Reconstructing Kinetic Models for Dynamical Studies of Metabolism using Generative Adversarial Networks

Kinetic models of metabolic networks relate metabolic fluxes, metabolite concentrations, and enzyme levels through well-defined mechanistic relations rendering them an essential tool for systems biology studies aiming to capture and understand the behavior of living organisms. However, due to the lack of information about the kinetic properties of enzymes and the uncertainties associated with available experimental data, traditional kinetic modeling approaches often yield only a few or no kinetic models with desirable dynamical properties making the computational analysis unreliable and computationally inefficient. We present REKINDLE (REconstruction of KINetic models using Deep LEarning), a deep-learning-based framework for efficiently generating large-scale kinetic models with dynamic properties matching the ones observed in living organisms. We showcase REKINDLE's efficiency and capabilities through three studies where we: (i) generate large populations of kinetic models that allow reliable in silico testing of hypotheses and systems biology designs, (ii) navigate the phenotypic space by leveraging the transfer learning capability of generative adversarial networks, demonstrating that the generators trained for one physiology can be fine-tuned for another physiology using a low amount of data, and (iii) expand upon existing datasets, making them amenable to thorough computational biology and data-science analyses. The results show that data-driven neural networks assimilate implicit kinetic knowledge and structure of metabolic networks and generate novel kinetic models with tailored properties and statistical diversity. We anticipate that our framework will advance our understanding of metabolism and accelerate future research in health, biotechnology, and systems and synthetic biology. REKINDLE is available as an open-access tool.

Poly(vinylalcohol) (PVA) Assisted Sol-Gel Fabrication of Porous Carbon Network-Na3V2(PO4)3 (NVP) Composites Cathode for Enhanced Kinetics in Sodium Ion Batteries

Na3V2(PO4)3 is regarded as one of the promising cathode materials for next-generation sodium ion batteries, but its undesirable electrochemical performances due to inherently low electrical conductivity have limited its direct use for applications. Motivated by the limit, this study employed a porous carbon network to obtain a porous carbon network–Na3V2(PO4)3 composite by using poly(vinylalcohol) assised sol-gel method. Compared with the typical carbon-coating approach, the formation of a porous carbon network ensured short ion diffusion distances, percolating electrolytes by distributing nanosized Na3V2(PO4)3 particles in the porous carbon network and suppressing the particle aggregation. As a result, the porous carbon network–Na3V2(PO4)3 composite exhibited improved electrochemical performances, i.e., a higher specific discharge capacity (~110 mAh g−1 at 0.1 C), outstanding kinetic properties (~68 mAh g−1 at 50 C), and stable cyclic stability (capacity retention of 99% over 100 cycles at 1 C).

Hydrogen Sorption Behavior of Cast Ag-Mg Alloys

In this paper, the hydrogen sorption properties of casted Ag-Mg alloys were investigated. The obtained alloys were structurally analyzed by X-ray diffraction (XRD) and observed by scanning electron microscopy (SEM). The study was carried out for four alloys from the two-phase region (Mg) + γ′ (AgMg4) with nominal concentrations of 5 wt. %, 10 wt. %, 15 wt. %, and 20 wt. % Ag, four alloys with nominal compositions equivalent to intermetallic phases: AgMg4, AgMg3, AgMg, and Ag3Mg, one alloy from the two-phase region AgMg + Ag3Mg (Ag60Mg40), and one alloy from the two-phase region AgMg + AgMg3 (Ag40Mg60). The hydrogenation process was performed using a Sievert-type sorption analyzer. The hydride decomposition temperature and kinetic properties of the synthesized hydrides were investigated by differential scanning calorimetry (DSC) coupled with thermogravimetric analysis (TGA). Samples with high magnesium content were found to readily absorb significant amounts of hydrogen, while hydrogen absorption was not observed for samples with silver concentrations higher than 50 at. % (AgMg intermetallic phase).

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

THE STUDY OF THE SORPTION PROPERTIES OF FILTERING MATERIALS BASED ON TITANIUM PHOSPHATE - POROUS TITANIUM COMPOSITION

Inorganic sorbents are more selective in comparison with commercial ion exchange resins towards of metal ions. However, inorganic sorbents characterized not high kinetic properties. One of the way to increase the kinetic rate of inorganic sorbents is to reduce the particle size of these materials, other way is synthesizing inorganic sorbents as porous products from powder materials. A sample of such inorganic sorbents is titanium phosphate of various compositions. Studying the properties of microfilters based on composition titanium phosphate - porous titanium has been developed. The sorbents based on acidic titanium phosphate Ti(HPO4)2∙H2O were used for filtering solution with Fe(II) content. It is found that the number of impregnations with inorganic sorbent modificator is important and influence filtration process. The obtained results demonstrated that after the first impregnation of porous material with a smaller pore size, it is possible to obtain such sorbent as a mass content of powder material. By varying the ionic form of titanium phosphate, the porosity of titanium, the amount of impregnation, it could be possible effect on the sorption Fe(II). The sorption properties of titanium-titanium phosphate microfilters were studied by potentiometric titration in the NaCl-NaOH system, as well as the sorption of Fe2+ ions. The degree of purification for Fe(II) from solution with a concentration of 10 mg/l is 64 %. Application an electric potential to the microfilter of porous titanium - phosphate titanium increases the degree of purification of Fe(II) to 88 %.

Theoretical and Experimental Considerations for a Rapid and High Throughput Measurement of Catalase In Vitro

A rapid and high throughput protocol to measure the catalase activity in vitro has been designed. Catalase is an enzyme with unusual kinetic properties because it does not follow the standard Michaelis–Menten model and is inactivated by H2O2. This makes the analysis of the two rate equations of the second-ordered reactions of the kinetic model rather complex. A two-degree polynomial fitting of the experimental data is proposed after transforming the exponential form of the integrated rate equation of the [H2O2] into a polynomial using the Taylor series. The fitting is validated by establishing an experimental linear relationship between the initial rate of the H2O2 decomposition and the protein concentration, regardless of the suicide inactivation that catalase might undergo beyond t > 0. In addition, experimental considerations are taken into account to avoid statistical bias in the analysis of the catalase activity. ANOVA analyses show that the proposed protocol can be utilized to measure the initial rate of the H2O2 decomposition by catalase in 32 samples in triplicates if kept below 8 mM min−1 in the microplate wells. These kinetic and statistical analyses can pave the way for other antioxidant enzyme activity assays in microplate readers at small scale and low cost.

Luminescence efficiency of cerium-doped yttrium aluminum garnet ceramics formed by radiation assisted synthesis

The variety of applications of yttrium-aluminum garnet (YAG)-based luminescent materials and the morphology necessary for these purposes required the development of many technologies for their synthesis. All synthesis technologies used are complex. The structural phase of yttrium-aluminum garnet is formed with any technology, at temperatures exceeding 1,500 °C. The starting materials for the synthesis are metal oxides of aluminum, yttrium and other oxides for activation and modification. It seems possible to use hard radiation to form a new phase. Radiation synthesis of ceramics is realized in less than 1 s, without the use of any additives and influences. The synthesis was carried out at the electron accelerator of the Institute of Nuclear Physics (Novosibirsk). In this work, we studied the spectral-kinetic and quantitative characteristics of luminescence for the first time obtained by the method of radiation synthesis of ceramic samples of yttrium-aluminum garnet doped with cerium with statistical processing of their values. The dependences of the reproducibility of the spectral characteristics of the luminescence of the samples on the preliminary preparation of the charge for synthesis have been investigated. Several cycles of luminophore brightness studies have been performed. It is shown that the obtained ceramics based on yttrium-aluminum garnet doped with cerium possesses the required spectral-kinetic properties, and the efficiency of conversion of the chip radiation into luminescence is achieved, which is comparable to that available in commercial phosphors. The maximum measured values of the position of the bands are from 553.5 to 559.6 nm. Brightness values range from 4,720 to 1,960 cd/m2. It was found that the main reason for the scatter in the characteristics of the luminescent properties of ceramics of yttrium-aluminum garnet, activated by cerium obtained by radiation assisted synthesis is the high rate of synthesis and, especially, the high rate of cooling of the samples.

Characterization of a Novel Chromosome-Encoded AmpC β-Lactamase Gene, blaPRC–1, in an Isolate of a Newly Classified Pseudomonas Species, Pseudomonas wenzhouensis A20, From Animal Farm Sewage

In this work, we characterized a novel chromosome-encoded AmpC β-lactamase gene, blaPRC–1, in an isolate of a newly classified Pseudomonas species designated Pseudomonas wenzhouensis A20, which was isolated from sewage discharged from an animal farm in Wenzhou, China. Susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis were performed to determine the function and enzymatic properties of the β-lactamase. Sequencing and comparative genomic analysis were conducted to clarify the phylogenetic relationship and genetic context of the blaPRC–1 gene. PRC-1 is a 379-amino acid AmpC β-lactamase with a molecular weight of 41.48 kDa and a predicted pI of 6.44, sharing the highest amino acid identity (57.7%) with the functionally characterized AmpC β-lactamase PDC-211 (ARX71249). blaPRC–1 confers resistance to many β-lactam antibiotics, including penicillins (penicillin G, amoxicillin, and amoxicillin-clavulanic acid) and cephalosporins (cefazolin, ceftriaxone, and cefotaxime). The kinetic properties of PRC-1 were compatible with those of a typical class C β-lactamase showing hydrolytic activities against β-lactam antibiotics, and the hydrolytic activity was strongly inhibited by avibactam. The genetic context of blaPRC–1 was relatively conserved, and no mobile genetic element was predicted in its surrounding region. Identification of a novel β-lactamase gene in an unusual environmental bacterium reveals that there might be numerous unknown resistance mechanisms in bacterial populations, which may pose potential risks to human health due to universal horizontal gene transfer between microorganisms. It is therefore of great value to carry out extensive research on the mechanism of antibiotic resistance.

The properties of highly concentrated aqueous CH3COOK/Na binary electrolyte and its use in sodium-ion batteries

Highly concentrated aqueous binary solutions of acetate salts are emerging as promising systems for advanced energy storage applications. Together with superior solubility of CH3COOK helpful in achieving water-in-salt electrolyte concentrations, the presence of CH3COOLi or CH3COONa permits intercalation of desired cations in electrode crystalline phases. Although these systems have captured profound scientific attention in recent years, a fundamental understanding of their physicochemical properties is still lacking. In this work, the thermal, rheological, transport, and electrochemical properties for a series of solutions comprising of 20 mol kg-1 of CH3COOK with different concentrations of CH3COONa are reported and discussed. The most concentrated solution, i.e., 20 mol kg-1 of CH3COOK with 7 mol kg-1 of CH3COONa came out to be the best in terms of a compromise between transport properties and electrochemical stability window. Such a solution has a conductivity of 21.2 mS cm-1 at 25°C and shows a stability window up to 3 V in “ideal” conditions, i.e., using small surface area and highly electrocatalytic electrode in a flooded cell. As a proof of concept of using this solution in sodium-ion batteries, carbon-coated LiTi2(PO4)3 (NASICON) demonstrated the ability to reversibly insert and de-insert Na+ ions at about -0.7 V vs. SHE with a first cycle anodic capacity of 85 mAh g-1, average charge efficiency of 96% at low current and a 90% capacity retention after 60 cycles. The very good kinetic properties of the interface are also demonstrated by the low value of activation energy for the charge transfer process (0.12 eV).

Phosphorus Acquisition and Utilization in Plants

Tremendous progress has been made on molecular aspects of plant phosphorus (P) nutrition, often without heeding information provided by soil scientists, ecophysiologists, and crop physiologists. This review suggests ways to integrate information from different disciplines. When soil P availability is very low, P-mobilizing strategies are more effective than mycorrhizal strategies. Soil parameters largely determine how much P roots can acquire from P-impoverished soil, and kinetic properties of P transporters are less important. Changes in the expression of P transporters avoid P toxicity. Plants vary widely in photosynthetic P-use efficiency, photosynthesis per unit leaf P. The challenge is to discover what the trade-offs are of different patterns of investment in P fractions. Less investment may save P, but are costs incurred? Are these costs acceptable for crops? These questions can be resolved only by the concerted action of scientists working at both molecular and physiological levels, rather than pursuing these problems independently. Expected final online publication date for the Annual Review of Plant Biology, Volume 73 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.