Improved Sendai viral system for reprogramming to naive pluripotency

優れた多分化能を持つヒトのナイーブ型iPS細胞を迅速に作製する方法を発明. 京都大学プレスリリース. 2022-10-18.A novel method for generating naive human iPS cells with significantly higher differentiation potency. 京都大学プレスリリース. 2022-11-15.Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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An Efficient Level-Set Flame Propagation Model for Hybrid Unstructured Grids Using the G-Equation

Computational fluid dynamics of gas-fueled large-bore spark ignition engines with pre-chamber ignition can speed up the design process of these engines provided that 1) the reliability of the results is not affected by poor meshing and 2) the time cost of the meshing process does not negatively compensate for the advantages of running a computer simulation. In this work a flame propagation model that runs with arbitrary hybrid meshes was developed and coupled with the KIVA4-MHI CFD solver, in order to address these aims. The solver follows the G-Equation level-set method for turbulent flame propagation by Tan and Reitz, and employs improved numerics to handle meshes featuring different cell types such as hexahedra, tetrahedra, square pyramids and triangular prisms. Detailed reaction kinetics from the SpeedCHEM solver are used to compute the non-equilibrium composition evolution downstream and upstream of the flame surface, where chemical equilibrium is instead assumed. A generalized least-squares gradient reconstruction algorithm is employed to evaluate spatial derivatives with arbitrary node and cell connectivities, instead of the original ENO scheme. Finally, a new, extended version of the “marching cubes” algorithm for iso-surface tracking was developed and implemented for all four employed cell types. The solver was tested across different cell types and cell resolutions by simulating spherical ignition in a simple cylindrical combustion chamber. Validation was performed against experimental measurements of torch jet ignition with a diaphragm and of prechamber gaseous fuel combustion two-chamber experimental vessel separated by a variable-diameter nozzle, with different grid resolutions

Prominent structural dependence of quantum capacitance unraveled by nitrogen-doped graphene mesosponge

Porous carbons are important electrode materials for supercapacitors. One of the challenges associated with supercapacitors is improving their energy density without relying on pseudocapacitance, which is based on fast redox reactions that often shorten device lifetimes. A possible solution involves achieving high total capacitance (Ctot), which comprises Helmholtz capacitance (CH) and possibly quantum capacitance (CQ), in high-surface carbon materials comprising minimally stacked graphene walls. In this work, a templating method is used to synthesize 3D mesoporous graphenes with largely identical pore structures (≈2100 m2 g−1 with an average pore size of ≈7 nm) but different concentrations of oxygen-containing functional groups (0.3–6.7 wt.%) and nitrogen dopants (0.1–4.5 wt.%). Thus, the impact of the heteroatom functionalities on Ctot is systematically investigated in an organic electrolyte excluding the effect of pore structures. It is found that heteroatom functionalities determine Ctot, resulting in the cyclic voltammetry curves being rectangular or butterfly-shaped. The nitrogen functionalities are found to significantly enhance Ctot owing to increased CQ

Numerical investigation of oil droplet combustion using single particle ignition cell model

Pre-ignition in internal combustion engines is an abnormal combustion phenomenon which often results in structural damage to the engine. It occurs when an ignition event takes place in the combustion chamber before the designed ignition time. In this work, a numerical study was done to investigate the pre-ignition with potential application to natural gas marine engines. This was done by simulating experiments of lube oil–induced ignition and subsequent combustion in a constant volume combustion chamber using an in-house version of the KIVA4-CFD code. Initial conditions of the chamber gases are obtained from the pre-burn process of a known composition of C2H2/oxidizer mixture. Natural gas was injected from a single-hole injector at an injection temperature and pressure of 300 K and 105 Pa, respectively. A rotating fan was modeled, as is in the experimental setup. Oil droplet of known size and velocity is injected into the constant volume combustion chamber. For accurate prediction of oil droplet ignition, the computational cells that contain the droplets are to be refined. Combustion calculations are then carried out on the refined grid. Ignition delay times of both lube oil and methane/air mixtures were calculated. Parametric studies were also conducted by varying droplet conditions, and their results are also presented

Autopsy findings in a rare case of pleomorphic carcinoma in a patient on dialysis

Key Clinical Message Pleomorphic lung cancer is a very rare type of cancer and very few cases have been reported in the literature. We present a case of pleomorphic lung cancer in a patient with history of IgA nephropathy on hemodialysis

Activation of the endocannabinoid system by organophosphorus nerve agents

D 9 -Tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana, has useful medicinal properties but also undesirable side effects. The brain receptor for THC, CB 1 , is also activated by the endogenous cannabinoids anandamide and 2-arachidonylglycerol (2-AG). Augmentation of endocannabinoid signaling by blockade of their metabolism may offer a more selective pharmacological approach compared with CB 1 agonists. Consistent with this premise, inhibitors of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH) produce analgesic and anxiolytic effects without cognitive defects. In contrast, we show that dual blockade of the endocannabinoid-degrading enzymes monoacylglycerol lipase (MAGL) and FAAH by selected organophosphorus agents leads to greater than ten-fold elevations in brain levels of both 2-AG and anandamide and to robust CB 1 -dependent behavioral effects that mirror those observed with CB 1 agonists. Arachidonic acid levels are decreased by the organophosphorus agents in amounts equivalent to elevations in 2-AG, which indicates that endocannabinoid and eicosanoid signaling pathways may be coordinately regulated in the brain. The endogenous cannabinoid ('endocannabinoid') system consists of G protein-coupled cannabinoid receptors (CB 1 and CB 2 ) that bind two principal endogenous ligands: 2-AG (1) 1 and N-arachidonoylethanolamine (anandamide, 2) 2 (Scheme 1). Endocannabinoids regulate a diverse array of neurological (for example, memory and motility) and metabolic (for example, feeding and lipolysis) functions, and their levels are altered under pathophysiological conditions, including pain, anxiety, neurodegenerative disease, brain injury and metabolic disorders Cannabinoid receptors not only recognize endogenous lipid ligands but are also targets of exogenous agonists, the best known of which is THC (3), the principal psychoactive constituent of marijuana 14 . THC and other CB 1 agonists produce an array of intense behavioral effects, some of which, such as pain relief, have possible therapeutic utility. However, the beneficial properties of CB 1 agonists are accompanied by a number of untoward side effects, including hypomotility, hypothermia and cognitive dysfunction 14 . CB 1 agonists have also shown abuse potential in rodents, leading to dependence and withdrawal 14 . These findings raise legitimate concerns about the therapeutic potential of direct CB 1 agonists. Augmentation of endocannabinoid signaling by blockade of 2-AG and/or anandamide degradation has been proposed as an alternative therapeutic strategy that might produce a selective subset of the behavioral effects observed with direct CB 1 agonists 15 . Consistent with this premise, Faah -/-mice or rodents treated with FAAH inhibitors show elevated brain levels of anandamide (but not 2-AG) and exhibit analgesic, anxiolytic and antidepressant phenotypes without concomitant alterations in motility, cognition or body temperature Organophosphorus (OP) nerve agents produce their primary neurotoxicity through inactivation of acetylcholinesterase (AChE). However, many of the pharmacological effects of OP agents cannot be explained by disruption of cholinergic transmissio