial returns. We conclude that the IPO market is efficient.
Plug-in Electric Vehicle (PEV) user charging behavior has a significant influence on a distribution network and its reliability. Generally, monitoring energy consumption has become one of the most ...important factors in green and micro grids; therefore, predicting the charging demand of PEVs (the energy consumed during the charging session) could help to efficiently manage the electric grid. Consequently, three machine learning methods are applied in this research to predict the charging demand for the PEV user after a charging session starts. This approach is validated using a dataset consisting of seven years of charging events collected from public charging stations in the state of Nebraska, USA. The results show that the regression method, XGBoost, slightly outperforms the other methods in predicting the charging demand, with an RMSE equal to 6.68 kWh and R2 equal to 51.9%. The relative importance of input variables is also discussed, showing that the user’s historical average demand has the most predictive value. Accurate prediction of session charging demand, as opposed to the daily or hourly demand of multiple users, has many possible applications for utility companies and charging networks, including scheduling, grid stability, and smart grid integration.
We introduce a new experimental approach to measuring the effects of health insurance policy alternatives on behavior and health outcomes over the life course. In a virtual environment with ...multi-period lives, subjects earn virtual income and allocate spending, to maximize utility, which is converted into cash payment. We compare behavior across age, income and insurance plans-one priced according to an individual's expected cost and the other uniformly priced through employer-implemented cost sharing. We find that 1) subjects in the employer-implemented plan purchased insurance at higher rates; 2) the employer-based plan reduced differences due to income and age; 3) subjects in the actuarial plan engaged in more health-promoting behaviors, but still below optimal levels, and did save at the level required, so did realize the full benefits of the plan. Subjects had more difficulty optimizing choices in the Actuarial treatment, because it required more long term planning and evaluating benefits that compounded over time. Contrary, to model predictions, the actuarial priced insurance plan did not increase utility relative to the employer-based plan.
Neurons in the brain can be damaged or lost from neurodegenerative disease, stroke, or traumatic injury. Although neurogenesis occurs in mammalian adult brains, the levels of natural neurogenesis are ...insufficient to restore function in these cases. Gene therapy has been pursued as a promising strategy to induce differentiation of neural progenitor cells into functional neurons. Non-viral vectors are a preferred method of gene transfer due to potential safety and manufacturing benefits but suffer from lower delivery efficiencies compared to viral vectors. Since the neural stem and progenitor cells reside in the subventricular zone of the brain, intraventricular injection has been used as an administration route for gene transfer to these cells. However, the choroid plexus epithelium remains an obstacle to delivery. Recently, transient disruption of the blood–brain barrier by microbubble-enhanced ultrasound has been used to successfully improve drug delivery to the brain after intravenous injection. In this work, we demonstrate that microbubble-enhanced ultrasound can similarly improve gene transfer to the subventricular zone after intraventricular injection. Microbubbles of different surface charges (neutral, slightly cationic, and cationic) were prepared, characterized by acoustic flow cytometry, and evaluated for their ability to increase the permeability of immortalized choroid plexus epithelium monolayers in vitro. Based on these results, slightly cationic microbubbles were evaluated for microbubble and ultrasound-mediated enhancement of non-viral gene transfer in vivo. When coupled with our previously reported gene delivery vehicles, the slightly cationic microbubbles significantly increased ultrasound-mediated transfection of the murine brain when compared to commercially available Definity® microbubbles. Temporary disruption of the choroid plexus by microbubble-enhanced ultrasound is therefore a viable way of enhancing gene delivery to the brain and merits further research.
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The architecture of polycations plays an important role in both gene transfection efficiency and cytotoxicity. In this work, a new polymer, sunflower poly(2‐dimethyl amino)ethyl methacrylate) ...(pDMAEMA), is prepared by atom transfer radical polymerization and employed as nucleic acid carriers compared to linear pDMAEMA homopolymer and comb pDMAEMA. The sunflower pDMAEMAs show higher IC50, greater buffering capacity, and stronger binding capacity toward plasmid DNA than their linear and comb counterparts. In vitro transfection studies demonstrate that sunflower pDMAEMAs exhibit high transfection efficiency as well as relatively low cytotoxicity in complete growth medium. In vivo gene delivery by intraventricular injection to the brain shows that sunflower polymer delivers plasmid DNA more effectively than comb polymer. This study provides a new insight into the relationship between polymeric architecture and gene delivery capability, and as well as a useful means to design potent vectors for successful gene delivery.
A new polymer, termed “sunflower polymer,” is reported and employed as nucleic acid carrier in vitro and in vivo. The sunflower polymers exhibit high transfection efficiency as well as relative low cytotoxicity in serum‐containing medium in comparison to their linear and comb counterparts, and efficiently deliver nucleic acid cargoes into mice brain.
This article reconstructs a theory of mind in the Mengzi 孟子. It argues that recent studies in favor of mind-body dualism import Cartesianism through the vocabulary their arguments are couched in. ...This article exposes this “Cartesian language game” in order to effect a gestalt shift in our understanding of Mengzian philosophy. It then appeals to John Dewey’s conception of mind as both “minding” and “discourse” where mind is a function of attentive engagement predicated on a background of traditional values and meanings. This article then shows how the Mengzi’s concepts of ren 仁 and tian 天 contribute to a theory of mind where the former is defined as xin 心 thus to be understood as “mindful engagement” and the latter implies tradition as shared reservoir of social and cultural meaning. Through the interpretive comparison of the philosophies of the Mengzi and Dewey, we can reconstruct a Mengzian theory of mind.
Abstract Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive ...polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)- co -poly(2-(dimethylamino)ethyl methacrylate)- block - poly(propargyl methacrylate- graft -propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)– b -(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery.
The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks ...and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the ATP site, and may enhance allosteric cooperativity with the substrate binding region by increasing communication capabilities of mediating residues.
Recent research shows that placement of an intraluminal shunt during a carotid endarterectomy (CEA) can be associated with postoperative complications. Therefore, we compared CEA operations with or ...without shunting to further analyze their clinical outcomes.
From the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, 13,736 cases between 2016 and 2019 were analyzed to compare adult symptomatic and asymptomatic carotid stenosis patients who underwent a CEA operation, with or without shunt placement.
Rates of stroke with a neurological deficit (p = 0.012), myocardial infarction (p = 0.021), and urinary tract infection (p = 0.030) were higher among symptomatic patients with shunting. Multivariate logistic regression revealed that risk of CNI was higher among both symptomatic (93.63%, p < 0.001) and asymptomatic (69.58%, p = 0.001) patients with shunting, irrespective of confounding variables.
Shunting was found to be associated with higher rates of postoperative complications in both symptomatic and asymptomatic patient populations.
•Carotid endarterectomies carry an associated risk depending on the extent of arterial occlusion.•Shunting can lead to additional postoperative complications such as stroke or cranial nerve injury (CNI).•Shunting was found to increase the risk of CNI in both symptomatic and asymptomatic patients.•Symptomatic patients who underwent CEA with shunting had an increased risk of neurological deficit, myocardial infarction, and urinary tract infection.
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