Chain Termination Research Articles

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

Mechanism of action of favipiravir against SARS-CoV-2: Mutagenesis or chain termination?

Mechanism of action of favipiravir against SARS-CoV-2: Mutagenesis or chain termination?

Interface-based design of the favipiravir-binding site in SARS-CoV-2 RNA-dependent RNA polymerase reveals mutations conferring resistance to chain termination.

Favipiravir is a broad‐spectrum inhibitor of viral RNA‐dependent RNA polymerase (RdRp) currently being used to manage COVID‐19. Accumulation of mutations in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RdRp may facilitate antigenic drift, generating favipiravir resistance. Focussing on the chain‐termination mechanism utilized by favipiravir, we used high‐throughput interface‐based protein design to generate > 100 000 designs of the favipiravir‐binding site of RdRp and identify mutational hotspots. We identified several single‐point mutants and designs having a sequence identity of 97%–98% with wild‐type RdRp, suggesting that SARS‐CoV‐2 can develop favipiravir resistance with few mutations. Out of 134 mutations documented in the CoV‐GLUE database, 63 specific mutations were already predicted as resistant in our calculations, thus attaining ˜ 47% correlation with the sequencing data. These findings improve our understanding of the potential signatures of adaptation in SARS‐CoV‐2 against favipiravir.

A molecular relay race: sequential first-passage events to the terminal reaction centre in a cascade of diffusion controlled processes

We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive ‘messengers’: the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary.

Unraveling surface functionalization of Cr2B2T2 (T = OH, O, Cl, H) MBene by first-principles calculations

Synthesis of two-dimensional (2D) materials by wet-chemical methods is usually accompanied by surface functionalization, which plays critical roles in stabilizing and functionalizing the targeted materials. These termination reactions can bring thermodynamically stable products and versatile applications, however, leaving experimental characterization of surface structures challenging as well. In this work, newly emerging 2D conductive transition metal borides, Cr2B2 MBene is selected as a prototype to investigate the surface functionalization phenomenon. By first-principles calculation plus efficient structural exploration, we provide an atomistic understanding of the chemical origin and kinetics of surface functionalization occurred in aqueous environment, and screen the surface structure of Cr2B2T2 (T = OH, O, Cl, and H) MBenes. Results clearly unravel the functionalization process of MBenes and the stable surface structures of functionalized MBenes. It is found that both H2O and HCl molecules can split on the bare Cr2B2 in a nearly spontaneous manner, enabling functionalization of Cr2B2T2. Binding energy of termination groups on Cr2B2 quantifies the relative stability of functionalized Cr2B2T2 in the order: Cr2B2O2 > Cr2B2Cl2 > Cr2B2(OH)2 > Cr2B2H2. Furthermore, we demonstrate that both Cr2B2 and functionalized Cr2B2T2 MBenes are electronically conductive 2D materials with zero band gap, which is beneficial for electrochemical applications.

Effect of Steric Structure on the Mechanism of Antioxidant Activity of Alkyl Gallates in Soybean Oil Triacylglycerols—A Kinetic Approach

AbstractFrom an interfacial phenomena standpoint, the effect of the alkyl chain length is evaluated on the mechanism of antioxidant activity of gallic acid ester derivatives (methyl, propyl, octyl, dodecyl, and stearyl gallates) in bulk phase oil. A combinational kinetic model is used to estimate the oxidation kinetic parameters, such as induction period, the maximum concentration of lipid hydroperoxides, and critical reverse micelle concentration. These kinetic parameters are estimated much better with the combinational model compared to the tangent method. The nonlinear behavior is observed for inhibitory activities of homologous series of antioxidants in soybean triacylglycerols. In terms of different kinetics parameters, including antioxidant effectiveness and activity, methyl gallate has the highest inhibitory effect during lipid peroxidation. Gallic acid and alkyl gallates are able to protect bulk oils against peroxidation (induction period > 336 h) in terms of the extent of their participation in the main reaction of chain termination and pro‐oxidative side reactions of chain initiation, and anti‐oxidative side reactions of chain propagation.Practical Applications: This work explains the effect of the esterification in the inhibitory activity of alkyl gallates, mechanism action of alkyl gallates in bulk oil systems, antiradical potency as a function of the interfacial phenomena, and free radical chain mechanism, the impact of antioxidant activity on critical reverse micelle concentration of hydroperoxides. Moreover, in this study, it is confirmed that the combinational kinetic model can be employed as a reliable method for determining the oxidation kinetic parameters.

Numerical study on oscillatory propagation dynamics and physics near the limits of planar freely propagating premixed flames

An oscillatory phenomenon of the freely propagating premixed flames for dimethyl ether–air mixtures at near-limit conditions was systematically analyzed to understand the underlying physicochemical processes that control the oscillation and extinction of hot-lean flames. The flame oscillation dynamics and extinction mechanism were first investigated using the analyses of flame oscillating structure and phase function. It was found that the leading cool-flame front and tailing hot-flame front present a significant separation during the oscillatory propagation, and the formation of flame oscillation was the consequence of the interaction between the two flame fronts which can be explained as the competition of reactions between low-, intermediate-, and high-temperature pathways. Meanwhile, due to the excessive heat losses of the lower half period, the flame will eventually extinguish in the divergent oscillating process. Furthermore, the key processes in the flame oscillation were further revealed by chemical explosive mode analysis-based diagnosis. The results show that the oscillations are primarily originated from the species and reactions of the intermediate-temperature pathway, including H2O2 and CH2O, and chain-branching/-termination reactions. These key processes eventually lead to the flame oscillatory extinction presenting an O(2) frequency.

Chemical insights into the multi-regime low-temperature oxidation of di-n-propyl ether: Jet-stirred reactor experiments and kinetic modeling

To further understand the combustion characteristics and the reaction pathways of acyclic ethers, the oxidation of di-n-propyl ether (DPE) was investigated in a jet-stirred reactor (JSR) combined with a photoionization molecular-beam mass spectrometer. The experiments were carried out at near-atmospheric pressure (700 Torr) and over a temperature range of 425–850 K. Based on the experimental data and previous studies on ether oxidation, a new kinetic model was constructed and used to interpret the oxidation chemistry of DPE. In DPE oxidation, a high reactivity at low temperatures and two negative temperature coefficient (NTC) zones were observed. These behaviors are explained in this work by taking advantage of the obtained species information and the modeling analyses: the two NTC zones are caused by the competition of chain branching and termination reactions of the fuel itself and specific oxidation intermediates, respectively. Furthermore, the general requirements to have double-NTC behavior are discussed. A variety of crucial fuel-specific C6 species, such as ketohydroperoxides and diones, were detected in the species pool of DPE oxidation. Their formation pathways are illuminated based on rate-of-production (ROP) analyses. Propanal was identified as the most abundant small molecule intermediate, and its related reactions have an important impact on the oxidation process of DPE. Both acetic acid and propionic acid were detected in high concentrations. A new formation pathway of propionic acid is proposed and incorporated into the kinetic model to achieve a more accurate prediction for propionic acid mole fractions.

Boosting activity, thermostability, and lifetime of iron ethylene polymerization catalysts through gem‐dimethyl substitution and incorporation of ortho‐cycloalkyl substituents

AbstractSix types of ferrous chloride complex, [2‐(ArN=CMe)‐8‐(ArN)‐7,7‐Me2C9H6N]FeCl2 (Ar=2‐(C5H9)‐6‐MeC6H3 Fe1, 2‐(C6H11)‐6‐MeC6H3 Fe2, 2‐(C8H15)‐6‐MeC6H3 Fe3, 2‐(C5H9)‐4,6‐Me2C6H2 Fe4, 2‐(C6H11)‐4,6‐Me2C6H2 Fe5, 2‐(C8H15)‐4,6‐Me2C6H2 Fe6), each bearing a gem‐dimethyl‐substituted N,N,N‐chelating ligand that differs in the ortho‐cycloalkyl ring size and para‐substituent of the N‐aryl groups, are disclosed. All complexes have been prepared by a straightforward one‐flask route and characterized by FT‐IR spectroscopy and elemental analysis. In the case of Fe1, oxidation to form the oxo‐bridged diferric species [2‐(2‐(C5H9)‐6‐MeC6H3N=CMe)‐8‐(2‐(C5H9)‐6‐MeC6H3N)‐7,7‐Me2C9H6N]FeCl(μ‐O)FeCl3 (Fe1') has been demonstrated and its structural identity confirmed by single crystal X‐ray diffraction. Following treatment with either methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), Fe1–Fe6 exhibited optimal catalytic activities at 60°C for ethylene polymerization [up to 2.35 × 107 g of PE (mol of Fe)−1 h−1 for Fe1/MMAO] producing linear polyethylene; even over prolonged run times, high activities were maintained. Moreover, this family of iron catalysts exhibited remarkable thermostability by displaying appreciable activity at temperatures as high as 100°C [activity up to 7.8 × 106 g of PE (mol of Fe)−1 h−1]. By varying the ring size of the ortho‐cycloalkyl and para‐R2 group (R2 = H, Me), excellent control over molecular weight of the polyethylenes could be achieved with values in the range 1.4–67.8 kg mol−1 obtainable. In addition, end‐group analysis of the polymers generated with Fe/MAO or Fe/MMAO revealed that both β‐H elimination and chain transfer to aluminum are competitive processes during chain termination.

Self-Stable Precipitation Polymerization Molecular Entanglement Effect and Molecular Weight Simulations and Experiments.

In this paper, we developed a reactive molecular dynamics (RMD) scheme to simulate the Self-Stable Precipitation (SP) polymerization of 1-pentene and cyclopentene (C5) with maleic anhydride (MAn) in an all-atom resolution. We studied the chain propagation mechanism by tracking the changes in molecular conformation and analyzing end-to-end distance and radius of gyration. The results show that the main reason of chain termination in the reaction process was due to intramolecular cyclic entanglement, which made the active center wrapped in the center of the globular chain. After conducting the experiment in the same condition with the simulation, we found that the distribution trend and peak value of the molecular-weight-distribution curve in the simulation were consistent with experimental results. The simulated number average molecular weight (Mn) and weight average molecular weight (Mw) were in good agreement with the experiment. Moreover, the simulated molecular polydispersity index (PDI) for cyclopentene reaction with maleic anhydride was accurate, differing by 0.04 from the experimental value. These show that this model is suitable for C5–maleic anhydride self-stable precipitation polymerization and is expected to be used as a molecular weight prediction tool for other maleic anhydride self-stable precipitation polymerization system.

Highly oxygenated organic molecule (HOM) formation in the isoprene oxidation by NO<sub>3</sub> radical

Abstract. Highly oxygenated organic molecules (HOM) are found to play an important role in the formation and growth of secondary organic aerosol (SOA). SOA is an important type of aerosol with significant impact on air quality and climate. Compared with the oxidation of volatile organic compounds by ozone (O3) and hydroxyl radical (OH), HOM formation in the oxidation by nitrate radical (NO3), an important oxidant at nighttime and dawn, has received less attention. In this study, HOM formation in the reaction of isoprene with NO3 was investigated in the SAPHIR chamber (Simulation of Atmospheric PHotochemistry In a large Reaction chamber). A large number of HOM, including monomers (C5), dimers (C10), and trimers (C15), both closed-shell compounds and open-shell peroxy radicals (RO2), were identified and were classified into various series according to their formula. Their formation pathways were proposed based on the peroxy radicals observed and known mechanisms in the literature, which were further constrained by the time profiles of HOM after sequential isoprene addition to differentiate first- and second-generation products. HOM monomers containing one to three N atoms (1–3N-monomers) were formed, starting with NO3 addition to carbon double bond, forming peroxy radicals, followed by autoxidation. 1N-monomers were formed by both the direct reaction of NO3 with isoprene and of NO3 with first-generation products. 2N-monomers (e.g., C5H8N2On(n=7–13), C5H10N2On(n=8–14)) were likely the termination products of C5H9N2On⚫, which was formed by the addition of NO3 to C5-hydroxynitrate (C5H9NO4), a first-generation product containing one carbon double bond. 2N-monomers, which were second-generation products, dominated in monomers and accounted for ∼34 % of all HOM, indicating the important role of second-generation oxidation in HOM formation in the isoprene + NO3 reaction under our experimental conditions. H shift of alkoxy radicals to form peroxy radicals and subsequent autoxidation (“alkoxy–peroxy” pathway) was found to be an important pathway of HOM formation. HOM dimers were mostly formed by the accretion reaction of various HOM monomer RO2 and via the termination reactions of dimer RO2 formed by further reaction of closed-shell dimers with NO3 and possibly by the reaction of C5–RO2 with isoprene. HOM trimers were likely formed by the accretion reaction of dimer RO2 with monomer RO2. The concentrations of different HOM showed distinct time profiles during the reaction, which was linked to their formation pathway. HOM concentrations either showed a typical time profile of first-generation products, second-generation products, or a combination of both, indicating multiple formation pathways and/or multiple isomers. Total HOM molar yield was estimated to be 1.2 %-0.7%+1.3%, which corresponded to a SOA yield of ∼3.6 % assuming the molecular weight of C5H9NO6 as the lower limit. This yield suggests that HOM may contribute a significant fraction to SOA yield in the reaction of isoprene with NO3.

Electrochemical Impedance Spectroscopy Study of Surface Film Formation on Lithium Anodes and the Role of Chain Termination on Poly(Ethylene Oxide) Electrolytes

The contact between solid polymer electrolytes and electrodes is a hot topic of investigation in lithium-ion batteries since the structure and composition of the interfaces is the limiting factor to both cell capacitance and life; a small change at the molecular level can have a dramatic effect on the cell behavior and performance. In this study, low-molecular polyethylene glycol electrolytes with two different chain termination groups are examined in terms of their electrochemical stability in contact with metallic lithium as a potential means of surface wetting. Using impedance spectroscopy, the ion transport mechanisms and time evolution of different phases are probed. It is shown that the electrolyte with hydroxy chain ends presents a very poor behavior with a high degree of electrolyte decomposition, which leads to a weak passivation layer and a significant inorganic phase development. This extreme case of electrolyte decomposition highlights the underlying mechanisms of film formation and the local environment of lithium ion transport. In contrast, methoxy chain ends lead to a stable electrolytic system that forms a robust passivating film accompanied by the development of a thin inorganic second phase.

The Oligosaccharyltransferase AglB Supports Surface-Associated Growth and Iron Oxidation in Methanococcus maripaludis.

Most microbial organisms grow as surface-attached communities known as biofilms. However, the mechanisms whereby methanogenic archaea grow attached to surfaces have remained understudied. Here, we show that the oligosaccharyltransferase AglB is essential for growth of Methanococcus maripaludis strain JJ on glass or metal surfaces. AglB glycosylates several cellular structures, such as pili, archaella, and the cell surface layer (S-layer). We show that the S-layer of strain JJ, but not strain S2, is a glycoprotein, that only strain JJ was capable of growth on surfaces, and that deletion of aglB blocked S-layer glycosylation and abolished surface-associated growth. A strain JJ mutant lacking structural components of the type IV-like pilus did not have a growth defect under any conditions tested, while a mutant lacking the preflagellin peptidase (ΔflaK) was defective for surface growth only when formate was provided as the sole electron donor. Finally, for strains that are capable of Fe0 oxidation, we show that deletion of aglB decreases the rate of anaerobic Fe0 oxidation, presumably due to decreased association of biomass with the Fe0 surface. Together, these data provide an initial characterization of surface-associated growth in a member of the methanogenic archaea. IMPORTANCE Methanogenic archaea are responsible for producing the majority of methane on Earth and catalyze the terminal reactions in the degradation of organic matter in anoxic environments. Methanogens often grow as biofilms associated with surfaces or partner organisms; however, the molecular details of surface-associated growth remain uncharacterized. We have found evidence that glycosylation of the cell surface layer is essential for growth of M. maripaludis on surfaces and can enhance rates of anaerobic iron corrosion. These results provide insight into the physiology of surface-associated methanogenic organisms and highlight the importance of surface association for anaerobic iron corrosion.

Bacterial RF3 senses chaperone function in co-translational folding

Molecular chaperones assist with protein folding by interacting with nascent polypeptide chains (NCs) during translation. Whether the ribosome can sense chaperone defects and, in response, abort translation of misfolding NCs has not yet been explored. Here we used quantitative proteomics to investigate the ribosome-associated chaperone network in E.coli and the consequences of its dysfunction. Trigger factor and the DnaK (Hsp70) system are the major NC-binding chaperones. HtpG (Hsp90), GroEL, and ClpB contribute increasingly when DnaK is deficient. Surprisingly, misfolding because of defects in co-translational chaperone function or amino acid analog incorporation results in recruitment of the non-canonical release factor RF3. RF3 recognizes aberrant NCs and then moves to the peptidyltransferase site to cooperate with RF2 in mediating chain termination, facilitating clearance by degradation. This function of RF3 reduces the accumulation of misfolded proteins and is critical for proteostasis maintenance and cell survival under conditions of limited chaperone availability.

Effects of methane addition on laminar flame characteristics of premixed blast furnace gas/air mixtures

As a typical low heating value fuel, blast furnace gas (BFG) is used as an alternative fuel for gas turbine combustion. Due to its high concentration of inert gas components, natural gas is usually added to improve ignition and stable combustion in the combustion chamber. In this paper, laminar flame characteristics of BFG/CH4/air mixtures were investigated using constant volume combustion chamber and CHEMKIN package using the Gri-Mech 3.0 model. Experiments and numerical simulations were conducted at an elevated pressure and temperature of 0.2 MPa and 453 K, equivalence ratios of 0.8–1.4, and mixing ratios of methane of 0, 5, 10, 15%. The results show that the laminar burning velocity decreases rapidly from 24.19 cm/s to 13.90 cm/s at ϕ = 1.4 with the increase of methane addition from 0% to 15%, but obviously increases from 16.49 cm/s to 28.68 cm/s at ϕ = 0.8, from 21.05 cm/s to 35.65 cm/s at ϕ = 1.0, from 23.52 cm/s to 32.09 cm/s at ϕ = 1.2 with the increase of methane addition from 0% to 15%. Meanwhile, methane addition has an opposite effect on the Markstein length at ϕ = 0.8–1.2 and ϕ = 1.4. The thermal, transport and chemical effects were examined, exhibiting a major role of the thermal effect in the range of ϕ = 0.8–1.2 and a significant contribution of the chemical effect at ϕ = 1.4 to the laminar flame propagation of BFG/CH4/air mixtures. Further sensitivity analysis shows that R38 (H + O2 ↔ O + OH) and R52 (H + CH3 (+M) ↔ CH4 (+M)) are the main chain branching and chain termination reactions, respectively. Analysis on flame structure indicates that concentrations free radicals, especially OH and H evidently increase with methane addition. The maximum mole fraction of OH increases almost linearly from 1.02×10-3 to 3.82×10-3 with the increase of methane addition from 0% to 15%. The maximum mole fraction of H increases with a lower gradient than that of OH from 1.31×10-3 to 2.89×10-3 with the increase of methane addition from 0% to 15%.

Attenuation of gaseous detonations by porous media of fine microstructure

This article reports on numerical simulations of detonation propagation in channels that contain one or more porous obstructions. The porous media considered herein have high porosity and are of fine microstructure, i.e. the diameter of the fibres of the solid matrix is smaller than the characteristic chemical length scale. Our study is based on a thermo-mechanical model for flows in superposed porous and pure-fluid regions. According to it, the solid matrix is represented as a rigid continuum and its porosity is introduced as a distribution that varies in space. With regard to chemical kinetics, two different three-step chain-branching schemes are considered; their difference being in the termination reaction. Our simulations predict that, even at high porosity, the porous obstructions act as a highly efficient momentum sink, thereby causing the detonation to attenuate significantly. In the case of a single porous section, the detonation re-initiates downstream via chain-branching explosion. However, arrays of porous zones that span the entire cross section of the domain produce a decoupling of the reaction zone from the leading shock, thereby effectively suppressing the detonation. Also, our study reveals that in domains with arrays of porous blocks that only partially cover the cross section of the channel, the detonations do not quench. Instead, they propagate as low-velocity detonations, the properties of which are elaborated herein as well.

Mechanisms of CoII and Acid Jointly Catalyzed Domino Conversion of CO2, H2, and CH3OH to Dialkoxymethane: A DFT Study

The conversion mechanisms of CO2 and H2 in methanol to dimethoxymethane catalyzed jointly by metallic [P3Co-H]+ catalyst and acidic HNTf2 cocatalyst in a domino sequence were investigated at the M06L-SCRF level of density functional theory. The whole conversion has the steps of the Co-catalyzed hydrogenation (CO2 + H2 = HCOOH; HCOOCH3 + H2 = CH3OCH2OH) and acid-catalyzed esterification (HCOOH + CH3OH = HCOOCH3 + H2O; CH3OCH2OH + CH3OH = CH3OCH2OCH3 + H2O) reactions. The full Gibbs free energy profiles show that the bidentate formate complex κ2-[P3Co-OCHO]+ is the resting state and methylating CH3OCH2OH with CH3-NTf2 is the rate-determining step. The whole reaction kinetics is controlled by both [P3Co-H]+ and HNTf2 cocatalyst. Our study clearly shows the individual role of metal catalyst and acid cocatalyst and the need to combine both catalysts for this reaction and explains rationally why this process needs CO2 + H2 + CH3OH rather than only CO2 + H2. Compared to HNTf2 as a cocatalyst, the lower activity of p-TsOH is due to the weaker interaction between acid and substrate. A mechanism for the chain growth and termination of oxymethylene ether is proposed.

Catalytic Conversion of CO and H2 into Hydrocarbons on the Cobalt Co(111) Surface: Implications for the Fischer–Tropsch Process

The Fischer–Tropsch (FT) process consists of the reaction of a synthesis gas (syngas) mixture containing carbon monoxide (CO) and hydrogen (H2), which are polymerized into liquid hydrocarbon chains, often using a cobalt catalyst, although the mechanistic pathway is not yet fully understood. Here, we have employed unrestricted density functional theory calculations with a Hubbard Hamiltonian and long-range dispersion corrections [DFT+U−D3−(BJ)] to investigate the reaction of syngas and the selectivity toward the hydrocarbons formed on the cobalt Co(111) surface. The single CO and dissociated H2 molecules prefer to adsorb at two different types of trigonal surface sites, and we discuss how the interatomic distances, fundamental vibrational modes, charge transfers, surface-free energies, and work functions are modified by the adsorbates. The coadsorption of the syngas molecules in close proximity provides enough energy for the system to cross the saddle points on the minimum energy pathway (MEP), leading to the catalytic hydrogenolysis of the C–O bond. The adsorbed CO, alongside the intermediates CH and OH, are further stabilized when the ratio of equilibrium coverage (C) is CH/CCO,CH,OH > 6:1 under the temperature conditions required for the FT process. We propose several mechanistic pathways to account for the formation of ethane (C2H6), as a model for long-chain hydrocarbons, as well as methane (CH4) which is an undesirable product. The MEPs for these processes show that the coupling of the C–C bond followed by hydrogenation is the most favorable process, which takes precedence over the production of CH4. The termination reaction suggests that water (H2O) remains weakly physisorbed to the surface, allowing the reutilization of its catalytic site. The simulated fundamental vibrational frequencies and scanning tunneling microscopy images of the surface-bound intermediates are in agreement with the available experimental data. Our findings are important in the interpretation of the elementary steps of the FT process on the Co(111) surface.

Effect of absorbed dose on post-irradiation coloration and interpretation of polymerization reaction in the Gafchromic EBT3 film

The change in the optical density/transmittance obtained for dose delivered to EBT3 films by 15 MeV photon beam in the range 0.1–20 Gy as a function of the time elapsed between film irradiation and readout is analyzed. The polymerization chain reaction expected for monomer unit i.e., di-acetylene, in EBT3 film is predicted. These films are repeatedly scanned up to 104 h after irradiation by EPSON expression 11000XL flatbed scanner and analyzed by ImageJ software. At doses, ≤ 1 Gy, the average change in net transmittance over 104 hours, is 19.6% and for dose range between 1.5 Gy-7 Gy and 8 Gy–20 Gy, the values are 5.7% and 2.7%, respectively. During initial 24 hours, the increase in net transmittance for dose range 0.1 Gy–1 Gy, 1.5 Gy–5 Gy and 6 Gy–20 Gy are 0.5%–29.6% (mean 14.2%), 2.4%–6.8% (mean 3.6%) and 1.5% - 3.3% (mean 2.3%), respectively. The di-acetylene monomer in Gafchromic film undergoes addition at 1, 4 positions and polymerization reaction involves three different steps i.e., chain initiation, propagation and termination. At low absorbed doses i.e., ≤1 Gy, the chain termination step is prolonged and post-irradiation changes have attained a saturated value (plateau region within ±2%) for a considerably longer period (average 24 h) as compared to the film irradiated with higher doses. The Optical density (OD)/transmittance increases with elapsed time while its rate of change decreases with time and saturation in OD is a dose-dependent phenomenon. At high absorbed doses, the changes due to post-irradiation coloration will be least significant as the RCF saturates rapidly i.e. within 6 hours. It is necessary to scan EBT3 film after 24 h and 6 h of irradiation for doses ≤1 Gy and above 1 Gy, respectively.

A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population.

ContextPseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient.ObjectiveThis study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman.MethodsThis study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia). All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. We isolated DNA from peripheral blood and PCR-sequenced all exons and exon-intron boundaries of SCNN1A and, if negative, SCNN1B and SCNN1G using the Dideoxy Chain termination method.ResultsWe found a total of 8 mutations in 13 families as follows: 6 mutations in SCNN1A, 1 in SCNN1B, and 1 in SCNN1G. All of these mutations were novel except one. SCNN1A mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs*41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs*76 (a known mutation) in 8 patients of 5 families; and whole SCNN1A gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense SCNN1B mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an SCNN1G deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family.ConclusionWe characterized a unique genotype of PHA 1b with several novel gene structure–disrupting mutations in SCNN1A, SCNN1B, and SCNN1G in a highly consanguineous population.