Quantitative Kinetic Model Research Articles

Critical micellar concentration determination of pure phospholipids and lipid-raft and their mixtures with cholesterol.

Phospholipids in biological membranes establish a chemical equilibrium between free phospholipids in the aqueous phase (CMC) and self-assembled phospholipids in vesicles, keeping the CMC constant. The CMC is different for each phospholipid, depends on the amount of cholesterol, and, according to the lipid-chaperone hypothesis, controls the interaction between free phospholipids and amyloidogenic proteins (such as amylin, amyloid-β, and α-synuclein, all of which are, respectively, associated with a different proteinopathy), which governs the formation of a toxic complex between free lipids and proteins that leads to membrane destruction. Here, we provide quantitative measurements of CMCs and bilayer stability of pure phospholipids, lipid rafts, and their mixture with cholesterol by fluorescence methods (using pyrene as a probe) and light scattering techniques (resonance Rayleigh scattering and fixed-angle light scattering) performed on LUVs, as well as AFM to measure LUV dimensions. Also, we test the lipid-chaperone hypothesis on human IAPP interacting with different mixture of POPC cholesterol. Stated the importance of CMC in membrane stability and protein aggregation processes, these results could be a starting point for the development of a quantitative kinetic model for the lipid chaperone hypothesis.

Vesicular neurotransmitters exocytosis monitored by amperometry: theoretical quantitative links between experimental current spikes shapes and intravesicular structures.

Single cell amperometry has proven to be a powerful and well-established method for characterizing single vesicular exocytotic events elicited at the level of excitable cells under various experimental conditions. Nevertheless, most of the reported characteristics are descriptive, being mostly concerned with the morphological characteristics of the recorded current spikes (maximum current intensities, released charge, rise and fall times, etc.) which are certainly important but do not provide sufficient kinetic information on exocytotic mechanisms due to lack of quantitative models. Here, continuing our previous efforts to provide rigorous models rationalizing the kinetic structures of frequently encountered spike types (spikes with unique exponential decay tails and kiss-and-run events), we describe a new theoretical approach enabling a quantitative kinetic modeling of all types of exocytotic events giving rise to current spikes exhibiting exponential decay tails. This model follows directly from the fact that the condensation of long intravesicular polyelectrolytic strands by high concentrations of monocationic neurotransmitter molecules leads to a matrix structure involving two compartments in constant kinetic exchanges during release. This kinetic model has been validated theoretically (direct and inverse problems) and its experimental interest established by the analysis of the amperometric spikes relative to chromaffin and PC12 cells previously published by some of us.

Improving Cell-Free Expression of Model Membrane Proteins by Tuning Ribosome Cotranslational Membrane Association and Nascent Chain Aggregation.

Cell-free gene expression (CFE) systems are powerful tools for transcribing and translating genes outside of a living cell. Synthesis of membrane proteins is of particular interest, but their yield in CFE is substantially lower than that for soluble proteins. In this paper, we study the CFE of membrane proteins and develop a quantitative kinetic model. We identify that ribosome stalling during the translation of membrane proteins is a strong predictor of membrane protein synthesis due to aggregation between the ribosome nascent chains. Synthesis can be improved by the addition of lipid membranes, which incorporate protein nascent chains and, therefore, kinetically compete with aggregation. We show that the balance between peptide-membrane association and peptide aggregation rates determines the yield of the synthesized membrane protein. We define a membrane protein expression score that can be used to rationalize the engineering of lipid composition and the N-terminal domain of a native and computationally designed membrane proteins produced through CFE.

Cyanide Bioremediation by Bacillus subtilis under Alkaline Conditions

Cyanide (CN) is a toxic environmental pollutant generated by various industrial activities, necessitating the application of bioremediation techniques for its degradation. Biodegradation is a more cost-effective and environmentally friendly technique with high efficiency in CN removal. This study isolated cyanide-degrading bacteria from Tutupaca mining site soil from Tacna, Peru. Bacillus subtilis strain TT10s was selected for its exceptional capacity to rapidly and completely eliminate cyanide under alkaline conditions (pH 10.5), removing 1000 ppm cyanide within 48 h. A kinetic analysis revealed that the biodegradation follows second-order rate kinetics (k2 = 0.08649 mg/(mg·h), R2 = 0.96622), consistent with the literature attribution of the rate-limiting step to the inducible cyanide dihydratase enzyme, which converts cyanide into ammonia and formate via the Michaelis–Menten model. Fourier-transform infrared spectroscopy (FTIR) spectral analysis further corroborated this enzymatic mechanism, showing the disappearance of CN peaks coupled with the emergence of ammonia (NH) and formate (C=O) peaks. Quantitative kinetic modelling integrated with FTIR profiles and degradation curves implicates cyanide dihydratase as the key rate-controlling enzyme in alkaline cyanide biodegradation without the need for an extra carbon source, generating interest for future bioremediation applications in highly contaminated environments.

Hydrogen production by kraft black liquor supercritical water gasification: Reaction pathway and kinetic

Kraft black liquor (KBL) supercritical water gasification (SCWG) has significant implications for carbon emission reduction and energy efficiency improvement in the pulp industry. This research focuses on investigating the SCWG of KBL under different reaction conditions, including reaction times (5–30 min), temperatures (450–650 °C), and feed concentrations (5%–20%), utilizing a high heating rate batch reactor. The performance of the gasification process is evaluated by analyzing gaseous, liquid, and solid products. Remarkable achievements in carbon gasification efficiency (CGE) of 95.28% and COD removal of 99.90% are attained at 650 °C, 30 min, and 10 wt% feed concentration. The liquid-phase products primarily comprise aromatic compounds, particularly phenolics, with the possible presence of reactive nonaromatic compounds such as cyclopentanone. Lower temperatures favor the formation of solid products, which result from phenolic agglomeration reactions leading to char formation. The research also explores the SCWG reaction pathway of KBL and develops a comprehensive twelve-lumped quantitative kinetic model. This work provides valuable engineering parameters for reactor design, optimization, and numerical simulations, facilitating advancements in SCWG of KBL technology.

Flow-Assisted Corrosion of Carbon Steel in Simulated Nuclear Plant Steam Generator Conditions

Flow-assisted corrosion occurs via increased dissolution and/or mechanical degradation of protective oxide formed on the surface of construction materials in direct contact with coolant liquids. In the present paper, this phenomenon is studied on carbon steel in an ammonia-ethanolamine-hydrazine electrolyte by in situ electrochemical impedance spectroscopy in conditions that closely simulate those that prevail in nuclear plant steam generators. Based on the obtained results, a quantitative kinetic model of the process is proposed and parameterized by nonlinear regression of experimental data to the respective transfer function. On the basis of the experimental and calculational results, it is concluded that flow-assisted corrosion of carbon steel is limited by oxide dissolution and cation ejection processes and the protective layer–coolant interface. Expressions for the film growth and corrosion release processes are proposed and successfully compared to operational data.

Annealing parameters effect on microstructure evolution, tensile properties and deformation behaviors of direct-cold-rolled UNS S32101 duplex stainless steel with heterogeneous layered structure

Microstructure evolution, strain-induced martensite transformation (SIMT) kinetics, tensile properties, deformation behaviors of UNS S32101 duplex stainless steel (DSS) with heterogeneous layered structure (HLS) were investigated. HLS composed of multiscale grains (spanning coarse, fine, and ultrafine grains) was prepared by direct cold rolling in combination with short-time annealing, being dominated by coarse-grained ferrite (CGed α) and fine-grained austenite (FGed γ). A quantitative SIMT kinetics model was established to predict the α′-martensite fraction at various strain/annealing parameters, indicating that increased average grain size (AGS) for γ not only contributed to the SIM formation but also promoted the monotonic increase of SIMT rate until annealing for 10 min. Relatively high stacking fault energy (SFE, 35.89∼39.34 mJ/m2) favored mechanical twinning as the dominant deformation mode of γ accompanied by SIMT and dislocation glide. And α deformation was mainly coordinated by wavy slip. Both SFE and Olson-Cohen parameters were strongly correlated with the γ AGS, which could reasonably interpret the dependence of SIMT on the AGS. The A and B values increased progressively with grain coarsening along with the rapid decline in SFE, facilitating the martensite formation. Further increasing the AGS beyond the peak region severely suppressed SIMT probably due to the low probability of martensite embryo generation at deformation twins (DTs) intersections, coinciding with the sharp decrease A value.

The Road to Quantitative Lipid Biochemistry in Living Cells.

Traditional cell biological techniques are not readily suitable for studying lipid signaling events because genetic perturbations are much slower than the interconversion of lipids in complex metabolic networks. For this reason, novel chemical biological approaches have been developed. One approach is to chemically modify a lipid with a so-called "caging group" that renders it inactive, but this cage can be removed photochemically inside cells to release the bioactive molecule. These caged compounds offer unique advantages for studying the kinetics of cellular biochemistry and have been extensively used in the past. However, a limitation of conventional caged compounds is their ability to diffuse freely inside the cell, which does not permit localized activation below optical precision. This poses a challenge for studying lipid signaling as lipid function inside cells is tightly linked to their parent membrane. An ideal lipid probe should, therefore, be restricted to a single organelle membrane or preferentially to a single leaflet. We first demonstrated the plasma-membrane-specific photorelease of fatty acids by employing sulfonated caging groups. Using these caged fatty acid probes we demonstrated that lipid localization determines signaling outcome. Generalizing this approach, we designed a so-called "click cage" that can be coupled to lipids and offers the possibility to attach organelle targeting groups via click chemistry. Using this strategy, we have synthesized plasma membrane, lysosomal, mitochondria, and endoplasmic-reticulum-targeted lipids that can be used to dissect organelle-specific signaling events. To reduce the synthetic effort associated with generating caged compounds, we designed a coumarin triflate reagent that allows the direct functionalization of phosphate- or carboxylate-containing compounds. With this novel reagent, we synthesized a small library of photocaged G-protein-coupled receptor (GPCR) ligands to study the underlying lipid signaling dynamics. Most recently, we have focused on quantifying the kinetics of lipid signaling for different diacylglycerol (DAG) species using plasma-membrane-targeted caged DAGs. Using this approach, we quantitatively measured lipid-protein affinities and lipid transbilayer dynamics in living cells. After analyzing DAGs with different acyl chain length and saturation degree, we discovered that affinities can vary by up to an order of magnitude. This finding clearly shows that cells are able to distinguish between individual DAG species, thereby demonstrating that lipid diversity matters in cellular signal processing. Although the recent advances have yielded valuable tools to study lipid signaling, challenges remain on specifically targeting the different leaflets of organelle membranes. Furthermore, it is necessary to simplify the experimental approaches required for parametrizing and corroborating quantitative kinetic models of lipid signaling. In the future, we envision that the application of leaflet-specific caged lipids to model membrane systems will be of crucial importance for understanding lipid asymmetry.

Reaction pathway and kinetics study on supercritical water gasification of oily sludge

Supercritical water gasification of oily sludge is a clean technology for waste disposal and energy recovery. In this work, gaseous productions from supercritical water gasification (SCWG) of oily sludge in a batch reactor under different temperatures (550–650 °C) and residence times (1–40 min) was studied. Then, a quantitative kinetic model was employed to study the reaction mechanism and optimize the H2 and CH4 productions. The H2 yield was promoted with the increase in temperature and residence time. The CH4 yield and carbon gasification efficiency (CE) increased with the prolongation of residence time, but reached the maximum when the temperature was 600 °C. The liquid products were mainly composed of alkene, acetone, benzene, toluene, ethylbenzene and xylene, phenolic substances and polycyclic aromatic hydrocarbons (PAHs). Higher temperatures promoted the formation of phenol and PAHs in liquid products, which were hard for gasification. The results of kinetic model indicated that higher temperatures accelerated the reaction rate and intermediates formation, but the effect on gas formation was limited. Reaction rate analysis at 650 °C indicated that H2 was mainly produced from pyrolysis rather than steam reforming. CH4 was produced mostly from pyrolysis and methanation reaction can be neglected.

Experimental and kinetic study of heavy metals transformation in supercritical water gasification of oily sludge

As an industrial organic waste, oily sludge can be transformed into valuable syngas by supercritical water gasification (SCWG) technology. The transformation behaviors of heavy metals in SCWG of oily sludge must be considered to prevent the secondary pollution attributed to the high contents of heavy metals in oily sludge. In this work, the gasification products distribution after SCWG of oily sludge in a batch reactor under different reaction conditions (550–700 °C, 1–15 min) was studied. The distributions of heavy metals (Cu, Cr and Zn) in different forms including acid-soluble and exchangeable fraction (F1), reducible fraction (F2), oxidizable fraction (F3), residual fraction (F4) and heavy metal ions in liquid residues (M+) were presented and the transformation trend of those five fractions during the SCWG process was demonstrated. A reaction pathway and quantitative kinetic model of Zn transformation in SCWG were proposed. The results indicated that gas yield was enhanced at higher reaction temperature and longer residence time. Heavy metals in oily sludge were mainly composed of F3 and M+, they tended to deposit in F4 with increasing reaction temperature and residence time, which was stable and environmentally harmless. F3 showed better reactivity than F2 and contributed more to the formation of F4. Enhancing the transformation of Zn ions in liquid residues to more stable forms was necessary. This study highlighted that SCWG of oily sludge could realize energy utilization and heavy metals stabilization.

Small ionic radii limit time step in Martini 3 molecular dynamics simulations.

Among other improvements, the Martini 3 coarse-grained force field provides a more accurate description of the solvation of protein pockets and channels through the consistent use of various bead types and sizes. Here, we show that the representation of Na+ and Cl- ions as "tiny" (TQ5) beads limits the accessible time step to 25fs. By contrast, with Martini 2, time steps of 30-40fs were possible for lipid bilayer systems without proteins. This limitation is relevant for systems that require long equilibration times. We derive a quantitative kinetic model of time-integration instabilities in molecular dynamics (MD) as a function of the time step, ion concentration and mass, system size, and simulation time. We demonstrate that ion-water interactions are the main source of instability at physiological conditions, followed closely by ion-ion interactions. We show that increasing the ionic masses makes it possible to use time steps up to 40fs with minimal impact on static equilibrium properties and dynamical quantities, such as lipid and solvent diffusion coefficients. Increasing the size of the bead representing the ions (and thus changing their hydration) also permits longer time steps. For a soluble protein, we find that increasing the mass of tiny beads also on the protein permits simulations with 30-fs time steps. The use of larger time steps in Martini 3 results in a more efficient exploration of configuration space. The kinetic model of MD simulation crashes can be used to determine the maximum allowed time step upfront for an efficient use of resources and whenever sampling efficiency is critical.

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI

Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm3 voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (Tmax) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (Kt) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MRglc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (vb) was 0.006 ± 0.005 mL/mL. Values in tumour were: Tmax = 7.1 ± 2.7 µmol/min/mL, Kt = 14 ± 1.7 mM, MRglc = 0.22 ± 0.09 µmol/min/mL, vb = 0.030 ± 0.035 mL/mL. Tmax and Kt were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (kd) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).

Experimental investigation on kinetic behavior of the deformation-induced α→β transformation during hot working of Ti–6Al–2Zr–1Mo–1V alloy below the β-transus

Hot compression test was performed on Ti–6Al–2Zr–1Mo–1V alloy below the β-transus (Tβ) with the temperature range of 940–970 °C. Microstructural evolution, especially on the equiaxed primary α phase (αp), was characterized by scanning electron microscope (SEM), electron backscatter diffraction (EBSD) and transmission electron microscope (TEM). The results showed that the αp could transform into β during hot deformation at α+β two-phase region, i.e., deformation-induced transformation of α→β (DIT). DIT, as an additional softening mechanism, caused the unusual stress response on the flow curves, which was reflected by the fact of the steady stress (σst)<initial yield stress (σ0.2). The fraction of transformed αp was influenced by various hot working parameters (such as temperature, strain and strain rate). Even complete dissolution of αp was present in some cases, indicating a premature Tβ during straining. The DIT is considered as a displacive nucleation and diffusion-controlled growth process. Its mechanism can currently be divided into two types: internal penetration of αp and α/β interface migration. The αp particles with higher favorable orientation preferentially undergo phase transformation. A kinetic model based on the transformed αp fraction (ωαp(t)) during DIT was developed by taking into account the thermal activation contribution (corresponding to heating duration) and mechanical driving force contribution (corresponding to deformation). The model was fitted to the ωαp(t) as a sigmoidal function of time (t) based on the classical Johnson–Mehl–Avrami (JMA) equation. Such a quantitative kinetic model for DIT can be used to accurately tailor the required balance between αp and β in Ti–6Al–2Zr–1Mo–1V alloy during hot working.

Optimize hydrogen production from chicken manure gasification in supercritical water by experimental and kinetics study

In this work, H2 production from supercritical water gasification (SCWG) of chicken manure in a high heating rate batch reactor under different temperatures (500–620 °C) and residence times (1–12 min) was studied, and a quantitative kinetic model was employed to study the reaction mechanism and optimize the H2 production. The H2 yield, hydrogen gasification efficiency (HE) and carbon gasification efficiency (CE) were promoted with the growth of temperature and residence time. The maximum H2 yield, HE and CE reached 22.47 mol/kg, 174.53% and 81.34% at 620 °C and 12 min, respectively. The results of kinetic model indicated that higher temperature accelerated the reaction rate and more intermediates were converted into gas products. H2 was mainly produced by the steam reforming reaction and the generation rate of each gas decreased to be negligible after 10 min. High temperature from nearly 580 °C was preferred to accelerate water gas shift reaction (WGSR) to promote H2 production in SCWG of chicken manure. Hydrolysis reaction of chicken manure has a very important effect on H2 production.

Continuous Pyrolysis Microreactors: Hot Sources with Little Cooling? New Insights Utilizing Cation Velocity Map Imaging and Threshold Photoelectron Spectroscopy.

Resistively heated silicon carbide microreactors are widely applied as continuous sources to selectively prepare elusive and reactive intermediates with astrochemical, catalytic, or combustion relevance to measure their photoelectron spectrum. These reactors also provide deep mechanistic insights into uni- and bimolecular chemistry. However, the sampling conditions and effects have not been fully characterized. We use cation velocity map imaging to measure the velocity distribution of the molecular beam signal and to quantify the scattered, rethermalized background sample. Although translational cooling is efficient in the adiabatic expansion from the reactor, the breakdown diagrams of methane and chlorobenzene confirm that the molecular beam component exhibits a rovibrational temperature comparable with that of the reactor. Thus, rovibrational cooling is practically absent in the expansion from the microreactor. The high rovibrational temperature also affects the threshold photoelectron spectrum of both benzene and the allyl radical in the molecular beam, but to different degrees. While the extreme broadening of the benzene TPES suggests a complex ionization mechanism, the allyl TPES is in fact consistent with an internal temperature close to that of the reactor. The background, room-temperature spectra of both are superbly reproduced by Franck-Condon simulations at 300 K. On the one hand, this leads us to suggest that room-temperature reference spectra should be used in species identification. On the other hand, analysis of the allyl iodide pyrolysis data shows that iodine atoms often recombine to form molecular iodine on the chamber surfaces. Such sampling effects may distort the chemical composition of the scattered background with respect to the molecular beam signal emanating directly from the reactor. This must be considered in quantitative analyses and kinetic modeling.

A kinetic model predicts SpCas9 activity, improves off-target classification, and reveals the physical basis of targeting fidelity

The S. pyogenes (Sp) Cas9 endonuclease is an important gene-editing tool. SpCas9 is directed to target sites based on complementarity to a complexed single-guide RNA (sgRNA). However, SpCas9-sgRNA also binds and cleaves genomic off-targets with only partial complementarity. To date, we lack the ability to predict cleavage and binding activity quantitatively, and rely on binary classification schemes to identify strong off-targets. We report a quantitative kinetic model that captures the SpCas9-mediated strand-replacement reaction in free-energy terms. The model predicts binding and cleavage activity as a function of time, target, and experimental conditions. Trained and validated on high-throughput bulk-biochemical data, our model predicts the intermediate R-loop state recently observed in single-molecule experiments, as well as the associated conversion rates. Finally, we show that our quantitative activity predictor can be reduced to a binary off-target classifier that outperforms the established state-of-the-art. Our approach is extensible, and can characterize any CRISPR-Cas nuclease – benchmarking natural and future high-fidelity variants against SpCas9; elucidating determinants of CRISPR fidelity; and revealing pathways to increased specificity and efficiency in engineered systems.

Fine‐Tuning the Thermal Relaxation Dynamics of Indigo‐Based Photoswitches Using Selective Non‐Covalent Interactions Without Chemical Modification

AbstractUnderstanding the thermal relaxation dynamics of photoswitches is of crucial importance when considering application scenarios. Strategies for regulating the thermal relaxation rates of photoswitches have been mostly limited to modifying the chemical structures. Herein we demonstrate a complementary method of manipulating the thermal relaxation rate of indigo‐based photoswitches that does not require chemical modification. We used indigo‐based photoswitches in aprotic solvents as a model system to demonstrate this strategy. Our method creates a deactivated pathway that extends the thermal relaxation half‐life by selectively stabilizing the parent structure of the metastable Z‐isomer via non‐covalent interaction. In addition, by establishing a quantitative kinetic model, we showed that controlling the strength of such selective stabilization enables fine‐tuning of the thermal relaxation rates to precisely access to targeted values.

General principles of secondary active transporter function.

Transport of ions and small molecules across the cell membrane against electrochemical gradients is catalyzed by integral membrane proteins that use a source of free energy to drive the energetically uphill flux of the transported substrate. Secondary active transporters couple the spontaneous influx of a "driving" ion such as Na+ or H+ to the flux of the substrate. The thermodynamics of such cyclical non-equilibrium systems are well understood, and recent work has focused on the molecular mechanism of secondary active transport. The fact that these transporters change their conformation between an inward-facing and outward-facing conformation in a cyclical fashion, called the alternating access model, is broadly recognized as the molecular framework in which to describe transporter function. However, only with the advent of high resolution crystal structures and detailed computer simulations, it has become possible to recognize common molecular-level principles between disparate transporter families. Inverted repeat symmetry in secondary active transporters has shed light onto how protein structures can encode a bi-stable two-state system. Based on structural data, three broad classes of alternating access transitions have been described as rocker-switch, rocking-bundle, and elevator mechanisms. More detailed analysis indicates that transporters can be understood as gated pores with at least two coupled gates. These gates are not just a convenient cartoon element to illustrate a putative mechanism but map to distinct parts of the transporter protein. Enumerating all distinct gate states naturally includes occluded states in the alternating access picture and also suggests what kind of protein conformations might be observable. By connecting the possible conformational states and ion/substrate bound states in a kinetic model, a unified picture emerges in which the symporter, antiporter, and uniporter functions are extremes in a continuum of functionality. As usual with biological systems, few principles and rules are absolute and exceptions are discussed as well as how biological complexity may be integrated in quantitative kinetic models that may provide a bridge from the structure to function.

Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1

The NMDA receptor GluN2B subunit is a target of interest in neuropsychiatric disorders but to date there is no selective radiotracer available to quantify its availability in vivo. Here we report direct comparisons in non-human primates of three GluN2B-targeting radioligands: (R)-[11C]NR2B-Me, (R)-[18F]OF-Me-NB1, and (S)-[18F]OF-NB1. Plasma free fraction, metabolism, tissue distribution and kinetics, and quantitative kinetic modeling methods and parameters were evaluated in two adult rhesus macaques. Free fraction in plasma was <2% for (R)-[11C]NR2B-Me and (R)-[18F]OF-Me-NB1 and higher for (S)-[18F]OF-NB1 (15%). All radiotracers showed good brain uptake and distribution throughout grey matter, with substantial (>68%) blockade across the brain by the GluN2B-targeting drug Co-101,244 (0.25 mg/kg), including in the cerebellum. Time-activity curves were well-fitted by the one-tissue compartment model, with volume of distribution values of 20–40 mL/cm3 for (R)-[11C]NR2B-Me, 8–16 mL/cm3 for (R)-[18F]OF-Me-NB1, and 15–35 mL/cm3 for (S)-[18F]OF-NB1. Estimates of regional non-displaceable binding potential were in the range of 2–3 for (R)-[11C]NR2B-Me and (S)-[18F]-OF-NB1, and 0.5-1 for (R)-[18F]OF-Me-NB1. Altogether, each radiotracer showed an acceptable profile for quantitative imaging of GluN2B. (S)-[18F]OF-NB1 has particularly promising imaging characteristics for potential translation into humans. However, the source of unexpected displaceable binding in the cerebellum for each of these compounds requires further investigation.

Pyrolysis characteristics and quantitative kinetic model of microalgae Tetralselmis sp.

Pyrolysis characteristics and quantitative kinetic model of microalgae Tetralselmis sp.