In Silico Modeling and Scoring of PROTAC-Mediated Ternary Complex Poses

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce ubiquitination and subsequent degradation of proteins via formation of ternary complexes between an E3 ubiquitin ligase and a target protein. Rational design of PROTACs requires accurate knowledge of the native configuration of the PROTAC induced ternary complex. This study demonstrates that native and non-native ternary complex poses can be distinguished based on pose occupancy time in MD, where native poses exhibit longer occupancy times than non-native ones at both room and higher temperatures. Candidate poses are generated by MD sampling and pre-ranked by the classic MM/GBSA method. A specific heating scheme is then applied to induce ternary pose departure, generating an occupancy score and temperature score reflecting pose occupancy time and fraction. The scoring approach enables identification of the native pose in all the test systems. Beyond providing a relative rank of hypothetical poses of a given ternary system, the method could also provide empirical guidance to whether a given ternary pose is likely a native one or not. The success of the method is in part attributed to the dynamic nature of the pose departure analysis which accounts for solute entropic effects, typically neglected in the faster static pose scoring methods, while solute entropic contributions play a greater role in protein-protein interactions than in protein-ligand systems.

MAIN CONCEPTUAL APPROACHES AND TECHNICAL SOLUTIONS OF THE HEAT SUPPLY SCHEME OF KYIV FOR THE PERIOD UNTIL 2030

The analysis of the district heating system of the city of Kyiv and its main operational indicators is presented. The main problems that need to be solved in the development of a new District Heating Scheme are described. The basic conceptual directions and technical decisions concerning development of system of heat supply of the city for the settlement period are resulted. As part of the development of the Heat Supply Scheme of Kyiv for the period up to 2030, a powerful heat source in the city center will be gradually converted to hydrogen fuel obtained from "green" energy by electrolysis (until the needs of ST-1 are fully met after 2030).

Critical Conditions for the Ignition of a Gel Fuel under Different Heating Schemes

A model was developed to research the critical conditions and time characteristics of the ignition of gel fuels in the course of conductive, convective, radiant and mixed heat transfer. MATLAB was used for numerical modeling. Original MATLAB code was established pursuant to the developed mathematical model. For gel fuel ignition at initial temperatures corresponding to cryogenic storage conditions with different heating schemes, a numerical analysis of interconnected processes of heat and mass transfer in the chemical reaction conditions and exothermic and endothermic phase transitions was conducted. The model was tested by comparing the theoretical results with the experimental data. Dependencies were established between the key process characteristic (i.e., the ignition delay time) and the ambient temperature when the following parameters were varied: emissivity, heat emission coefficient, activation energy and pre-exponential factor of the fuel vapor oxidation reaction. The critical values of the main parameters of the energy source were determined. For these values, gel fuel ignition conditions were consistently realized for each heating scheme. The critical heat fluxes necessary and sufficient for the ignition of typical gel fuels were determined.

Peculiarities of High-Energy Induction Heating during Surface Hardening in Hybrid Processing Conditions

This paper presents the results obtained when combining mechanical and surface-thermal operations, using the same process equipment. The paper also demonstrates the possibility of implementing high-energy heating with high-frequency currents, and proposes using an integral temperature–time characteristic as the main parameter to specify surface quenching modes. The numerical values of the integral temperature–time characteristic are to be related to the processing modes and the depth of hardening. The experiments confirmed that an increase in the capacity will be commensurate with an increase in power consumption when a volumetric heating scheme (with a hardening depth of 0.5 mm) is realized. However, during the realization of a volumetric heating scheme, when the 0.7 mm depth of the hardened layer is at the boundary of the “hot” depth of the current penetration into the metal (the beginning of the intermediate heating scheme), the increase in the processing capacity will be higher than that in power consumption.

ANALYSIS OF THERMOLUMINESCENCE GLOW CURVES RECORDED UNDER THE HYPERBOLIC HEATING SCHEME BY USING AN ALTERNATIVE CONCEPT OF SYMMETRY

Usually, the order of kinetics of thermoluminescence (TL) glow curve is evaluated by using the concept of traditional symmetry factor (μ_g) in which only three points of a glow curve are used. From the statistical point of view of the reliability of any method of analysis of glow, curve improves if instead of a few points the method can use a larger portion of the glow curve. In the present work, a technique is proposed to determine the order of kinetics associated with a TL peak by using the concept of skewness. The method is applied to experimental thermoluminescence (TL) curves recorded in a hyperbolic heating scheme.

Carbonaceous Chondrite Outgassing Experiments: Implications for Methane Replenishment on Titan

<p>Titan is the only known moon in the Solar System with a substantial atmosphere of N2 and CH4. However, its origin and evolution are not well understood. Titan’s present amount of atmospheric CH4 was predicted to be destroyed photochemically on very short timescales (~ 10 Myrs, Yung et al. 1984). This suggests that a methane resupply mechanism is necessary. The Huygens probe GCMS measurements of noble gases suggest that Titan’s atmosphere is likely linked to its interior instead of being incorporated during formation (Nieman et al., 2005). Recent theoretical modeling works of Titan’s atmosphere and interior suggest that its atmosphere could have originated partly by outgassing primordial organics in its interior (Neri et al. 2019; Miller et al. 2019). If this theory holds, volatiles like methane could be outgassing from Titan’s interior to sustain its current observed abundances. Insoluble organic matter (IOM) found in carbonaceous chondrites may serve as an analog for the organic material in Titan’s interior and provide experimental constraints on the outgassed component of its atmosphere (Thompson et al. 2021). By heating carbonaceous chondrite samples and measuring the abundances of their released volatiles, specifically methane, we may be able to connect what we see in the lab to species in Titan’s atmosphere today.</p> <p>We performed outgassing experiments using three primordial CM carbonaceous chondrites: Murchison, Aguas Zarcas, and Jbilet Winselwan. The first two are "fall" meteorite (1969 and 2019), and Jbilet Winselwan is a desert "find'' meteorite (2013). We used two sizes of samples for each CM chondrite for the measurements: a small grain sample with diameters < 20 µm and a normal grain sample with diameters of 20-100µm. Each sample underwent a step heating scheme where they are heated and held at every 100°C from room temperature to 1200° C. The whole heating scheme takes 12 hours. We continuously monitored the partial pressures of 10 outgassed mass peaks using a residual gas analyzer (RGA).</p> <p>We can estimate how much methane can be outgassed from the insoluble organics in the CM chondrites with the RGA data. We found that chondrite outgassing can resupply methane that can last for ~0.5-2 Gyrs. If organics indeed makes a significant fraction of Titan's interior, outgassing through thermal instability of Titan's interior can potentially resupply Titan's atmospheric methane for a period of time.</p>

Distributed solar panel heating scheme with auxiliary energy in Tibet

Tibet is located in the high cold and high altitude, the ecological environment is fragile, and the clean utilization of energy has attracted much attention. On the basis of clean energy and reliable power supply, winter heating in Tibet is an urgent livelihood problem to be solved. Based on the current situation of solar heating in Tibet, a distributed solar flat heating scheme with auxiliary energy is proposed, and the heating dispatching mode is analyzed. The research results not only provide a solution for energy efficient and clean heating in Tibet, but also have a certain reference value for the construction of clean energy base in Tibet.

Response to Comment on “Light-induced lattice expansion leads to high-efficiency solar cells”

Rolston et al. suggest through a convective heating scheme that the mechanism of light-induced lattice expansion is from light-induced thermal heating. We bring out key differences in the physical observables that are not discussed and different from what is observed in the original paper by Tsai et al.