Computational study of non-catalytic T-loop pocket on CDK proteins for drug development

Cyclin-dependent kinases （CDKs） are critical to the cell cycle and many other biological processes, and as such, are considered as one of the promising targets for therapy against cancer and other diseases. Most pan-CDK inhibitors bind to the highly conserved catalytic ATP-binding pocket and therefore lack the specificity to prevent side effects. It is desirable to develop drugs targeting non-catalytic pockets for specificity towards individual CDKs. Here we performed a systematic analysis of non-catalytic pockets on CDKs and identified a region underneath the T-loop, which we term TL pocket, for potential inhibitor development. Specifically, we compared the TL pockets of human CDK2 and CDK7-homolog Pfmrk of Plasmodium falciparum, a malaria-causing parasite. Molecular dynamics simulations of several short peptides revealed that this less conserved TL pocket could be used to design potentially specific inhibitors against malaria disease.

N₂O Formation in Selective Non-catalytic NO_xReduction Processes

Nitrous oxide is not an environmentally regulated species in the U.S., but it does participate in the stratospheric ozone chemistry and contributes to the greenhouse effect. Nitrous oxide has been found to be a by-product of the selective non-catalytic reduction process. Chemical kinetic calculations demonstrated that the formation of nitrous oxide in the urea-based selective non-catalytic reduction process is linked to the conversion of NO by cyano species released from the process parent compounds. This conversion occurs within in temperature window between 850 and 1050℃. With urea injection, nitrous oxide emissions represent up to 20 percent conversion of the NOx reduced. The amount of nitrous oxide formed depends primarily on the process temperature, the amount of chemical injected, the initial NOx level, and the carbon monoxide level in the gas stream. These observations, which were based on the chemical kinetics of the process, should be considered in designing selective non-catalytic reduction systems to minimize nitrous oxide by- product formation.

Control of nitrogen oxides emission by selective non-catalytic reduction in preheating section during iron ore pellets production

Reducing the NO_(x) emission from pelletizing process is of great importance to the green development of iron and steel industry.The flue gas temperature of preheating(PH)section during grate-kiln iron ore pelletizing process typically ranges within 850–1050℃,which meets the temperature requirements of selective non-catalytic reduction(SNCR)for NO_(x).The in-bed SNCR behavior of NO_(x) in the PH section was investigated,and the influence of relevant parameters was revealed.Results show that with the flue gas temperature rising,the denitration rate reached a peak value and then declined,where the appropriate temperature range was 950–1000℃.Increasing the NH_(3)/NO ratio(NSR)contributed to improving the denitration rate,and the appropriate NSR was 1.0.Oxygen content in the flue gas also showed an important influence on denitration rate,which reached a peak value and then dropped with the oxygen content rising.Under the condition of 18 vol.%oxygen content,the denitration reaction mainly occurred in the form of 4NO+4NH_(3)+O_(2)=4N_(2)+6H_(2)O.For restricting the competitive reaction of NH_(3) oxidation,the oxygen content in flue gas of PH section should be kept at an appropriate range.In general,the denitration rate reached about 25%in the PH section through spraying ammonia.

A generalized mathematical model for non-catalytic gas-solid reactions

Based on a general classification and characteristic comparison of the existing models, a new model for non-catalytic gas-solid reactions is proposed and a general formulation for the model in terms of the solid conversion, X, is presented in mis paper. The model, referred to the generalized model, is demonstrated to be applicable to any solid reactant of general structure ranging from highly porous to nonporous materials. It is shown that the generalized model incorporates the grain and pore structure for a solid pellet and can be reduced to the grain and random pore models as extreme cases.

Hydrogen-based direct reduction of industrial iron ore pellets:Statistically designed experiments and computational simulation

As part of efforts to reduce anthropogenic CO_(2) emissions by the steelmaking industry,this study investigated the direct reduction of industrially produced hematite pellets with H_(2) using the Doehlert experimental design to evaluate the effect of pellet diameter(10.5-16.5 mm),porosity(0.36-0.44),and temperature(600-1200℃).A strong interactive effect between temperature and pellet size was observed,indicating that these variables cannot be considered independently.The increase in temperature and decrease in pellet size considerably favor the reduction rate,while porosity did not show a relevant effect.The change in pellet size during the reduction was negligible,except at elevated temperatures due to crack formation.A considerable decrease in mechanical strength at high temperatures suggests a maximum process operating temperature of 900℃.Good predictive capacity was achieved using the modified grain model to simulate the three consecutive non-catalytic gas-solid reactions,considering different pellet sizes and porosities,changes during the reaction from 800 to 900℃.However,for other temperatures,different mechanisms of structural modifications must be considered in the modeling.These results represent significant contributions to the development of ore pellets for CO_(2)-free steelmaking technology.

Numerical Simulation of Urea Based SNCR Process in a Trinal-Sprayed Precalciner

In order to study the combustion characteristics,NOx emission and NH3 slip in a new trinal-sprayed precalciner,the simulations of combustion and aqueous urea solution based selective non-catalytic reduction(SNCR)process were conducted by computational fluid dynamics in this precalciner,the effects of different injection heights,different injection flow rates and stratified injection under different flow rates on SNCR process were studied.The results showed that the flow field was symmetrically distributed in the precalciner,and the flue gas from the rotary kiln formed the recirculation region on both sides of the cone body,which increased the residence time of the solid particles.The temperature was mainly between 1100 K and 1250 K in the middle and upper column of the precalciner,which met the demand of the pulverized coal combustion and raw material decomposition.The concentration of NO at the outlet of the precalciner was 559 ppm,moreover,different injection heights and different injection flow rates had a strong influence on NOX removal efficiency and NH3 slip.The aqueous urea solution should be injected at SNCR-1 to prolong the residence time of NH3,and injection flow rate had an optimal flow rate but not the higher the better.When the injection flow rate under stratified injection was 0.019 kg/s,which could play a better optimization role on NO removal efficiency on the basic of the injection flow rate.In consideration of cost effective,a stratified injection with an injection flow rate of 0.019 kg/s and an injection height of 20 m,25 m and 30 m was suggested as a compromise of a satisfactory NOx reduction rates and reasonable NH3 slip.Under this condition,numerical simulation result showed that NOx concentration at the outlet of precalciner was 297.27 mg/Nm3 and NH3 slip was 4.67 mg/Nm3,meeting emission standard.

Production of Biodiesel with Seed Soybean and Supercritical Ethanol

This paper presents a study of biodiesel production by a non-catalytical process. The innovation in this study is the use of novel materials for production: seed soybean (Glycine Max) “in natura” and ethanol in a supercritical state. To conduct the experiments, a bench reactor with a capacity of 150 mL, resistant to pressure of up to 300 bar and temperature of 350°C was developed. The fractional factorial experimental design () was used to evaluate the temperature, seed granulometry, molar ratio ethanol/oil and water percent of the mixture. The best yield observed was that of 94.07%, 10 minutes after the reactor entered a supercritical condition. Significant effects on seed granulometry, molar ratio ethanol, oil and temperature were verified. From the proposed process, biodiesel and toasted soybean seed were obtained. To purify the biodiesel sample it was necessary to use ultra-centrifugation to separate seed particles, and rotoevaporation to separate the fatty acid ethyl ester and unreacted ethanol. The chemical analyses were conducted directly by gas chromatography. The yield was calculated in accordance with concentrations obtained in the chromatographic analysis and seed mass of the experiment. Also checked was the presence of palmitate esters, stearate, oleate, linoleate and linolenate. By analyzing the ester composition it was possible to assess whether a good quality biodiesel was available. The roasted soybean seeds obtained after the reaction showed a calorific potential of 2203.17 kcal/kg and also be used as fuel.

Hole-growth phenomenon during pyrolysis of a cation-exchange resin particle

A novel central hole-expansion phenomenon is identified, in which the cation-exchange resin is pyrolyzed in a mixed atmosphere of nitrogen and oxygen at 400–500 ℃. In this reaction, the reaction path is predictable and always starts from the center of the resin particle to form a central hole, then continues and expands around the hole, finally forming a uniformly distributed hole group;the particle surface remains intact. Analysis shows that this formation mode is due to the different reaction paths of sulfonic groups between the surface and interior of the particle, caused by the temperature difference. On the surface, transformation reactions happen at high temperatures(410–500 ℃) to form stable organic sulfur structures, while decomposition occurs inside the particle at a relatively low temperature(<410 ℃) and promotes complete pyrolysis of the copolymer matrix to form holes.