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We develop an equilibrium model with moral hazard, which arises because some productivity shocks are privately observed by firm managers only. We characterize the optimal contract and its implications for firm size, growth, and ma...
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We develop an equilibrium model with moral hazard, which arises because some productivity shocks are privately observed by firm managers only. We characterize the optimal contract and its implications for firm size, growth, and managerial pay-performance sensitivity and exploit them to quantify the severity of the moral hazard problem. Our estimation suggests that unobservable shocks are relatively modest and account for about 10% of the total variation of firm output. Nonetheless, moral-hazard-induced incentive pay is quantitatively significant and accounts for 50% of managerial compensation. Eliminating moral hazard would result in about a 1% increase in aggregate output.
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In this paper, we consider a model with tumor microenvironment involving nutrient density, extracellular matrix and matrix degrading enzymes, which satisfy a coupled system of PDEs with a free boundary. For this coupled parabolic-...
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In this paper, we consider a model with tumor microenvironment involving nutrient density, extracellular matrix and matrix degrading enzymes, which satisfy a coupled system of PDEs with a free boundary. For this coupled parabolic-hyperbolic free boundary problem, we prove that there is a unique radially symmetric solution globally in time. The stationary problem involves an ODE system which is transformed into a singular integro-differential equation. We establish a well-posed theorem for such general types of equations by the shooting method; the theorem is then applied to our problem for the existence of a stationary solution. In addition, for this highly nonlinear problem, we also prove the uniqueness of the stationary solution, which is a nontrivial result. Moreover, numerical simulations indicate that the stationary solution is likely locally asymptotically stable for reasonable range of parameters. (c) 2019 Elsevier Inc. All rights reserved.
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Construction of next-generation sequencing (NGS) libraries involves RNA manipulation, which often creates noisy, biased, and artifactual data that contribute to errors in transcriptome analysis. In this study, a total of 19 whole ...
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Construction of next-generation sequencing (NGS) libraries involves RNA manipulation, which often creates noisy, biased, and artifactual data that contribute to errors in transcriptome analysis. In this study, a total of 19 whole transcriptome termini site sequencing (WTTS-seq) and seven RNA sequencing (RNA-seq) libraries were prepared from Xenopus tropicalis adult and embryo samples to determine the most effective library preparation method to maximize transcriptomics investigation. We strongly suggest that appropriate primers/adaptors are designed to inhibit amplification detours and that PCR overamplification is minimized to maximize transcriptome coverage. Furthermore, genome annotation must be improved so that missing data can be recovered. In addition, a complete understanding of sequencing platforms is critical to limit the formation of false-positive results. Technically, the WTTS-seq method enriches both poly(A)+ RNA and complementary DNA, adds 5'- and 3'-adaptors in one step, pursues strand sequencing and mapping, and profiles both gene expression and alternative polyadenylation (APA). Although RNA-seq is cost prohibitive, tends to produce false-positive results, and fails to detect APA diversity and dynamics, its combination with WTTS-seq is necessary to validate transcriptome-wide APA.
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Cells communicate with each other via receptor-ligand interactions. Here, we describe lentiviral-mediated cell entry by engineered receptor-ligand interaction (ENTER) to display ligand proteins, deliver payloads, and record recept...
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Cells communicate with each other via receptor-ligand interactions. Here, we describe lentiviral-mediated cell entry by engineered receptor-ligand interaction (ENTER) to display ligand proteins, deliver payloads, and record receptor specificity. We optimize ENTER to decode interactions between T cell receptor (TCR)-MHC peptides, antibody-antigen, and other receptor-ligand pairs. A viral presentation strategy allows ENTER to capture interactions between B cell receptor and any antigen. We engineer ENTER to deliver ge-netic payloads to antigen-specific T or B cells to selectively modulate cellular behavior in mixed populations. Single-cell readout of ENTER by RNA sequencing (ENTER-seq) enables multiplexed enumeration of antigen specificities, TCR clonality, cell type, and states of individual T cells. ENTER-seq of CMV-seropositive patient blood samples reveals the viral epitopes that drive effector memory T cell differentiation and inter-clonal vs. intra-clonal phenotypic diversity targeting the same epitope. ENTER technology enables systematic discov-ery of receptor specificity, linkage to cell fates, and antigen-specific cargo delivery.
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We develop a unified theory of dynamic contracting and assortative matching to explain firm dynamics. In our model, neither firms nor managers can commit to arrangements that yield lower payoffs than their outside options, which a...
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We develop a unified theory of dynamic contracting and assortative matching to explain firm dynamics. In our model, neither firms nor managers can commit to arrangements that yield lower payoffs than their outside options, which are microfounded by the equilibrium conditions in a matching market. The model endogenously generates power laws in firm size and CEO compensation, and explains differences in their right tails. We also show that our model quantitatively accounts for many salient features of the time-series dynamics and the cross-sectional distribution of firm investment, dividend payout, and CEO compensation.
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Swertia L., as a commonly used ethnic medicine, is widely distributed in Sichuan, Yunnan, and Xizang in China. Moreover, the medicinal plants of Swertia L. have been widely used and constitute one of the most important sources of ...
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Swertia L., as a commonly used ethnic medicine, is widely distributed in Sichuan, Yunnan, and Xizang in China. Moreover, the medicinal plants of Swertia L. have been widely used and constitute one of the most important sources of various traditional medicines in China due to their prominent activities. In this review, the information on the classification, distribution, genetic relationship, chemical composition, pharmacological effects, toxicities, and applications of the medicinal plants in Swertia L. was summarized based on the scientific literature. The results indicated that the medicinal plants of Swertia L. mainly contained chemical components including triterpenes, xanthones, and iridoids. These compounds exert pharmacological effects including ameliorating diseases related to the liver and gallbladder. They also exert antiviral and antibacterial effects and can alleviate the increase in blood glucose levels. Especially, prescriptions related to Swertia L. have been widely adopted in preclinical and clinical studies to protect against diseases affecting the liver and the gallbladder, including hepatitis, cirrhosis, and cholecystitis. In addition, it also discusses toxicity studies and future perspectives and provides a reference for their clinical development and utilization.
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In this paper, a discontinuous finite volume element method was presented to solve the nonstationary Stokes-Darcy problem for the coupling fluid flow in conduits with porous media flow. The proposed numerical method is constructed...
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In this paper, a discontinuous finite volume element method was presented to solve the nonstationary Stokes-Darcy problem for the coupling fluid flow in conduits with porous media flow. The proposed numerical method is constructed on a baseline finite element family of discontinuous linear elements for the approximation of the velocity and hydraulic head, whereas the pressure is approximated by piecewise constant elements. The unique solvability of the approximate solution for the discrete problem is derived. Optimal error estimates of the semi-discretization and full discretization with backward Euler scheme in standard -norm and broken -norm are obtained for three discontinuous finite volume element methods (symmetric, non-symmetric and incomplete types). A series of numerical experiments are provided to illustrate the features of the proposed method, such as the optimal accuracy orders, mass conservation, capability to deal with complicated geometries, and applicability to the problems with realistic parameters.
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The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes antitumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TIL...
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The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes antitumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8(+) TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226(hi) TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226(+)CD8(+) T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226.
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