A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop

Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer cell growth and survival and has been implicated in cancer pathophysiology and treatment. Here we report a novel function for IGF-1R in p53-dependent apoptotic response. We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein. Notably, IGF-1R inhibition increases p53 protein stability by reducing p53 ubiquitination and maintains p53 at low levels by decreasing p53 synthesis, thus rendering p53 insensitive to stabilization after DNA damage. The accumulation and apoptosis of DNA-damage–induced p53 is therefore reduced in Igf-1r−/− mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5′ untranslated region of p53 and mdm2 messenger RNA. The eukaryotic translation initiation factor 4F complex is also involved in this translational inhibition. These results demonstrate an unexpected role for translational control by IGF-1R in p53-mediated apoptosis

Effects of Trehalose, Bovine Serum Albumin, and Sucrose, on the Integrity of the Plasma Membrane of Pseudosciaena crocea Semen after Cryopreservation

Cryopreservation and the effect of additives on the plasma membrane stability, motility, enzyme activity, membrane lipid composition, and ultrastructural injury of sperm of Pseudosciaena crocea, were examined in this study. Results indicated that the addition of trehalose (TH) and bovine serum albumin (BSA) provided significantly better results in the motility test compared to sucrose. Some BSA groups, showed significantly increased semen motility and effective enzyme activity. There were no significant differences between the cholesterol (CHO) composition for fresh sperm and cryopreserved sperm stored in 3 g/L BSA or 8.56 g/L TH+3 g/L BSA. Ultrastructural injury included damaged membrane, lost mitochondria, or broken flagella, whereas the majority of the freeze-thawed sperm remained morphologically normal. In conclusion, the addition of 3 g/L BSA and 8.56 g/L TH+3 g/L BSA significantly increased semen quality

A Kind of Change Management Method for Global Value Chain Optimization and Its Case Study

Any successful change in an organization requires an appropriate change management method and a process for involved staff and department to accept the change and become engaged in order to achieve its success. It is even more important and difficult to adopt a novel change management method to bring multiple organizations across the business value chain into the change implementation. This research does not focused on change management within a single organization but rather emphasizes a change management method, including an appropriate change framework, well-defined critical success factors (CSFs), and related tools for implementing change in multiple organizations. This article introduces one kind of change management method to support a process change through global value chain (GVC) in multiple organizations, and the method is used in a case study to achieve a successful change. In order to succeed in optimizing GVC performance, this research applies the proposed change management method to the case GVC, to support technical change by obtaining the staff's full commitment and engagement. The achieved results from the case study prove that successful change comes not only through technical solutions implemented in the problem process throughout the GVC but also through strong support and engagement from all organizations and involved staff. The proposed change management method not only helped the case GVC to implement change successfully but also can help the relevant multiple organizations to improve the GVC performance and add value by optimizing their problem process.©2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.fi=vertaisarvioitu|en=peerReviewed

DialogRE^C+: An Extension of DialogRE to Investigate How Much Coreference Helps Relation Extraction in Dialogs

Dialogue relation extraction (DRE) that identifies the relations between argument pairs in dialogue text, suffers much from the frequent occurrence of personal pronouns, or entity and speaker coreference. This work introduces a new benchmark dataset DialogRE^C+, introducing coreference resolution into the DRE scenario. With the aid of high-quality coreference knowledge, the reasoning of argument relations is expected to be enhanced. In DialogRE^C+ dataset, we manually annotate total 5,068 coreference chains over 36,369 argument mentions based on the existing DialogRE data, where four different coreference chain types namely speaker chain, person chain, location chain and organization chain are explicitly marked. We further develop 4 coreference-enhanced graph-based DRE models, which learn effective coreference representations for improving the DRE task. We also train a coreference resolution model based on our annotations and evaluate the effect of automatically extracted coreference chains demonstrating the practicality of our dataset and its potential to other domains and tasks.Comment: Accepted by NLPCC 202

General calculation method of power boundary of multiport power electronic transformer

In the multiport power electronic transformer (MPET), cascaded H-bridge (CHB) converters form the medium voltage AC port, while multiple low voltage DC ports are constructed by paralleling dual active bridge (DAB) converters into clusters. Uneven power distribution among these ports leads to power imbalances, risking over modulation in CHB converters with high power generation or load power. This study proposes a general calculation method (GCM) for determining the power boundary of MPETs, enabling the adjustment of reference power for each DC port to prevent over modulation. The GCM is designed to handle scenarios with multiple simultaneous power flow directions. The effectiveness of the GCM is verified by DC port power boundary simulation results of two independent DC bus structure multiport power electronic transformers. The proposed method provides a straightforward approach to calculating power boundary for MPETs with multiple power flow directions, ensuring efficient power management

Pareto-Optimal Estimation and Policy Learning on Short-term and Long-term Treatment Effects

This paper focuses on developing Pareto-optimal estimation and policy learning to identify the most effective treatment that maximizes the total reward from both short-term and long-term effects, which might conflict with each other. For example, a higher dosage of medication might increase the speed of a patient's recovery (short-term) but could also result in severe long-term side effects. Although recent works have investigated the problems about short-term or long-term effects or the both, how to trade-off between them to achieve optimal treatment remains an open challenge. Moreover, when multiple objectives are directly estimated using conventional causal representation learning, the optimization directions among various tasks can conflict as well. In this paper, we systematically investigate these issues and introduce a Pareto-Efficient algorithm, comprising Pareto-Optimal Estimation (POE) and Pareto-Optimal Policy Learning (POPL), to tackle them. POE incorporates a continuous Pareto module with representation balancing, enhancing estimation efficiency across multiple tasks. As for POPL, it involves deriving short-term and long-term outcomes linked with various treatment levels, facilitating an exploration of the Pareto frontier emanating from these outcomes. Results on both the synthetic and real-world datasets demonstrate the superiority of our method