Escalated and inappropriate levels of aggressive behavior referred to as pathological in psychiatry can lead to violent outcomes with detrimental impact on health and society. Early life stressful experiences might increase the risk of developing pathological aggressive behavior in adulthood, though molecular mechanisms remain elusive. Here, we provide prefrontal cortex and hypothalamus specific transcriptome profiles of peripubertal stress (PPS) exposed Balb/c adult male mice exhibiting escalated aggression and adult female mice resilient to such aberrant behavioral responses. We identify transthyretin (TTR), a well known thyroid hormone transporter, as a key regulator of PPS induced escalated aggressive behavior in males. Brain region specific long-term changes in Ttr gene expression and thyroid hormone (TH) availability were evident in PPS induced escalated aggressive male mice, circulating TH being unaltered. Ttr promoter methylation marks were also altered being hypermethylated in hypothalamus and hypomethylated in prefrontal cortex corroborating with its expression pattern. Further, Ttr knockdown in hypothalamus resulted in escalated aggressive behavior in males without PPS and also reduced TH levels and expression of TH responsive genes (Nrgn, Trh and Hr). Escalated aggressive behavior along with reduced Ttr gene expression and TH levels in hypothalamus was also evident in next generation F1 male progenies. Our findings reveal that stressful experiences during puberty might trigger lasting escalated aggression by modulating TTR expression in brain. TTR can serve as a potential target in reversal of escalated aggression and related psychopathologies.

Purpose The quality of production is an essential factor for the performance measure of a system; a casting process is the same section. It is a type of metal-forming practice in which the required shape of metal is acquired by pouring molten metal into the mold cavity and allowing it to solidify. Casting is done to provide strength and rigidity to the parts of a system for bearing mechanical impacts. The purpose of this paper is to investigate the various aspects which affect the casting process in the foundry industry, in order to optimize the quality of casting, with the assumption that sufficient repair facility is always available. Design/methodology/approach The considered casting system can have many defects such as the mold shift defect, blowhole defect, defect of shrinkage and porosity, defect of inclusion, defect of cold shut and much more. The studied system can be in three states during the process, namely, good state, failed state and degraded state. The system can repair after minor failures as well as a major failure. The average failure rates of various defects of the system considered as constant and repairs follow the general time distribution. The system is analyzed with the help of the supplementary variable technique and the Laplace transformation for evaluating its various performance measures in order to improve its performance/production. Findings This work provides a strong understanding of the casting industry, that which failure affects the production of casting and how much. For better understanding, the results have been demonstrated with the help of graphs. Originality/value In the present paper, a mathematical model based on the casting process in manufacturing industry has been developed.

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