Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system.

Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists.We acknowledge the Wellcome Trust Programmes in Translational Medicine and Therapeutics (085686) and in Metabolic and Cardiovascular Disease (096822/Z/11/Z), the British Heart Foundation PG/09/050/27734, MRC and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.tips.2015.06.00

DDColor: Towards Photo-Realistic Image Colorization via Dual Decoders

Image colorization is a challenging problem due to multi-modal uncertainty and high ill-posedness. Directly training a deep neural network usually leads to incorrect semantic colors and low color richness. While transformer-based methods can deliver better results, they often rely on manually designed priors, suffer from poor generalization ability, and introduce color bleeding effects. To address these issues, we propose DDColor, an end-to-end method with dual decoders for image colorization. Our approach includes a pixel decoder and a query-based color decoder. The former restores the spatial resolution of the image, while the latter utilizes rich visual features to refine color queries, thus avoiding hand-crafted priors. Our two decoders work together to establish correlations between color and multi-scale semantic representations via cross-attention, significantly alleviating the color bleeding effect. Additionally, a simple yet effective colorfulness loss is introduced to enhance the color richness. Extensive experiments demonstrate that DDColor achieves superior performance to existing state-of-the-art works both quantitatively and qualitatively. The codes and models are publicly available at https://github.com/piddnad/DDColor.Comment: ICCV 2023; Code: https://github.com/piddnad/DDColo

Size Effect on the Behavior of Thermal Elastohydrodynamic Lubrication of Roller Pairs

In order to investigate the size effect on elastohydrodynamic lubrication (EHL) of roller pairs, complete numerical solutions for both the Newtonian fluid and the Eyring fluid thermal EHL problems of roller pairs under steady state conditions have been achieved. It can be seen that there is no size effect on the isothermal EHL performance; however, there is a very strong size effect on the thermal EHL performance. Results show that the term of shearing heat is the most important factor for the film temperature when the size of a contact changes. Comparison between the Newtonian solution and the Eyring solution has been made under some operating conditions. It is interesting to see that the effective viscosity of the Eyring fluid is nearly the same as that of the Newtonian fluid when the size of a contact is large enough. The non-Newtonian effect, therefore, can be ignored when the size of a contact is very large. It is equally interesting to see that the thermal effect can be ignored when the size of a contact is very small. In addition, the influence of the velocity parameter, the load parameter, and the slide-roll ratio on the lubricating performance for various sizes of contacts has been investigated

Apelin receptor in GtoPdb v.2023.1

The apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [73] and subsequently updated [75]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) [88]. A second family of peptides discovered independently and named Elabela [13] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [97, 71]. The enzymatic pathways generating biologically active apelin and Elabela isoforms have not been determined but both propeptides include sites for potential proprotein convertase processing [81]. Structure-activity relationship Elabela analogues have been described [65, 90]. The stoichiometry of apelin receptor-heterotrimeric G protein complexes has been studied using cryogenic-electron microscopy [98]

Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [68]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) by a so far unidentified enzymatic pathway [80]. A second family of peptides discovered independently and named Elabela [11] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [87, 67]. Structure-activity relationship Elabela analogues have been described [61]

Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [68]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) by a so far unidentified enzymatic pathway [80]. A second family of peptides discovered independently and named Elabela [11] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [87, 67]. Structure-activity relationship Elabela analogues have been described [61]