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Deciphering the unique dynamic activation pathway in a G protein-coupled receptor enables unveiling biased signaling and identifying cryptic allosteric sites in conformational intermediates

arXiv.org Artificial Intelligence

N eurotensin receptor 1 (NTSR1), a member of the C lass A G protein - coupled receptor superfamily, plays a n important role in modulating dopamine rgic neuronal activity and eliciting opioid - independent analgesia. Recent studies suggest that promoting β - arrestin - bias ed signaling in NTSR1 may diminish drugs of abuse, such as psychostimulants, thereby offering a potential avenue for treating human addiction - related disorders . In this study, we utiliz e d a novel computational and experimental approach that combined nudged elastic band - based molecular dynamics simulations, Markov state models, temporal communication network analysis, site - directed mutagenesis, and conformational biosensors, to explore the intricate mechanisms underlying NTSR1 activation and bias ed signal ing . Our study reveal s a dynamic stepwise transition mechanism and activat ed transmission network associated with NTSR1 activation. It also yield s valuable insights into the complex interplay between the unique polar network, non - conserved ion locks, and aromatic clusters in NTSR1 signaling. Moreover, we identif ied a cryptic allosteric site located in the intracellular r egion of the receptor that exists in an intermediate state within the activation pathway. Collectively, these findings contribute to a more profound understanding of NTSR1 activation and biased signal ing at the atomic level, thereby providing a potential strateg y for the development of NTSR1 allosteric modulators in the realm of G protein - coupled receptor biology, biophysics, and medicine.


A new solution and concrete implementation steps for Artificial General Intelligence

arXiv.org Artificial Intelligence

At present, the mainstream artificial intelligence generally adopts the technical path of "attention mechanism + deep learning" + "reinforcement learning". It has made great progress in the field of AIGC (Artificial Intelligence Generated Content), setting off the technical wave of big models[ 2][13 ]. But in areas that need to interact with the actual environment, such as elderly care, home nanny, agricultural production, and vehicle driving, trial and error are expensive and a reinforcement learning process that requires much trial and error is difficult to achieve. Therefore, in order to achieve Artificial General Intelligence(AGI) that can be applied to any field, we need to use both existing technologies and solve the defects of existing technologies, so as to further develop the technological wave of artificial intelligence. In this paper, we analyze the limitations of the technical route of large models, and by addressing these limitations, we propose solutions, thus solving the inherent defects of large models. In this paper, we will reveal how to achieve true AGI step by step.


DJI says it will cripple drones unless users register them

Daily Mail - Science & tech

Drone owners may not have to register their machines with the Federal Aviation Administration, but users of a DJI model will experience restrictions if they do not verify their craft with the manufacturer. The China-based firm has announced it will introduce a new application activation process for users that provides the necessary information to power the drone. For those who do not comply, their unmanned aerial vehicle (UAV) will experience camera malfunctions and flight will be limited to a 164-foot (50m) radius up to 98 feet (30m) high. Anyone who owns or purchased a DJI drone'will have to log in once when you update the new version of DJI GO or GO 4 App,' DJI said. 'If this activation process is not performed, the aircraft will not have access to the correct geospatial information and flight functions for that region, and its operations will be restricted if you update the upcoming firmware,' the firm continued.


Register your drone with DJI or it will throttle it

Engadget

You might not have to register your drones through the Federal Aviation Administration anymore, but if your flyer of choice is a DJI model, you'll have to activate it online, or take a hit in flight range and functionality. The company is adding a new application activation process, tied to a firmware update for its family of drones. It'll come into effect at the end of this week, and is aimed at ensuring pilots use "the correct set of geospatial information and flight functions for your aircraft", determined by your location and user profile. The activation process will require users to connect to the internet through DJI's app, to verify your account and activate the update. Your drone won't be able to access the geospatial info and flight functions, camera streaming will be disabled and flight range will be curtailed to a 164-foot radius, up to 98 feet high. These rules will apply to all of DJI's "aircraft" running the latest firmware, whether you own a Phantom 4 or one of its cheaper drones.