Hierarchical and stage-specific regulation of murine cardiomyocyte maturation by serum response factor

After birth, cardiomyocytes (CM) acquire numerous adaptations in order to efficiently pump blood throughout an animal’s lifespan. How this maturation process is regulated and coordinated is poorly understood. Here, we perform a CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many aspects of their maturation, including sarcomere expansion, mitochondrial biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of maturity in adult CMs is less dependent on SRF. This stage-specific activity is associated with developmentally regulated SRF chromatin occupancy and transcriptional regulation. SRF directly activates genes that regulate sarcomere assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression also perturbs CM maturation. Together, these data indicate that carefully balanced SRF activity is essential to promote CM maturation through a hierarchy of cellular processes orchestrated by sarcomere assembly

Hierarchical and stage-specific regulation of murine cardiomyocyte maturation by serum response factor

After birth, cardiomyocytes (CM) acquire numerous adaptations in order to efficiently pump blood throughout an animal’s lifespan. How this maturation process is regulated and coordinated is poorly understood. Here, we perform a CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many aspects of their maturation, including sarcomere expansion, mitochondrial biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of maturity in adult CMs is less dependent on SRF. This stage-specific activity is associated with developmentally regulated SRF chromatin occupancy and transcriptional regulation. SRF directly activates genes that regulate sarcomere assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression also perturbs CM maturation. Together, these data indicate that carefully balanced SRF activity is essential to promote CM maturation through a hierarchy of cellular processes orchestrated by sarcomere assembly

A Comparison of Different Shipment Policies in an Integrated Inventory System for Imperfect Quality Items with Inspection Errors

Considering a production-ordering system where items are not perfect and quality screening is conducted with inspection errors, we develop integrated inventory models under different shipment policies and make a comprehensive comparison among them to select an optimal one, so as to improve the supply chain’s performance. It is assumed that all items classified as defective during the screening process are sold as a single batch at a discounted price at the end of this screening process; items returned from the market are accumulating; and all of them are stored and sold as a single batch at a discounted price at the end of the next screening process. All the numerical results show that the proportional size shipment policy is always optimal, except for one situation where the difference between the vendor’s and the buyer’s unit inventory holding costs is considerably large. Therefore, we mainly recommend the proportional size shipment policy

Contract Strategies in Competing Supply Chains with Risk-Averse Suppliers

This paper investigates the equilibrium contract strategies of two competing supply chains. Each chain is composed of one risk-averse supplier and one risk-neutral retailer. The two suppliers, as Stackelberg leaders, can choose either wholesale price or revenue sharing contract. We compare the outcomes obtained from different scenarios and study the impact of competition density and risk attitudes on the suppliers’ contract choices. We find that it is always optimal for the first-moving supplier to choose revenue sharing contract if the follower chooses wholesale price contract. We also find that the retail price under revenue sharing contract is lower than that under wholesale price contract. Compared to Pan et al. (2010), we find that a threshold policy with respect to the degree of product substitutability holds in a sequential competition environment. There also exists a threshold policy with respect to the degree of risk aversion for the suppliers to choose their individual contract types and the corresponding chain-to-chain contract strategies

Discrete-time retrial queue with Bernoulli vacation, preemptive resume and feedback customers

Purpose: We consider a discrete-time Geo/G/1 retrial queue where the retrial time follows a general distribution, the server subject to Bernoulli vacation policy and the customer has preemptive resume priority, Bernoulli feedback strategy. The main purpose of this paper is to derive the generating functions of the stationary distribution of the system state, the orbit size and some important performance measures. Design/methodology: Using probability generating function technique, some valuable and interesting performance measures of the system are obtained. We also investigate two stochastic decomposition laws and present some numerical results. Findings: We obtain the probability generating functions of the system state distribution as well as those of the orbit size and the system size distributions. We also obtain some analytical expressions for various performance measures such as idle and busy probabilities, mean orbit and system sizes. Originality/value: The analysis of discrete-time retrial queues with Bernoulli vacation, preemptive resume and feedback customers is interesting and to the best of our knowledge, no other scientific journal paper has dealt with this question. This fact gives the reason why efforts should be taken to plug this gap

The Principal–Agent Leasing Model of “Company + n Farmers” under Two Division Modes

The principal–agent leasing model consisting of one risk-neutral company and n risk-averse farmers is proposed by taking into consideration the characteristics of contract-farming and the fulfilment issues existing in the production process of agricultural products. We also discuss the optimal incentive coefficients and rents for n farmers under the two strategies of decentralization and concentration. The analysis suggests that the two division modes have no influence on the determination of the optimal effort level and the incentive coefficient of each party, and under the n farmers, the incentive coefficient given by the company to a single farmer household is not affected by the conditions of other farmer households. In terms of rent, land rent in the decentralized mode is strictly higher than land rent under the centralized mode. In the two modes of division, the total income of the company and the farmers is equal. Taking into account the randomness of the production process of agricultural products, the company will prefer to choose the centralized mode, and the farmers will tend to choose the decentralized mode in cooperation

The complete mitochondrial genome of Black Drongo Dicrurus macrocercus (Passeriformes, Dicruridae)

The Black Drongo (Dicrurus macrocercus) is an important beneficial bird widespread in China and other Asian countries. In this study, a complete mitochondrial genome of D. macrocercus has been obtained by polymerase chain reaction method for the first time. This circular molecule is 17,017 bp in length with A + T contents of 56.9% and contains 2 rRNA genes, 13 protein-coding genes, and 22 tRNA genes. Phylogenetic analysis shows that D. macrocercus is genetically closest to D. hottentottus

Selection and use of LIMS

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