Artificial Ego Machines. the Problem of Artificial Intelligence in Neurophilosophy

In these theses, the author describes the content of the article devoted to the problem of artificial intelligence, namely, the problem of creating an artificial conscious subject. It is necessary to involve both modern neuroscience and modern neurophilosophy in solving this problem. The proposition is put forward that the conscious subject does not necessarily have to be a living being. The author gives the questions that need to be resolved when creating an artificial conscious subject. The author postulates the conclusion that it is necessary to refrain from any attempts to create an artificial conscious subject before solving these issues, but at the same time, the author also States the need to continue research in this area in order to prevent the accidental creation of such a subject.В данных тезисах, автор описывает содержание статьи, посвященной проблеме искусственного интеллекта, а именно, проблеме создания искусственного сознающего субъекта. Высказывается необходимость привлечения к решению этой проблемы как современных нейронаук, так и современной нейрофилософии. Выдвигается положение, что сознающий субъект необязательно должен быть живым существом. Автором даются вопросы, которые необходимо разрешить при создании искусственного сознающего субъекта. Постулируется вывод о необходимости воздержаться от всяких попыток создания искусственного сознающего субъекта, до решения этих вопросов, но вместе с тем, автором заявляется и необходимость продолжения исследований в данной области для того, чтобы не допустить случайного создания подобного субъекта

Role of SRC-Family Kinases in Hypoxic Vasoconstriction of Rat Pulmonary Artery

Aims: We investigated the role of src-family kinases (srcFKs) in hypoxic pulmonary vasoconstriction (HPV) and how this relates to Rho-kinase-mediated Ca(2+) sensitization and changes in intracellular Ca(2+) concentration ([Ca(2+)](i)). Methods and results: Intra-pulmonary arteries (IPAs) were obtained from male Wistar rats. HPV was induced in myograph-mounted IPAs. Auto-phosphorylation of srcFKs and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and myosin light-chain (MLC(20)) in response to hypoxia were determined by western blotting. Translocation of Rho-kinase and effects of siRNA knockdown of src and fyn were examined in cultured pulmonary artery smooth muscle cells (PASMCs). [Ca(2+)](i) was estimated in Fura-PE3-loaded IPA. HPV was inhibited by two blockers of srcFKs, SU6656 and PP2. Hypoxia enhanced phosphorylation of three srcFK proteins at Tyr-416 (60, 59, and 54 kDa, corresponding to src, fyn, and yes, respectively) and enhanced srcFK-dependent tyrosine phosphorylation of multiple target proteins. Hypoxia caused a complex, time-dependent enhancement of MYPT-1 and MLC(20) phosphorylation, both in the absence and presence of pre-constriction. The sustained component of this enhancement was blocked by SU6656 and the Rho-kinase inhibitor Y27632. In PASMCs, hypoxia caused translocation of Rho-kinase from the nucleus to the cytoplasm, and this was prevented by anti-src siRNA and to a lesser extent by anti-fyn siRNA. The biphasic increases in [Ca(2+)](i) that accompany HPV were also inhibited by PP2. Conclusion: Hypoxia activates srcFKs and triggers protein tyrosine phosphorylation in IPA. Hypoxia-mediated Rho-kinase activation, Ca(2+) sensitization, and [Ca(2+)](i) responses are depressed by srcFK inhibitors and/or siRNA knockdown, suggesting a central role of srcFKs in HPV

Fabrication, microstructure and optical characterizations of holmium oxide (Ho2O3) transparent ceramics

Ho2O3 transparent ceramics were fabricated by vacuum pre-sintering combined with hot isostatic pressing (HIP) post-treatment at relatively low temperature from high-purity Ho2O3 powder calcined at 1000 °C for 4 h. The optimal Ho2O3 ceramic sample prepared by vacuum pre-sintering at 1250 °C and HIP post-treating at 1450 °C has a dense microstructure with average grain size of 0.77 μm, and the in-line transmittances reach 80.7 % at 1550 nm and 76.7 % at 1064 nm. The effect of air annealing on the optical quality of Ho2O3 ceramics was studied, and the existence of compressed pores in the HIP-ed Ho2O3 ceramics was confirmed. The Verdet constants of Ho2O3 ceramics were measured to be -47.4 rad/(T m at 1064 nm and -15.4 rad/(T m at 1561 nm. High transmittance and large Verdet constant in the wavelength regions 1–1.07 μm, 1.3–1.5 μm make Ho2O3 transparent ceramics promising for magneto-optical devices for lasers based on Yb-, Nd-doped materials and telecom lasers. © 2020 Elsevier Ltd19-52-53014; Chinese Academy of Sciences, CAS: QYZDB-SSW-JSC022; Russian Science Foundation, RSF: 18-13-00355; National Key Research and Development Program of China, NKRDPC: 2017YFB0310500This work was supported by the National Key R&D Program of China (Grant No. 2017YFB0310500 ), the Special Exchange Program of Chinese Academy of Sciences (Plan B) , the key research project of the frontier science of the Chinese Academy of Sciences (No. QYZDB-SSW-JSC022 ), partially by the Research Project of the Russian Science Foundation (No. 18-13-00355 ) and Verdet constant measurements was done under NSFC-RFBR Cooperative Research Projects Grant 19-52-53014

Glabridin-induced vasorelaxation: Evidence for a role of BK_Ca channels and cyclic GMP

AbstractBackground and purposeGlabridin is a major flavonoid in Glycyrrhiza glabra (licorice) root, a traditional Asian medicine. Glabridin is reported to have anti-atherogenic, anti-inflammatory and anti-nephritic properties; however its effects on vascular tone remain unexplored.Experimental approachWe examined the effect of glabridin on rat main mesenteric artery using isometric myography and also ELISA to measure cGMP levels.Key resultsGlabridin (30μM) relaxed arteries pre-constricted with the thromboxane A2 analog U46619 (0.2μM) by ~60% in an endothelium-independent manner. Relaxation to 30μM glabridin was abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1μM) and by the BKCa channel blocker tetraethyammonium (1mM) but was unaffected by the estrogen receptor antagonist ICI182780. The concentration-response curve to glabridin (0.1 to 30μM) was downshifted by the KATP channel blocker glibenclamide (10μM), the KV channel blocker 4-aminopyridine (300μM), and the KIR blocker BaCl2 (30μM). In U46619-contracted arteries partially relaxed by 0.1μM sodium nitroprusside, application of 10 and 30nM glabridin caused additional vasorelaxation. Glabridin (30μM) approximately doubled tissue [cyclic GMP]. Application of the phosphodiesterase inhibitor isobutylmethylxanthine caused a much larger rise in [cyclic GMP], and glabridin failed to cause vasorelaxation or a further rise in [cGMP] when co-applied with IBMX.Conclusions and implicationsVasorelaxation to glabridin is dependent on the opening of K+ channels, particularly BKCa, probably caused by a rise in cellular [cyclic GMP] owing to phosphodiesterase inhibition. In the presence of sodium nitroprusside an effect of glabridin is observed at nM concentrations, similar those measured in plasma following human ingestion of licorice flavonoid oil

Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization

AIMS: To determine the role of gap junctions (GJs) in hypoxic pulmonary vasoconstriction (HPV). METHODS AND RESULTS: Studies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F(2α) (PGF(2α), 3 µM) or 20 mM K(+). The GJ inhibitors 18β-glycyrrhetinic acid (18β-GA, 30 µM), heptanol (3.5 mM), or 2-aminoethoxydiphenyl borate (2-APB) (75 µM) had little effect on the transient Phase 1 of HPV, but abolished the sustained Phase 2 which is associated with Ca(2+) sensitization. The voltage-dependent Ca(2+) channel blocker diltiazem (10 µM) had no effect on HPV, and did not alter the inhibitory action of 18β-GA. Sustained HPV is enhanced by high glucose (15 mM) via potentiation of Ca(2+) sensitization, in the presence of high glucose 18β-GA still abolished sustained HPV. Simultaneous measurement of tension and intracellular Ca(2+) using Fura PE-3 demonstrated that whilst 18β-GA abolished tension development during sustained HPV, it did not affect the elevation of intracellular Ca(2+). Consistent with this, 18β-GA abolished hypoxia-induced phosphorylation of the Rho kinase target MYPT-1. In anaesthetized rats hypoxia caused a biphasic increase in systolic right ventricular pressure. Treatment with oral 18β-GA (25 mg/kg) abolished the sustained component of the hypoxic pressor response. CONCLUSION: These results imply that GJs are critically involved in the signalling pathways leading to Rho kinase-dependent Ca(2+) sensitization during sustained HPV, but not elevation of intracellular Ca(2+), and may explain the dependence of the former on an intact endothelium