Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC50 values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.

The flow-cytometric (FCM) analysis of bivariate DNA/lgG distributions has been conducted to study the cell cycle kinetics and monoclonal antibody (MAb) production during perfusion culture of hybridoma cells. Three different perfusion rates were employed to demonstrate the dependency of MAb synthesis and secretion on cell cycle and growth rate. The results showed that, during the rapid growth period of perfusion culture, the level of intracellular igG contents of hybridoma cells changed significantly at each perfusion rate, while the DNA histograms showing cell cycle phases were almost constant. Meanwhile, during the reduced growth period of perfusion culture, the fraction of cells in the S phase decreased, and the fraction cells in the G1/G0 phase increased with decreasing growth rate. The fraction of cells in the G2/M phase was relatively constant during the whole period of perfusion culture. Positive correlation was found between mean intracellular IgG contents and the specific MAb production rate, suggesting that the deletion of intracellular IgG contents by a flow cytometer could be used as a good indicator for the prediction of changes in specific MAb productivity following manipulation of the culture condition.

The optimal temperature control policy for an immobilized glucose isomerase reactor system was studied. This optimization study takes into consideration the enzyme deactivation during the continuous reactor operation. The kinetic parameters including reduced Michaelis-Menten constant (i?,,,), reduced maximum reaction rate (V,,,), equilibrium constant (&), and enzyme deactivation constant ( k d ) and their functional relationships to temperature were determined experimentally. The optimization problem was formulated in terms of maximization of fructose productivity as the objective function. The optimization problem was solved by making use of a maximum principle and the control vector iteration method. Approximately 8% improvement in terms of fructose productivity was achieved when the preprogrammed optimal temperature control policy was employed as compared with the reactor operation at an optimum constant temperature.

Solvents with weak coordination bonding (e.g., TCM and DCM) confined in the nanopores of a metal–organic framework undergo dynamic coordination exchange with stronger Lewis-basic solvents (e.g., H2O), and they lead to enhanced catalytic efficiency.

Electrospun polyacrylonitrile (PAN) nanofibers were carbonized with or without iron (III) acetylacetonate to induce catalytic graphitization within the range of 900-1,500 o C, resulting in ultrafine carbon fibers with a diameter of about 90-300 nm. Their structural properties and morphologies were investigated. The carbon nanofibers (CNF) prepared without a catalyst showed amorphous structures and very low surface areas of 22-31 m 2 /g. The carbonization in the presence of the catalyst produced graphite nanofibers (GNF). The hydrogen storage capacities of these CNF and GNF materials were evaluated through the gravimetric method using magnetic suspension balance (MSB) at room temperature and 100 bar. The CNFs showed hydrogen storage capacities which increased in the range of 0.16-0.50 wt% with increasing carbonization temperature. The hydrogen storage capacities of the GNFs with low surface areas of 60-253 m 2 /g were 0.14-1.01 wt%. Micropore and mesopore, as calculated using the nitrogen gas adsorption-desorption isotherms, were not the effective pore for hydrogen storage.