Influence of mechanical-biological pretreatment of municipal solid waste on landfill behaviour

Mechanical-biological pretreatment of municipal solid waste (MSW) can significantly improve the behaviour of landfills. Chemical oxygen demand (COD) and total nitrogen in the leachate, as well as the gas production rate, are about 90% lower than for untreated waste. The volume to be landfilled decreases by mechanical-biological pretreatment by up to 60%

Aerobic in situ stabilization of completed landfills and old sites

Investigations of aerobic m situ stabilization of old sites in laboratory-scale tests show that a significant reduction of the nitrogen concentration in the leachate takes place. The degradation and release of organic compounds via the gas phase could be accelerated. The required aeration volumes for the biological stabilization are technically realizable as the total oxygen demand is relatively low

Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction

Since the late 1980s, mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. Such mutations reduce the ability of the small GTPase RAS to hydrolyze GTP, keeping this molecular switch in a constitutively active GTP-bound form that drives, unchecked, oncogenic downstream signaling. One strategy to reduce the levels of active RAS is to target guanine nucleotide exchange factors, which allow RAS to cycle from the inactive GDP-bound state to the active GTP-bound form. Here, we describe the identification of potent and cell-active small-molecule inhibitors which efficiently disrupt the interaction between KRAS and its exchange factor SOS1, a mode of action confirmed by a series of biophysical techniques. The binding sites, mode of action, and selectivity were elucidated using crystal structures of KRAS$^{G12C}$–SOS1, SOS1, and SOS2. By preventing formation of the KRAS–SOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. The final compound 23 (BAY-293) selectively inhibits the KRAS–SOS1 interaction with an IC$_{50}$ of 21 nM and is a valuable chemical probe for future investigations