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BackgroundConsidering the potential cumulative effects of repetitive head impact (HI) exposure, we need sensitive biomarkers to track short- and long-term effects. Circulating small extracellular vesicles (sEVs) (<200 nm) traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease. The purpose of this study was to identify the microRNA (miRNA) profile in circulating sEVs derived from human plasma following repetitive HI exposure.MethodsHealthy adult (aged 18–35 years) soccer players were randomly assigned to one of 3 groups: the HI group performed 10 standing headers, the leg impact group performed 10 soccer ball trapping maneuvers over 10 min, and the control group did not participate in any soccer drills. Plasma was collected before testing and 24 h afterward, and sEVs were isolated and characterized via nanoparticle tracking analysis. Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs, and candidate microRNAs were analyzed via quantitative polymerase chain reaction. In silico target prediction was performed using TargetScan (Version 7.0; targetscan.org) and miRWalk (http://mirwalk.umm.uni-heidelberg.de/) programs, and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney (HEK) 293T/17 cells.ResultsPlasma sEV concentration and size were not affected across time and group following repetitive HI exposure. After 24 h, the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p, miR-423-5p, and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p, miR-144-5p, miR-221-5p, and miR-22-3p. Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels. To our knowledge, miR-7844-5p is a previously unknown miRNA. We identified 8 miR-7844-5p mRNA targets: protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B), LIM and senescent cell antigen-like domains 1 (LIMS1), autophagy-related 12 (ATG12), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), integrin subunit alpha-1 (ITGA1), mitogen-activated protein kinase 1 (MAPK1), glycogen synthase kinase 3β (GSK3β), and mitogen-activated protein kinase 8 (MAPK8).ConclusionCollectively, these data indicate repetitive HI exposure alters plasma sEV miRNA content, but not sEV size or number. Furthermore, for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis, autophagy regulation, mood disorders, and neurodegenerative disease.  相似文献   
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The shortage of qualified managers to assign to overseas positions has necessitated rethinking of the viable candidates pools. A relatively new group of global managers have emerged, inpatriate managers. These are foreign nationals and third-country nationals who are relocated to the organization's domestic headquarters to serve as a “linking-pin” to the global marketplace. This paper examines challenges to effectively incorporating these inpatriate managers into the domestic organization. The various issues with inpatriate manager adjustment to the domestic macro and organizational culture are examined. In addition, the necessary social support in work and non-work contexts is discussed.  相似文献   
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This study assessed muscular torque and rate of torque development following concentric (CON) or eccentric (ECC) isokinetic training. Thirty-eight women were randomly assigned to either CON or ECC training groups. Training consisted of knee extension and flexion of the nondominant leg three times per week for 20 weeks (SD = 1). Eccentric training increased ECC knee extension and flexion peak torque more than CON training. The ECC group improved acceleration time and time to peak torque with ECC movements versus the CON group. Slow-velocity ECC isokinetic training yielded greater ECC and similar CON torque development gains versus CON training over the course of 20 weeks in young women.  相似文献   
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This paper introduces a polynomial operator called the DT-polynomial as a novel approach to network flow problems. The class of networks dealt with is time-varying in the sense that the capacity, cost, and travel-time of each edge may vary in discrete time. The Dt-polynomial is a polynomial in two operators, D (delay) and T (time), which is used for describing the time-varying transmission characteristics. The paper starts with the mathematics involving the DT-polynomials. A new shortest arrival route algorithm is presented, and its computational complexity is found to be favorable in comparison with others such as Dijkstra's method and the potential method derived from Ford-Fulkerson's technique. Furthermore, a dynamic flow problem is formulated and analyzed in terms of DT-polynomials, and a latest-departure earliest-arrival schedule is given. Finally, a modified DT-polynomial is applied to digital filter networks.  相似文献   
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