Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles

CRISPR-Cas12a is a leading technology for development of model organisms, therapeutics, and diagnostics. These applications could benefit from chemical modifications that stabilize or tune enzyme properties. Here we chemically modify ribonucleotides of the AsCas12a CRISPR RNA 5′ handle, a pseudoknot structure that mediates binding to Cas12a. Gene editing in human cells required retention of several native RNA residues corresponding to predicted 2′-hydroxyl contacts. Replacing these RNA residues with a variety of ribose-modified nucleotides revealed 2′-hydroxyl sensitivity. Modified 5′ pseudoknots with as little as six out of nineteen RNA residues, with phosphorothioate linkages at remaining RNA positions, yielded heavily modified pseudoknots with robust cell-based editing. High trans activity was usually preserved with cis activity. We show that the 5′ pseudoknot can tolerate near complete modification when design is guided by structural and chemical compatibility. Rules for modification of the 5′ pseudoknot should accelerate therapeutic development and be valuable for CRISPR-Cas12a diagnostics.

Improvement of the Thermocouple Method for Testing Energy-Intensive Emulsions for Compatibility with the Sulfide Ores

The results are presented concerning improving the thermostatic method for studying the chemical compatibility of modern industrial emulsion explosives based on the ammonium nitrate with surrounding materials, the increased reactivity of which can lead to spontaneous ignition and even explosion. An assessment of the compatibility of emulsion explosives with sulphide ores was conducted using an original thermocouple methodology developed at the D. Mendeleyev University of Chemical Technology of Russia, fixation of the thermal effects of the interaction of shell-free explosives based on the ammonium nitrate with sulfide minerals. Improved thermocouple method allows to determine chemical compatibility of the industrial explosives with the reactive rocks. It is distinguished by the possibility of continuous recording of the thermocouple measurements during tests using an oscilloscope and combines the reliability of the results with small laboratory weights of the test samples (no more than 20 g, which ensures safety testing). Temperature measurement accuracy is ± 2 °С. It is concluded that the method used is able to identify the cases of the most dangerous interaction from the practice point of view using the emulsion explosives when the pyrite content in the ore exceeds 85 %. The results of experiments on the applicability of thermocouple measurements to testing low-activity rocks, highly reactive pyrite ores, mixed sulfide ores of medium activity, as well as on the identification of the main regularities of heat release during the interaction of emulsion explosives with the sulfide ores are considered.

Chemical and biological compatibility of different injection waters with Zubair Formation Water of Upper Sand Member in Zubair Oil Field, South of Iraq

Water injection by water flooding was used to enhance and increase oil production in Zubair oil field, southern Iraq. Physical-chemical and biological analysis of five water samples from different sources were collected to evaluate its compatibility with formation water using biological experiments and chemical compatibility simulation. The results show that injection water is classified weakly acidic-weakly alkaline and saline water, whereas surface water samples are considered weakly acid-weakly alkaline. The total dissolved solids results show brackish types accept for Formation water which classified weakly acid and Brine water. All the studied water samples contain bacteria colonies of Escherichia coli and Coliform expect for one sample, while Sulfate Reducing Bacteria was founded in all studied samples. Mathematical model of chemical compatibility between studied water samples and Zubair Formation water of the scale prediction model show that there are no needs for any inhibition treatments of all scales except for Geothite and Dolomite that should be treated before water injection. The biological compatibility experiments results show Formation damage about (61%) and (69%) in the studied core samples, while Bactria in water injection caused formation damage about (20%) and (51%).

Physical and Chemical Compatibility of Etomidate and Propofol Injectable Emulsions

<b><i>Introduction:</i></b> The mixture of etomidate and propofol is widely used in clinical practice to improve efficacy of general anesthesia and to minimize side effects. As a thermodynamically unstable system, emulsion is prone to destabilization through mechanisms including coalescence, flocculation, and creaming. Such unwanted phenomenon can induce fat embolism after intravenous administration. This study was aimed to investigate the physical and chemical stability of the mixture of etomidate and propofol in the dosage form of emulsion. <b><i>Methods:</i></b> This compatibility study focused on the critical quality attributes (CQAs) of drug-containing emulsions, such as appearance, pH, particle size and distribution, <i>zeta</i> potential, the observation under centrifugation, and drug content and impurity. <b><i>Results:</i></b> As the results, there were no significant changes in the CQAs of the mixed emulsions up to 24 h after mixing at refrigeration temperature (4°C), room temperature (25°C), and body temperature (37°C). <b><i>Conclusions:</i></b> These results demonstrate that etomidate emulsion is physically and chemically compatible with propofol emulsions up to 24 h at 4°C, 25°C, and 37°C, suggesting that etomidate and propofol can be administrated in mixture without adversely affecting product characteristics, at least in vitro.

Phase Change Material of Copper–Germanium Alloy as Solar Latent Heat Storage at High Temperatures

A copper–germanium alloy (Cu–Ge alloy) was examined as a phase change material, at temperatures exceeding 600°C, for latent heat storage in solar thermal applications. First, the thermo-physical properties of the Cu–Ge alloy were examined using differential scanning calorimetry, thermomechanical analysis, and laser flash analysis. Second, to evaluate the thermal response and reliability of the Cu–Ge alloy, the cyclic properties of thermal charge/discharge were examined under various thermal conditions. The alloys obtained after the tests were examined for their chemical compatibility with the stainless steel container using an electron probe micro analyzer. The elemental distribution of each Cu–Ge alloy was evaluated using cyclic performance tests. Finally, the chemical compatibility of the Cu–Ge alloy was evaluated using a high-temperature test with candidate materials of a phase change material container vessel [stainless steel (SUS310S), Inconel625, silicon carbide (SiC), and alumina (Al2O3)]. The Cu–Ge alloy exhibited significant potential as a latent heat storage material in next-generation solar thermal power plants because it demonstrates various advantages, including a superior storage capacity at a temperature of 644°C, temperature coherence to the phase diagram, a quick thermal response, satisfactory cyclic behavior of charge/discharge modes, a thermodynamically stable metallographic structure, and non-reactivity with container ceramic materials (SiC and Al2O3).

Design of the MIDES plant

This chapter presents the full design of two microbial desalination cells (MDCs) at pilot-plant scale from the MIDES project. The final MDC pilot unit design was based on the knowledge gained through up scaling of the MDC from lab- to prepilot scale. The MDC pilot plant consists of one stack of 15 MDC pilot units with 0.4 m2 electrode area. This chapter also presents the piping and instrumentation diagram (P&ID) and layout of the MDC pilot plant. The MIDES pilot plants are comprised of an MDC pilot plant housed in a 40-ft container with the rest of the peripheral elements. Finally, this chapter presents the improvement made from the first to the second MDC stack in terms of stability and the chemical compatibility of the end plates.

Bonding SiCp/Al Composites via Laser-Induced Exothermic Reactions

In this paper, the SiCp/Al composites were bonded via laser-induced exothermic reactions of a Ni–Al–Zr interlayer. The Ni–Al–Zr interlayer was designed based on its exothermic property and chemical compatibility with the SiCp/Al composites. The influences of the interlayer composition and bonding pressure on the joint microstructure and shear strength were investigated. Results indicated that high exothermic reactions occurred in the Ni–Al–Zr interlayer and realized the reliable bonding with the SiCp/Al composites. The interlayer products were the eutectic structure of NiAl+Ni2AlZr+Ni3Al5Zr2. NiAl3 and Ni2Al3 reaction layers were formed at the bonding interfaces. The interlayer composition and the bonding pressure determined the morphology and distribution of the voids and the reaction layers, thus controlling the joint shear strength. When the SiCp/Al composites were bonded using the interlayer with the Zr content of 15 wt.% under the bonding pressure of 3 MPa, the joint shear strength reached the maximum of 24 MPa.