Crystal structures reveal transient <scp>PERK</scp> luminal domain tetramerization in endoplasmic reticulum stress signaling

Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining protein-folding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear. Here, we describe the crystal structures of mammalian PERK luminal domains captured in dimeric state as well as in a novel tetrameric state. Small angle X-ray scattering analysis (SAXS) supports the existence of both crystal structures also in solution. The salient feature of the tetramer interface, a helix swapped between dimers, implies transient association. Moreover, interface mutations that disrupt tetramer formation in vitro reduce phosphorylation of PERK and its target eIF2α in cells. These results suggest that transient conversion from dimeric to tetrameric state may be a key regulatory step in UPR activation. Synopsis Activation of unfolded protein response (UPR) upon ER stress involves key regulatory roles of ER-luminal sensor/transducer domains in UPR signaling factors. Structural and functional analyses of the PERK luminal domain reveal a novel tetrameric arrangement, whose transient formation may be an important step in UPR activation. Crystal structure of human PERK luminal domain shows a novel tetramer arrangement. Crystal structure of mouse PERK luminal domain is captured in dimeric form. Biophysical analysis confirm that both mouse and human proteins exist as dimers as well as tetramers in solution. Mutations that disrupt tetramerization in solution reduce phosphorylation of PERK and its target eIF2α in cells. Structural and functional analyses of the PERK luminal domain reveal a novel tetrameric arrangement, whose transient formation may be an important step in activation of the unfolded protein response

Friction and Wear Performance Evaluation of Bio-Lubricants and DLC Coatings on Cam/Tappet Interface of Internal Combustion Engines.

The environmental concerns associated with artificially formulated engine oils have forced a shift towards bio-based lubricants. The deposition of hard coatings on engine components and migrating to environmentally friendly green lubricants can help in this regard. Chemically modified forms of vegetable oils, with better low-temperature characteristics and enhanced thermo-oxidative stability, are suitable substitutes to conventional lubricant base oils. The research presented in this manuscript was undertaken to experimentally investigate the wear and friction performance of a possible future generation of an environmentally friendly bio-based lubricant as a potential replacement for conventional engine lubricants. In order to quantify the tribological benefits which can be gained by the deposition of DLC coatings, (an (a-C:H) hydrogenated DLC coating and an (a-C:H:W) tungsten-doped DLC coating) were applied on the cam/tappet interface of a direct acting valve train assembly of an internal combustion engine. The tribological correlation between DLC-coated engine components, lubricant base oils and lubricant additives have been thoroughly investigated in this study using actual engine operating conditions. Two additive-free base oils (polyalphaolefines (PAO) and chemically-modified palm oil (TMP)) and two multi-additive-containing lubricants were used in this investigation. Real-time drive torque was measured to determine the friction force, detailed post-test analysis was performed, which involved the use of a specialized jig to measure camlobe wear. An optical profilometer was used to measure the wear on the tappet, high-resolution scanning electron microscopy was employed to study the wear mechanism and energy-dispersive X-ray spectroscopy was performed on the tested samples to qualitatively access the degradation of the coating. When using additive-free TMP, a low friction coefficient was observed for the cam/tappet interface. The presence of additives further improved the friction characteristics of TMP, resulting in reduced average friction torque values. A tremendous enhancement in wear performance was recorded with a-C:H-coated parts and the coating was able to withstand the test conditions with little or no delamination

Hasil unplag Optimizing machining time for CAD / CAM milling programming using the Taguchi method yang dipublikasikan pada Journal of Physics: Conference Series IOP Publishing 1402 (2019) 044043 Doi :10.1088/1742-6596/1402/4/044043

ini adalah hasil unplag dari artikel yang berjudul Optimizing machining time for CAD / CAM milling programming using the Taguchi methodcyang dipublikasikan pada Journal of Physics: Conference Series IOP Publishing 1402 (2019) 044043 Doi :10.1088/1742-6596/1402/4/04404

Quality of Experience Experimentation Prediction Framework through Programmable Network Management

Quality of experience (QoE) metrics can be used to assess user perception and satisfaction in data services applications delivered over the Internet. End-to-end metrics are formed because QoE is dependent on both the users’ perception and the service used. Traditionally, network optimization has focused on improving network properties such as the quality of service (QoS). In this paper we examine adaptive streaming over a software-defined network environment. We aimed to evaluate and study the media streams, aspects affecting the stream, and the network. This was undertaken to eventually reach a stage of analysing the network’s features and their direct relationship with the perceived QoE. We then use machine learning to build a prediction model based on subjective user experiments. This will help to eliminate future physical experiments and automate the process of predicting QoE

User Access Control and Bandwidth Allocation for Slice-Based 5G-and-Beyond Radio Access Networks

In this paper, we investigate the resource management for radio access network slicing from user access control and wireless bandwidth allocation perspectives. First, to guarantee users' QoS, we propose two admission control (AC) policies to select admissible users from the perspective of optimizing the QoS and the number of serving users respectively. Then, to optimize the bandwidth utilization for the selected admissible users, we investigate the slice association and bandwidth allocation (SABA) problem and propose network centric and UE centric SABA policies respectively. Numerical results show that in typical scenarios, our proposed AC and SABA policies can significantly outperform traditional policies in terms of wireless bandwidth utilization and number of admissible users

Two-Stage Focused Inference for Resource-Constrained Collision-Free Navigation

Long-term operations of resource-constrained robots typically require hard decisions be made about which data to process and/or retain. The question then arises of how to choose which data is most useful to keep to achieve the task at hand. As spacial scale grows, the size of the map will grow without bound, and as temporal scale grows, the number of measurements will grow without bound. In this work, we present the first known approach to tackle both of these issues. The approach has two stages. First, a subset of the variables (focused variables) is selected that are most useful for a particular task. Second, a task-agnostic and principled method (focused inference) is proposed to select a subset of the measurements that maximizes the information over the focused variables. The approach is then applied to the specific task of robot navigation in an obstacle-laden environment. A landmark selection method is proposed to minimize the probability of collision and then select the set of measurements that best localizes those landmarks. It is shown that the two-stage approach outperforms both only selecting measurement and only selecting landmarks in terms of minimizing the probability of collision. The performance improvement is validated through detailed simulation and real experiments on a Pioneer robot.United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-11-1-0391)United States. Office of Naval Research (Grant N00014-11-1-0688)National Science Foundation (U.S.) (Award IIS-1318392