Discovery of Hits That Can Specifically Inhibit Necroptosis but Not Apoptosis

Necroptosis or programmed necrosis is a specialized and regulated necrosis, and is unmasked when apoptotic machinery for death stress is defective. Initially, it was proposed that necroptotic cell death was pathologically associated with ischemic brain injury and retinal disorders. In contrast, it plays a beneficial significance in innate immune response to viral infection that can evade host’s apoptotic surveillance. Also, it has been therapeutically emerging as the strategy to overcome the cancers with acquired anticancer drug resistance. Presently, a few small molecules to interfere with signaling pathways for necroptosis have been disclosed since necrostatin-1 (Nec-1) was for the first time identified as an inhibitor of receptor interacting protein 1 (RIP1), a key necroptosis regulator. In an effort to discover hits that can selectively inhibit necroptotic cell death, in this study, we screened in-house and in silico chemical libraries in a cell-based format. Eventually, 7 hits were identified from in-house chemical library while 2 hits were from computer modeling. Most hits less protected cells from tumor necrosis factor alpha (TNFα)- and zVAD-mediated necroptosis than a reference compound necrostatin-1, without affecting apoptotic cell death induced in HeLa. Interestingly, a few of hits had preferential protective effects on zVAD or TNFα while Nec-1 exhibited EC50 values at the similar concentrations against both necroptosis inducers, suggesting that chemicals deduced in our study can discriminate signaling pathways leading to receptor or nonreceptor-mediated necroptotic cell death.Therefore, some potent hits will be further improved to use for the treatment of necroptosis-associated disorders. &nbsp

Public Supervisors and Reflectors: Role Fulfillment of the Chinese Peoples Congress Deputies in the Market Socialist Era

This paper analyses the role fulfilment of Chinese people's congress deputies in the reform era. It argues the role fulfilments have changed in the 1990s. First, Chinese legislators have conducted three roles, i.e., supervision, reflection, and policy-providing, and regarded the first two as their dominant roles. This implies that deputies act mainly as public supervisors and reflectors rather than "regime agents." Second, deputies' role fulfilments have differentiated depending on their social backgrounds. Deputies from worker and peasant backgrounds tend to act as reflectors and supervisors, while deputies with intellectual backgrounds and some official deputies are more orientated to policy-providing. Private entrepreneurs and businesspersons who become deputies are more interested in exemplary leadership and economic roles, the closest role of "regime agents." Finally, the power from below —- deputies and the public —- will be the main force in the Chinese legislative development, and resultantly Chinese legislatures will be more representative than now.This study was supported by the Overhead Research fund of Seoul National Universit

Law Dissemination Campaign in China: The Origin of Chinese Rule of Law Policy

This article analyzes the law dissemination campaign (pufa huodong) that China has implemented for almost three decades, and sheds light on recent development of the rule of law policy in China. It first examines the background of the campaign. Then, the article delves into the process of the campaign as well as the legal knowledge education of leading cadres as a case study. Third, it takes stock of the campaigns achievements and limitations. This article suggests that the campaign has played a vital role in encouraging ordinary peoples legal practices. Furthermore, it argues that the campaign provided important experience by which China set the rule of law policy as a guiding principle of government at the 15th Party Congress in October 1997 and more recently the Fourth Plenum of 18th Central Committee of the CCP in October 2014

Governing the Country according to the Law: Chinas Rule of Law Policy as Political Reform

This article analyzes Chinas rule of law policy—that is, governing the country according to the law (yifa zhiguo)—in terms of political reform. It addresses two issues: one is the formation and actual implementation of the rule of law policy. The other is the nature and implementation of the rule of law policy. To this end, the article investigates specific policies of the rule of law. It then looks into the processes of the rule of law policys emergence and development at both the central and local levels. Finally it closely examines the implementation of the rule of law policy. The article argues that the rule of law policy is not just legal or judicial reform but comprehensive political reform which aims at transforming the way that the Chinese Communist Party rules the country. Moreover, it has developed for about 17 years through the processes of mutual influence between the central and local levels

Perception-Oriented Single Image Super-Resolution using Optimal Objective Estimation

Single-image super-resolution (SISR) networks trained with perceptual and adversarial losses provide high-contrast outputs compared to those of networks trained with distortion-oriented losses, such as L1 or L2. However, it has been shown that using a single perceptual loss is insufficient for accurately restoring locally varying diverse shapes in images, often generating undesirable artifacts or unnatural details. For this reason, combinations of various losses, such as perceptual, adversarial, and distortion losses, have been attempted, yet it remains challenging to find optimal combinations. Hence, in this paper, we propose a new SISR framework that applies optimal objectives for each region to generate plausible results in overall areas of high-resolution outputs. Specifically, the framework comprises two models: a predictive model that infers an optimal objective map for a given low-resolution (LR) input and a generative model that applies a target objective map to produce the corresponding SR output. The generative model is trained over our proposed objective trajectory representing a set of essential objectives, which enables the single network to learn various SR results corresponding to combined losses on the trajectory. The predictive model is trained using pairs of LR images and corresponding optimal objective maps searched from the objective trajectory. Experimental results on five benchmarks show that the proposed method outperforms state-of-the-art perception-driven SR methods in LPIPS, DISTS, PSNR, and SSIM metrics. The visual results also demonstrate the superiority of our method in perception-oriented reconstruction. The code and models are available at https://github.com/seungho-snu/SROOE.Comment: Code and trained models will be available at https://github.com/seungho-snu/SROO

A Case of Ocular Toxoplasmosis Imaged with Spectral Domain Optical Coherence Tomography

A 54-year-old man presented with blurred central vision in the right eye of two weeks' duration. On presentation, visual acuity was 40 / 50 in the right eye and fundus examination showed a whitish-yellow inflammatory lesion near an atrophic, pigmented retinochoroidal scar located in the superotemporal quadrant. Serologic assessment was negative for IgM, but serum IgG to toxoplasma was elevated. Spectral domain optical coherence tomography (SD-OCT) revealed increased reflectivity from the inner retinal layer, retinal thickening, and choroidal shadowing while focal posterior hyaloid thickening and detachment were observed in the new lesion. He was treated with trimethoprim/sulfamethoxazole, clindamycin, and prednisone. SD-OCT is helpful for definitively differentiating ocular toxoplasmosis from other retinal diseases