Analytical solutions of one-dimensional multispecies reactive transport in a permeable reactive barrier-aquifer system

NASA Astrophysics Data System (ADS)

Mieles, John; Zhan, Hongbin

2012-06-01

The permeable reactive barrier (PRB) remediation technology has proven to be more cost-effective than conventional pump-and-treat systems, and has demonstrated the ability to rapidly reduce the concentrations of specific chemicals of concern (COCs) by up to several orders of magnitude in some scenarios. This study derives new steady-state analytical solutions to multispecies reactive transport in a PRB-aquifer (dual domain) system. The advantage of the dual domain model is that it can account for the potential existence of natural degradation in the aquifer, when designing the required PRB thickness. The study focuses primarily on the steady-state analytical solutions of the tetrachloroethene (PCE) serial degradation pathway and secondly on the analytical solutions of the parallel degradation pathway. The solutions in this study can also be applied to other types of dual domain systems with distinct flow and transport properties. The steady-state analytical solutions are shown to be accurate and the numerical program RT3D is selected for comparison. The results of this study are novel in that the solutions provide improved modeling flexibility including: 1) every species can have unique first-order reaction rates and unique retardation factors, and 2) daughter species can be modeled with their individual input concentrations or solely as byproducts of the parent species. The steady-state analytical solutions exhibit a limitation that occurs when interspecies reaction rate factors equal each other, which result in undefined solutions. Excel spreadsheet programs were created to facilitate prompt application of the steady-state analytical solutions, for both the serial and parallel degradation pathways.

Inflammation, vitamin B6 and related pathways.

PubMed

Ueland, Per Magne; McCann, Adrian; Midttun, Øivind; Ulvik, Arve

2017-02-01

The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), serves as a co-factor in more than 150 enzymatic reactions. Plasma PLP has consistently been shown to be low in inflammatory conditions; there is a parallel reduction in liver PLP, but minor changes in erythrocyte and muscle PLP and in functional vitamin B6 biomarkers. Plasma PLP also predicts the risk of chronic diseases like cardiovascular disease and some cancers, and is inversely associated with numerous inflammatory markers in clinical and population-based studies. Vitamin B6 intake and supplementation improve some immune functions in vitamin B6-deficient humans and experimental animals. A possible mechanism involved is mobilization of vitamin B6 to the sites of inflammation where it may serve as a co-factor in pathways producing metabolites with immunomodulating effects. Relevant vitamin B6-dependent inflammatory pathways include vitamin B6 catabolism, the kynurenine pathway, sphingosine 1-phosphate metabolism, the transsulfuration pathway, and serine and glycine metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic Coevolution in the Bacterial Symbiosis of Whiteflies and Related Plant Sap-Feeding Insects.

PubMed

Luan, Jun-Bo; Chen, Wenbo; Hasegawa, Daniel K; Simmons, Alvin M; Wintermantel, William M; Ling, Kai-Shu; Fei, Zhangjun; Liu, Shu-Sheng; Douglas, Angela E

2015-09-15

Genomic decay is a common feature of intracellular bacteria that have entered into symbiosis with plant sap-feeding insects. This study of the whitefly Bemisia tabaci and two bacteria (Portiera aleyrodidarum and Hamiltonella defensa) cohoused in each host cell investigated whether the decay of Portiera metabolism genes is complemented by host and Hamiltonella genes, and compared the metabolic traits of the whitefly symbiosis with other sap-feeding insects (aphids, psyllids, and mealybugs). Parallel genomic and transcriptomic analysis revealed that the host genome contributes multiple metabolic reactions that complement or duplicate Portiera function, and that Hamiltonella may contribute multiple cofactors and one essential amino acid, lysine. Homologs of the Bemisia metabolism genes of insect origin have also been implicated in essential amino acid synthesis in other sap-feeding insect hosts, indicative of parallel coevolution of shared metabolic pathways across multiple symbioses. Further metabolism genes coded in the Bemisia genome are of bacterial origin, but phylogenetically distinct from Portiera, Hamiltonella and horizontally transferred genes identified in other sap-feeding insects. Overall, 75% of the metabolism genes of bacterial origin are functionally unique to one symbiosis, indicating that the evolutionary history of metabolic integration in these symbioses is strongly contingent on the pattern of horizontally acquired genes. Our analysis, further, shows that bacteria with genomic decay enable host acquisition of complex metabolic pathways by multiple independent horizontal gene transfers from exogenous bacteria. Specifically, each horizontally acquired gene can function with other genes in the pathway coded by the symbiont, while facilitating the decay of the symbiont gene coding the same reaction. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles.

PubMed

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F; Perez, Danny

2017-10-21

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F.; Perez, Danny

2017-10-01

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Automated synthesis of a library of triazolated 1,2,5-thiadiazepane 1,1-dioxides via a double aza-Michael strategy.

PubMed

Zang, Qin; Javed, Salim; Hill, David; Ullah, Farman; Bi, Danse; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H; Santini, Conrad; Organ, Michael G; Hanson, Paul R

2012-08-13

The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products.

Automated Synthesis of a Library of Triazolated 1,2,5-Thiadiazepane 1,1-Dioxides via a Double aza-Michael Strategy

PubMed Central

Zang, Qin; Javed, Salim; Hill, David; Ullah, Farman; Bi, Danse; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H.; Santini, Conrad; Organ, Michael G.; Hanson, Paul R.

2013-01-01

The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3+2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products. PMID:22853708

Multichannel quench-flow microreactor chip for parallel reaction monitoring.

PubMed

Bula, Wojciech P; Verboom, Willem; Reinhoudt, David N; Gardeniers, Han J G E

2007-12-01

This paper describes a multichannel silicon-glass microreactor which has been utilized to investigate the kinetics of a Knoevenagel condensation reaction under different reaction conditions. The reaction is performed on the chip in four parallel channels under identical conditions but with different residence times. A special topology of the reaction coils overcomes the common problem arising from the difference in pressure drop of parallel channels having different length. The parallelization of reaction coils combined with chemical quenching at specific locations results in a considerable reduction in experimental effort and cost. The system was tested and showed good reproducibility in flow properties and reaction kinetic data generation.

Parallel Stochastic discrete event simulation of calcium dynamics in neuron.

PubMed

Ishlam Patoary, Mohammad Nazrul; Tropper, Carl; McDougal, Robert A; Zhongwei, Lin; Lytton, William W

2017-09-26

The intra-cellular calcium signaling pathways of a neuron depends on both biochemical reactions and diffusions. Some quasi-isolated compartments (e.g. spines) are so small and calcium concentrations are so low that one extra molecule diffusing in by chance can make a nontrivial difference in its concentration (percentage-wise). These rare events can affect dynamics discretely in such way that they cannot be evaluated by a deterministic simulation. Stochastic models of such a system provide a more detailed understanding of these systems than existing deterministic models because they capture their behavior at a molecular level. Our research focuses on the development of a high performance parallel discrete event simulation environment, Neuron Time Warp (NTW), which is intended for use in the parallel simulation of stochastic reaction-diffusion systems such as intra-calcium signaling. NTW is integrated with NEURON, a simulator which is widely used within the neuroscience community. We simulate two models, a calcium buffer and a calcium wave model. The calcium buffer model is employed in order to verify the correctness and performance of NTW by comparing it to a serial deterministic simulation in NEURON. We also derived a discrete event calcium wave model from a deterministic model using the stochastic IP3R structure.

Direct Observation of Parallel Folding Pathways Revealed Using a Symmetric Repeat Protein System

PubMed Central

Aksel, Tural; Barrick, Doug

2014-01-01

Although progress has been made to determine the native fold of a polypeptide from its primary structure, the diversity of pathways that connect the unfolded and folded states has not been adequately explored. Theoretical and computational studies predict that proteins fold through parallel pathways on funneled energy landscapes, although experimental detection of pathway diversity has been challenging. Here, we exploit the high translational symmetry and the direct length variation afforded by linear repeat proteins to directly detect folding through parallel pathways. By comparing folding rates of consensus ankyrin repeat proteins (CARPs), we find a clear increase in folding rates with increasing size and repeat number, although the size of the transition states (estimated from denaturant sensitivity) remains unchanged. The increase in folding rate with chain length, as opposed to a decrease expected from typical models for globular proteins, is a clear demonstration of parallel pathways. This conclusion is not dependent on extensive curve-fitting or structural perturbation of protein structure. By globally fitting a simple parallel-Ising pathway model, we have directly measured nucleation and propagation rates in protein folding, and have quantified the fluxes along each path, providing a detailed energy landscape for folding. This finding of parallel pathways differs from results from kinetic studies of repeat-proteins composed of sequence-variable repeats, where modest repeat-to-repeat energy variation coalesces folding into a single, dominant channel. Thus, for globular proteins, which have much higher variation in local structure and topology, parallel pathways are expected to be the exception rather than the rule. PMID:24988356

Stochastic surface walking reaction sampling for resolving heterogeneous catalytic reaction network: A revisit to the mechanism of water-gas shift reaction on Cu

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Jie; Shang, Cheng; Liu, Zhi-Pan

2017-10-01

Heterogeneous catalytic reactions on surface and interfaces are renowned for ample intermediate adsorbates and complex reaction networks. The common practice to reveal the reaction mechanism is via theoretical computation, which locates all likely transition states based on the pre-guessed reaction mechanism. Here we develop a new theoretical method, namely, stochastic surface walking (SSW)-Cat method, to resolve the lowest energy reaction pathway of heterogeneous catalytic reactions, which combines our recently developed SSW global structure optimization and SSW reaction sampling. The SSW-Cat is automated and massively parallel, taking a rough reaction pattern as input to guide reaction search. We present the detailed algorithm, discuss the key features, and demonstrate the efficiency in a model catalytic reaction, water-gas shift reaction on Cu(111) (CO + H2O → CO2 + H2). The SSW-Cat simulation shows that water dissociation is the rate-determining step and formic acid (HCOOH) is the kinetically favorable product, instead of the observed final products, CO2 and H2. It implies that CO2 and H2 are secondary products from further decomposition of HCOOH at high temperatures. Being a general purpose tool for reaction prediction, the SSW-Cat may be utilized for rational catalyst design via large-scale computations.

Structural aspects of denitrifying enzymes.

PubMed

Moura, I; Moura, J J

2001-04-01

The reduction of nitrate to nitrogen gas via nitrite, nitric oxide and nitrous oxide is the metabolic pathway usually known as denitrification, a key step in the nitrogen cycle. As observed for other elemental cycles, a battery of enzymes are utilized, namely the reductases for nitrate, nitrite, nitric oxide and nitrous oxide, as well as multiple electron donors that interact with these enzymes, in order to carry out the stepwise reactions that involve key intermediates. Because of the importance of this pathway (of parallel importance to the nitrogen-fixation pathway), efforts are underway to understand the structures of the participating enzymes and to uncover mechanistic aspects. Three-dimensional structures have been solved for the majority of these enzymes in the past few years, revealing the architecture of the active metal sites as well as global structural aspects, and possible mechanistic aspects. In addition, the recognition of specific electron-transfer partners raises important questions regarding specific electron-transfer pathways, partner recognition and control of metabolism.

The parallel reaction monitoring method contributes to a highly sensitive polyubiquitin chain quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuchiya, Hikaru; Tanaka, Keiji, E-mail: tanaka-kj@igakuken.or.jp; Saeki, Yasushi, E-mail: saeki-ys@igakuken.or.jp

2013-06-28

Highlights: •The parallel reaction monitoring method was applied to ubiquitin quantification. •The ubiquitin PRM method is highly sensitive even in biological samples. •Using the method, we revealed that Ufd4 assembles the K29-linked ubiquitin chain. -- Abstract: Ubiquitylation is an essential posttranslational protein modification that is implicated in a diverse array of cellular functions. Although cells contain eight structurally distinct types of polyubiquitin chains, detailed function of several chain types including K29-linked chains has remained largely unclear. Current mass spectrometry (MS)-based quantification methods are highly inefficient for low abundant atypical chains, such as K29- and M1-linked chains, in complex mixtures thatmore » typically contain highly abundant proteins. In this study, we applied parallel reaction monitoring (PRM), a quantitative, high-resolution MS method, to quantify ubiquitin chains. The ubiquitin PRM method allows us to quantify 100 attomole amounts of all possible ubiquitin chains in cell extracts. Furthermore, we quantified ubiquitylation levels of ubiquitin-proline-β-galactosidase (Ub-P-βgal), a historically known model substrate of the ubiquitin fusion degradation (UFD) pathway. In wild-type cells, Ub-P-βgal is modified with ubiquitin chains consisting of 21% K29- and 78% K48-linked chains. In contrast, K29-linked chains are not detected in UFD4 knockout cells, suggesting that Ufd4 assembles the K29-linked ubiquitin chain(s) on Ub-P-βgal in vivo. Thus, the ubiquitin PRM is a novel, useful, quantitative method for analyzing the highly complicated ubiquitin system.« less

The mechanism of hydrothermal hydrolysis for glycyrrhizic acid into glycyrrhetinic acid and glycyrrhetinic acid 3-O-mono-β-D-glucuronide in subcritical water.

PubMed

Fan, Rui; Li, Nan; Xu, Honggao; Xiang, Jun; Wang, Lei; Gao, Yanxiang

2016-01-01

To improve the bioactivity and sweetness properties of glycyrrhizic acid (GL), the hydrothermal hydrolysis of GL into glycyrrhetinic acid (GA) and glycyrrhetinic acid 3-O-mono-β-D-glucuronide (GAMG) in subcritical water was investigated. The effects of temperature, time and their interaction on the conversion ratios were analyzed and the reactions were elaborated with kinetics and thermodynamics. The results showed that GL hydrothermal hydrolysis was significantly (P < 0.05) affected by reaction time and temperature, as well as their interaction, and could be fitted into first-order kinetics. The thermodynamic analysis indicated that the hydrolysis of GL was endergonic and non-spontaneous. The hydrolytic pathways were composed of complex consecutive and parallel reactions. It was concluded that subcritical water may be a potential medium for producing GAMG and GA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiresponse kinetic modelling of Maillard reaction and caramelisation in a heated glucose/wheat flour system.

PubMed

Kocadağlı, Tolgahan; Gökmen, Vural

2016-11-15

The study describes the kinetics of the formation and degradation of α-dicarbonyl compounds in glucose/wheat flour system heated under low moisture conditions. Changes in the concentrations of glucose, fructose, individual free amino acids, lysine and arginine residues, glucosone, 1-deoxyglucosone, 3-deoxyglucosone, 3,4-dideoxyglucosone, 5-hydroxymethyl-2-furfural, glyoxal, methylglyoxal and diacetyl concentrations were determined to form a multiresponse kinetic model for isomerisation and degradation reactions of glucose. Degradation of Amadori product mainly produced 1-deoxyglucosone. Formation of 3-deoxyglucosone proceeded directly from glucose and also Amadori product degradation. Glyoxal formation was predominant from glucosone while methylglyoxal and diacetyl originated from 1-deoxyglucosone. Formation of 5-hydroxymethyl-2-furfural from fructose was found to be a key step. Multi-response kinetic modelling of Maillard reaction and caramelisation simultaneously indicated quantitatively predominant parallel and consecutive pathways and rate limiting steps by estimating the reaction rate constants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Free-energy landscapes from adaptively biased methods: Application to quantum systems

NASA Astrophysics Data System (ADS)

Calvo, F.

2010-10-01

Several parallel adaptive biasing methods are applied to the calculation of free-energy pathways along reaction coordinates, choosing as a difficult example the double-funnel landscape of the 38-atom Lennard-Jones cluster. In the case of classical statistics, the Wang-Landau and adaptively biased molecular-dynamics (ABMD) methods are both found efficient if multiple walkers and replication and deletion schemes are used. An extension of the ABMD technique to quantum systems, implemented through the path-integral MD framework, is presented and tested on Ne38 against the quantum superposition method.

Implementation of logic functions and computations by chemical kinetics

NASA Astrophysics Data System (ADS)

Hjelmfelt, A.; Ross, J.

We review our work on the computational functions of the kinetics of chemical networks. We examine spatially homogeneous networks which are based on prototypical reactions occurring in living cells and show the construction of logic gates and sequential and parallel networks. This work motivates the study of an important biochemical pathway, glycolysis, and we demonstrate that the switch that controls the flux in the direction of glycolysis or gluconeogenesis may be described as a fuzzy AND operator. We also study a spatially inhomogeneous network which shares features of theoretical and biological neural networks.

Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

PubMed Central

Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

2016-01-01

Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

A combined PHREEQC-2/parallel fracture model for the simulation of laminar/non-laminar flow and contaminant transport with reactions

NASA Astrophysics Data System (ADS)

Masciopinto, Costantino; Volpe, Angela; Palmiotta, Domenico; Cherubini, Claudia

2010-09-01

A combination of a parallel fracture model with the PHREEQC-2 geochemical model was developed to simulate sequential flow and chemical transport with reactions in fractured media where both laminar and turbulent flows occur. The integration of non-laminar flow resistances in one model produced relevant effects on water flow velocities, thus improving model prediction capabilities on contaminant transport. The proposed conceptual model consists of 3D rock-blocks, separated by horizontal bedding plane fractures with variable apertures. Particle tracking solved the transport equations for conservative compounds and provided input for PHREEQC-2. For each cluster of contaminant pathways, PHREEQC-2 determined the concentration for mass-transfer, sorption/desorption, ion exchange, mineral dissolution/precipitation and biodegradation, under kinetically controlled reactive processes of equilibrated chemical species. Field tests have been performed for the code verification. As an example, the combined model has been applied to a contaminated fractured aquifer of southern Italy in order to simulate the phenol transport. The code correctly fitted the field available data and also predicted a possible rapid depletion of phenols as a result of an increased biodegradation rate induced by a simulated artificial injection of nitrates, upgradient to the sources.

Development and Evaluation of a Parallel Reaction Monitoring Strategy for Large-Scale Targeted Metabolomics Quantification.

PubMed

Zhou, Juntuo; Liu, Huiying; Liu, Yang; Liu, Jia; Zhao, Xuyang; Yin, Yuxin

2016-04-19

Recent advances in mass spectrometers which have yielded higher resolution and faster scanning speeds have expanded their application in metabolomics of diverse diseases. Using a quadrupole-Orbitrap LC-MS system, we developed an efficient large-scale quantitative method targeting 237 metabolites involved in various metabolic pathways using scheduled, parallel reaction monitoring (PRM). We assessed the dynamic range, linearity, reproducibility, and system suitability of the PRM assay by measuring concentration curves, biological samples, and clinical serum samples. The quantification performances of PRM and MS1-based assays in Q-Exactive were compared, and the MRM assay in QTRAP 6500 was also compared. The PRM assay monitoring 237 polar metabolites showed greater reproducibility and quantitative accuracy than MS1-based quantification and also showed greater flexibility in postacquisition assay refinement than the MRM assay in QTRAP 6500. We present a workflow for convenient PRM data processing using Skyline software which is free of charge. In this study we have established a reliable PRM methodology on a quadrupole-Orbitrap platform for evaluation of large-scale targeted metabolomics, which provides a new choice for basic and clinical metabolomics study.

Emergence of dynamic cooperativity in the stochastic kinetics of fluctuating enzymes

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Chatterjee, Sambarta; Nandi, Mintu; Dua, Arti

2016-08-01

Dynamic co-operativity in monomeric enzymes is characterized in terms of a non-Michaelis-Menten kinetic behaviour. The latter is believed to be associated with mechanisms that include multiple reaction pathways due to enzymatic conformational fluctuations. Recent advances in single-molecule fluorescence spectroscopy have provided new fundamental insights on the possible mechanisms underlying reactions catalyzed by fluctuating enzymes. Here, we present a bottom-up approach to understand enzyme turnover kinetics at physiologically relevant mesoscopic concentrations informed by mechanisms extracted from single-molecule stochastic trajectories. The stochastic approach, presented here, shows the emergence of dynamic co-operativity in terms of a slowing down of the Michaelis-Menten (MM) kinetics resulting in negative co-operativity. For fewer enzymes, dynamic co-operativity emerges due to the combined effects of enzymatic conformational fluctuations and molecular discreteness. The increase in the number of enzymes, however, suppresses the effect of enzymatic conformational fluctuations such that dynamic co-operativity emerges solely due to the discrete changes in the number of reacting species. These results confirm that the turnover kinetics of fluctuating enzyme based on the parallel-pathway MM mechanism switches over to the single-pathway MM mechanism with the increase in the number of enzymes. For large enzyme numbers, convergence to the exact MM equation occurs in the limit of very high substrate concentration as the stochastic kinetics approaches the deterministic behaviour.

Emergence of dynamic cooperativity in the stochastic kinetics of fluctuating enzymes.

PubMed

Kumar, Ashutosh; Chatterjee, Sambarta; Nandi, Mintu; Dua, Arti

2016-08-28

Dynamic co-operativity in monomeric enzymes is characterized in terms of a non-Michaelis-Menten kinetic behaviour. The latter is believed to be associated with mechanisms that include multiple reaction pathways due to enzymatic conformational fluctuations. Recent advances in single-molecule fluorescence spectroscopy have provided new fundamental insights on the possible mechanisms underlying reactions catalyzed by fluctuating enzymes. Here, we present a bottom-up approach to understand enzyme turnover kinetics at physiologically relevant mesoscopic concentrations informed by mechanisms extracted from single-molecule stochastic trajectories. The stochastic approach, presented here, shows the emergence of dynamic co-operativity in terms of a slowing down of the Michaelis-Menten (MM) kinetics resulting in negative co-operativity. For fewer enzymes, dynamic co-operativity emerges due to the combined effects of enzymatic conformational fluctuations and molecular discreteness. The increase in the number of enzymes, however, suppresses the effect of enzymatic conformational fluctuations such that dynamic co-operativity emerges solely due to the discrete changes in the number of reacting species. These results confirm that the turnover kinetics of fluctuating enzyme based on the parallel-pathway MM mechanism switches over to the single-pathway MM mechanism with the increase in the number of enzymes. For large enzyme numbers, convergence to the exact MM equation occurs in the limit of very high substrate concentration as the stochastic kinetics approaches the deterministic behaviour.

Emergence of dynamic cooperativity in the stochastic kinetics of fluctuating enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Ashutosh; Chatterjee, Sambarta; Nandi, Mintu

Dynamic co-operativity in monomeric enzymes is characterized in terms of a non-Michaelis-Menten kinetic behaviour. The latter is believed to be associated with mechanisms that include multiple reaction pathways due to enzymatic conformational fluctuations. Recent advances in single-molecule fluorescence spectroscopy have provided new fundamental insights on the possible mechanisms underlying reactions catalyzed by fluctuating enzymes. Here, we present a bottom-up approach to understand enzyme turnover kinetics at physiologically relevant mesoscopic concentrations informed by mechanisms extracted from single-molecule stochastic trajectories. The stochastic approach, presented here, shows the emergence of dynamic co-operativity in terms of a slowing down of the Michaelis-Menten (MM) kineticsmore » resulting in negative co-operativity. For fewer enzymes, dynamic co-operativity emerges due to the combined effects of enzymatic conformational fluctuations and molecular discreteness. The increase in the number of enzymes, however, suppresses the effect of enzymatic conformational fluctuations such that dynamic co-operativity emerges solely due to the discrete changes in the number of reacting species. These results confirm that the turnover kinetics of fluctuating enzyme based on the parallel-pathway MM mechanism switches over to the single-pathway MM mechanism with the increase in the number of enzymes. For large enzyme numbers, convergence to the exact MM equation occurs in the limit of very high substrate concentration as the stochastic kinetics approaches the deterministic behaviour.« less

Two Parallel Olfactory Pathways for Processing General Odors in a Cockroach

PubMed Central

Watanabe, Hidehiro; Nishino, Hiroshi; Mizunami, Makoto; Yokohari, Fumio

2017-01-01

In animals, sensory processing via parallel pathways, including the olfactory system, is a common design. However, the mechanisms that parallel pathways use to encode highly complex and dynamic odor signals remain unclear. In the current study, we examined the anatomical and physiological features of parallel olfactory pathways in an evolutionally basal insect, the cockroach Periplaneta americana. In this insect, the entire system for processing general odors, from olfactory sensory neurons to higher brain centers, is anatomically segregated into two parallel pathways. Two separate populations of secondary olfactory neurons, type1 and type2 projection neurons (PNs), with dendrites in distinct glomerular groups relay olfactory signals to segregated areas of higher brain centers. We conducted intracellular recordings, revealing olfactory properties and temporal patterns of both types of PNs. Generally, type1 PNs exhibit higher odor-specificities to nine tested odorants than type2 PNs. Cluster analyses revealed that odor-evoked responses were temporally complex and varied in type1 PNs, while type2 PNs exhibited phasic on-responses with either early or late latencies to an effective odor. The late responses are 30–40 ms later than the early responses. Simultaneous intracellular recordings from two different PNs revealed that a given odor activated both types of PNs with different temporal patterns, and latencies of early and late responses in type2 PNs might be precisely controlled. Our results suggest that the cockroach is equipped with two anatomically and physiologically segregated parallel olfactory pathways, which might employ different neural strategies to encode odor information. PMID:28529476

Formation of diacylglycerol by a phospholipase D-phosphatidate phosphatase pathway specific for phosphatidylcholine in endothelial cells.

PubMed

Martin, T W

1988-10-14

The conversion of phosphatidylcholine (PC) to diacylglycerol (DAG) was studied in sonicated endothelial cells and in subcellular fractions in the presence of 0.05% Triton X-100 and 2 mM EDTA. DAG formation occurred predominantly in an organelle fraction that sedimented at 15,000 x g. In parallel reactions with exogenous 1-oleoyl-2-[3H]oleoyl-PC (sn-2-[3H]DOPC) and phosphatidyl[3H]choline ([choline-3H]PC), [3H]DAG was formed by a reaction pathway in which [3H]choline was the only product derived from [choline-3H]PC. [3H]Choline was not formed secondarily from [3H]glycerophosphocholine or [3H]phosphocholine. Small amounts of [3H]phosphatidate ([3H]PA) were isolated from reactions with sn-2-[3H]DOPC at short incubation times, and substantial PA phosphatase activity was demonstrated. These data, taken together, supported a phospholipase D-PA phosphatase pathway of DAG formation. Kinetic data established that the low ratio of [3H]PA/[3H]DAG formed in reactions with sn-2-[3H]DOPC was due to a 15-fold higher Vmax and 7-fold lower apparent Km of the PA phosphatase. The [3H]PA/[3H]DAG product ratio was increased by addition of unlabeled PA or by selective extraction of phospholipase D with Triton X-100. The characteristics of the phospholipase D indicated a unique enzyme. Activity was optimal in the presence of EDTA and was almost totally dependent upon Triton X-100. The pH profile displayed a peak at 7.0. Of particular significance was the stringent substrate specificity. Phosphatidylinositol was not hydrolyzed, and activities towards phosphatidylethanolamine and sphingomyelin were at most 30- to 50-fold lower than those towards PC. Phospholipase D and PA phosphatase were identified in a number of rat tissues and other cells. The highest activities of phospholipase D were present in lung and endothelial cells. Phospholipase D was partially purified from rat lung by Triton X-100 extraction and anion exchange chromatography. When linked with PA phosphatase, the phospholipase D could initiate a pathway of DAG formation that is highly specific for PC.

Excited-State Dynamics of Dithienylethenes Functionalized for Self-Supramolecular Assembly.

PubMed

Hamdi, I; Buntinx, G; Poizat, O; Perrier, A; Le Bras, L; Delbaere, S; Barrau, S; Louati, M; Takeshita, M; Tokushige, K; Takao, M; Aloïse, S

2018-04-12

The photoswitching and competitive processes of two photochromic dithienylethenes (DTEs) functionalized at both sides with 2-ureido-4[1H]-pyrimidone (UPy) quadruple hydrogen-bonding recognition patterns have been investigated with NMR experiments, ultrafast spectroscopy, and density functional theory (DFT) calculations. The originality of these molecules is their ability to form large supramolecular assemblies induced by light for the closed form (CF) species while the open form (OF) species exist as small oligomers. Photochromic parameters have been determined and photochemical pathways have been rationalized with clear distinction between the antiparallel (OF-AP) and parallel (OF-P) species. A new photocyclization pathway via triplet manifold has been evidenced. The effect of the supramolecular assembly on the photochemical response is discussed. Unlike the photoreversion process, which is unaffected by supramolecular assembly, rate constants of the photocyclization reaction and intersystem crossing process are sensitive to the presence of small OF oligomers.

Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin

NASA Astrophysics Data System (ADS)

Yao, Jianzhuang; Yuan, Yaxia; Zheng, Fang; Zhan, Chang-Guo

2016-02-01

Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions catalyzed by a serine esterase. This is the first time demonstrating that a single-step reaction pathway is possible for an ester hydrolysis reaction catalyzed by a serine esterase and, therefore, one no longer can simply assume that the acylation process must follow the well-known two-step reaction pathway.

DEPOSITION DISTRICUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE.

EPA Science Inventory

DEPOSITION DISTRIBUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE. Chong S. Kim*, USEPA National Health and Environmental Effects Research Lab. RTP, NC 27711; Z. Zhang and C. Kleinstreuer, Department of Mechanical and Aerospace Engineering, North C...

Catalytic routes and oxidation mechanisms in photoreforming of polyols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanwald, Kai E.; Berto, Tobias F.; Eisenreich, Wolfgang

2016-12-01

Photocatalytic reforming of biomass-derived oxygenates leads to H 2 generation and evolution of CO 2 via parallel formation of organic intermediates through anodic oxidations on a Rh/TiO 2 photocatalyst. The reaction pathways and kinetics in the photoreforming of C 3–C 6 polyols were explored. Polyols are converted via direct and indirect hole transfer pathways resulting in (i) oxidative rupture of C–C bonds, (ii) oxidation to a-oxygen functionalized aldoses and ketoses (carbonyl group formation) and (iii) light-driven dehydration. Direct hole transfer to chemisorbed oxygenates on terminal Ti(IV)-OH groups, generating alkoxy-radicals that undergo ß-C–C-cleavage, is proposed for the oxidative C–C rupture. Carbonylmore » group formation and dehydration are attributed to indirect hole transfer at surface lattice oxygen sites [Ti_ _ _O_ _ _Ti] followed by the generation of carbon-centered radicals. Polyol chain length impacts the contribution of the oxidation mechanisms favoring the C–C bond cleavage (internal preferred over terminal) as the dominant pathway with higher polyol carbon number.« less

Aligning Metabolic Pathways Exploiting Binary Relation of Reactions.

PubMed

Huang, Yiran; Zhong, Cheng; Lin, Hai Xiang; Huang, Jing

2016-01-01

Metabolic pathway alignment has been widely used to find one-to-one and/or one-to-many reaction mappings to identify the alternative pathways that have similar functions through different sets of reactions, which has important applications in reconstructing phylogeny and understanding metabolic functions. The existing alignment methods exhaustively search reaction sets, which may become infeasible for large pathways. To address this problem, we present an effective alignment method for accurately extracting reaction mappings between two metabolic pathways. We show that connected relation between reactions can be formalized as binary relation of reactions in metabolic pathways, and the multiplications of zero-one matrices for binary relations of reactions can be accomplished in finite steps. By utilizing the multiplications of zero-one matrices for binary relation of reactions, we efficiently obtain reaction sets in a small number of steps without exhaustive search, and accurately uncover biologically relevant reaction mappings. Furthermore, we introduce a measure of topological similarity of nodes (reactions) by comparing the structural similarity of the k-neighborhood subgraphs of the nodes in aligning metabolic pathways. We employ this similarity metric to improve the accuracy of the alignments. The experimental results on the KEGG database show that when compared with other state-of-the-art methods, in most cases, our method obtains better performance in the node correctness and edge correctness, and the number of the edges of the largest common connected subgraph for one-to-one reaction mappings, and the number of correct one-to-many reaction mappings. Our method is scalable in finding more reaction mappings with better biological relevance in large metabolic pathways.

Calculation of biochemical net reactions and pathways by using matrix operations.

PubMed Central

Alberty, R A

1996-01-01

Pathways for net biochemical reactions can be calculated by using a computer program that solves systems of linear equations. The coefficients in the linear equations are the stoichiometric numbers in the biochemical equations for the system. The solution of the system of linear equations is a vector of the stoichiometric numbers of the reactions in the pathway for the net reaction; this is referred to as the pathway vector. The pathway vector gives the number of times the various reactions have to occur to produce the desired net reaction. Net reactions may involve unknown numbers of ATP, ADP, and Pi molecules. The numbers of ATP, ADP, and Pi in a desired net reaction can be calculated in a two-step process. In the first step, the pathway is calculated by solving the system of linear equations for an abbreviated stoichiometric number matrix without ATP, ADP, Pi, NADred, and NADox. In the second step, the stoichiometric numbers in the desired net reaction, which includes ATP, ADP, Pi, NADred, and NADox, are obtained by multiplying the full stoichiometric number matrix by the calculated pathway vector. PMID:8804633

Investigating uncultured microbes and their role in a deep subseafloor ammonium sink

NASA Astrophysics Data System (ADS)

Kirkpatrick, J. B.; Spivack, A. J.; Smith, D. C.; D'Hondt, S. L.

2013-12-01

The marine deep biosphere is thought to hold a large reservoir of both microbial cells and untapped genetic diversity. One potential driving force behind the vast amount of uncultured organisms are unconventional redox pairs which may not be favorable at benchtop conditions, but can support life in other circumstances. One instance of this is the previously documented thermodynamic favorability of ammonium oxidation with sulfate in sediments such as those investigated here from the Indian Ocean. Using 454 tag sequencing of 16S DNA, we identified uncultured archaea and bacteria potentially playing key roles at the sulfate and ammonium interface. First, the phylogenetic identity of organisms potentially involved in this reaction is inferred, as well as thermodynamic considerations of potential pathways. Several novel phyla, as well as Clostridiales, appear over-represented at the reaction zone. Secondly, to understand the metabolic capability of these target organisms, these sequences have been cross-referenced with assemblies from metagenomic data sets, and connections to functional genes are being elucidated. Finally, we discuss parallels with near-shore coastal sediment from Narragansett Bay, Rhode Island, where geochemical similarities have been found. While the thermodynamic regime is similar to the Indian Ocean, suggesting the potential for a broad geographic distribution, accessibility provides the opportunity to construct bioreactors to test rates and pathways of ammonium and sulfate fluxes. Iron content may be a key factor in determining reaction favorability. We present ongoing work in this area and the pros and cons of different bioreactor designs.

Contact allergy to air-exposed geraniol: clinical observations and report of 14 cases.

PubMed

Hagvall, Lina; Karlberg, Ann-Therese; Christensson, Johanna Bråred

2012-07-01

The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways. To investigate whether testing with oxidized geraniol detects more cases of contact allergy than testing with pure geraniol. The pattern of reactions to pure and oxidized geraniol, and metabolites/autoxidation products, was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Pure and oxidized geraniol were tested at 2.0% petrolatum in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626 and 1055 consecutive patients, respectively. Pure and oxidized geraniol gave positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to oxidized geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients' dermatitis was found in 11 of 14 cases. Testing with oxidized geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol. © 2012 John Wiley & Sons A/S.

Parallel replica dynamics with a heterogeneous distribution of barriers: Application to n-hexadecane pyrolysis

NASA Astrophysics Data System (ADS)

Kum, Oyeon; Dickson, Brad M.; Stuart, Steven J.; Uberuaga, Blas P.; Voter, Arthur F.

2004-11-01

Parallel replica dynamics simulation methods appropriate for the simulation of chemical reactions in molecular systems with many conformational degrees of freedom have been developed and applied to study the microsecond-scale pyrolysis of n-hexadecane in the temperature range of 2100-2500 K. The algorithm uses a transition detection scheme that is based on molecular topology, rather than energetic basins. This algorithm allows efficient parallelization of small systems even when using more processors than particles (in contrast to more traditional parallelization algorithms), and even when there are frequent conformational transitions (in contrast to previous implementations of the parallel replica algorithm). The parallel efficiency for pyrolysis initiation reactions was over 90% on 61 processors for this 50-atom system. The parallel replica dynamics technique results in reaction probabilities that are statistically indistinguishable from those obtained from direct molecular dynamics, under conditions where both are feasible, but allows simulations at temperatures as much as 1000 K lower than direct molecular dynamics simulations. The rate of initiation displayed Arrhenius behavior over the entire temperature range, with an activation energy and frequency factor of Ea=79.7 kcal/mol and log A/s-1=14.8, respectively, in reasonable agreement with experiment and empirical kinetic models. Several interesting unimolecular reaction mechanisms were observed in simulations of the chain propagation reactions above 2000 K, which are not included in most coarse-grained kinetic models. More studies are needed in order to determine whether these mechanisms are experimentally relevant, or specific to the potential energy surface used.

Investigation of the oxygen exchange mechanism on Pt|yttria stabilized zirconia at intermediate temperatures: Surface path versus bulk path

PubMed Central

Opitz, Alexander K.; Lutz, Alexander; Kubicek, Markus; Kubel, Frank; Hutter, Herbert; Fleig, Jürgen

2011-01-01

The oxygen exchange kinetics of platinum on yttria-stabilized zirconia (YSZ) was investigated by means of geometrically well-defined Pt microelectrodes. By variation of electrode size and temperature it was possible to separate two temperature regimes with different geometry dependencies of the polarization resistance. At higher temperatures (550–700 °C) an elementary step located close to the three phase boundary (TPB) with an activation energy of ∼1.6 eV was identified as rate limiting. At lower temperatures (300–400 °C) the rate limiting elementary step is related to the electrode area and exhibited a very low activation energy in the order of 0.2 eV. From these observations two parallel pathways for electrochemical oxygen exchange are concluded. The nature of these two elementary steps is discussed in terms of equivalent circuits. Two combinations of parallel rate limiting reaction steps are found to explain the observed geometry dependencies: (i) Diffusion through an impurity phase at the TPB in parallel to diffusion of oxygen through platinum – most likely along Pt grain boundaries – as area-related process. (ii) Co-limitation of oxygen diffusion along the Pt|YSZ interface and charge transfer at the interface with a short decay length of the corresponding transmission line (as TPB-related process) in parallel to oxygen diffusion through platinum. PMID:22210951

Understanding the hydrogen transfer mechanism for the biodegradation of 2,4,6-trinitrotoluene catalyzed by pentaerythritol tetranitrate reductase: molecular dynamics simulations.

PubMed

Yang, Zhilin; Chen, Junxian; Zhou, Yang; Huang, Hui; Xu, Dingguo; Zhang, Chaoyang

2018-05-03

The explosive 2,4,6-trinitrotoluene (TNT) is a highly toxic pollutant. Biodegradation is inevitably one of the most cost-effective and enviromentally friendly means of removing TNT pollution. However, the aromatic derivatives from the reduction of nitro groups by several classic enzymes are still toxic. Besides the reduction of nitro groups, pentaerythritol tetranitrate reductase (PETNR) offers a potential route to ring fission and complete degradation of TNT through the pathway of the Meisenheimer complex. This work is devoted to deeply understand the essence of the Meisenheimer pathway and mainly focus on the crucial hydrogen-transfer reaction by means of molecular dynamics (MD) simulations. We obtain three valuable findings. Firstly, the parallel π-π stacking between TNT and the flavin mononucleotide (FMN) cofactor is a precondition. The key residue controlling this conformation is His181. Although His184 does not interact with TNT, the mutation from His184 to Asn184 would abolish the π-π structure. Secondly, the data of the empirical valence bond (EVB) show that the Meisenheimer pathway is predominant because its activation barrier is 6.7 kcal mol-1 far less than that of nitro reduction (26.6 kcal mol-1). Finally, based on the results of thermodynamic integration (TI), the type of transferred hydrogen is also ensured, that is, the H anion (H-) for the Meisenheimer complex and the H radical (H˙) for nitro reduction. Our findings provide an exhaustive understanding for the first hydrogen transfer reaction that has a decisive effect on two competing pathways, and help in searching for and designing new enzymes that can effectively degrade TNT.

Evidence of Parallel Pathways: Gender Similarity in the Impact of Social Support on Adolescent Depression and Delinquency

ERIC Educational Resources Information Center

Meadows, Sarah O.

2007-01-01

Despite an apparent connection, depression and delinquency have rarely been examined simultaneously. Instead, research has examined each topic separately and emphasized gender differences--rather than similarities--in outcomes. Using the National Longitudinal Study of Adolescent Health, this paper examines possible parallel pathways between social…

Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

PubMed Central

Otsuna, Hideo; Shinomiya, Kazunori; Ito, Kei

2014-01-01

Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior. PMID:24574974

A Digitally Programmable Cytomorphic Chip for Simulation of Arbitrary Biochemical Reaction Networks.

PubMed

Woo, Sung Sik; Kim, Jaewook; Sarpeshkar, Rahul

2018-04-01

Prior work has shown that compact analog circuits can faithfully represent and model fundamental biomolecular circuits via efficient log-domain cytomorphic transistor equivalents. Such circuits have emphasized basis functions that are dominant in genetic transcription and translation networks and deoxyribonucleic acid (DNA)-protein binding. Here, we report a system featuring digitally programmable 0.35 μm BiCMOS analog cytomorphic chips that enable arbitrary biochemical reaction networks to be exactly represented thus enabling compact and easy composition of protein networks as well. Since all biomolecular networks can be represented as chemical reaction networks, our protein networks also include the former genetic network circuits as a special case. The cytomorphic analog protein circuits use one fundamental association-dissociation-degradation building-block circuit that can be configured digitally to exactly represent any zeroth-, first-, and second-order reaction including loading, dynamics, nonlinearity, and interactions with other building-block circuits. To address a divergence issue caused by random variations in chip fabrication processes, we propose a unique way of performing computation based on total variables and conservation laws, which we instantiate at both the circuit and network levels. Thus, scalable systems that operate with finite error over infinite time can be built. We show how the building-block circuits can be composed to form various network topologies, such as cascade, fan-out, fan-in, loop, dimerization, or arbitrary networks using total variables. We demonstrate results from a system that combines interacting cytomorphic chips to simulate a cancer pathway and a glycolysis pathway. Both simulations are consistent with conventional software simulations. Our highly parallel digitally programmable analog cytomorphic systems can lead to a useful design, analysis, and simulation tool for studying arbitrary large-scale biological networks in systems and synthetic biology.

Different Relative Orientation of Static and Alternative Magnetic Fields and Cress Roots Direction of Growth Changes Their Gravitropic Reaction

NASA Astrophysics Data System (ADS)

Sheykina, Nadiia; Bogatina, Nina

The following variants of roots location relatively to static and alternative components of magnetic field were studied. At first variant the static magnetic field was directed parallel to the gravitation vector, the alternative magnetic field was directed perpendicular to static one; roots were directed perpendicular to both two fields’ components and gravitation vector. At the variant the negative gravitropysm for cress roots was observed. At second variant the static magnetic field was directed parallel to the gravitation vector, the alternative magnetic field was directed perpendicular to static one; roots were directed parallel to alternative magnetic field. At third variant the alternative magnetic field was directed parallel to the gravitation vector, the static magnetic field was directed perpendicular to the gravitation vector, roots were directed perpendicular to both two fields components and gravitation vector; At forth variant the alternative magnetic field was directed parallel to the gravitation vector, the static magnetic field was directed perpendicular to the gravitation vector, roots were directed parallel to static magnetic field. In all cases studied the alternative magnetic field frequency was equal to Ca ions cyclotron frequency. In 2, 3 and 4 variants gravitropism was positive. But the gravitropic reaction speeds were different. In second and forth variants the gravitropic reaction speed in error limits coincided with the gravitropic reaction speed under Earth’s conditions. At third variant the gravitropic reaction speed was slowed essentially.

Parallel STEPS: Large Scale Stochastic Spatial Reaction-Diffusion Simulation with High Performance Computers

PubMed Central

Chen, Weiliang; De Schutter, Erik

2017-01-01

Stochastic, spatial reaction-diffusion simulations have been widely used in systems biology and computational neuroscience. However, the increasing scale and complexity of models and morphologies have exceeded the capacity of any serial implementation. This led to the development of parallel solutions that benefit from the boost in performance of modern supercomputers. In this paper, we describe an MPI-based, parallel operator-splitting implementation for stochastic spatial reaction-diffusion simulations with irregular tetrahedral meshes. The performance of our implementation is first examined and analyzed with simulations of a simple model. We then demonstrate its application to real-world research by simulating the reaction-diffusion components of a published calcium burst model in both Purkinje neuron sub-branch and full dendrite morphologies. Simulation results indicate that our implementation is capable of achieving super-linear speedup for balanced loading simulations with reasonable molecule density and mesh quality. In the best scenario, a parallel simulation with 2,000 processes runs more than 3,600 times faster than its serial SSA counterpart, and achieves more than 20-fold speedup relative to parallel simulation with 100 processes. In a more realistic scenario with dynamic calcium influx and data recording, the parallel simulation with 1,000 processes and no load balancing is still 500 times faster than the conventional serial SSA simulation. PMID:28239346

Parallel STEPS: Large Scale Stochastic Spatial Reaction-Diffusion Simulation with High Performance Computers.

PubMed

Chen, Weiliang; De Schutter, Erik

2017-01-01

Stochastic, spatial reaction-diffusion simulations have been widely used in systems biology and computational neuroscience. However, the increasing scale and complexity of models and morphologies have exceeded the capacity of any serial implementation. This led to the development of parallel solutions that benefit from the boost in performance of modern supercomputers. In this paper, we describe an MPI-based, parallel operator-splitting implementation for stochastic spatial reaction-diffusion simulations with irregular tetrahedral meshes. The performance of our implementation is first examined and analyzed with simulations of a simple model. We then demonstrate its application to real-world research by simulating the reaction-diffusion components of a published calcium burst model in both Purkinje neuron sub-branch and full dendrite morphologies. Simulation results indicate that our implementation is capable of achieving super-linear speedup for balanced loading simulations with reasonable molecule density and mesh quality. In the best scenario, a parallel simulation with 2,000 processes runs more than 3,600 times faster than its serial SSA counterpart, and achieves more than 20-fold speedup relative to parallel simulation with 100 processes. In a more realistic scenario with dynamic calcium influx and data recording, the parallel simulation with 1,000 processes and no load balancing is still 500 times faster than the conventional serial SSA simulation.

Magnocellular pathway for rotation invariant Neocognitron.

PubMed

Ting, C H

1993-03-01

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

Real-Time Cognitive Computing Architecture for Data Fusion in a Dynamic Environment

NASA Technical Reports Server (NTRS)

Duong, Tuan A.; Duong, Vu A.

2012-01-01

A novel cognitive computing architecture is conceptualized for processing multiple channels of multi-modal sensory data streams simultaneously, and fusing the information in real time to generate intelligent reaction sequences. This unique architecture is capable of assimilating parallel data streams that could be analog, digital, synchronous/asynchronous, and could be programmed to act as a knowledge synthesizer and/or an "intelligent perception" processor. In this architecture, the bio-inspired models of visual pathway and olfactory receptor processing are combined as processing components, to achieve the composite function of "searching for a source of food while avoiding the predator." The architecture is particularly suited for scene analysis from visual data and odorant.

Supervised de novo reconstruction of metabolic pathways from metabolome-scale compound sets

PubMed Central

Kotera, Masaaki; Tabei, Yasuo; Yamanishi, Yoshihiro; Tokimatsu, Toshiaki; Goto, Susumu

2013-01-01

Motivation: The metabolic pathway is an important biochemical reaction network involving enzymatic reactions among chemical compounds. However, it is assumed that a large number of metabolic pathways remain unknown, and many reactions are still missing even in known pathways. Therefore, the most important challenge in metabolomics is the automated de novo reconstruction of metabolic pathways, which includes the elucidation of previously unknown reactions to bridge the metabolic gaps. Results: In this article, we develop a novel method to reconstruct metabolic pathways from a large compound set in the reaction-filling framework. We define feature vectors representing the chemical transformation patterns of compound–compound pairs in enzymatic reactions using chemical fingerprints. We apply a sparsity-induced classifier to learn what we refer to as ‘enzymatic-reaction likeness’, i.e. whether compound pairs are possibly converted to each other by enzymatic reactions. The originality of our method lies in the search for potential reactions among many compounds at a time, in the extraction of reaction-related chemical transformation patterns and in the large-scale applicability owing to the computational efficiency. In the results, we demonstrate the usefulness of our proposed method on the de novo reconstruction of 134 metabolic pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG). Our comprehensively predicted reaction networks of 15 698 compounds enable us to suggest many potential pathways and to increase research productivity in metabolomics. Availability: Softwares are available on request. Supplementary material are available at http://web.kuicr.kyoto-u.ac.jp/supp/kot/ismb2013/. Contact: goto@kuicr.kyoto-u.ac.jp PMID:23812977

A density functional theory study of the decomposition mechanism of nitroglycerin.

PubMed

Pei, Liguan; Dong, Kehai; Tang, Yanhui; Zhang, Bo; Yu, Chang; Li, Wenzuo

2017-08-21

The detailed decomposition mechanism of nitroglycerin (NG) in the gas phase was studied by examining reaction pathways using density functional theory (DFT) and canonical variational transition state theory combined with a small-curvature tunneling correction (CVT/SCT). The mechanism of NG autocatalytic decomposition was investigated at the B3LYP/6-31G(d,p) level of theory. Five possible decomposition pathways involving NG were identified and the rate constants for the pathways at temperatures ranging from 200 to 1000 K were calculated using CVT/SCT. There was found to be a lower energy barrier to the β-H abstraction reaction than to the α-H abstraction reaction during the initial step in the autocatalytic decomposition of NG. The decomposition pathways for CHOCOCHONO 2 (a product obtained following the abstraction of three H atoms from NG by NO 2 ) include O-NO 2 cleavage or isomer production, meaning that the autocatalytic decomposition of NG has two reaction pathways, both of which are exothermic. The rate constants for these two reaction pathways are greater than the rate constants for the three pathways corresponding to unimolecular NG decomposition. The overall process of NG decomposition can be divided into two stages based on the NO 2 concentration, which affects the decomposition products and reactions. In the first stage, the reaction pathway corresponding to O-NO 2 cleavage is the main pathway, but the rates of the two autocatalytic decomposition pathways increase with increasing NO 2 concentration. However, when a threshold NO 2 concentration is reached, the NG decomposition process enters its second stage, with the two pathways for NG autocatalytic decomposition becoming the main and secondary reaction pathways.

Clinical implications of parallel visual pathways.

PubMed

Bassi, C J; Lehmkuhle, S

1990-02-01

Visual information travels from the retina to visual cortical areas along at least two parallel pathways. In this paper, anatomical and physiological evidence is presented to demonstrate the existence of, and trace these two pathways throughout the visual systems of the cat, primate, and human. Physiological and behavioral experiments are discussed which establish that these two pathways are differentially sensitive to stimuli that vary in spatial and temporal frequency. One pathway (M-pathway) is more sensitive to coarse visual form that is modulated or moving at fast rates, whereas the other pathway (P-pathway) is more sensitive to spatial detail that is stationary or moving at slow rates. This difference between the M- and P-pathways is related to some spatial and temporal effects observed in humans. Furthermore, evidence is presented that certain diseases selectively comprise the functioning of M- or P-pathways (i.e., glaucoma, Alzheimer's disease, and anisometropic amblyopia), and some of the spatial and temporal deficits observed in these patients are presented within the context of the dysfunction of the M- or P-pathway.

Deoxygenation of Palmitic and Lauric Acids over Pt/ZIF-67 Membrane/Zeolite 5A Bead Catalysts.

PubMed

Yang, Liqiu; Carreon, Moises A

2017-09-20

The deoxygenation of palmitic and lauric acids over 0.5 wt % Pt/ZIF-67 membrane/zeolite 5A bead catalysts is demonstrated. Almost complete conversion (% deoxygenation of ≥95%) of these two fatty acids was observed over both fresh and recycled catalyst after a 2 h reaction time. The catalysts displayed high selectivity to pentadecane and undecane via decarboxylation reaction pathway even at low 0.5 wt % Pt loading. Selectivity to pentadecane and undecane as high as ∼92% and ∼94% was observed under CO 2 atmosphere when palmitic and lauric acids were used respectively as reactants. Depending on the reaction gas atmosphere, two distinctive reaction pathways were observed: decarboxylation and hydrodeoxygenation. Specifically, it was found that decarboxylation reaction pathway was more favorable in the presence of helium and CO 2 , while hydrodeoxygenation pathway strongly competed against the decarboxylation pathway when hydrogen was employed during the deoxygenation reactions. Esters were identified as the key reaction intermediates leading to decarboxylation and hydrodeoxygenation pathways.

The mechanism for enhanced oxidation degradation of dioxin-like PCBs (PCB-77) in the atmosphere by the solvation effect.

PubMed

Xin, Mei-Ling; Yang, Jia-Wen; Li, Yu

2017-07-11

The reaction pathways of PCB-77 in the atmosphere with ·OH, O 2 , NO x , and 1 O 2 were inferred based on density functional theory calculations with the 6-31G* basis set. The structures the reactants, transition states, intermediates, and products were optimized. The energy barriers and reaction heats were obtained to determine the energetically favorable reaction pathways. To study the solvation effect, the energy barriers and reaction rates for PCB-77 with different polar and nonpolar solvents (cyclohexane, benzene, carbon tetrachloride, chloroform, acetone, dichloromethane, ethanol, methanol, acetonitrile, dimethylsulfoxide, and water) were calculated. The results showed that ·OH preferentially added to the C5 atom of PCB-77, which has no Cl atom substituent, to generate the intermediate IM5. This intermediate subsequently reacted with O 2 via pathway A to generate IM5a, with an energy barrier of 7.27 kcal/mol and total reaction rate of 8.45 × 10 -8  cm 3 /molecule s. Pathway B involved direct dehydrogenation of IM5 to produce the OH-PCBs intermediate IM5b, with an energy barrier of 28.49 kcal/mol and total reaction rate of 1.15 × 10 -5  cm 3 /molecule s. The most likely degradation pathway of PCB-77 in the atmosphere is pathway A to produce IM5a. The solvation effect results showed that cyclohexane, carbon tetrachloride, and benzene could reduce the reaction energy barrier of pathway A. Among these solvents, the solvation effect of benzene was the largest, and could reduce the total reaction energy barrier by 25%. Cyclohexane, carbon tetrachloride, benzene, dichloromethane, acetone, and ethanol could increase the total reaction rate of pathway A. The increase in the reaction rate of pathway A with benzene was 8%. The effect of solvents on oxidative degradation of PCB-77 in the atmosphere is important. Graphical abstract The reaction pathways of PCB-77 in the atmosphere with •OH, O2, NOx, and 1O2 were inferred based on density functional theory calculations with the 6-31G* basis set. Different polar and nonpolar solvents: cyclohexane, benzene, carbon tetrachloride, chloroform, acetone, dichloromethane, ethanol, methanol, acetonitrile, dimethylsulfoxide, and water were selected to study the solvation effect on the favorable reaction pathways. The investigated results showed what kind of pathway was most likely to occur and the solvent effect on the reaction pathway.

An asymptotic induced numerical method for the convection-diffusion-reaction equation

NASA Technical Reports Server (NTRS)

Scroggs, Jeffrey S.; Sorensen, Danny C.

1988-01-01

A parallel algorithm for the efficient solution of a time dependent reaction convection diffusion equation with small parameter on the diffusion term is presented. The method is based on a domain decomposition that is dictated by singular perturbation analysis. The analysis is used to determine regions where certain reduced equations may be solved in place of the full equation. Parallelism is evident at two levels. Domain decomposition provides parallelism at the highest level, and within each domain there is ample opportunity to exploit parallelism. Run time results demonstrate the viability of the method.

Techniques used to study the DNA polymerase reaction pathway

PubMed Central

Joyce, Catherine M.

2009-01-01

Summary A minimal reaction pathway for DNA polymerases was established over 20 years ago using chemical quench methods. Since that time there has been considerable interest in noncovalent steps in the reaction pathway, conformational changes involving the polymerase or its DNA substrate that may play a role in substrate specificity. Fluorescence-based assays have been devised in order to study these conformational transitions and the results obtained have added new detail to the reaction pathway. PMID:19665596

A Networks Approach to Modeling Enzymatic Reactions.

PubMed

Imhof, P

2016-01-01

Modeling enzymatic reactions is a demanding task due to the complexity of the system, the many degrees of freedom involved and the complex, chemical, and conformational transitions associated with the reaction. Consequently, enzymatic reactions are not determined by precisely one reaction pathway. Hence, it is beneficial to obtain a comprehensive picture of possible reaction paths and competing mechanisms. By combining individually generated intermediate states and chemical transition steps a network of such pathways can be constructed. Transition networks are a discretized representation of a potential energy landscape consisting of a multitude of reaction pathways connecting the end states of the reaction. The graph structure of the network allows an easy identification of the energetically most favorable pathways as well as a number of alternative routes. © 2016 Elsevier Inc. All rights reserved.

Understanding Biological Rates and their Temperature Dependence, from Enzymes to Ecosystems

NASA Astrophysics Data System (ADS)

Prentice, E.; Arcus, V. L.

2017-12-01

Temperature responses over various scales in biological systems follow a similar pattern; negative curvature results in an optimum temperature (Topt) for activity/growth/turnover, with decreases in rates on either side of Topt. Previously this downturn in rates at high temperatures has been attributed to enzyme denaturation, where a failing of the basic driving units of metabolism was used to describe curvature at the enzyme and organism level. However, recent developments in our understanding of the factors governing enzyme rates at different temperatures have guided a new understanding of the responses of biological systems. Enzymes catalyse reactions by driving the substrate through a high energy species, which is tightly bound to the enzyme. Macromolecular rate theory (MMRT) has recently been developed to account for the changes in the system brought about by this tight binding, specifically the change in the physical parameter heat capacity (ΔCǂp), and the effect this has on the temperature dependence of enzyme reactions. A negative ΔCǂp imparts the signature negative curvature to rates in the absence of denaturation, and finds that Topt, ΔCǂp and curvature are all correlated, placing constraints on biological systems. The simplest of cells comprise thousands of enzymatically catalysed reactions, functioning in series and in parallel in metabolic pathways to determine the overall growth rate of an organism. Intuitively, the temperature effects of enzymes play a role in determining the overall temperature dependence of an organism, in tandem with cellular level regulatory responses. However, the effect of individual Topt values and curvature on overall pathway behaviour is less apparent. Here, this is investigated in the context of MMRT through the in vitro characterisation of a six-step metabolic pathway to understand the steps in isolation and functioning in series. Pathway behaviour is found to be approximately an average of the properties of the individual steps, indicating all enzymes have an influence on organism temperature dependence. This has implications for our understanding of how organisms respond to fluctuations in environmental temperature.

The reactions of thiophene on Mo(110) and Mo(110)-p(2×2)-S

NASA Astrophysics Data System (ADS)

Roberts, Jeffrey T.; Friend, C. M.

1987-07-01

The reactions of thiophene and 2,5-dideuterothiophene on Mo(110) and Mo(110)-p(2×2)-S have been investigated under ultrahigh vacuum conditions using temperature programmed reaction spectroscopy and Auger electron spectroscopy. Thiophene chemisorbed on Mo(110) decomposes during temperature programmed reaction to yield only gaseous dihydrogen, surface carbon, and surface sulfur. At low thiophene exposures, dihydrogen evolves from Mo(110) in a symmetric peak at 440 K. At saturation exposures, three dihydrogen peaks are detected at 360 K, at 420 K and at 565 K. Multilayers of thiophene desorb at 180 K. Temperature programmed reaction of 2,5-dideuterothiophene demonstrates that at high thiophene coverages, one of the α-C-H bonds (those nearest sulfur) breaks first. No bond breaking selectivity is observed at low thiophene exposures. The Mo(110)-p(2×2)-S surface is less active for thiophene decomposition. Thiophene adsorbed on Mo(110)-p(2×2)-S to low coverages decomposes to surface carbon surface sulfur, and hydrogen at 430 K. At reaction saturation, dihydrogen production is observed at 375 and 570 K. In addition, at moderate and high exposures, chemisorbed thiophene desorbs from Mo(110)-p(2×2)-S. At saturation the desorption temperature of the reversibly chemisorbed state is 215 K. Experiments with 2,5-dideuterothiophene demonstrate no surface selectivity for α-C-H bond breaking reactions on Mo(110)-p(2×2)-S. The decomposition mechanism and energetics of thiophene decomposition are proposed to be dependent on the coverage of thiophene. At low thiophene exposures, the ring is proposed to bond parallel to the surface. All C-H bonds in the parallel geometry are sterically available for activation by the surface, accounting for the lack of selectivity in C-H bond breaking. High thiophene coverages are suggested to result in perpendicularly bound thiophene which undergoes selective α-dehydrogenation to an α)-thiophenyl intermediate. The presence of sulfur leads to a high energy pathway for cleavage of C-H bonds in a thiophene derived intermediate. Carbon-hydrogen bonds survive on the surface up to temperatures of 650 K. Comparison of this study with work on Mo(100) demonstrates that the reaction of thiophene on molybdenum is relatively insensitive to the surface geometric structure.

Coordination polymer flexibility leads to polymorphism and enables a crystalline solid-vapour reaction: a multi-technique mechanistic study.

PubMed

Vitórica-Yrezábal, Iñigo J; Libri, Stefano; Loader, Jason R; Mínguez Espallargas, Guillermo; Hippler, Michael; Fletcher, Ashleigh J; Thompson, Stephen P; Warren, John E; Musumeci, Daniele; Ward, Michael D; Brammer, Lee

2015-06-08

Despite an absence of conventional porosity, the 1D coordination polymer [Ag4 (O2 C(CF2 )2 CF3 )4 (TMP)3 ] (1; TMP=tetramethylpyrazine) can absorb small alcohols from the vapour phase, which insert into AgO bonds to yield coordination polymers [Ag4 (O2 C(CF2 )2 CF3 )4 (TMP)3 (ROH)2 ] (1-ROH; R=Me, Et, iPr). The reactions are reversible single-crystal-to-single-crystal transformations. Vapour-solid equilibria have been examined by gas-phase IR spectroscopy (K=5.68(9)×10(-5) (MeOH), 9.5(3)×10(-6) (EtOH), 6.14(5)×10(-5) (iPrOH) at 295 K, 1 bar). Thermal analyses (TGA, DSC) have enabled quantitative comparison of two-step reactions 1-ROH→1→2, in which 2 is the 2D coordination polymer [Ag4 (O2 C(CF2 )2 CF3 )4 (TMP)2 ] formed by loss of TMP ligands exclusively from singly-bridging sites. Four polymorphic forms of 1 (1-A(LT) , 1-A(HT) , 1-B(LT) and 1-B(HT) ; HT=high temperature, LT=low temperature) have been identified crystallographically. In situ powder X-ray diffraction (PXRD) studies of the 1-ROH→1→2 transformations indicate the role of the HT polymorphs in these reactions. The structural relationship between polymorphs, involving changes in conformation of perfluoroalkyl chains and a change in orientation of entire polymers (A versus B forms), suggests a mechanism for the observed reactions and a pathway for guest transport within the fluorous layers. Consistent with this pathway, optical microscopy and AFM studies on single crystals of 1-MeOH/1-A(HT) show that cracks parallel to the layers of interdigitated perfluoroalkyl chains develop during the MeOH release/uptake process. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction between hormonal and mitochondrial signalling during growth, development and in plant defence responses.

PubMed

Berkowitz, Oliver; De Clercq, Inge; Van Breusegem, Frank; Whelan, James

2016-05-01

Mitochondria play a central role in plant metabolism as they are a major source of ATP through synthesis by the oxidative phosphorylation pathway and harbour key metabolic reactions such as the TCA cycle. The energy and building blocks produced by mitochondria are essential to drive plant growth and development as well as to provide fuel for responses to abiotic and biotic stresses. The majority of mitochondrial proteins are encoded in the nuclear genome and have to be imported into the organelle. For the regulation of the corresponding genes intricate signalling pathways exist to adjust their expression. Signals directly regulate nuclear gene expression (anterograde signalling) to adjust the protein composition of the mitochondria to the needs of the cell. In parallel, mitochondria communicate back their functional status to the nucleus (retrograde signalling) to prompt transcriptional regulation of responsive genes via largely unknown signalling mechanisms. Plant hormones are the major signalling components regulating all layers of plant development and cellular functions. Increasing evidence is now becoming available that plant hormones are also part of signalling networks controlling mitochondrial function and their biogenesis. This review summarizes recent advances in understanding the interaction of mitochondrial and hormonal signalling pathways. © 2016 John Wiley & Sons Ltd.

Combined loss of three DNA damage response pathways renders C. elegans intolerant to light.

PubMed

van Bostelen, Ivo; Tijsterman, Marcel

2017-06-01

Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced chlorine dioxide decay in the presence of metal oxides: relevance to drinking water distribution systems.

PubMed

Liu, Chao; von Gunten, Urs; Croué, Jean-Philippe

2013-08-06

Chlorine dioxide (ClO2) decay in the presence of typical metal oxides occurring in distribution systems was investigated. Metal oxides generally enhanced ClO2 decay in a second-order process via three pathways: (1) catalytic disproportionation with equimolar formation of chlorite and chlorate, (2) reaction to chlorite and oxygen, and (3) oxidation of a metal in a reduced form (e.g., cuprous oxide) to a higher oxidation state. Cupric oxide (CuO) and nickel oxide (NiO) showed significantly stronger abilities than goethite (α-FeOOH) to catalyze the ClO2 disproportionation (pathway 1), which predominated at higher initial ClO2 concentrations (56-81 μM). At lower initial ClO2 concentrations (13-31 μM), pathway 2 also contributed. The CuO-enhanced ClO2 decay is a base-assisted reaction with a third-order rate constant of 1.5 × 10(6) M(-2) s(-1) in the presence of 0.1 g L(-1) CuO at 21 ± 1 °C, which is 4-5 orders of magnitude higher than in the absence of CuO. The presence of natural organic matter (NOM) significantly enhanced the formation of chlorite and decreased the ClO2 disproportionation in the CuO-ClO2 system, probably because of a higher reactivity of CuO-activated ClO2 with NOM. Furthermore, a kinetic model was developed to simulate CuO-enhanced ClO2 decay at various pH values. Model simulations that agree well with the experimental data include a pre-equilibrium step with the rapid formation of a complex, namely, CuO-activated Cl2O4. The reaction of this complex with OH(-) is the rate-limiting and pH-dependent step for the overall reaction, producing chlorite and an intermediate that further forms chlorate and oxygen in parallel. These novel findings suggest that the possible ClO2 loss and the formation of chlorite/chlorate should be carefully considered in drinking water distribution systems containing copper pipes.

Selective Conversion of Lignin-Derivable 4-Alkylguaiacols to 4-Alkylcyclohexanols over Noble and Non-Noble-Metal Catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schutyser, Wouter; Van den Bossche, Gil; Raaffels, Anton

2016-10-03

Recent lignin-first catalytic lignocellulosic biorefineries produce large quantities of two potential platform chemicals, 4-n-propylguaiacol (PG) and 4-n-propylsyringol. Because conversion into 4-n-propylcyclohexanol (PCol), a precursor for novel polymer building blocks, presents a promising valorization route, reductive demethoxylation of PG was examined here in the liquid-phase over three commercial hydrogenation catalysts, viz. 5 wt % Ru/C, 5 wt % Pd/C and 65 wt % Ni/SiO2-Al2O3, at elevated temperatures ranging from 200 to 300 degrees C under hydrogen atmosphere. Kinetic profiles suggest two parallel conversion pathways: Pathway I involves PG hydrogenation to 4-n-propyl-2-methoxycyclohexanol (PMCol), followed by its demethoxylation to PCol, whereas Pathway IImore » constitutes PG hydrodemethoxylation to 4-n-propylphenol (PPh), followed by its hydrogenation into PCol. The slowest step in the catalytic formation of PCol is the reductive methoxy removal from PMCol. Moreover, under the applied reaction conditions, PCol may react further into hydrocarbons. The following criteria are therefore essential to reach a high PCol yield: (i) catalytic pathway II is preferred as this route does not involve stable intermediates; (ii) reactivity of PMCol should be higher than that of PCol, and (iii) the overall carbon balance should be high. Both the catalyst type and the reaction conditions have a substantial impact on the PCol yield. Only the commercial Ni catalyst meets the three criteria, provided the reaction is performed at 250 degrees C in hexadecane. Additional advantages of this solvent choice are a high boiling point (low operational pressure in closed reactor systems), high solubility of PG and derived products, high thermal, reductive stability, and easy derivability from fatty biomass feedstock. This Ni catalyst also showed an excellent stability in recycling runs and is capable of converting highly concentrated (up to 20 wt %) PG in hexadecane. Ru and Pd on carbon showed a low PCol yield, as they are not conform the three criteria. Low hydrogen pressure favors Pathway II, resulting in a very high PCol yield of 85% at 10 bar. Catalytic conversion of guaiacol, 4-methyl- and 4-ethylguaiacol in comparable circumstances showed similarly high yields of the corresponding cyclohexanols.« less

Covalent binding of aniline to humic substances. 1. Kinetic studies

USGS Publications Warehouse

Weber, E.J.; Spidle, D.L.; Thorn, K.A.

1996-01-01

The reaction kinetics for the covalent binding of aniline with reconstituted IHSS humic and fulvic acids, unfractionated DOM isolated from Suwannee River water, and whole samples of Suwannee River water have been investigated. The reaction kinetics in each of these systems can be adequately described by a simple second-order rate expression. The effect of varying the initial concentration of aniline on reaction kinetics suggested that approximately 10% of the covalent binding sites associated with Suwannee River fulvic acid are highly reactive sites that are quickly saturated. Based on the kinetic parameters determined for the binding of aniline with the Suwannee River fulvic and humic acid isolates, it was estimated that 50% of the aniline concentration decrease in a Suwannee River water sample could be attributed to reaction with the fulvic and humic acid components of the whole water sample. Studies with Suwannee River fulvic acid demonstrated that the rate of binding decreased with decreasing pH, which parallels the decrease in the effective concentration of the neutral form, or reactive nucleophilic species of aniline. The covalent binding of aniline with Suwannee River fulvic acid was inhibited by prior treatment of the fulvic acid with hydrogen sulfide, sodium borohydride, or hydroxylamine. These observations are consistent with a reaction pathway involving nucleophilic addition of aniline to carbonyl moieties present in the fulvic acid.

An in Situ NMR Study of the Mechanism for the Catalytic Conversion of Fructose to 5-Hydroxymethylfurfural and then to Levulinic Acid Using 13 C Labeled d -Fructose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jing; Weitz, Eric

The pathways for the formation of 5-hydroxymethylfurfural (HMF) by dehydration of d-fructose and for the formation of levulinic acid and formic acid from HMF by rehydration were investigated by in situ13C and 1H NMR using both unlabeled and 13C-labeled fructose. Water or DMSO was used as the solvent with Amberlyst 70, PO43–/niobic acid, or sulfuric acid as catalysts. Only HMF is observed using NMR for fructose dehydration in DMSO with any of the three catalysts or without a catalyst. For each system, results with 13C-labeled fructose indicate that the first carbon (C-1) or sixth carbon (C-6) of fructose maps ontomore » the corresponding carbons of HMF. For fructose dehydration in H2O with a PO43–/niobic acid catalyst, in addition to HMF, furfural was observed as a product. However, we show that furfural is not a reaction product deriving from HMF under our conditions. Rather our data indicate that there is a parallel reaction pathway open to fructose when the reaction takes place in H2O with a PO43–/niobic acid catalyst. The corresponding 13C-labeled results show that the first carbon in fructose maps onto the first carbon (aldehyde carbon) in furfural. Using 13C-enriched HMF formed from dehydration of 13C-labeled fructose in DMSO or H2O, we investigated the pathway for HMF rehydration to levulinic and formic acid. The data in different solvents and with different catalysts are consistent with a common mechanism for HMF rehydration, which results in the C-1 and C-6 carbon of HMF being transformed to the carbon of formic acid and methyl carbon (C-5) of levulinic acid, respectively.« less

Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With Amplified Thermal Noise in Silicon Chips.

PubMed

Kim, Jaewook; Woo, Sung Sik; Sarpeshkar, Rahul

2018-04-01

The analysis and simulation of complex interacting biochemical reaction pathways in cells is important in all of systems biology and medicine. Yet, the dynamics of even a modest number of noisy or stochastic coupled biochemical reactions is extremely time consuming to simulate. In large part, this is because of the expensive cost of random number and Poisson process generation and the presence of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we can amplify inherent thermal noise in chips to emulate randomness physically, thus alleviating these costs significantly. Concurrently, molecular flux in thermodynamic biochemical reactions maps to thermodynamic electronic current in a transistor such that stiff nonlinear biochemical differential equations are emulated exactly in compact, digitally programmable, highly parallel analog "cytomorphic" transistor circuits. For even small-scale systems involving just 80 stochastic reactions, our 0.35-μm BiCMOS chips yield a 311× speedup in the simulation time of Gillespie's stochastic algorithm over COPASI, a fast biochemical-reaction software simulator that is widely used in computational biology; they yield a 15 500× speedup over equivalent MATLAB stochastic simulations. The chip emulation results are consistent with these software simulations over a large range of signal-to-noise ratios. Most importantly, our physical emulation of Poisson chemical dynamics does not involve any inherently sequential processes and updates such that, unlike prior exact simulation approaches, they are parallelizable, asynchronous, and enable even more speedup for larger-size networks.

The Application of the Weighted k-Partite Graph Problem to the Multiple Alignment for Metabolic Pathways.

PubMed

Chen, Wenbin; Hendrix, William; Samatova, Nagiza F

2017-12-01

The problem of aligning multiple metabolic pathways is one of very challenging problems in computational biology. A metabolic pathway consists of three types of entities: reactions, compounds, and enzymes. Based on similarities between enzymes, Tohsato et al. gave an algorithm for aligning multiple metabolic pathways. However, the algorithm given by Tohsato et al. neglects the similarities among reactions, compounds, enzymes, and pathway topology. How to design algorithms for the alignment problem of multiple metabolic pathways based on the similarity of reactions, compounds, and enzymes? It is a difficult computational problem. In this article, we propose an algorithm for the problem of aligning multiple metabolic pathways based on the similarities among reactions, compounds, enzymes, and pathway topology. First, we compute a weight between each pair of like entities in different input pathways based on the entities' similarity score and topological structure using Ay et al.'s methods. We then construct a weighted k-partite graph for the reactions, compounds, and enzymes. We extract a mapping between these entities by solving the maximum-weighted k-partite matching problem by applying a novel heuristic algorithm. By analyzing the alignment results of multiple pathways in different organisms, we show that the alignments found by our algorithm correctly identify common subnetworks among multiple pathways.

Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.

PubMed

Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

2016-09-01

Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations. © 2016 Cold Spring Harbor Laboratory Press.

Time-resolved spectroscopic studies of photosynthetic reaction centers and tetrapyrrole chromophores for biomedical and solar-energy applications

NASA Astrophysics Data System (ADS)

Kee, Hooi Ling

2008-10-01

The photophysical properties of diverse tetrapyrrole chromophores as well as energy and electron transfer processes in tetrapyrrole dyads are investigated using static and time-resolved (femtoseconds to seconds) absorption and fluorescence spectroscopy. The goal of these studies is to elucidate the molecular design principals necessary to construct chromophores with the specific and tunable properties that will enhance applications in optical molecular imaging, photodynamic therapy, and solar-energy conversion. The kinetic properties of the transient intermediate P+H B- involving the bacteriopheophytin molecule HB on the normally inactive (B) cofactor branch of the bacterial photosynthetic reaction center are examined in Rhodobacter capsulatus mutants. Using nanosecond flash photolysis and F(L181)Y/Y(M208)F/L(M212)H mutant, the decay pathways and yields of P+HB- were measured, giving an overall yield of 13% for B-side charge separation P* → P+HB- → P+ QB- in this mutant. The goal of these studies is to understand the fundamental differences in the rates, yields, and mechanisms of charge separation and charge recombination along the two parallel electron-transport chains in the bacterial reaction center.

A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.

PubMed

Vivot, Kevin; Benahmed, Malika A; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

2016-01-01

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1 H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1 H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation.

A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers

PubMed Central

Vivot, Kevin; Benahmed, Malika A.; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

2016-01-01

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation. PMID:27766032

Three-Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers

PubMed Central

Montavon, Timothy J.; Li, Jing; Cabrera-Pardo, Jaime R.; Mrksich, Milan; Kozmin, Sergey A.

2011-01-01

Multi-component reactions have been extensively employed in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform, which can be used for identification of new multi-component transformations. Our approach is based on the parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyze a previously unknown condensation of siloxy alkynes, aldehydes and amines to produce 3-hydroxy amides with high efficiency and diastereoselectivity. The reaction was further optimized using solution phase methods. PMID:22169871

CRUNCH_PARALLEL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shumaker, Dana E.; Steefel, Carl I.

The code CRUNCH_PARALLEL is a parallel version of the CRUNCH code. CRUNCH code version 2.0 was previously released by LLNL, (UCRL-CODE-200063). Crunch is a general purpose reactive transport code developed by Carl Steefel and Yabusake (Steefel Yabsaki 1996). The code handles non-isothermal transport and reaction in one, two, and three dimensions. The reaction algorithm is generic in form, handling an arbitrary number of aqueous and surface complexation as well as mineral dissolution/precipitation. A standardized database is used containing thermodynamic and kinetic data. The code includes advective, dispersive, and diffusive transport.

RRKM and master equation kinetic analysis of parallel addition reactions of isomeric radical intermediates in hydrocarbon flames

NASA Astrophysics Data System (ADS)

Winter, Pierre M.; Rheaume, Michael; Cooksy, Andrew L.

2017-08-01

We have calculated the temperature-dependent rate coefficients of the addition reactions of butadien-2-yl (C4H5) and acroylyl (C3H3O) radicals with ethene (C2H4), carbon monoxide (CO), formaldehyde (H2CO), hydrogen cyanide (HCN), and ketene (H2CCO), in order to explore the balance between kinetic and thermodynamic control in these combustion-related reactions. For the C4H5 radical, the 1,3-diene form of the addition products is more stable than the 1,2-diene, but the 1,2-diene form of the radical intermediate is stabilized by an allylic delocalization, which may influence the relative activation energies. For the reactions combining C3H3O with C2H4, CO, and HCN, the opposite is true: the 1,2-enone form of the addition products is more stable than the 1,3-enone, whereas the 1,3-enone is the slightly more stable radical species. Optimized geometries and vibrational modes were computed with the QCISD/aug-cc-pVDZ level and basis, followed by single-point CCSD(T)-F12a/cc-pVDZ-F12 energy calculations. Our findings indicate that the kinetics in all cases favor reaction along the 1,3 pathway for both the C4H5 and C3H3O systems. The Rice-Ramsperger-Kassel-Marcus (RRKM) microcanonical rate coefficients and subsequent solution of the chemical master equation were used to predict the time-evolution of our system under conditions from 500 K to 2000 K and from 10-5 bar to 10 bars. Despite the 1,3 reaction pathway being more favorable for the C4H5 system, our results predict branching ratios of the 1,2 to 1,3 product as high as 0.48 at 1 bar. Similar results hold for the acroylyl system under these combustion conditions, suggesting that under kinetic control the branching of these reactions may be much more significant than the thermodynamics would suggest. This effect may be partly attributed to the low energy difference between 1,2 and 1,3 forms of the radical intermediate. No substantial pressure-dependence is found for the overall forward reaction rates until pressures decrease below 0.1 bar.

VitisCyc: a metabolic pathway knowledgebase for grapevine (Vitis vinifera)

PubMed Central

Naithani, Sushma; Raja, Rajani; Waddell, Elijah N.; Elser, Justin; Gouthu, Satyanarayana; Deluc, Laurent G.; Jaiswal, Pankaj

2014-01-01

We have developed VitisCyc, a grapevine-specific metabolic pathway database that allows researchers to (i) search and browse the database for its various components such as metabolic pathways, reactions, compounds, genes and proteins, (ii) compare grapevine metabolic networks with other publicly available plant metabolic networks, and (iii) upload, visualize and analyze high-throughput data such as transcriptomes, proteomes, metabolomes etc. using OMICs-Viewer tool. VitisCyc is based on the genome sequence of the nearly homozygous genotype PN40024 of Vitis vinifera “Pinot Noir” cultivar with 12X v1 annotations and was built on BioCyc platform using Pathway Tools software and MetaCyc reference database. Furthermore, VitisCyc was enriched for plant-specific pathways and grape-specific metabolites, reactions and pathways. Currently VitisCyc harbors 68 super pathways, 362 biosynthesis pathways, 118 catabolic pathways, 5 detoxification pathways, 36 energy related pathways and 6 transport pathways, 10,908 enzymes, 2912 enzymatic reactions, 31 transport reactions and 2024 compounds. VitisCyc, as a community resource, can aid in the discovery of candidate genes and pathways that are regulated during plant growth and development, and in response to biotic and abiotic stress signals generated from a plant's immediate environment. VitisCyc version 3.18 is available online at http://pathways.cgrb.oregonstate.edu. PMID:25538713

Parallel processing in the honeybee olfactory pathway: structure, function, and evolution.

PubMed

Rössler, Wolfgang; Brill, Martin F

2013-11-01

Animals face highly complex and dynamic olfactory stimuli in their natural environments, which require fast and reliable olfactory processing. Parallel processing is a common principle of sensory systems supporting this task, for example in visual and auditory systems, but its role in olfaction remained unclear. Studies in the honeybee focused on a dual olfactory pathway. Two sets of projection neurons connect glomeruli in two antennal-lobe hemilobes via lateral and medial tracts in opposite sequence with the mushroom bodies and lateral horn. Comparative studies suggest that this dual-tract circuit represents a unique adaptation in Hymenoptera. Imaging studies indicate that glomeruli in both hemilobes receive redundant sensory input. Recent simultaneous multi-unit recordings from projection neurons of both tracts revealed widely overlapping response profiles strongly indicating parallel olfactory processing. Whereas lateral-tract neurons respond fast with broad (generalistic) profiles, medial-tract neurons are odorant specific and respond slower. In analogy to "what-" and "where" subsystems in visual pathways, this suggests two parallel olfactory subsystems providing "what-" (quality) and "when" (temporal) information. Temporal response properties may support across-tract coincidence coding in higher centers. Parallel olfactory processing likely enhances perception of complex odorant mixtures to decode the diverse and dynamic olfactory world of a social insect.

Parallel processing via a dual olfactory pathway in the honeybee.

PubMed

Brill, Martin F; Rosenbaum, Tobias; Reus, Isabelle; Kleineidam, Christoph J; Nawrot, Martin P; Rössler, Wolfgang

2013-02-06

In their natural environment, animals face complex and highly dynamic olfactory input. Thus vertebrates as well as invertebrates require fast and reliable processing of olfactory information. Parallel processing has been shown to improve processing speed and power in other sensory systems and is characterized by extraction of different stimulus parameters along parallel sensory information streams. Honeybees possess an elaborate olfactory system with unique neuronal architecture: a dual olfactory pathway comprising a medial projection-neuron (PN) antennal lobe (AL) protocerebral output tract (m-APT) and a lateral PN AL output tract (l-APT) connecting the olfactory lobes with higher-order brain centers. We asked whether this neuronal architecture serves parallel processing and employed a novel technique for simultaneous multiunit recordings from both tracts. The results revealed response profiles from a high number of PNs of both tracts to floral, pheromonal, and biologically relevant odor mixtures tested over multiple trials. PNs from both tracts responded to all tested odors, but with different characteristics indicating parallel processing of similar odors. Both PN tracts were activated by widely overlapping response profiles, which is a requirement for parallel processing. The l-APT PNs had broad response profiles suggesting generalized coding properties, whereas the responses of m-APT PNs were comparatively weaker and less frequent, indicating higher odor specificity. Comparison of response latencies within and across tracts revealed odor-dependent latencies. We suggest that parallel processing via the honeybee dual olfactory pathway provides enhanced odor processing capabilities serving sophisticated odor perception and olfactory demands associated with a complex olfactory world of this social insect.

Structure of L-Xylulose-5-Phosphate 3-Epimerase (UlaE) from the Anaerobic L-Ascorbate Utilization Pathway of Escherichia coli: Identification of a Novel Phosphate Binding Motif within a TIM Barrel Fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Rong; Pineda, Marco; Ajamian, Eunice

2009-01-15

Three catabolic enzymes, UlaD, UlaE, and UlaF, are involved in a pathway leading to fermentation of L-ascorbate under anaerobic conditions. UlaD catalyzes a {beta}-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway. We describe here crystallographic studies of UlaE from Escherichia coli O157:H7 that complete the structural characterization of this pathway. UlaE has a triosephosphate isomerase (TIM) barrel fold and forms dimers. The active site is located at the C-terminal ends of the parallel {beta}-strands. The enzyme binds Zn{sup 2+},more » which is coordinated by Glu155, Asp185, His211, and Glu251. We identified a phosphate-binding site formed by residues from the {beta}1/{alpha}1 loop and {alpha}3' helix in the N-terminal region. This site differs from the well-characterized phosphate-binding motif found in several TIM barrel superfamilies that is located at strands {beta}7 and {beta}8. The intrinsic flexibility of the active site region is reflected by two different conformations of loops forming part of the substrate-binding site. Based on computational docking of the L-xylulose 5-phosphate substrate to UlaE and structural similarities of the active site of this enzyme to the active sites of other epimerases, a metal-dependent epimerization mechanism for UlaE is proposed, and Glu155 and Glu251 are implicated as catalytic residues. Mutation and activity measurements for structurally equivalent residues in related epimerases supported this mechanistic proposal.« less

Perturbation Experiments: Approaches for Metabolic Pathway Analysis in Bioreactors.

PubMed

Weiner, Michael; Tröndle, Julia; Albermann, Christoph; Sprenger, Georg A; Weuster-Botz, Dirk

2016-01-01

In the last decades, targeted metabolic engineering of microbial cells has become one of the major tools in bioprocess design and optimization. For successful application, a detailed knowledge is necessary about the relevant metabolic pathways and their regulation inside the cells. Since in vitro experiments cannot display process conditions and behavior properly, process data about the cells' metabolic state have to be collected in vivo. For this purpose, special techniques and methods are necessary. Therefore, most techniques enabling in vivo characterization of metabolic pathways rely on perturbation experiments, which can be divided into dynamic and steady-state approaches. To avoid any process disturbance, approaches which enable perturbation of cell metabolism in parallel to the continuing production process are reasonable. Furthermore, the fast dynamics of microbial production processes amplifies the need of parallelized data generation. These points motivate the development of a parallelized approach for multiple metabolic perturbation experiments outside the operating production reactor. An appropriate approach for in vivo characterization of metabolic pathways is presented and applied exemplarily to a microbial L-phenylalanine production process on a 15 L-scale.

Permanganate oxidation of α-amino acids: kinetic correlations for the nonautocatalytic and autocatalytic reaction pathways.

PubMed

Perez-Benito, Joaquin F

2011-09-08

The reactions of permanganate ion with seven α-amino acids in aqueous KH(2)PO(4)/K(2)HPO(4) buffers have been followed spectrophotometrically at two different wavelengths: 526 nm (decay of MnO(4)(-)) and 418 nm (formation of colloidal MnO(2)). All of the reactions studied were autocatalyzed by colloidal MnO(2), with the contribution of the autocatalytic reaction pathway decreasing in the order glycine > l-threonine > l-alanine > l-glutamic acid > l-leucine > l-isoleucine > l-valine. The rate constants corresponding to the nonautocatalytic and autocatalytic pathways were obtained by means of either a differential rate law or an integrated one, the latter requiring the use of an iterative method for its implementation. The activation parameters for the two pathways were determined and analyzed to obtain statistically significant correlations for the series of reactions studied. The activation enthalpy of the nonautocatalytic pathway showed a strong, positive dependence on the standard Gibbs energy for the dissociation of the protonated amino group of the α-amino acid. Linear enthalpy-entropy correlations were found for both pathways, leading to isokinetic temperatures of 370 ± 21 K (nonautocatalytic) and 364 ± 28 K (autocatalytic). Mechanisms in agreement with the experimental data are proposed for the two reaction pathways.

Constraining the role of iron in environmental nitrogen transformations. Dual stable isotope systematics of abiotic NO 2- reduction by Fe(II) and its production of N 2O

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, David; Wankel, Scott David; Buchwald, Carolyn

Redox reactions involving nitrogen and iron have been shown to have important implications for mobilization of priority contaminants. Thus, an understanding of the linkages between their biogeochemical cycling is critical for predicting subsurface mobilization of radionuclides such as uranium. Despite mounting evidence for biogeochemical interactions between iron and nitrogen, our understanding of their environmental importance remains limited. Here we present an investigation of abiotic nitrite (NO 2 -) reduction by Fe(II) or ‘chemodenitrification,’ and its relevance to the production of nitrous oxide (N 2O), specifically focusing on dual (N and O) isotope systematics under a variety of environmentally relevant conditions.more » We observe a range of kinetic isotope effects that are regulated by reaction rates, with faster rates at higher pH (~8), higher concentrations of Fe(II) and in the presence of mineral surfaces. A clear non-linear relationship between rate constant and kinetic isotope effects of NO 2 - reduction was evident (with larger isotope effects at slower rates) and is interpreted as reflecting the dynamics of Fe(II)-N reaction intermediates. N and O isotopic composition of product N 2O also suggests a complex network of parallel and/or competing pathways. Our findings suggest that NO 2 - reduction by Fe(II) may represent an important abiotic source of environmental N 2O, especially in iron-rich environments experiencing dynamic redox variations. This study provides a multi-compound, multi-isotope framework for evaluating the environmental occurrence of abiotic NO 2 - reduction and N 2O formation, helping future studies constrain the relative roles of abiotic and biological N 2O production pathways.« less

A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text

PubMed Central

Miwa, Makoto; Ohta, Tomoko; Rak, Rafal; Rowley, Andrew; Kell, Douglas B.; Pyysalo, Sampo; Ananiadou, Sophia

2013-01-01

Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/. Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23813008

Reconstruction of metabolic pathways by combining probabilistic graphical model-based and knowledge-based methods

PubMed Central

2014-01-01

Automatic reconstruction of metabolic pathways for an organism from genomics and transcriptomics data has been a challenging and important problem in bioinformatics. Traditionally, known reference pathways can be mapped into an organism-specific ones based on its genome annotation and protein homology. However, this simple knowledge-based mapping method might produce incomplete pathways and generally cannot predict unknown new relations and reactions. In contrast, ab initio metabolic network construction methods can predict novel reactions and interactions, but its accuracy tends to be low leading to a lot of false positives. Here we combine existing pathway knowledge and a new ab initio Bayesian probabilistic graphical model together in a novel fashion to improve automatic reconstruction of metabolic networks. Specifically, we built a knowledge database containing known, individual gene / protein interactions and metabolic reactions extracted from existing reference pathways. Known reactions and interactions were then used as constraints for Bayesian network learning methods to predict metabolic pathways. Using individual reactions and interactions extracted from different pathways of many organisms to guide pathway construction is new and improves both the coverage and accuracy of metabolic pathway construction. We applied this probabilistic knowledge-based approach to construct the metabolic networks from yeast gene expression data and compared its results with 62 known metabolic networks in the KEGG database. The experiment showed that the method improved the coverage of metabolic network construction over the traditional reference pathway mapping method and was more accurate than pure ab initio methods. PMID:25374614

A theoretical study on reaction mechanisms and kinetics of thiophene hydrodesulfurization over MoS 2 catalysts

DOE PAGES

Jin, Qiu; Chen, Biaohua; Ren, Zhibo; ...

2018-02-10

In the present study, thiophene hydrodesulphurization (HDS) over the Mo-edge, the S-edge, and the Mo-S connection edge of MoS 2 catalyst with 50% sulfur coverage was studied using first-principles based microkinetic modeling. Two parallel HDS routes, i.e., direct desulfurization (DDS) and hydrogenation (HYD) were taken into account. It has been found that the major reaction route of thiophene HDS on the Mo- and the Mo-S edges is temperature dependent. In the low temperature range of 500–600 K, the HYD route is dominant, leading to the C 4H 8 formation. As the temperature increases, the DDS route becomes competitive with themore » HYD route. At the temperature above 650 K, the DDS route will be the dominant HDS reaction route on the Mo- and the Mo-S edges. The DDS route leading to the formation of C 4H 6 is the major thiophene HDS reaction route on the S-edge in the entire temperature range of 500–750 K. The microkinetic modeling results show the overall HDS activity on the S-edge is lower than it on the Mo- and the Mo-S edges. The Mo-S edge also provides a preferential reaction pathway, which facilitates 2-hydrothiophene migration from the Mo-edge to the S-edge, followed by remaining elementary steps with lower activation barriers in the DDS route.« less

A theoretical study on reaction mechanisms and kinetics of thiophene hydrodesulfurization over MoS 2 catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Qiu; Chen, Biaohua; Ren, Zhibo

In the present study, thiophene hydrodesulphurization (HDS) over the Mo-edge, the S-edge, and the Mo-S connection edge of MoS 2 catalyst with 50% sulfur coverage was studied using first-principles based microkinetic modeling. Two parallel HDS routes, i.e., direct desulfurization (DDS) and hydrogenation (HYD) were taken into account. It has been found that the major reaction route of thiophene HDS on the Mo- and the Mo-S edges is temperature dependent. In the low temperature range of 500–600 K, the HYD route is dominant, leading to the C 4H 8 formation. As the temperature increases, the DDS route becomes competitive with themore » HYD route. At the temperature above 650 K, the DDS route will be the dominant HDS reaction route on the Mo- and the Mo-S edges. The DDS route leading to the formation of C 4H 6 is the major thiophene HDS reaction route on the S-edge in the entire temperature range of 500–750 K. The microkinetic modeling results show the overall HDS activity on the S-edge is lower than it on the Mo- and the Mo-S edges. The Mo-S edge also provides a preferential reaction pathway, which facilitates 2-hydrothiophene migration from the Mo-edge to the S-edge, followed by remaining elementary steps with lower activation barriers in the DDS route.« less

Mechanisms of Furfural Reduction on Metal Electrodes: Distinguishing Pathways for Selective Hydrogenation of Bioderived Oxygenates.

PubMed

Chadderdon, Xiaotong H; Chadderdon, David J; Matthiesen, John E; Qiu, Yang; Carraher, Jack M; Tessonnier, Jean-Philippe; Li, Wenzhen

2017-10-11

Electrochemical reduction of biomass-derived platform molecules is an emerging route for the sustainable production of fuels and chemicals. However, understanding gaps between reaction conditions, underlying mechanisms, and product selectivity have limited the rational design of active, stable, and selective catalyst systems. In this work, the mechanisms of electrochemical reduction of furfural, an important biobased platform molecule and model for aldehyde reduction, are explored through a combination of voltammetry, preparative electrolysis, thiol-electrode modifications, and kinetic isotope studies. It is demonstrated that two distinct mechanisms are operable on metallic Cu electrodes in acidic electrolytes: (i) electrocatalytic hydrogenation (ECH) and (ii) direct electroreduction. The contributions of each mechanism to the observed product distribution are clarified by evaluating the requirement for direct chemical interactions with the electrode surface and the role of adsorbed hydrogen. Further analysis reveals that hydrogenation and hydrogenolysis products are generated by parallel ECH pathways. Understanding the underlying mechanisms enables the manipulation of furfural reduction by rationally tuning the electrode potential, electrolyte pH, and furfural concentration to promote selective formation of important biobased polymer precursors and fuels.

Mechanisms of Furfural Reduction on Metal Electrodes: Distinguishing Pathways for Selective Hydrogenation of Bioderived Oxygenates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chadderdon, Xiaotong H.; Chadderdon, David J.; Matthiesen, John E.

Electrochemical reduction of biomass-derived platform molecules is an emerging route for the sustainable production of fuels and chemicals. Understanding gaps between reaction conditions, underlying mechanisms, and product selectivity have limited the rational design of active, stable, and selective catalyst systems. Here, the mechanisms of electrochemical reduction of furfural, an important biobased platform molecule and model for aldehyde reduction, are explored through a combination of voltammetry, preparative electrolysis, thiol-electrode modifications, and kinetic isotope studies. It is demonstrated that two distinct mechanisms are operable on metallic Cu electrodes in acidic electrolytes: (i) electrocatalytic hydrogenation (ECH) and (ii) direct electroreduction. The contributions ofmore » each mechanism to the observed product distribution are clarified by evaluating the requirement for direct chemical interactions with the electrode surface and the role of adsorbed hydrogen. Further analysis reveals that hydrogenation and hydrogenolysis products are generated by parallel ECH pathways. By understanding the underlying mechanisms it enables the manipulation of furfural reduction by rationally tuning the electrode potential, electrolyte pH, and furfural concentration to promote selective formation of important biobased polymer precursors and fuels.« less

Mechanisms of Furfural Reduction on Metal Electrodes: Distinguishing Pathways for Selective Hydrogenation of Bioderived Oxygenates

DOE PAGES

Chadderdon, Xiaotong H.; Chadderdon, David J.; Matthiesen, John E.; ...

2017-09-13

Electrochemical reduction of biomass-derived platform molecules is an emerging route for the sustainable production of fuels and chemicals. Understanding gaps between reaction conditions, underlying mechanisms, and product selectivity have limited the rational design of active, stable, and selective catalyst systems. Here, the mechanisms of electrochemical reduction of furfural, an important biobased platform molecule and model for aldehyde reduction, are explored through a combination of voltammetry, preparative electrolysis, thiol-electrode modifications, and kinetic isotope studies. It is demonstrated that two distinct mechanisms are operable on metallic Cu electrodes in acidic electrolytes: (i) electrocatalytic hydrogenation (ECH) and (ii) direct electroreduction. The contributions ofmore » each mechanism to the observed product distribution are clarified by evaluating the requirement for direct chemical interactions with the electrode surface and the role of adsorbed hydrogen. Further analysis reveals that hydrogenation and hydrogenolysis products are generated by parallel ECH pathways. By understanding the underlying mechanisms it enables the manipulation of furfural reduction by rationally tuning the electrode potential, electrolyte pH, and furfural concentration to promote selective formation of important biobased polymer precursors and fuels.« less

Brucine diol-copper-catalyzed asymmetric synthesis of endo-pyrrolidines: the mechanistic dichotomy of imino esters.

PubMed

Li, Jian-Yuan; Kim, Hun Young; Oh, Kyungsoo

2015-03-06

Enantio- and diastereodivergent approaches to pyrrolidines are described by using catalyst- and substrate-controlled reaction pathways. A concerted endo-selective [3 + 2]-cycloaddition pathway is developed for the reaction of methyl imino ester, whereas endo-pyrrolidines with an opposite absolute stereochemical outcome are prepared by using the stepwise reaction pathway of tert-butyl imino ester. The development of catalyst- and substrate-controlled stereodivergent approaches highlights the inherent substrate-catalyst interactions in the [3 + 2]-cycloaddition reactions of metalated azomethine ylides.

Divergent pathways in the reaction of Fischer carbenes and palladium.

PubMed

López-Alberca, María P; Mancheño, María J; Fernandez, Israel; Gómez-Gallego, Mar; Sierra, Miguel A; Torres, Rosario

2007-04-26

[reaction: see text] The Pd-catalyzed reaction of beta-arylaminochromium(0) carbene complexes produces by transmetalation the first isolated and X-ray structurally characterized bis-Pd(II) carbene complex, as well as other alternative reaction pathways, such as the oxidative addition-transmetalation sequence, not seen before in this chemistry.

Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovacik, Meric A.; Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu; Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854

2013-09-15

Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogeneticmore » relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.« less

Encoding of social signals in all three electrosensory pathways of Eigenmannia virescens.

PubMed

Stöckl, Anna; Sinz, Fabian; Benda, Jan; Grewe, Jan

2014-11-01

Extracting complementary features in parallel pathways is a widely used strategy for a robust representation of sensory signals. Weakly electric fish offer the rare opportunity to study complementary encoding of social signals in all of its electrosensory pathways. Electrosensory information is conveyed in three parallel pathways: two receptor types of the tuberous (active) system and one receptor type of the ampullary (passive) system. Modulations of the fish's own electric field are sensed by these receptors and used in navigation, prey detection, and communication. We studied the neuronal representation of electric communication signals (called chirps) in the ampullary and the two tuberous pathways of Eigenmannia virescens. We first characterized different kinds of chirps observed in behavioral experiments. Since Eigenmannia chirps simultaneously drive all three types of receptors, we studied their responses in in vivo electrophysiological recordings. Our results demonstrate that different electroreceptor types encode different aspects of the stimuli and each appears best suited to convey information about a certain chirp type. A decoding analysis of single neurons and small populations shows that this specialization leads to a complementary representation of information in the tuberous and ampullary receptors. This suggests that a potential readout mechanism should combine information provided by the parallel processing streams to improve chirp detectability. Copyright © 2014 the American Physiological Society.

A chain reaction approach to modelling gene pathways.

PubMed

Cheng, Gary C; Chen, Dung-Tsa; Chen, James J; Soong, Seng-Jaw; Lamartiniere, Coral; Barnes, Stephen

2012-08-01

BACKGROUND: Of great interest in cancer prevention is how nutrient components affect gene pathways associated with the physiological events of puberty. Nutrient-gene interactions may cause changes in breast or prostate cells and, therefore, may result in cancer risk later in life. Analysis of gene pathways can lead to insights about nutrient-gene interactions and the development of more effective prevention approaches to reduce cancer risk. To date, researchers have relied heavily upon experimental assays (such as microarray analysis, etc.) to identify genes and their associated pathways that are affected by nutrient and diets. However, the vast number of genes and combinations of gene pathways, coupled with the expense of the experimental analyses, has delayed the progress of gene-pathway research. The development of an analytical approach based on available test data could greatly benefit the evaluation of gene pathways, and thus advance the study of nutrient-gene interactions in cancer prevention. In the present study, we have proposed a chain reaction model to simulate gene pathways, in which the gene expression changes through the pathway are represented by the species undergoing a set of chemical reactions. We have also developed a numerical tool to solve for the species changes due to the chain reactions over time. Through this approach we can examine the impact of nutrient-containing diets on the gene pathway; moreover, transformation of genes over time with a nutrient treatment can be observed numerically, which is very difficult to achieve experimentally. We apply this approach to microarray analysis data from an experiment which involved the effects of three polyphenols (nutrient treatments), epigallo-catechin-3-O-gallate (EGCG), genistein, and resveratrol, in a study of nutrient-gene interaction in the estrogen synthesis pathway during puberty. RESULTS: In this preliminary study, the estrogen synthesis pathway was simulated by a chain reaction model. By applying it to microarray data, the chain reaction model computed a set of reaction rates to examine the effects of three polyphenols (EGCG, genistein, and resveratrol) on gene expression in this pathway during puberty. We first performed statistical analysis to test the time factor on the estrogen synthesis pathway. Global tests were used to evaluate an overall gene expression change during puberty for each experimental group. Then, a chain reaction model was employed to simulate the estrogen synthesis pathway. Specifically, the model computed the reaction rates in a set of ordinary differential equations to describe interactions between genes in the pathway (A reaction rate K of A to B represents gene A will induce gene B per unit at a rate of K; we give details in the "method" section). Since disparate changes of gene expression may cause numerical error problems in solving these differential equations, we used an implicit scheme to address this issue. We first applied the chain reaction model to obtain the reaction rates for the control group. A sensitivity study was conducted to evaluate how well the model fits to the control group data at Day 50. Results showed a small bias and mean square error. These observations indicated the model is robust to low random noises and has a good fit for the control group. Then the chain reaction model derived from the control group data was used to predict gene expression at Day 50 for the three polyphenol groups. If these nutrients affect the estrogen synthesis pathways during puberty, we expect discrepancy between observed and expected expressions. Results indicated some genes had large differences in the EGCG (e.g., Hsd3b and Sts) and the resveratrol (e.g., Hsd3b and Hrmt12) groups. CONCLUSIONS: In the present study, we have presented (I) experimental studies of the effect of nutrient diets on the gene expression changes in a selected estrogen synthesis pathway. This experiment is valuable because it allows us to examine how the nutrient-containing diets regulate gene expression in the estrogen synthesis pathway during puberty; (II) global tests to assess an overall association of this particular pathway with time factor by utilizing generalized linear models to analyze microarray data; and (III) a chain reaction model to simulate the pathway. This is a novel application because we are able to translate the gene pathway into the chemical reactions in which each reaction channel describes gene-gene relationship in the pathway. In the chain reaction model, the implicit scheme is employed to efficiently solve the differential equations. Data analysis results show the proposed model is capable of predicting gene expression changes and demonstrating the effect of nutrient-containing diets on gene expression changes in the pathway. One of the objectives of this study is to explore and develop a numerical approach for simulating the gene expression change so that it can be applied and calibrated when the data of more time slices are available, and thus can be used to interpolate the expression change at a desired time point without conducting expensive experiments for a large amount of time points. Hence, we are not claiming this is either essential or the most efficient way for simulating this problem, rather a mathematical/numerical approach that can model the expression change of a large set of genes of a complex pathway. In addition, we understand the limitation of this experiment and realize that it is still far from being a complete model of predicting nutrient-gene interactions. The reason is that in the present model, the reaction rates were estimated based on available data at two time points; hence, the gene expression change is dependent upon the reaction rates and a linear function of the gene expressions. More data sets containing gene expression at various time slices are needed in order to improve the present model so that a non-linear variation of gene expression changes at different time can be predicted.

Photochemical transformation of azoxystrobin in aqueous solutions.

PubMed

Boudina, A; Emmelin, C; Baaliouamer, A; Païssé, O; Chovelon, J M

2007-07-01

The photochemical behaviour of azoxystrobin fungicide (AZX) in water was studied under laboratory conditions. Photodegradation was initiated using a solar simulator (xenon arc lamp) or a jacketed Pyrex reaction cell equipped with a 125 W, high-pressure mercury lamp. HPLC/MS analysis (APCI and ESI in positive and negative modes) was used to identify AZX photoproducts. The calculated polychromatic quantum efficiencies (phi) of AZX at pH 4.5, 7 and 9 were 5.42 x 10(-3), 3.47 x 10(-3) and 3.06 x 10(-3) (degraded molecules per absorbed photon), respectively. The relatively narrow range of values indicates the stability of AZX with respect to photodegradation in the studied pH range. Results from the HPLC/MS analysis suggest that the phototransformation of AZX proceeds via multiple, parallel reaction pathways including: (1) photo-isomerization (E-->Z), (2) photo-hydrolysis of the methyl ester and of the nitrile group, (3) cleavage of the acrylate double bond, (4) photohydrolytic ether cleavage between the aromatic ring giving phenol, and (5) oxidative cleavage of the acrylate double bond.

Elucidation of metabolic pathways from enzyme classification data.

PubMed

McDonald, Andrew G; Tipton, Keith F

2014-01-01

The IUBMB Enzyme List is widely used by other databases as a source for avoiding ambiguity in the recognition of enzymes as catalytic entities. However, it was not designed for metabolic pathway tracing, which has become increasingly important in systems biology. A Reactions Database has been created from the material in the Enzyme List to allow reactions to be searched by substrate/product, and pathways to be traced from any selected starting/seed substrate. An extensive synonym glossary allows searches by many of the alternative names, including accepted abbreviations, by which a chemical compound may be known. This database was necessary for the development of the application Reaction Explorer ( http://www.reaction-explorer.org ), which was written in Real Studio ( http://www.realsoftware.com/realstudio/ ) to search the Reactions Database and draw metabolic pathways from reactions selected by the user. Having input the name of the starting compound (the "seed"), the user is presented with a list of all reactions containing that compound and then selects the product of interest as the next point on the ensuing graph. The pathway diagram is then generated as the process iterates. A contextual menu is provided, which allows the user: (1) to remove a compound from the graph, along with all associated links; (2) to search the reactions database again for additional reactions involving the compound; (3) to search for the compound within the Enzyme List.

A Structure-Toxicity Study of Aß42 Reveals a New Anti-Parallel Aggregation Pathway

PubMed Central

Vignaud, Hélène; Bobo, Claude; Lascu, Ioan; Sörgjerd, Karin Margareta; Zako, Tamotsu; Maeda, Mizuo; Salin, Benedicte; Lecomte, Sophie; Cullin, Christophe

2013-01-01

Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer’s disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel ß-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar Aβ. Here, we present a novel approach to determining the molecular aspects of Aß assembly that is responsible for its in vivo toxicity. We selected Aß mutants with varying intracellular toxicities. In vitro, only toxic Aß (including wild-type Aß42) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel ß-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of Aß . PMID:24244667

Molecular and Biochemical Basis for Stress-Induced Accumulation of Free and Bound p-Coumaraldehyde in Cucumber1[W][OA

PubMed Central

Varbanova, Marina; Porter, Katie; Lu, Fachuang; Ralph, John; Hammerschmidt, Ray; Jones, A. Daniel; Day, Brad

2011-01-01

To elucidate the genetic and biochemical regulation of elicitor-induced p-coumaraldehyde accumulation in plants, we undertook a multifaceted approach to characterize the metabolic flux through the phenylpropanoid pathway via the characterization and chemical analysis of the metabolites in the p-coumaryl, coniferyl, and sinapyl alcohol branches of this pathway. Here, we report the identification and characterization of four cinnamyl alcohol dehydrogenases (CADs) from cucumber (Cucumis sativus) with low activity toward p-coumaraldehyde yet exhibiting significant activity toward other phenylpropanoid hydroxycinnamaldehydes. As part of this analysis, we identified and characterized the activity of a hydroxycinnamoyl-coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) capable of utilizing shikimate and p-coumaroyl-coenzyme A to generate p-coumaroyl shikimate. Following pectinase treatment of cucumber, we observed the rapid accumulation of p-coumaraldehyde, likely the result of low aldehyde reductase activity (i.e. alcohol dehydrogenase in the reverse reaction) of CsCAD enzymes on p-coumaraldehyde. In parallel, we noted a concomitant reduction in the activity of CsHCT. Taken together, our findings support the hypothesis that the up-regulation of the phenylpropanoid pathway upon abiotic stress greatly enhances the overall p-coumaryl alcohol branch of the pathway. The data presented here point to a role for CsHCT (as well as, presumably, p-coumarate 3-hydroxylase) as a control point in the regulation of the coniferyl and sinapyl alcohol branches of this pathway. This mechanism represents a potentially evolutionarily conserved process to efficiently and quickly respond to biotic and abiotic stresses in cucurbit plants, resulting in the rapid lignification of affected tissues. PMID:21940999

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schachtl, Eva; Yoo, Jong Suk; Gutiérrez, Oliver Y.

The reaction network and elementary steps of the hydrogenation of phenanthrene are explored on parent and Ni-promoted MoS2/c-Al2O3. Two pathways were identified, i.e., Path 1: Phenanthrene _ 9,10-dihydrophenanthrene (DiHPhe)?1,2,3,4,4a,9,10,10a-octahydro-phenanthrene (asymOHPhe), and Path 2: Phenanthrene ?1,2,3,4-tetrahydrophenanthrene (TetHPhe)?1,2,3,4,5,6,7,8-octahydrophenan threne. The steps TetHPhe?asymOHPhe (hydrogenation), and DiHPhe?TetHPhe (hydrogenationisomerization) become notable at phenanthrene conversions above 20%. The reaction preferentially proceeds via Path 1 (90% selectivity) on MoS2/Al2O3. Ni promotion (Ni/(Ni + Mo) molar ratio of 0.3 at the edges on MoS2) increases the hydrogenation activity per active edge twofold and leads to 50% selectivity to both pathways. The reaction orders in H2 vary from _0.8more » on MoS2/Al2O3 to _1.2 on Ni-MoS2/Al2O3, whereas the reaction orders in phenanthrene (_0.6) hardly depend on Ni promotion. The reaction orders in H2S are zero on MoS2/Al2O3 and slightly negative on Ni-MoS2/Al2O3. DFT calculations indicate that phenanthrene is preferentially adsorbed parallel to the basal planes, while H is located at the edges perpendicular to the basal planes. Theory also suggests that Ni atoms, incorporated preferentially on the S-edges, increase the stability of hydrogenated intermediates. Hydrogenation of phenanthrene proceeds through quasi-equilibrated adsorption of the reactants followed by consecutive addition of hydrogen pairs to the adsorbed hydrocarbon. The rate determining steps for the formation of DiHPhe and TetHPhe are the addition of the first and second hydrogen pair, respectively. The concentration of SH groups (activated H at the edges) increases with Ni promotion linearly correlating the rates of Path 1 and Path 2, albeit with different functions. The enhancing effect of Ni on Path 2 is attributed to accelerated hydrogen addition to adsorbed hydrocarbons without important changes in their coverages.« less

Kinetics of thermal decomposition of some biomasses in an inert environment. An investigation of the effect of lead loaded by biosorption.

PubMed

Martín-Lara, María Ángeles; Iáñez-Rodríguez, Irene; Blázquez, Gabriel; Quesada, Lucía; Pérez, Antonio; Calero, Mónica

2017-12-01

The thermal behavior of some types of raw and lead-polluted biomasses typical in south Spain was studied by non-isothermal thermogravimetry. Experiments were carried out in nitrogen atmosphere at three heating rates (5, 10 and 20°C/min). The results of thermogravimetric tests carried out proved that the presence of lead did not change the main degradation pathways of selected biomass (almond shell (AS) and olive pomace (OP)). However, from a point of view of mass loss, lead-polluted samples showed higher decomposition temperatures and decomposition at higher rate. The determination of activation energies was performed by isoconversional methods of Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS) and Friedman (FR). In general, lead-polluted samples showed lower activation energies than raw ones. Then, Coast-Redfern method was applied to determine kinetic function. The kinetic function that seems to determine the mechanism of thermal degradation of main components of all samples was nth order reaction. Finally, a model based on three parallel reactions (for three pseudocomponents) that fit to nth order reactions was evaluated. This model was appropriate to predict the pyrolysis behavior of the raw and lead-polluted samples in all pyrolysis conditions studied. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the deduction of chemical reaction pathways from measurements of time series of concentrations.

PubMed

Samoilov, Michael; Arkin, Adam; Ross, John

2001-03-01

We discuss the deduction of reaction pathways in complex chemical systems from measurements of time series of chemical concentrations of reacting species. First we review a technique called correlation metric construction (CMC) and show the construction of a reaction pathway from measurements on a part of glycolysis. Then we present two new improved methods for the analysis of time series of concentrations, entropy metric construction (EMC), and entropy reduction method (ERM), and illustrate (EMC) with calculations on a model reaction system. (c) 2001 American Institute of Physics.

Pyridine adsorption and diffusion on Pt(111) investigated with density functional theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolsbjerg, Esben L.; Groves, Michael N.; Hammer, Bjørk, E-mail: hammer@phys.au.dk

2016-04-28

The adsorption, diffusion, and dissociation of pyridine, C{sub 5}H{sub 5}N, on Pt(111) are investigated with van der Waals-corrected density functional theory. An elaborate search for local minima in the adsorption potential energy landscape reveals that the intact pyridine adsorbs with the aromatic ring parallel to the surface. Piecewise interconnections of the local minima in the energy landscape reveal that the most favourable diffusion path for pyridine has a barrier of 0.53 eV. In the preferred path, the pyridine remains parallel to the surface while performing small single rotational steps with a carbon-carbon double bond hinged above a single Pt atom.more » The origin of the diffusion pathway is discussed in terms of the C{sub 2}–Pt π-bond being stronger than the corresponding CN–Pt π-bond. The energy barrier and reaction enthalpy for dehydrogenation of adsorbed pyridine into an adsorbed, upright bound α-pyridyl species are calculated to 0.71 eV and 0.18 eV, respectively (both zero-point energy corrected). The calculations are used to rationalize previous experimental observations from the literature for pyridine on Pt(111).« less

Stereodynamics of the photodissociation of nitromethane at 193 nm: unravelling the dissociation mechanism.

PubMed

Rodríguez, J D; González, M G; Rubio-Lago, L; Bañares, L; Samartzis, P C; Kitsopoulos, T N

2013-08-29

The photodissociation of nitromethane at 193 nm is reviewed in terms of new stereodynamical information provided by the measurement of the first four Dixon's bipolar moments, β0(2)(20), β0(0)(22), β0(2)(02), and β0(2)(22), using slice imaging. The measured speed-dependent β0(2)(20) (directly related with the spatial anisotropy parameter β) indicates that after one-photon absorption to the S3(2 (1)A″) state by an allowed perpendicular transition, two reaction pathways can compete with similar probability, a direct dissociation process yielding ground-state CH3 and NO2(1 (2)A2) radicals and a indirect dissociation through conical intersections in which NO2 radicals are formed in lower-lying electronic states. A particularly important result from our measurements is that the low recoil energy part of the methyl fragment translational energy distribution presents a contribution with parallel character, irrespective of the experimental conditions employed, that we attribute to parent cluster dissociation. Moreover, the positive values found for the β0(0)(22) bipolar moment indicates some propensity for the fragment's recoil velocity and angular momentum vectors to be parallel.

Hydrogen oxidation mechanisms on Ni/yttria stabilized zirconia anodes: Separation of reaction pathways by geometry variation of pattern electrodes

NASA Astrophysics Data System (ADS)

Doppler, M. C.; Fleig, J.; Bram, M.; Opitz, A. K.

2018-03-01

Nickel/yttria stabilized zirconia (YSZ) electrodes are affecting the overall performance of solid oxide fuel cells (SOFCs) in general and strongly contribute to the cell resistance in case of novel metal supported SOFCs in particular. The electrochemical fuel conversion mechanisms in these electrodes are, however, still only partly understood. In this study, micro-structured Ni thin film electrodes on YSZ with 15 different geometries are utilized to investigate reaction pathways for the hydrogen electro-oxidation at Ni/YSZ anodes. From electrodes with constant area but varying triple phase boundary (TPB) length a contribution to the electro-catalytic activity is found that does not depend on the TPB length. This additional activity could clearly be attributed to a yet unknown reaction pathway scaling with the electrode area. It is shown that this area related pathway has significantly different electrochemical behavior compared to the TPB pathway regarding its thermal activation, sulfur poisoning behavior, and H2/H2O partial pressure dependence. Moreover, possible reaction mechanisms of this reaction pathway are discussed, identifying either a pathway based on hydrogen diffusion through Ni with water release at the TPB or a path with oxygen diffusion through Ni to be a very likely explanation for the experimental results.

Parallelization of Catalytic Packed-Bed Microchannels with Pressure-Drop Microstructures for Gas-Liquid Multiphase Reactions

NASA Astrophysics Data System (ADS)

Murakami, Sunao; Ohtaki, Kenichiro; Matsumoto, Sohei; Inoue, Tomoya

2012-06-01

High-throughput and stable treatments are required to achieve the practical production of chemicals with microreactors. However, the flow maldistribution to the paralleled microchannels has been a critical problem in achieving the productive use of multichannel microreactors for multiphase flow conditions. In this study, we newly designed and fabricated a glass four-channel catalytic packed-bed microreactor for the scale-up of gas-liquid multiphase chemical reactions. We embedded microstructures generating high pressure losses at the upstream side of each packed bed, and experimentally confirmed the efficacy of the microstructures in decreasing the maldistribution of the gas-liquid flow to the parallel microchannels.

ReactPRED: a tool to predict and analyze biochemical reactions.

PubMed

Sivakumar, Tadi Venkata; Giri, Varun; Park, Jin Hwan; Kim, Tae Yong; Bhaduri, Anirban

2016-11-15

Biochemical pathways engineering is often used to synthesize or degrade target chemicals. In silico screening of the biochemical transformation space allows predicting feasible reactions, constituting these pathways. Current enabling tools are customized to predict reactions based on pre-defined biochemical transformations or reaction rule sets. Reaction rule sets are usually curated manually and tailored to specific applications. They are not exhaustive. In addition, current systems are incapable of regulating and refining data with an aim to tune specificity and sensitivity. A robust and flexible tool that allows automated reaction rule set creation along with regulated pathway prediction and analyses is a need. ReactPRED aims to address the same. ReactPRED is an open source flexible and customizable tool enabling users to predict biochemical reactions and pathways. The tool allows automated reaction rule creation from a user defined reaction set. Additionally, reaction rule degree and rule tolerance features allow refinement of predicted data. It is available as a flexible graphical user interface and a console application. ReactPRED is available at: https://sourceforge.net/projects/reactpred/ CONTACT: anirban.b@samsung.com or ty76.kim@samsung.comSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Distinct and Parallel Pathway for the Nuclear Import of an mRNA-binding Protein

PubMed Central

Pemberton, Lucy F.; Rosenblum, Jonathan S.; Blobel, Günter

1997-01-01

Three independent pathways of nuclear import have so far been identified in yeast, each mediated by cognate nuclear transport factors, or karyopherins. Here we have characterized a new pathway to the nucleus, mediated by Mtr10p, a protein first identified in a screen for strains defective in polyadenylated RNA export. Mtr10p is shown to be responsible for the nuclear import of the shuttling mRNA-binding protein Npl3p. A complex of Mtr10p and Npl3p was detected in cytosol, and deletion of Mtr10p was shown to lead to the mislocalization of nuclear Npl3p to the cytoplasm, correlating with a block in import. Mtr10p bound peptide repeat-containing nucleoporins and Ran, suggesting that this import pathway involves a docking step at the nuclear pore complex and is Ran dependent. This pathway of Npl3p import is distinct and does not appear to overlap with another known import pathway for an mRNA-binding protein. Thus, at least two parallel pathways function in the import of mRNA-binding proteins, suggesting the need for the coordination of these pathways. PMID:9412460

Origin of fatty acid synthesis - Thermodynamics and kinetics of reaction pathways

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

1991-01-01

The primitiveness of contemporary fatty acid biosynthesis was evaluated by using the thermodynamics and kinetics of its component reactions to estimate the extent of its dependence on powerful and selective catalysis by enzymes. Since this analysis indicated that the modern pathway is not primitive because it requires sophisticated enzymatic catalysis, an alternative pathway of primitive fatty acid synthesis is proposed that uses glycolaldehyde as a substrate. In contrast to the modern pathway, this primitive pathway is not dependent on an exogenous source of phosphoanhydride energy. Furthermore, the chemical spontaneity of its reactions suggests that it could have been readily catalyzed by the rudimentary biocatalysts available at an early stage in the origin of life.

Solution-phase parallel synthesis of aryloxyimino amides via a novel multicomponent reaction among aromatic (Z)-chlorooximes, isocyanides, and electron-deficient phenols.

PubMed

Mercalli, Valentina; Giustiniano, Mariateresa; Del Grosso, Erika; Varese, Monica; Cassese, Hilde; Massarotti, Alberto; Novellino, Ettore; Tron, Gian Cesare

2014-11-10

A library of 41 aryloxyimino amides was prepared via solution phase parallel synthesis by extending the multicomponent reaction of (Z)-chlorooximes and isocyanides to the use of electron-deficient phenols. The resulting aryloxyiminoamide derivatives can be used as intermediates for the synthesis of benzo[d]isoxazole-3-carboxamides, dramatically reducing the number of synthetic steps required by other methods reported in literature.

Kinetic Studies on the Reaction of Chlorosulfonyl Isocyanate with Monofluoralkenes: Experimental Evidence for Both Stepwise and Concerted Mechanisms, and a Pre-equilibrium Complex on the Reaction Pathway

DTIC Science & Technology

2012-12-14

lactams that are readily reduced to β-lactams. Substitution of a vinyl hydrogen for a vinyl fluorine changes the dynamics for reaction with CSI so...hydrogen for a vinyl fluorine changes the dynamics for reaction with CSI so that a concerted pathway is favored. Rate constants were measured for...step pathway has not been demonstrated experimentally.3c In a recent paper, we found that substituting a hydrogen for a fluorine on the π-bond of an

Pathway Thermodynamics Highlights Kinetic Obstacles in Central Metabolism

PubMed Central

Flamholz, Avi; Reznik, Ed; Liebermeister, Wolfram; Milo, Ron

2014-01-01

In metabolism research, thermodynamics is usually used to determine the directionality of a reaction or the feasibility of a pathway. However, the relationship between thermodynamic potentials and fluxes is not limited to questions of directionality: thermodynamics also affects the kinetics of reactions through the flux-force relationship, which states that the logarithm of the ratio between the forward and reverse fluxes is directly proportional to the change in Gibbs energy due to a reaction (ΔrG′). Accordingly, if an enzyme catalyzes a reaction with a ΔrG′ of -5.7 kJ/mol then the forward flux will be roughly ten times the reverse flux. As ΔrG′ approaches equilibrium (ΔrG′ = 0 kJ/mol), exponentially more enzyme counterproductively catalyzes the reverse reaction, reducing the net rate at which the reaction proceeds. Thus, the enzyme level required to achieve a given flux increases dramatically near equilibrium. Here, we develop a framework for quantifying the degree to which pathways suffer these thermodynamic limitations on flux. For each pathway, we calculate a single thermodynamically-derived metric (the Max-min Driving Force, MDF), which enables objective ranking of pathways by the degree to which their flux is constrained by low thermodynamic driving force. Our framework accounts for the effect of pH, ionic strength and metabolite concentration ranges and allows us to quantify how alterations to the pathway structure affect the pathway's thermodynamics. Applying this methodology to pathways of central metabolism sheds light on some of their features, including metabolic bypasses (e.g., fermentation pathways bypassing substrate-level phosphorylation), substrate channeling (e.g., of oxaloacetate from malate dehydrogenase to citrate synthase), and use of alternative cofactors (e.g., quinone as an electron acceptor instead of NAD). The methods presented here place another arrow in metabolic engineers' quiver, providing a simple means of evaluating the thermodynamic and kinetic quality of different pathway chemistries that produce the same molecules. PMID:24586134

O/S-1/ interactions - The product channels. [collisional electron quenching and chemical reaction pathway frequencies

NASA Technical Reports Server (NTRS)

Slanger, T. G.; Black, G.

1978-01-01

The first measurements are reported of the reaction pathways for the interaction between oxygen atoms in the 4.19 eV S-1 state, and four molecules, N2O, CO2, H2O, and NO. Distinction is made between three possible paths - quenching to O(D-1), quenching to O(P-3), and chemical reaction. With N2O, the most reasonable interpretation of the data indicates that there no reaction, in sharp contrast with the interaction between O(D-1) and N2O, which proceeds entirely by reaction. Similarly, there is no reaction with CO2. With H2O, the reactive pathway is the dominant one, although electronic quenching is not negligible. With NO, O(D-1) is the preferred product.

Critical Role of Nitric Oxide-cGMP Cascade in the Formation of cAMP-Dependent Long-Term Memory

ERIC Educational Resources Information Center

Aonuma, Hitoshi; Mizunami, Makoto; Matsumoto, Yukihisa; Unoki, Sae

2006-01-01

Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have…

A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

Sochol, R. D.; Casavant, B. P.; Dueck, M. E.; Lee, L. P.; Lin, L.

2011-05-01

A microfluidic system has been designed and constructed by means of micromachining processes to integrate both microfluidic mixing of mobile microbeads and hydrodynamic microbead arraying capabilities on a single chip to simultaneously detect multiple bio-molecules. The prototype system has four parallel reaction chambers, which include microchannels of 18 × 50 µm2 cross-sectional area and a microfluidic mixing section of 22 cm length. Parallel detection of multiple DNA oligonucleotide sequences was achieved via molecular beacon probes immobilized on polystyrene microbeads of 16 µm diameter. Experimental results show quantitative detection of three distinct DNA oligonucleotide sequences from the Hepatitis C viral (HCV) genome with single base-pair mismatch specificity. Our dynamic bead-based microarray offers an effective microfluidic platform to increase parallelization of reactions and improve microbead handling for various biological applications, including bio-molecule detection, medical diagnostics and drug screening.

Ubiquitin-protein ligases in muscle wasting: multiple parallel pathways?

NASA Technical Reports Server (NTRS)

Lecker, Stewart H.; Goldberg, A. L. (Principal Investigator)

2003-01-01

PURPOSE OF REVIEW: Studies in a wide variety of animal models of muscle wasting have led to the concept that increased protein breakdown via the ubiquitin-proteasome pathway is responsible for the loss of muscle mass seen as muscle atrophy. The complexity of the ubiquitination apparatus has hampered our understanding of how this pathway is activated in atrophying muscles and which ubiquitin-conjugating enzymes in muscle are responsible. RECENT FINDINGS: Recent experiments have shown that two newly identified ubiquitin-protein ligases (E3s), atrogin-1/MAFbx and MURF-1, are critical in the development of muscle atrophy. Other in-vitro studies also implicated E2(14k) and E3alpha, of the N-end rule pathway, as playing an important role in the process. SUMMARY: It seems likely that multiple pathways of ubiquitin conjugation are activated in parallel in atrophying muscle, perhaps to target for degradation specific classes of muscle proteins. The emerging challenge will be to define the protein targets for, as well as inhibitors of, these E3s.

The olfactory pathway mediates sheltering behavior of Caribbean spiny lobsters, Panulirus argus, to conspecific urine signals.

PubMed

Horner, Amy J; Weissburg, Marc J; Derby, Charles D

2008-03-01

The "noses" of diverse taxa are organized into different subsystems whose functions are often not well understood. The "nose" of decapod crustaceans is organized into two parallel pathways that originate in different populations of antennular sensilla and project to specific neuropils in the brain-the aesthetasc/olfactory lobe pathway and the non-aesthetasc/lateral antennular neuropil pathway. In this study, we investigated the role of these pathways in mediating shelter selection of Caribbean spiny lobsters, Panulirus argus, in response to conspecific urine signals. We compared the behavior of ablated animals and intact controls. Our results show that control and non-aesthetasc ablated lobsters have a significant overall preference for shelters emanating urine over control shelters. Thus the non-aesthetasc pathway does not play a critical role in shelter selection. In contrast, spiny lobsters with aesthetascs ablated did not show a preference for either shelter, suggesting that the aesthetasc/olfactory pathway is important for processing social odors. Our results show a difference in the function of these dual chemosensory pathways in responding to social cues, with the aesthetasc/olfactory lobe pathway playing a major role. We discuss our results in the context of why the noses of many animals contain multiple parallel chemosensory systems.

Information technology in chemistry research and education: Part I. Ab initio studies on the hydrolysis of aromatic diazonium ions. Part II. Theoretical study and molecular modeling of non-covalent interactions. Part III. Applying information technology in chemistry education

NASA Astrophysics Data System (ADS)

Wu, Zhengyu

Part I of this dissertation studies the bonding in chemical reactions, while Part II studies the bonding related to inter- and intra-molecular interactions. Part III studies the application of IT technology in chemistry education. Part I of this dissertation (chapter 1 and chapter 2) focuses on the theoretical studies on the mechanism of the hydrolysis reactions of benzenediazonium ion and guaninediazonium ion. The major conclusion is that in hydrolysis reactions the "unimolecular mechanism" actually has to involve the reacting solvent molecule. Therefore, the unimolecular pathway can only serve as a conceptual model but will not happen in the reality. Chapter I concludes that the hydrolysis reaction of benzenediazonium ion takes the direct SN2Ar mechanism via a transition state but without going through a pre-coordination complex. Chapter 2 concludes that the formation of xanthine from the dediazoniation reaction of guaninediazonium ion in water takes the SN2Ar pathway without a transition state. And oxanine might come from an intermediate formed by the bimolecular deprotonation of the H atom on N3 of guaninediazonium ion synchronized with the pyrimidine ring opening reaction. Part II of this dissertation includes chapters 3, 4, and 5. Chapter 3 studies the quadrupole moment of benzene and quadrupole-quadrupole interactions. We concluded that the quadrupole-quadrupole interaction is important in the arene-arene interactions. Our study shows the most stable structure of benzene dimer is the point-to-face T-shaped structure. Chapter 4 studies the intermolecular interactions that result in the disorder of the crystal of 4-Chloroacetophenone-(4-methoxyphenylethylidene). We analyzed all the nearest neighbor interactions within that crystal and found that the crystal structure is determined by its thermo-dynamical properties. Our calculation perfectly reproduced the percentage of parallel-alignment of the crystal. Part III of this dissertation is focused on the application of database management system and computer technology on chemistry education. A database-supported webtool was developed to support the creation of news portfolio and peer reviews online. The responses to an in-class survey show that students embrace the use of this webtool for its conceptually clear design and its easiness of use.

Reaction paths of alane dissociation on the Si(0 0 1) surface

NASA Astrophysics Data System (ADS)

Smith, Richard; Bowler, David R.

2018-03-01

Building on our earlier study, we examine the kinetic barriers to decomposition of alane, AlH3, on the Si(0 0 1) surface, using the nudged elastic band approach within density functional theory. We find that the initial decomposition to AlH with two H atoms on the surface proceeds without a significant barrier. There are several pathways available to lose the final hydrogen, though these present barriers of up to 1 eV. Incorporation is more challenging, with the initial structures less stable in several cases than the starting structures, just as was found for phosphorus. We identify a stable route for Al incorporation following selective surface hydrogen desorption (e.g. by scanning tunneling microscope tip). The overall process parallels PH3, and indicates that atomically precise acceptor doping should be possible.

The underlying pathway structure of biochemical reaction networks

PubMed Central

Schilling, Christophe H.; Palsson, Bernhard O.

1998-01-01

Bioinformatics is yielding extensive, and in some cases complete, genetic and biochemical information about individual cell types and cellular processes, providing the composition of living cells and the molecular structure of its components. These components together perform integrated cellular functions that now need to be analyzed. In particular, the functional definition of biochemical pathways and their role in the context of the whole cell is lacking. In this study, we show how the mass balance constraints that govern the function of biochemical reaction networks lead to the translation of this problem into the realm of linear algebra. The functional capabilities of biochemical reaction networks, and thus the choices that cells can make, are reflected in the null space of their stoichiometric matrix. The null space is spanned by a finite number of basis vectors. We present an algorithm for the synthesis of a set of basis vectors for spanning the null space of the stoichiometric matrix, in which these basis vectors represent the underlying biochemical pathways that are fundamental to the corresponding biochemical reaction network. In other words, all possible flux distributions achievable by a defined set of biochemical reactions are represented by a linear combination of these basis pathways. These basis pathways thus represent the underlying pathway structure of the defined biochemical reaction network. This development is significant from a fundamental and conceptual standpoint because it yields a holistic definition of biochemical pathways in contrast to definitions that have arisen from the historical development of our knowledge about biochemical processes. Additionally, this new conceptual framework will be important in defining, characterizing, and studying biochemical pathways from the rapidly growing information on cellular function. PMID:9539712

Insight into reaction pathways in CO hydrogenation reactions over K/MoS 2 supported catalysts via alcohol/olefin co-feed experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taborga Claure, Micaela; Morrill, Michael R.; Goh, Jin Wai

2016-01-01

Reaction pathways for higher alcohol synthesis from syngas are studied over K/MoS 2domains supported on mesoporous carbon (C) and mixed MgAl oxide (MMO)viaaddition of methanol, ethanol, and ethylene co-feeds.

Experimental evolution reveals hidden diversity in evolutionary pathways.

PubMed

Lind, Peter A; Farr, Andrew D; Rainey, Paul B

2015-03-25

Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.

Modeling the optimal central carbon metabolic pathways under feedback inhibition using flux balance analysis.

PubMed

De, Rajat K; Tomar, Namrata

2012-12-01

Metabolism is a complex process for energy production for cellular activity. It consists of a cascade of reactions that form a highly branched network in which the product of one reaction is the reactant of the next reaction. Metabolic pathways efficiently produce maximal amount of biomass while maintaining a steady-state behavior. The steady-state activity of such biochemical pathways necessarily incorporates feedback inhibition of the enzymes. This observation motivates us to incorporate feedback inhibition for modeling the optimal activity of metabolic pathways using flux balance analysis (FBA). We demonstrate the effectiveness of the methodology on a synthetic pathway with and without feedback inhibition. Similarly, for the first time, the Central Carbon Metabolic (CCM) pathways of Saccharomyces cerevisiae and Homo sapiens have been modeled and compared based on the above understanding. The optimal pathway, which maximizes the amount of the target product(s), is selected from all those obtained by the proposed method. For this, we have observed the concentration of the product inhibited enzymes of CCM pathway and its influence on its corresponding metabolite/substrate. We have also studied the concentration of the enzymes which are responsible for the synthesis of target products. We further hypothesize that an optimal pathway would opt for higher flux rate reactions. In light of these observations, we can say that an optimal pathway should have lower enzyme concentration and higher flux rates. Finally, we demonstrate the superiority of the proposed method by comparing it with the extreme pathway analysis.

Physical Properties and CO2 Reaction Pathway of 1-Ethyl-3-Methylimidazolium Ionic Liquids with Aprotic Heterocyclic Anions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, S; DeSilva, MA; Brennecke, JF

2014-12-25

Ionic liquids (ILs) with aprotic heterocyclic anions (AHA) are attractive candidates for CO2 capture technologies. In this study, a series of AHA ILs with 1-ethyl-3-methylimidazolium ([emim](+)) cations were synthesized, and their physical properties (density, viscosity, and ionic conductivity) were measured. In addition, CO2 solubility in each IL was determined at room temperature using a volumetric method at pressures between 0 and 1 bar. The AHAs are basic anions that are capable of reacting stoichiometrically with CO2 to form carbamate species. An interesting CO2 uptake isotherm behavior was observed, and this may be attributed to a parallel, equilibrium proton exchange processmore » between the imidazolium cation and the basic AHA in the presence of CO2, followed by the formation of "transient" carbene species that react rapidly with CO2. The presence of the imidazolium-carboxylate species and carbamate anion species was verified using H-1 and C-13 NMR spectroscopy. While the reaction between CO2 and the proposed transient carbene resulted in cation-CO2 binding that is stronger than the anion-CO2 reaction, the reactions of the imidazolium AHA ILs were fully reversible upon regeneration at 80 degrees C with nitrogen purging. The presence of water decreased the CO2 uptake due to the inhibiting effect of the neutral species (protonated form of AHA) that is formed.« less

The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans.

PubMed

Florica, Roxana Oriana; Hipolito, Victoria; Bautista, Stephen; Anvari, Homa; Rapp, Chloe; El-Rass, Suzan; Asgharian, Alimohammad; Antonescu, Costin N; Killeen, Marie T

2017-10-01

The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5. A mutation in the gene for the MIG-14/Wntless protein also enhances defects in a strain lacking either UNC-5 or UNC-6, suggesting that the ENU-3 and Wnt pathways function parallel to the Netrin pathway in directing motor neuron axon outgrowth. Our evidence suggests that the ENU-3 proteins are novel members of the Wnt pathway in nematodes. Five of the six members of the ENU-3 family are predicted to be single-pass trans-membrane proteins. The expression pattern of ENU-3.1 was consistent with plasma membrane localization. One family member, ENU-3.6, lacks the predicted signal peptide and the membrane-spanning domain. In HeLa cells ENU-3.6 had a cytoplasmic localization and caused actin dependent processes to appear. We conclude that the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Reaction pathways of producing and losing particles in atmospheric pressure methane nanosecond pulsed needle-plane discharge plasma

NASA Astrophysics Data System (ADS)

Zhao, Yuefeng; Wang, Chao; Li, Li; Wang, Lijuan; Pan, Jie

2018-03-01

In this work, a two-dimensional fluid model is built up to numerically investigate the reaction pathways of producing and losing particles in atmospheric pressure methane nanosecond pulsed needle-plane discharge plasma. The calculation results indicate that the electron collisions with CH4 are the key pathways to produce the neutral particles CH2 and CH as well as the charged particles e and CH3+. CH3, H2, H, C2H2, and C2H4 primarily result from the reactions between the neutral particles and CH4. The charge transfer reactions are the significant pathways to produce CH4+, C2H2+, and C2H4+. As to the neutral species CH and H and the charged species CH3+, the reactions between themselves and CH4 contribute to substantial losses of these particles. The ways responsible for losing CH3, H2, C2H2, and C2H4 are CH3 + H → CH4, H2 + CH → CH2 + H, CH4+ + C2H2 → C2H2+ + CH4, and CH4+ + C2H4 → C2H4+ + CH4, respectively. Both electrons and C2H4+ are consumed by the dissociative electron-ion recombination reactions. The essential reaction pathways of losing CH4+ and C2H2+ are the charge transfer reactions.

A new network representation of the metabolism to detect chemical transformation modules.

PubMed

Sorokina, Maria; Medigue, Claudine; Vallenet, David

2015-11-14

Metabolism is generally modeled by directed networks where nodes represent reactions and/or metabolites. In order to explore metabolic pathway conservation and divergence among organisms, previous studies were based on graph alignment to find similar pathways. Few years ago, the concept of chemical transformation modules, also called reaction modules, was introduced and correspond to sequences of chemical transformations which are conserved in metabolism. We propose here a novel graph representation of the metabolic network where reactions sharing a same chemical transformation type are grouped in Reaction Molecular Signatures (RMS). RMS were automatically computed for all reactions and encode changes in atoms and bonds. A reaction network containing all available metabolic knowledge was then reduced by an aggregation of reaction nodes and edges to obtain a RMS network. Paths in this network were explored and a substantial number of conserved chemical transformation modules was detected. Furthermore, this graph-based formalism allows us to define several path scores reflecting different biological conservation meanings. These scores are significantly higher for paths corresponding to known metabolic pathways and were used conjointly to build association rules that should predict metabolic pathway types like biosynthesis or degradation. This representation of metabolism in a RMS network offers new insights to capture relevant metabolic contexts. Furthermore, along with genomic context methods, it should improve the detection of gene clusters corresponding to new metabolic pathways.

Exploring the combinatorial space of complete pathways to chemicals.

PubMed

Wang, Lin; Ng, Chiam Yu; Dash, Satyakam; Maranas, Costas D

2018-04-06

Computational pathway design tools often face the challenges of balancing the stoichiometry of co-metabolites and cofactors, and dealing with reaction rule utilization in a single workflow. To this end, we provide an overview of two complementary stoichiometry-based pathway design tools optStoic and novoStoic developed in our group to tackle these challenges. optStoic is designed to determine the stoichiometry of overall conversion first which optimizes a performance criterion (e.g. high carbon/energy efficiency) and ensures a comprehensive search of co-metabolites and cofactors. The procedure then identifies the minimum number of intervening reactions to connect the source and sink metabolites. We also further the pathway design procedure by expanding the search space to include both known and hypothetical reactions, represented by reaction rules, in a new tool termed novoStoic. Reaction rules are derived based on a mixed-integer linear programming (MILP) compatible reaction operator, which allow us to explore natural promiscuous enzymes, engineer candidate enzymes that are not already promiscuous as well as design de novo enzymes. The identified biochemical reaction rules then guide novoStoic to design routes that expand the currently known biotransformation space using a single MILP modeling procedure. We demonstrate the use of the two computational tools in pathway elucidation by designing novel synthetic routes for isobutanol. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Criegee intermediate-hydrogen sulfide chemistry at the air/water interface.

PubMed

Kumar, Manoj; Zhong, Jie; Francisco, Joseph S; Zeng, Xiao C

2017-08-01

We carry out Born-Oppenheimer molecular dynamic simulations to show that the reaction between the smallest Criegee intermediate, CH 2 OO, and hydrogen sulfide (H 2 S) at the air/water interface can be observed within few picoseconds. The reaction follows both concerted and stepwise mechanisms with former being the dominant reaction pathway. The concerted reaction proceeds with or without the involvement of one or two nearby water molecules. An important implication of the simulation results is that the Criegee-H 2 S reaction can provide a novel non-photochemical pathway for the formation of a C-S linkage in clouds and could be a new oxidation pathway for H 2 S in terrestrial, geothermal and volcanic regions.

Influence of cellular and paracellular conductance patterns on epithelial transport and metabolism.

PubMed Central

Essig, A

1982-01-01

Theoretical analysis of transepithelial active Na transport is often based on equivalent electrical circuits comprising discrete parallel active and passive pathways. Recent findings show, however, that Na+ pumps are distributed over the entire basal lateral surface of epithelial cells. This suggests that Na+ that has been actively transported into paracellular channels may to some extent return to the apical (mucosal) bathing solution, depending on the relative conductances of the pathways via the tight junctions and the lateral intercellular spaces. Such circulation, as well as the relative conductance of cellular and paracellular pathways, may have an important influence on the relationships between parameters of transcellular and transepithelial active transport and metabolism. These relationships were examined by equivalent circuit analysis of active Na transport, Na conductance, the electromotive force of Na transport, the "stoichiometry" of transport, and the degree of coupling of transport to metabolism. Although the model is too crude to permit precise quantification, important qualitative differences are predicted between "loose" and "tight" epithelia in the absence and presence of circulation. In contrast, there is no effect on the free energy of metabolic reaction estimated from a linear thermodynamic formalism. Also of interest are implications concerning the experimental evaluation of passive paracellular conductance following abolition of active transport, and the use of the cellular voltage-divider ratio to estimate the relative conductances of apical and basal lateral plasma membranes. PMID:6284264

Computed Potential Energy Surfaces and Minimum Energy Pathways for Chemical Reactions

NASA Technical Reports Server (NTRS)

Walch, Stephen P.; Langhoff, S. R. (Technical Monitor)

1994-01-01

Computed potential energy surfaces are often required for computation of such parameters as rate constants as a function of temperature, product branching ratios, and other detailed properties. For some dynamics methods, global potential energy surfaces are required. In this case, it is necessary to obtain the energy at a complete sampling of all the possible arrangements of the nuclei, which are energetically accessible, and then a fitting function must be obtained to interpolate between the computed points. In other cases, characterization of the stationary points and the reaction pathway connecting them is sufficient. These properties may be readily obtained using analytical derivative methods. We have found that computation of the stationary points/reaction pathways using CASSCF/derivative methods, followed by use of the internally contracted CI method to obtain accurate energetics, gives usefull results for a number of chemically important systems. The talk will focus on a number of applications including global potential energy surfaces, H + O2, H + N2, O(3p) + H2, and reaction pathways for complex reactions, including reactions leading to NO and soot formation in hydrocarbon combustion.

Theoretical study on the identity ion pair SN2 reactions of LiX with CH3SX (X=Cl, Br, and I): structure, mechanism, and potential energy surface.

PubMed

Ren, Yi; Gai, Jing-Gang; Xiong, Yan; Lee, Kuo-Hsing; Chu, San-Yan

2007-07-26

Three archetypal ion pair nucleophilic substitution reactions at the methylsulfenyl sulfur atom LiX+CH3SX-->XSCH3+LiX (X=Cl, Br, and I) are investigated by the modified Gaussian-2 theory. Including lithium cation in the anionic models makes the ion pair reactions proceed along an SN2 mechanism, contrary to the addition-elimination pathway occurring in the corresponding anionic nucleophilic substitution reactions X-+CH3SX-->XSCH3+X-. Two reaction pathways for the ion pair SN2 reactions at sulfur, inversion and retention, are proposed. Results indicate the inversion pathway is favorable for all the halogens. Comparison of the transition structures and energetics for the ion pair SN2 at sulfur with the potential competition ion pair SN2 reactions at carbon LiX+CH3SX-->XCH3+LiXS shows that the SN2 reactions at carbon are not favorable from the viewpoints of kinetics and thermodynamics.

Kinetic studies of the folding of heterodimeric monellin: evidence for switching between alternative parallel pathways.

PubMed

Aghera, Nilesh; Udgaonkar, Jayant B

2012-07-13

Determining whether or not a protein uses multiple pathways to fold is an important goal in protein folding studies. When multiple pathways are present, defined by transition states that differ in their compactness and structure but not significantly in energy, they may manifest themselves by causing the dependence on denaturant concentration of the logarithm of the observed rate constant of folding to have an upward curvature. In this study, the folding mechanism of heterodimeric monellin [double-chain monellin (dcMN)] has been studied over a range of protein and guanidine hydrochloride (GdnHCl) concentrations, using the intrinsic tryptophan fluorescence of the protein as the probe for the folding reaction. Refolding is shown to occur in multiple kinetic phases. In the first stage of refolding, which is silent to any change in intrinsic fluorescence, the two chains of monellin bind to one another to form an encounter complex. Interrupted folding experiments show that the initial encounter complex folds to native dcMN via two folding routes. A productive folding intermediate population is identified on one route but not on both of these routes. Two intermediate subpopulations appear to form in a fast kinetic phase, and native dcMN forms in a slow kinetic phase. The chevron arms for both the fast and slow phases of refolding are shown to have upward curvatures, suggesting that at least two pathways each defined by a different intermediate are operational during these kinetic phases of structure formation. Refolding switches from one pathway to the other as the GdnHCl concentration is increased. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clustering and optimal arrangement of enzymes in reaction-diffusion systems.

PubMed

Buchner, Alexander; Tostevin, Filipe; Gerland, Ulrich

2013-05-17

Enzymes within biochemical pathways are often colocalized, yet the consequences of specific spatial enzyme arrangements remain poorly understood. We study the impact of enzyme arrangement on reaction efficiency within a reaction-diffusion model. The optimal arrangement transitions from a cluster to a distributed profile as a single parameter, which controls the probability of reaction versus diffusive loss of pathway intermediates, is varied. We introduce the concept of enzyme exposure to explain how this transition arises from the stochastic nature of molecular reactions and diffusion.

Learning from the Parallel Pathways of Makers to Broaden Pathways to Engineering

ERIC Educational Resources Information Center

Foster, Christina; Wigner, Aubrey; Lande, Micah; Jordan, Shawn S.

2018-01-01

Background: Makers are a growing community of STEM-minded people who bridge technical and non-technical backgrounds to imagine, build and fabricate engineering systems. Some have engineering training, some do not. This paper presents a study to explore the educational pathways of adult Makers and how they intersect with engineering. This research…

The Role of the Ventral and Dorsal Pathways in Reading Chinese Characters and English Words

ERIC Educational Resources Information Center

Sun, Yafeng; Yang, Yanhui; Desroches, Amy S.; Liu, Li; Peng, Danling

2011-01-01

Previous literature in alphabetic languages suggests that the occipital-temporal region (the ventral pathway) is specialized for automatic parallel word recognition, whereas the parietal region (the dorsal pathway) is specialized for serial letter-by-letter reading (and). However, few studies have directly examined the role of the ventral and…

Channeling by Proximity: The Catalytic Advantages of Active Site Colocalization Using Brownian Dynamics.

PubMed

Bauler, Patricia; Huber, Gary; Leyh, Thomas; McCammon, J Andrew

2010-05-06

Nature often colocalizes successive steps in a metabolic pathway. Such organization is predicted to increase the effective concentration of pathway intermediates near their recipient active sites and to enhance catalytic efficiency. Here, the pathway of a two-step reaction is modeled using a simple spherical approximation for the enzymes and substrate particles. Brownian dynamics are used to simulate the trajectory of a substrate particle as it diffuses between the active site zones of two different enzyme spheres. The results approximate distances for the most effective reaction pathways, indicating that the most effective reaction pathway is one in which the active sites are closely aligned. However, when the active sites are too close, the ability of the substrate to react with the first enzyme was hindered, suggesting that even the most efficient orientations can be improved for a system that is allowed to rotate or change orientation to optimize the likelihood of reaction at both sites.

A Simple Parallel Photochemical Reactor for Photodecomposition Studies

ERIC Educational Resources Information Center

Xiaobo Chen; Halasz, Sarah M.; Giles, Eric C.; Mankus, Jessica V.; Johnson, Joseph C.; Burda, Clemens

2006-01-01

A simple and useful parallel photochemical reactor intended to study the photodecomposition of dyes using semiconductor photocatalysis is presented. The photochemical reactions are followed through time-dependent changes in the ground-state absorption spectra of the dyes.

Metabolite recycling and bidirectional C fluxes: Revolutionizing our view on microbial C cycling in soils

NASA Astrophysics Data System (ADS)

Dippold, M. A.; Apostel, C.; Kuzyakov, Y.

2016-12-01

Biogeochemists' view on microbial C transformation in soil has rarely exceed a strongly simplified concept assuming that C gets either oxidized to CO2 via the microbial catabolism or incorporated into biomass via the anabolism. However, life in a C limited environment as challenging as soil requires microbial adaptation strategies at all levels of metabolism. By coupling of position-specific labeling of core metabolites with compound-specific isotope analysis we demonstrated that catabolic oxidation of these metabolites exists in parallel to reductive, energy consuming pathways, reducing them for anabolic purposes. Up to 55% of glucose, incorporated into the glucose derivative glucosamine, first passed glycolysis before allocated back via gluconeogenesis. Similarly, glutamate-derived C is allocated via anaplerotic pathways towards fatty acid synthesis and in parallel to its oxidation in the citric acid cycle. Furthermore, position-specific labeling of rather `cost-intensive' biomass compounds such as fatty acids revealed that intact recycling of metabolites is a crucial microbial adaptation to C scarcity in soils. Both processes are unlikely to occur in pure cultures, where constant growth conditions under high C supply allow a straight unidirectional regulation of C metabolism. However, unstable environmental conditions, C scarcity and interactions between a still unknown diversity of microorganisms in soils are likely to induce the observed metabolic diversity. To understand how microorganisms catalyze the biogeochemical fluxes in soil, a profound understanding of their metabolic adaptation strategies such as recycling or switching between bidirectional fluxes is crucial. Metabolic flux models adapted to soil microbial communities and their regulatory strategies will not only deepen our understanding on the microorganims' reactions to environmental changes but also create the prerequisits for a quantitative prediction of biogeochemical fluxes based on the underlying microbial processes.

Measuring and modeling C flux rates through the central metabolic pathways in microbial communities using position-specific 13C-labeled tracers

NASA Astrophysics Data System (ADS)

Dijkstra, P.; van Groenigen, K.; Hagerty, S.; Salpas, E.; Fairbanks, D. E.; Hungate, B. A.; KOCH, G. W.; Schwartz, E.

2012-12-01

The production of energy and metabolic precursors occurs in well-known processes such as glycolysis and Krebs cycle. We use position-specific 13C-labeled metabolic tracers, combined with models of microbial metabolic organization, to analyze the response of microbial community energy production, biosynthesis, and C use efficiency (CUE) in soils, decomposing litter, and aquatic communities. The method consists of adding position-specific 13C -labeled metabolic tracers to parallel soil incubations, in this case 1-13C and 2,3-13C pyruvate and 1-13C and U-13C glucose. The measurement of CO2 released from the labeled tracers is used to calculate the C flux rates through the various metabolic pathways. A simplified metabolic model consisting of 23 reactions is solved using results of the metabolic tracer experiments and assumptions of microbial precursor demand. This new method enables direct estimation of fundamental aspects of microbial energy production, CUE, and soil organic matter formation in relatively undisturbed microbial communities. We will present results showing the range of metabolic patterns observed in these communities and discuss results from testing metabolic models.

Influences of growth parameters on the reaction pathway during GaN synthesis

NASA Astrophysics Data System (ADS)

Zhang, Zhi; Liu, Zhongyi; Fang, Haisheng

2018-01-01

Gallium nitride (GaN) film growth is a complicated physical and chemical process including fluid flow, heat transfer, species transport and chemical reaction. Study of the reaction mechanism, i.e., the reaction pathway, is important for optimizing the growth process in the actual manufacture. In the paper, the growth pathway of GaN in a closed-coupled showerhead metal-organic chemical vapor deposition (CCS-MOCVD) reactor is investigated in detail using computational fluid dynamics (CFD). Influences of the process parameters, such as the chamber pressure, the inlet temperature, the susceptor temperature and the pre-exponential factor, on the reaction pathway are examined. The results show that increases of the chamber pressure or the inlet temperature, as well as reductions of the susceptor temperature or the pre-exponential factor lead to the adduct route dominating the growth. The deposition rate contributed by the decomposition route, however, can be enhanced dramatically by increasing the inlet temperature, the susceptor temperature and the pre-exponential factor.

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

PubMed Central

Rauniyar, Navin

2015-01-01

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

Pre-recombination quenching of the radiation induced fluorescence as the approach to study kinetics of ion-molecular reactions

NASA Astrophysics Data System (ADS)

Borovkov, V. I.; Ivanishko, I. S.

2011-04-01

This study deals with the geminate ion recombination in the presence of bulk scavengers, that is the so-called scavenger problem, as well as with the effect of the scavenging reaction on the radiation-induced recombination fluorescence. Borovkov and Velizhanin (2004) have proposed a method to determine the rate constant of the bulk reaction between neutral scavengers and one of the geminate ions if the ion-molecular reaction prevented the formation of electronically excited states upon recombination involving a newly formed ion. If such pre-recombination quenching of the radiation-induced fluorescence took place, it manifested itself as a progressive decrease in the decay of the fluorescence intensity. The relative change in the fluorescence decay as caused by the scavengers was believed to be closely related to the kinetics of the scavenging reaction. The goal of the present study is to support this method, both computationally and experimentally because there are two factors, which cast doubt on the intuitively obvious approach to the scavenger problem: spatial correlations between the particles involved and the drift of the charged reagent in the electric field of its geminate partner. Computer simulation of geminate ions recombination with an explicit modeling of the motion trajectories of scavengers has been performed for media of low dielectric permittivity, i.e. for the maximal Coulomb interaction between the ions. The simulation has shown that upon continuous diffusion of the particles involved, the joint effect of the two above factors can be considered as insignificant with a high accuracy. Besides, it is concluded then that the method of pre-recombination quenching could be applied to study parallel and consecutive reactions where the yields of excited states in the reaction pathways are different with the use of very simple analytical relations of the formal chemical kinetics. The conclusion has been confirmed experimentally by the example of the reactions of electron transfer from the diphenylacetylene radical anion to dibromoethane and hexafluorobenzene in n-dodecane solutions.

The adverse outcome pathway knowledge base

EPA Science Inventory

The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Zachary A.; Drager, Andreas; Ebrahim, Ali

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

PubMed Central

King, Zachary A.; Dräger, Andreas; Ebrahim, Ali; Sonnenschein, Nikolaus; Lewis, Nathan E.; Palsson, Bernhard O.

2015-01-01

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools. PMID:26313928

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE PAGES

King, Zachary A.; Drager, Andreas; Ebrahim, Ali; ...

2015-08-27

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

Elucidation of the Pathway to Astaxanthin in the Flowers of Adonis aestivalis[C][W

PubMed Central

Cunningham, Francis X.; Gantt, Elisabeth

2011-01-01

A few species in the genus Adonis are the only land plants known to produce the valuable red ketocarotenoid astaxanthin in abundance. Here, we ascertain the pathway that leads from the β-rings of β-carotene, a carotenoid ubiquitous in plants, to the 3-hydroxy-4-keto-β-rings of astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4’-dione) in the blood-red flowers of Adonis aestivalis, an ornamental and medicinal plant commonly known as summer pheasant’s eye. Two gene products were found to catalyze three distinct reactions, with the first and third reactions of the pathway catalyzed by the same enzyme. The pathway commences with the activation of the number 4 carbon of a β-ring in a reaction catalyzed by a carotenoid β-ring 4-dehydrogenase (CBFD), continues with the further dehydrogenation of this carbon to yield a carbonyl in a reaction catalyzed by a carotenoid 4-hydroxy-β-ring 4-dehydrogenase, and concludes with the addition of an hydroxyl group at the number 3 carbon in a reaction catalyzed by the erstwhile CBFD enzyme. The A. aestivalis pathway is both portable and robust, functioning efficiently in a simple bacterial host. Our elucidation of the pathway to astaxanthin in A. aestivalis provides enabling technology for development of a biological production process and reveals the evolutionary origin of this unusual plant pathway, one unrelated to and distinctly different from those used by bacteria, green algae, and fungi to synthesize astaxanthin. PMID:21862704

A Graphical User Interface for a Method to Infer Kinetics and Network Architecture (MIKANA)

PubMed Central

Mourão, Márcio A.; Srividhya, Jeyaraman; McSharry, Patrick E.; Crampin, Edmund J.; Schnell, Santiago

2011-01-01

One of the main challenges in the biomedical sciences is the determination of reaction mechanisms that constitute a biochemical pathway. During the last decades, advances have been made in building complex diagrams showing the static interactions of proteins. The challenge for systems biologists is to build realistic models of the dynamical behavior of reactants, intermediates and products. For this purpose, several methods have been recently proposed to deduce the reaction mechanisms or to estimate the kinetic parameters of the elementary reactions that constitute the pathway. One such method is MIKANA: Method to Infer Kinetics And Network Architecture. MIKANA is a computational method to infer both reaction mechanisms and estimate the kinetic parameters of biochemical pathways from time course data. To make it available to the scientific community, we developed a Graphical User Interface (GUI) for MIKANA. Among other features, the GUI validates and processes an input time course data, displays the inferred reactions, generates the differential equations for the chemical species in the pathway and plots the prediction curves on top of the input time course data. We also added a new feature to MIKANA that allows the user to exclude a priori known reactions from the inferred mechanism. This addition improves the performance of the method. In this article, we illustrate the GUI for MIKANA with three examples: an irreversible Michaelis–Menten reaction mechanism; the interaction map of chemical species of the muscle glycolytic pathway; and the glycolytic pathway of Lactococcus lactis. We also describe the code and methods in sufficient detail to allow researchers to further develop the code or reproduce the experiments described. The code for MIKANA is open source, free for academic and non-academic use and is available for download (Information S1). PMID:22096591

A graphical user interface for a method to infer kinetics and network architecture (MIKANA).

PubMed

Mourão, Márcio A; Srividhya, Jeyaraman; McSharry, Patrick E; Crampin, Edmund J; Schnell, Santiago

2011-01-01

One of the main challenges in the biomedical sciences is the determination of reaction mechanisms that constitute a biochemical pathway. During the last decades, advances have been made in building complex diagrams showing the static interactions of proteins. The challenge for systems biologists is to build realistic models of the dynamical behavior of reactants, intermediates and products. For this purpose, several methods have been recently proposed to deduce the reaction mechanisms or to estimate the kinetic parameters of the elementary reactions that constitute the pathway. One such method is MIKANA: Method to Infer Kinetics And Network Architecture. MIKANA is a computational method to infer both reaction mechanisms and estimate the kinetic parameters of biochemical pathways from time course data. To make it available to the scientific community, we developed a Graphical User Interface (GUI) for MIKANA. Among other features, the GUI validates and processes an input time course data, displays the inferred reactions, generates the differential equations for the chemical species in the pathway and plots the prediction curves on top of the input time course data. We also added a new feature to MIKANA that allows the user to exclude a priori known reactions from the inferred mechanism. This addition improves the performance of the method. In this article, we illustrate the GUI for MIKANA with three examples: an irreversible Michaelis-Menten reaction mechanism; the interaction map of chemical species of the muscle glycolytic pathway; and the glycolytic pathway of Lactococcus lactis. We also describe the code and methods in sufficient detail to allow researchers to further develop the code or reproduce the experiments described. The code for MIKANA is open source, free for academic and non-academic use and is available for download (Information S1).

Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

PubMed

Kusko, Rebecca L; Brothers, John F; Tedrow, John; Pandit, Kusum; Huleihel, Luai; Perdomo, Catalina; Liu, Gang; Juan-Guardela, Brenda; Kass, Daniel; Zhang, Sherry; Lenburg, Marc; Martinez, Fernando; Quackenbush, John; Sciurba, Frank; Limper, Andrew; Geraci, Mark; Yang, Ivana; Schwartz, David A; Beane, Jennifer; Spira, Avrum; Kaminski, Naftali

2016-10-15

Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

Parallel replica dynamics method for bistable stochastic reaction networks: Simulation and sensitivity analysis

NASA Astrophysics Data System (ADS)

Wang, Ting; Plecháč, Petr

2017-12-01

Stochastic reaction networks that exhibit bistable behavior are common in systems biology, materials science, and catalysis. Sampling of stationary distributions is crucial for understanding and characterizing the long-time dynamics of bistable stochastic dynamical systems. However, simulations are often hindered by the insufficient sampling of rare transitions between the two metastable regions. In this paper, we apply the parallel replica method for a continuous time Markov chain in order to improve sampling of the stationary distribution in bistable stochastic reaction networks. The proposed method uses parallel computing to accelerate the sampling of rare transitions. Furthermore, it can be combined with the path-space information bounds for parametric sensitivity analysis. With the proposed methodology, we study three bistable biological networks: the Schlögl model, the genetic switch network, and the enzymatic futile cycle network. We demonstrate the algorithmic speedup achieved in these numerical benchmarks. More significant acceleration is expected when multi-core or graphics processing unit computer architectures and programming tools such as CUDA are employed.

Representing metabolic pathway information: an object-oriented approach.

PubMed

Ellis, L B; Speedie, S M; McLeish, R

1998-01-01

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) is a website providing information and dynamic links for microbial metabolic pathways, enzyme reactions, and their substrates and products. The Compound, Organism, Reaction and Enzyme (CORE) object-oriented database management system was developed to contain and serve this information. CORE was developed using Java, an object-oriented programming language, and PSE persistent object classes from Object Design, Inc. CORE dynamically generates descriptive web pages for reactions, compounds and enzymes, and reconstructs ad hoc pathway maps starting from any UM-BBD reaction. CORE code is available from the authors upon request. CORE is accessible through the UM-BBD at: http://www. labmed.umn.edu/umbbd/index.html.

Kynurenine pathway metabolites and enzymes involved in redox reactions.

PubMed

González Esquivel, D; Ramírez-Ortega, D; Pineda, B; Castro, N; Ríos, C; Pérez de la Cruz, V

2017-01-01

Oxido-reduction reactions are a fundamental part of the life due to support many vital biological processes as cellular respiration and glucose oxidation. In the redox reactions, one substance transfers one or more electrons to another substance. An important electron carrier is the coenzyme NAD + , which is involved in many metabolic pathways. De novo biosynthesis of NAD + is through the kynurenine pathway, the major route of tryptophan catabolism, which is sensitive to redox environment and produces metabolites with redox capacity, able to alter biological functions that are controlled by redox-responsive signaling pathways. Kynurenine pathway metabolites have been implicated in the physiology process and in the physiopathology of many diseases; processes that also share others factors as dysregulation of calcium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation and cell death, which impact the redox environment. This review examines in detail the available evidence in which kynurenine pathway metabolites participate in redox reactions and their effect on cellular redox homeostasis, since the knowledge of the main factors and mechanisms that lead to cell death in many neurodegenative disorders and other pathologies, such as mitochondrial dysfunction, oxidative stress and kynurenines imbalance, will allow to develop therapies using them as targets. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parallel, confocal, and complete spectrum imager for fluorescent detection of high-density microarray

NASA Astrophysics Data System (ADS)

Bogdanov, Valery L.; Boyce-Jacino, Michael

1999-05-01

Confined arrays of biochemical probes deposited on a solid support surface (analytical microarray or 'chip') provide an opportunity to analysis multiple reactions simultaneously. Microarrays are increasingly used in genetics, medicine and environment scanning as research and analytical instruments. A power of microarray technology comes from its parallelism which grows with array miniaturization, minimization of reagent volume per reaction site and reaction multiplexing. An optical detector of microarray signals should combine high sensitivity, spatial and spectral resolution. Additionally, low-cost and a high processing rate are needed to transfer microarray technology into biomedical practice. We designed an imager that provides confocal and complete spectrum detection of entire fluorescently-labeled microarray in parallel. Imager uses microlens array, non-slit spectral decomposer, and high- sensitive detector (cooled CCD). Two imaging channels provide a simultaneous detection of localization, integrated and spectral intensities for each reaction site in microarray. A dimensional matching between microarray and imager's optics eliminates all in moving parts in instrumentation, enabling highly informative, fast and low-cost microarray detection. We report theory of confocal hyperspectral imaging with microlenses array and experimental data for implementation of developed imager to detect fluorescently labeled microarray with a density approximately 103 sites per cm2.

Mechanistic Details and Reactivity Descriptors in Oxidation and Acid Catalysis of Methanol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deshlahra, Prashant; Carr, Robert T.; Chai, Song-Hai

2015-02-06

Acid and redox reaction rates of CH₃OH-O₂ mixtures on polyoxometalate (POM) clusters, together with isotopic, spectroscopic, and theoretical assessments of catalyst properties and reaction pathways, were used to define rigorous descriptors of reactivity and to probe the compositional effects for oxidative dehydrogenation (ODH) and dehydration reactions. ³¹P-MAS NMR, transmission electron microscopy and titrations of protons with di-tert-butylpyridine during catalysis showed that POM clusters retained their Keggin structure upon dispersion on SiO₂ and after use in CH₃OH reactions. The effects of CH₃OH and O₂ pressures and of D-substitution on ODH rates show that C-H activation in molecularly adsorbed CH₃OH is themore » sole kinetically relevant step and leads to reduced centers as intermediates present at low coverages; their concentrations, measured from UV-vis spectra obtained during catalysis, are consistent with the effects of CH₃OH/O₂ ratios predicted from the elementary steps proposed. First-order ODH rate constants depend strongly on the addenda atoms (Mo vs W) but weakly on the central atom (P vs Si) in POM clusters, because C-H activation steps inject electrons into the lowest unoccupied molecular orbitals (LUMO) of the clusters, which are the d-orbitals at Mo⁶⁺ and W⁶⁺ centers. H-atom addition energies (HAE) at O-atoms in POM clusters represent the relevant theoretical probe of the LUMO energies and of ODH reactivity. The calculated energies of ODH transition states at each O-atom depend linearly on their HAE values with slopes near unity, as predicted for late transition states in which electron transfer and C-H cleavage are essentially complete. HAE values averaged over all accessible O-atoms in POM clusters provide the appropriate reactivity descriptor for oxides whose known structures allow accurate HAE calculations. CH₃OH dehydration proceeds via parallel pathways mediated by late carbenium-ion transition states; effects of composition on dehydration reactivity reflect changes in charge reorganizations and electrostatic forces that stabilize protons at Brønsted acid sites.« less

Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

NASA Astrophysics Data System (ADS)

Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

2017-07-01

Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Kitao, Akio

2013-07-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin

PubMed Central

Yun, Jina; Puri, Rajat; Yang, Huan; Lizzio, Michael A; Wu, Chunlai; Sheng, Zu-Hang; Guo, Ming

2014-01-01

Parkinson's disease (PD) genes PINK1 and parkin act in a common pathway that regulates mitochondrial integrity and quality. Identifying new suppressors of the pathway is important for finding new therapeutic strategies. In this study, we show that MUL1 suppresses PINK1 or parkin mutant phenotypes in Drosophila. The suppression is achieved through the ubiquitin-dependent degradation of Mitofusin, which itself causes PINK1/parkin mutant-like toxicity when overexpressed. We further show that removing MUL1 in PINK1 or parkin loss-of-function mutant aggravates phenotypes caused by loss of either gene alone, leading to lethality in flies and degeneration in mouse cortical neurons. Together, these observations show that MUL1 acts in parallel to the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity. The MUL1 pathway compensates for loss of PINK1/parkin in both Drosophila and mammals and is a promising therapeutic target for PD. DOI: http://dx.doi.org/10.7554/eLife.01958.001 PMID:24898855

Reactivity of Free Malondialdehyde during In Vitro Simulated Gastrointestinal Digestion.

PubMed

Vandemoortele, Angelique; Babat, Pinar; Yakubu, Mariam; De Meulenaer, Bruno

2017-03-15

An aqueous buffer, a saturated glycerol triheptanoate oil, and a Tween 20 stabilized fully hydrogenated coconut oil-in-water emulsion, all spiked with malondialdehyde, were subjected to in vitro digestion. A dynamic equilibrium between malondialdehyde, its aldol self-condensation products, and its hydrolytic cleavage products was observed. This equilibrium depended upon the kind of sample and the temperature at which these samples were preincubated during 24 h. The presence of oil during gastric digestion protected the aldol self-condensation and cleavage products from conversion to malondialdehyde, which occurred in the aqueous acidic gastric chyme. In parallel, the presence of oil enhanced the reactivity of malondialdehyde throughout the gastrointestinal digestion process. Malondialdehyde recoveries after digestion varied between 42 and 90%, depending upon the model system studied, with the aldol self-condensation as the main reaction pathway. In conclusion, this study revealed that malondialdehyde is a very reactive molecule whose reactivity does not stop at the point of ingestion.

A comprehensive detailed chemical kinetic reaction mechanism for combustion of n-alkane hydrocarbons from n-octane to n-hexadecane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westbrook, Charles K.; Pitz, William J.; Herbinet, Olivier

2009-01-15

Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of nine n-alkanes larger than n-heptane, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on previous mechanisms for the primary reference fuels n-heptane and iso-octane, using the reaction classes first developed for n-heptane. Individual reaction class rules are as simple asmore » possible in order to focus on the parallelism between all of the n-alkane fuels included in the mechanisms. These mechanisms are validated through extensive comparisons between computed and experimental data from a wide variety of different sources. In addition, numerical experiments are carried out to examine features of n-alkane combustion in which the detailed mechanisms can be used to compare reactivities of different n-alkane fuels. The mechanisms for these n-alkanes are presented as a single detailed mechanism, which can be edited to produce efficient mechanisms for any of the n-alkanes included, and the entire mechanism, with supporting thermochemical and transport data, together with an explanatory glossary explaining notations and structural details, is available for download from our web page. (author)« less

Experimental evolution reveals hidden diversity in evolutionary pathways

PubMed Central

Lind, Peter A; Farr, Andrew D; Rainey, Paul B

2015-01-01

Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans. DOI: http://dx.doi.org/10.7554/eLife.07074.001 PMID:25806684

A Method for Finding Metabolic Pathways Using Atomic Group Tracking.

PubMed

Huang, Yiran; Zhong, Cheng; Lin, Hai Xiang; Wang, Jianyi

2017-01-01

A fundamental computational problem in metabolic engineering is to find pathways between compounds. Pathfinding methods using atom tracking have been widely used to find biochemically relevant pathways. However, these methods require the user to define the atoms to be tracked. This may lead to failing to predict the pathways that do not conserve the user-defined atoms. In this work, we propose a pathfinding method called AGPathFinder to find biochemically relevant metabolic pathways between two given compounds. In AGPathFinder, we find alternative pathways by tracking the movement of atomic groups through metabolic networks and use combined information of reaction thermodynamics and compound similarity to guide the search towards more feasible pathways and better performance. The experimental results show that atomic group tracking enables our method to find pathways without the need of defining the atoms to be tracked, avoid hub metabolites, and obtain biochemically meaningful pathways. Our results also demonstrate that atomic group tracking, when incorporated with combined information of reaction thermodynamics and compound similarity, improves the quality of the found pathways. In most cases, the average compound inclusion accuracy and reaction inclusion accuracy for the top resulting pathways of our method are around 0.90 and 0.70, respectively, which are better than those of the existing methods. Additionally, AGPathFinder provides the information of thermodynamic feasibility and compound similarity for the resulting pathways.

A Method for Finding Metabolic Pathways Using Atomic Group Tracking

PubMed Central

Zhong, Cheng; Lin, Hai Xiang; Wang, Jianyi

2017-01-01

A fundamental computational problem in metabolic engineering is to find pathways between compounds. Pathfinding methods using atom tracking have been widely used to find biochemically relevant pathways. However, these methods require the user to define the atoms to be tracked. This may lead to failing to predict the pathways that do not conserve the user-defined atoms. In this work, we propose a pathfinding method called AGPathFinder to find biochemically relevant metabolic pathways between two given compounds. In AGPathFinder, we find alternative pathways by tracking the movement of atomic groups through metabolic networks and use combined information of reaction thermodynamics and compound similarity to guide the search towards more feasible pathways and better performance. The experimental results show that atomic group tracking enables our method to find pathways without the need of defining the atoms to be tracked, avoid hub metabolites, and obtain biochemically meaningful pathways. Our results also demonstrate that atomic group tracking, when incorporated with combined information of reaction thermodynamics and compound similarity, improves the quality of the found pathways. In most cases, the average compound inclusion accuracy and reaction inclusion accuracy for the top resulting pathways of our method are around 0.90 and 0.70, respectively, which are better than those of the existing methods. Additionally, AGPathFinder provides the information of thermodynamic feasibility and compound similarity for the resulting pathways. PMID:28068354

Parallel labeling experiments for pathway elucidation and (13)C metabolic flux analysis.

PubMed

Antoniewicz, Maciek R

2015-12-01

Metabolic pathway models provide the foundation for quantitative studies of cellular physiology through the measurement of intracellular metabolic fluxes. For model organisms metabolic models are well established, with many manually curated genome-scale model reconstructions, gene knockout studies and stable-isotope tracing studies. However, for non-model organisms a similar level of knowledge is often lacking. Compartmentation of cellular metabolism in eukaryotic systems also presents significant challenges for quantitative (13)C-metabolic flux analysis ((13)C-MFA). Recently, innovative (13)C-MFA approaches have been developed based on parallel labeling experiments, the use of multiple isotopic tracers and integrated data analysis, that allow more rigorous validation of pathway models and improved quantification of metabolic fluxes. Applications of these approaches open new research directions in metabolic engineering, biotechnology and medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aromatic sulfonation with sulfur trioxide: mechanism and kinetic model.

PubMed

Moors, Samuel L C; Deraet, Xavier; Van Assche, Guy; Geerlings, Paul; De Proft, Frank

2017-01-01

Electrophilic aromatic sulfonation of benzene with sulfur trioxide is studied with ab initio molecular dynamics simulations in gas phase, and in explicit noncomplexing (CCl 3 F) and complexing (CH 3 NO 2 ) solvent models. We investigate different possible reaction pathways, the number of SO 3 molecules participating in the reaction, and the influence of the solvent. Our simulations confirm the existence of a low-energy concerted pathway with formation of a cyclic transition state with two SO 3 molecules. Based on the simulation results, we propose a sequence of elementary reaction steps and a kinetic model compatible with experimental data. Furthermore, a new alternative reaction pathway is proposed in complexing solvent, involving two SO 3 and one CH 3 NO 2 .

Interfacing Biocompatible Reactions with Engineered Escherichia coli.

PubMed

Wallace, Stephen; Balskus, Emily P

2017-01-01

Biocompatible chemistry represents a new way of merging chemical and biological synthesis by interfacing nonenzymatic reactions with metabolic pathways. This approach can enable the production of nonnatural molecules directly from renewable starting materials via microbial fermentation. When developing a new biocompatible reaction certain criteria must be satisfied, i.e., the reaction must be (1) functional in aqueous growth media at ambient temperature and pH, (2) nontoxic to the producing microorganism, and (3) have negligible effects on the targeted metabolic pathway. This chapter provides a detailed outline of two biocompatible reaction procedures (hydrogenation and cyclopropanation), and describes some of the chemical and microbiological experiments and considerations required during biocompatible reaction development.

Stochastic Kinetics on Networks: When Slow Is Fast

PubMed Central

2015-01-01

Most chemical and biological processes can be viewed as reaction networks in which different pathways often compete kinetically for transformation of substrates into products. An enzymatic process is an example of such phenomena when biological catalysts create new routes for chemical reactions to proceed. It is typically assumed that the general process of product formation is governed by the pathway with the fastest kinetics at all time scales. In contrast to the expectation, here we show theoretically that at time scales sufficiently short, reactions are predominantly determined by the shortest pathway (in the number of intermediate states), regardless of the average turnover time associated with each pathway. This universal phenomenon is demonstrated by an explicit calculation for a system with two competing reversible (or irreversible) pathways. The time scales that characterize this regime and its relevance for single-molecule experimental studies are also discussed. PMID:25140607

Combinatorial Partial Hydrogenation Reactions of 4-Nitroacetophenone: An Undergraduate Organic Laboratory

ERIC Educational Resources Information Center

Kittredge, Kevin W.; Marine, Susan S.; Taylor, Richard T.

2004-01-01

A molecule possessing other functional groups that could be hydrogenerated is examined, where a variety of metal catalysts are evaluated under similar reaction conditions. Optimizing organic reactions is both time and labor intensive, and the use of a combinatorial parallel synthesis reactor was great time saving device, as per summary.

Exploring the Reaction Pathways of Bioglycerol Hydrodeoxygenation to Propene over Molybdena-Based Catalysts.

PubMed

Zacharopoulou, Vasiliki; Vasiliadou, Efterpi S; Lemonidou, Angeliki A

2018-01-10

The one-step reaction of glycerol with hydrogen to form propene selectively is a particularly challenging catalytic pathway that has not yet been explored thoroughly. Molybdena-based catalysts are active and selective to C-O bond scission; propene is the only product in the gas phase under the standard reaction conditions, and further hydrogenation to propane is impeded. Within this context, this work focuses on the exploration of the reaction pathways and the investigation of various parameters that affect the catalytic performance, such as the role of hydrogen on the product distribution and the effect of the catalyst pretreatment step. Under a hydrogen atmosphere, propene is produced primarily via 2-propenol, whereas under an inert atmosphere propanal and glycerol dissociation products are formed mainly. The reaction most likely proceeds through a reverse Mars-van Krevelen mechanism as partially reduced Mo species drive the reaction to the formation of the desired product. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transcriptional Changes That Characterize the Immune Reactions of Leprosy

PubMed Central

Dupnik, Kathryn M.; Bair, Thomas B.; Maia, Andressa O.; Amorim, Francianne M.; Costa, Marcos R.; Keesen, Tatjana S. L.; Valverde, Joanna G.; Queiroz, Maria do Carmo A. P.; Medeiros, Lúcio L.; de Lucena, Nelly L.; Wilson, Mary E.; Nobre, Mauricio L.; Johnson, Warren D.; Jeronimo, Selma M. B.

2015-01-01

Background. Leprosy morbidity is increased by 2 pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL). Methods. To discover host factors related to immune reactions, global transcriptional profiles of peripheral blood mononuclear cells were compared between 11 RR, 11 ENL, and 19 matched control patients, with confirmation by quantitative polymerase chain reaction. Encoded proteins were investigated in skin biopsy specimens by means of immunohistochemistry. Results. There were 275 genes differentially expressed in RR and 517 differentially expressed in ENL on the microarray. Pathway analysis showed immunity-related pathways represented in RR and ENL transcriptional profiles, with the “complement and coagulation” pathway common to both. Interferon γ was identified as a significant upstream regulator of the expression changes for RR and ENL. Immunohistochemical staining of skin lesions showed increased C1q in both RR and ENL. Conclusions. These data suggest a previously underrecognized role for complement in the pathogenesis of both RR and ENL, and we propose new hypotheses for reaction pathogenesis. PMID:25398459

Reaction pathways for the deoxygenation of vegetable oils and related model compounds.

PubMed

Gosselink, Robert W; Hollak, Stefan A W; Chang, Shu-Wei; van Haveren, Jacco; de Jong, Krijn P; Bitter, Johannes H; van Es, Daan S

2013-09-01

Vegetable oil-based feeds are regarded as an alternative source for the production of fuels and chemicals. Paraffins and olefins can be produced from these feeds through catalytic deoxygenation. The fundamentals of this process are mostly studied by using model compounds such as fatty acids, fatty acid esters, and specific triglycerides because of their structural similarity to vegetable oils. In this Review we discuss the impact of feedstock, reaction conditions, and nature of the catalyst on the reaction pathways of the deoxygenation of vegetable oils and its derivatives. As such, we conclude on the suitability of model compounds for this reaction. It is shown that the type of catalyst has a significant effect on the deoxygenation pathway, that is, group 10 metal catalysts are active in decarbonylation/decarboxylation whereas metal sulfide catalysts are more selective to hydrodeoxygenation. Deoxygenation studies performed under H2 showed similar pathways for fatty acids, fatty acid esters, triglycerides, and vegetable oils, as mostly deoxygenation occurs indirectly via the formation of fatty acids. Deoxygenation in the absence of H2 results in significant differences in reaction pathways and selectivities depending on the feedstock. Additionally, using unsaturated feedstocks under inert gas results in a high selectivity to undesired reactions such as cracking and the formation of heavies. Therefore, addition of H2 is proposed to be essential for the catalytic deoxygenation of vegetable oil feeds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

From Position-Specific Labeling to Environmental Fluxomics: Elucidating Biogeochemical Cycles from the Metabolic Perspective (BG Division Outstanding ECS Award Lecture)

NASA Astrophysics Data System (ADS)

Dippold, Michaela; Apostel, Carolin; Dijkstra, Paul; Kuzyakov, Yakov

2017-04-01

Understanding soil and sedimentary organic matter (SOM) dynamics is one of the most important challenges in biogeoscience. To disentangle the fluxes and transformations of C in soils a detailed knowledge on the biochemical pathways and its controlling factors is required. Biogeochemists' view on the C transformation of microorganisms in soil has rarely exceed a strongly simplified concept assuming that C gets either oxidized to CO2 via the microbial catabolism or incorporated into biomass via the microbial anabolism. Biochemists, however, thoroughly identified in the past decades the individual reactions of glycolysis, pentose-phosphate pathway and citric acid cycle underlying the microbial catabolism. At various points within that metabolic network the anabolic fluxes feeding biomass formation branch off. Recent studies on metabolic flux tracing by position-specific isotope labeling allowed tracing these C transformations in soils in situ, an approach which is qunatitatively complemented by metabolic flux modeling. This approach has reached new impact by the cutting-edge combination of position-specific 13C labeling with compound-specific isotope analysis of microbial biomarkers and metabolites which allows 1) tracing specific anabolic pathways in diverse microbial communities in soils and 2) identification of specific pathways of individual functional microbial groups. Thus, the combination of position-specific labeling, compound-specific isotope incorporation in biomarkers and quantitative metabolic flux modelling provide the toolbox for quantitative soil fluxomics. Our studies combining position-specific labeled glucose with amino sugar 13C analysis showed that up to 55% of glucose, incorporated into the glucose derivative glucosamine, first passed glycolysis before allocated back via gluconeogenesis. Similarly, glutamate-derived C is allocated via anaplerotic pathways towards fatty acid synthesis and in parallel to its oxidation in citric acid cycle. Thus, oxidizing catabolic pathways and anabolic pathways, i.e. building-up new cellular compounds, occurred in soils simultaneously, a combination unlikely to occur in pure cultures, where constant growth conditions under high C supply allow a straight unidirectional regulation of C metabolism. However, unstable environmental conditions, C scarcity and interactions between a still unknown diversity of microorganisms in soils are likely to induce the observed metabolic diversity. Coupling these results with the position-specific fingerprint of microbial biomarkers revealed that microbial groups show deviating adaptation strategies and that they react on environmental changes by activation or deactivation of specific metabolic pathways such as anaplerotic fluxes. To understand how microorganisms catalyze the biogeochemical fluxes in soil a profound understanding of their metabolic adaptation strategies such as recycling or switching between pathways is crucial. Metabolic flux models adapted to soil microbial communities and their regulatory strategies will not only deepen our understanding on the microorganims' reactions to environmental changes but also create the prerequisits for a quantitative prediction of biogeochemical fluxes based on the underlying microbial processes.

Fundamental Reaction Pathway for Peptide Metabolism by Proteasome: Insights from First-principles Quantum Mechanical/Molecular Mechanical Free Energy Calculations

PubMed Central

Wei, Donghui; Fang, Lei; Tang, Mingsheng; Zhan, Chang-Guo

2013-01-01

Proteasome is the major component of the crucial nonlysosomal protein degradation pathway in the cells, but the detailed reaction pathway is unclear. In this study, first-principles quantum mechanical/molecular mechanical free energy calculations have been performed to explore, for the first time, possible reaction pathways for proteasomal proteolysis/hydrolysis of a representative peptide, succinyl-leucyl-leucyl-valyl-tyrosyl-7-amino-4-methylcoumarin (Suc-LLVY-AMC). The computational results reveal that the most favorable reaction pathway consists of six steps. The first is a water-assisted proton transfer within proteasome, activating Thr1-Oγ. The second is a nucleophilic attack on the carbonyl carbon of a Tyr residue of substrate by the negatively charged Thr1-Oγ, followed by the dissociation of the amine AMC (third step). The fourth step is a nucleophilic attack on the carbonyl carbon of the Tyr residue of substrate by a water molecule, accompanied by a proton transfer from the water molecule to Thr1-Nz. Then, Suc-LLVY is dissociated (fifth step), and Thr1 is regenerated via a direct proton transfer from Thr1-Nz to Thr1-Oγ. According to the calculated energetic results, the overall reaction energy barrier of the proteasomal hydrolysis is associated with the transition state (TS3b) for the third step involving a water-assisted proton transfer. The determined most favorable reaction pathway and the rate-determining step have provided a reasonable interpretation of the reported experimental observations concerning the substituent and isotopic effects on the kinetics. The calculated overall free energy barrier of 18.2 kcal/mol is close to the experimentally-derived activation free energy of ~18.3–19.4 kcal/mol, suggesting that the computational results are reasonable. PMID:24111489

Exploring the reaction channels between arsine and the hydroxyl radical

NASA Astrophysics Data System (ADS)

Viana, Rommel B.

2017-10-01

The aim of this study was to present the reaction mechanism channels between arsine (AsH3) and hydroxyl (OH) which was evaluated at CCSD(T)/CBS//CCSD/cc-pVTZ level. One potential channel is the hydrogen abstraction pathway (R1), leading to AsH2 and H2O products, which occurs due to the formation of an entrance complex (AsH3OH) followed by a 1,2-hydrogen shift pathway (involving the proton transfer from the arsine group to hydroxyls, with one leading to the products). Additional channels are accessed via H-elimination pathways of the entrance complexes, forming arsinous acid (AsH2OH; R2) and arsine oxide (AsH3O; R3). In this respect, R2 is the only exoergic route of the three exit channels, representing the major branching ratio at 200-1000 K and, after 2000 K, R1 increases gradually becoming the major route of this reaction. In contrast, even at 4000 K, R3 is a highly unfeasible pathway. Therefore, the information predicted here provides new insights into the neutral-neutral chemical reaction dynamics regarding the Group V hydrides. On the other side, the R2 pathway may have some potential to solve the arsine oxidation puzzle as a possible primary pathway to the arsenic-oxygen species formation.

New Developments in the Field of Reaction Technology: The Multiparallel Reactor HPMR 50-96

PubMed Central

Allwardt, Arne; Wendler, Christian; Thurow, Kerstin

2005-01-01

Catalytic high-pressure reactions play an important role in classic bulk chemistry. The optimization of common reactions, the search for new and more effective catalysts, and the increasing use of catalytic pressure reactions in the field of drug development call for high-parallel reaction systems. A crucial task of current developments, apart from the parameters of pressure, temperature, and number of reaction chambers, is, in this respect, the systems' integration into complex laboratory automation environments. PMID:18924722

Parallel comparative proteomics and phosphoproteomics reveal that cattle myostatin regulates phosphorylation of key enzymes in glycogen metabolism and glycolysis pathway

PubMed Central

Yang, Shuping; Li, Xin; Liu, Xinfeng; Ding, Xiangbin; Xin, Xiangbo; Jin, Congfei; Zhang, Sheng; Li, Guangpeng; Guo, Hong

2018-01-01

MSTN-encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis. Meanwhile, 149 differentially changed phosphopeptides corresponding to 76 unique phosphorylated proteins (DEPPs) were detected from 2,600 identified phosphopeptides in 702 phosphorylated proteins. Bioinformatics analyses suggested that majority of DEPs and DEPPs were closely related to glycolysis, glycogenolysis, and muscle contractile fibre processes. The global discovery results were validated by Multiple Reaction Monitoring (MRM)-based targeted peptide quantitation analysis, western blotting, and muscle glycogen content measurement. Our data revealed that increase in abundance of key enzymes and phosphorylation on their regulatory sites appears responsible for the enhanced glycogenolysis and glycolysis in MSTN−/−. The elevated glycogenolysis was assocaited with an enhanced phosphorylation of Ser1018 in PHKA1, and Ser641/Ser645 in GYS1, which were regulated by upstream phosphorylated AKT-GSK3β pathway and highly consistent with the lower glycogen content in gluteus of MSTN−/−. Collectively, this study provides new insights into the regulatory mechanisms of MSTN involved in energy metabolism and muscle growth. PMID:29541418

Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

PubMed

Imbernon, Monica; Beiroa, Daniel; Vázquez, María J; Morgan, Donald A; Veyrat-Durebex, Christelle; Porteiro, Begoña; Díaz-Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A; Al-Massadi, Omar; Varela, Luis; Gándara, Marina; López-Soriano, Francisco-Javier; Gallego, Rosalía; Seoane, Luisa M; Argiles, Josep M; López, Miguel; Davis, Roger J; Sabio, Guadalupe; Rohner-Jeanrenaud, Françoise; Rahmouni, Kamal; Dieguez, Carlos; Nogueiras, Ruben

2013-03-01

Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism. Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot. We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism. Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

The potential effects of Zataria multiflora Boiss essential oil on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes of toxigenic Aspergillus parasiticus.

PubMed

Yahyaraeyat, R; Khosravi, A R; Shahbazzadeh, D; Khalaj, V

2013-01-01

This study aims at evaluating the effects of Zataria multiflora (Z. multiflora) essential oil (EO) on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes. Total RNAs of Aspergillus parasiticus (A.parasiticus) ATCC56775 grown in yeast extract sucrose (YES) broth medium treated with Z. multiflora EO were subjected to reverse transcription- polymerase chain reaction (RT-PCR). Specific primers of nor-1, ver-1, omt-A and aflR genes were used. In parallel mycelial dry weight of samples were measured and all the media were assayed by high-pressure liquid chromatography (HPLC) for aflatoxinB1 (AFB1), aflatoxinB2 (AFB2), aflatoxinG1 (AFG1), aflatoxinG2 (AFG2) and aflatoxin total (AFTotal) production. The results showed that mycelial dry weight and aflatoxin production reduce in the presence of Z. multiflora EO (100 ppm) on day 5 of growth. It was found that the expression of nor-1, ver-1, omt-A and aflR genes was correlated with the ability of fungus to produce aflatoxins on day 5 in YES medium. RT-PCR showed that in the presence of Z.multiflora EO (100 ppm) nor-1, ver-1 and omtA genes expression was reduced. It seems that toxin production inhibitory effects of Z. multiflora EO on day 5 may be at the transcription level and this herb may cause reduction in aflatoxin biosynthesis pathway genes activity.

The potential effects of Zataria multiflora Boiss essential oil on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes of toxigenic Aspergillus parasiticus

PubMed Central

Yahyaraeyat, R.; Khosravi, A.R.; Shahbazzadeh, D.; Khalaj, V.

2013-01-01

This study aims at evaluating the effects of Zataria multiflora (Z. multiflora) essential oil (EO) on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes. Total RNAs of Aspergillus parasiticus (A.parasiticus) ATCC56775 grown in yeast extract sucrose (YES) broth medium treated with Z. multiflora EO were subjected to reverse transcription- polymerase chain reaction (RT-PCR). Specific primers of nor-1, ver-1, omt-A and aflR genes were used. In parallel mycelial dry weight of samples were measured and all the media were assayed by high-pressure liquid chromatography (HPLC) for aflatoxinB1 (AFB1), aflatoxinB2 (AFB2), aflatoxinG1 (AFG1), aflatoxinG2 (AFG2) and aflatoxin total (AFTotal) production. The results showed that mycelial dry weight and aflatoxin production reduce in the presence of Z. multiflora EO (100 ppm) on day 5 of growth. It was found that the expression of nor-1, ver-1, omt-A and aflR genes was correlated with the ability of fungus to produce aflatoxins on day 5 in YES medium. RT-PCR showed that in the presence of Z.multiflora EO (100 ppm) nor-1, ver-1 and omtA genes expression was reduced. It seems that toxin production inhibitory effects of Z. multiflora EO on day 5 may be at the transcription level and this herb may cause reduction in aflatoxin biosynthesis pathway genes activity. PMID:24294264

Reconstructing biochemical pathways from time course data.

PubMed

Srividhya, Jeyaraman; Crampin, Edmund J; McSharry, Patrick E; Schnell, Santiago

2007-03-01

Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data.

Sulfur Radical-Induced Redox Modifications in Proteins: Analysis and Mechanistic Aspects.

PubMed

Schöneich, Christian

2017-03-10

The sulfur-containing amino acids cysteine (Cys) and methionine (Met) are prominent protein targets of redox modification during conditions of oxidative stress. Here, two-electron pathways have received widespread attention, in part due to their role in signaling processes. However, Cys and Met are equally prone to one-electron pathways, generating intermediary radicals and/or radial ions. These radicals/radical ions can generate various reaction products that are not commonly monitored in redox proteomic studies, but they may be relevant for the fate of proteins during oxidative stress. Recent Advances: Time-resolved kinetic studies and product analysis have expanded our mechanistic understanding of radical reaction pathways of sulfur-containing amino acids. These reactions are now studied in some detail for Met and Cys in proteins, and homocysteine (Hcy) chemically linked to proteins, and the role of protein radical reactions in physiological processes is evolving. Radical-derived products from Cys, Hcy, and Met can react with additional amino acids in proteins, leading to secondary protein modifications, which are potentially remote from initial points of radical attack. These products may contain intra- and intermolecular cross-links, which may lead to protein aggregation. Protein sequence and conformation will have a significant impact on the formation of such products, and a thorough understanding of reaction mechanisms and specifically how protein structure influences reaction pathways will be critical for identification and characterization of novel reaction products. Future studies must evaluate the biological significance of novel reaction products that are derived from radical reactions of sulfur-containing amino acids. Antioxid. Redox Signal. 26, 388-405.

PumpKin: A tool to find principal pathways in plasma chemical models

NASA Astrophysics Data System (ADS)

Markosyan, A. H.; Luque, A.; Gordillo-Vázquez, F. J.; Ebert, U.

2014-10-01

PumpKin is a software package to find all principal pathways, i.e. the dominant reaction sequences, in chemical reaction systems. Although many tools are available to integrate numerically arbitrarily complex chemical reaction systems, few tools exist in order to analyze the results and interpret them in relatively simple terms. In particular, due to the large disparity in the lifetimes of the interacting components, it is often useful to group reactions into pathways that recycle the fastest species. This allows a researcher to focus on the slow chemical dynamics, eliminating the shortest timescales. Based on the algorithm described by Lehmann (2004), PumpKin automates the process of finding such pathways, allowing the user to analyze complex kinetics and to understand the consumption and production of a certain species of interest. We designed PumpKin with an emphasis on plasma chemical systems but it can also be applied to atmospheric modeling and to industrial applications such as plasma medicine and plasma-assisted combustion.

Azulene-to-naphthalene rearrangement: the Car-Parrinello metadynamics method explores various reaction mechanisms.

PubMed

Stirling, András; Iannuzzi, Marcella; Laio, Alessandro; Parrinello, Michele

2004-10-18

We studied the thermal intramolecular and radical rearrangement of azulene to naphthalene by employing a novel metadynamics method based on Car-Parrinello molecular dynamics. We demonstrate that relatively short simulations can provide us with several possible reaction mechanisms for the rearrangement. We show that different choices of the collective coordinates can steer the reaction along different pathways, thus offering the possibility of choosing the most probable mechanism. We consider herein three intramolecular mechanisms and two radical pathways. We found the norcaradiene pathway to be the preferable intramolecular mechanism, whereas the spiran mechanism is the favored radical route. We obtained high activation energies for all the intramolecular pathways (81.5-98.6 kcal mol(-1)), whereas the radical routes have activation energies of 24-39 kcal mol(-1). The calculations have also resulted in elementary steps and intermediates not yet considered. A few attractive features of the metadynamics method in studying chemical reactions are pointed out.

Bromamine Decomposition Revisited: A Holistic Approach for Analyzing Acid and Base Catalysis Kinetics.

PubMed

Wahman, David G; Speitel, Gerald E; Katz, Lynn E

2017-11-21

Chloramine chemistry is complex, with a variety of reactions occurring in series and parallel and many that are acid or base catalyzed, resulting in numerous rate constants. Bromide presence increases system complexity even further with possible bromamine and bromochloramine formation. Therefore, techniques for parameter estimation must address this complexity through thoughtful experimental design and robust data analysis approaches. The current research outlines a rational basis for constrained data fitting using Brønsted theory, application of the microscopic reversibility principle to reversible acid or base catalyzed reactions, and characterization of the relative significance of parallel reactions using fictive product tracking. This holistic approach was used on a comprehensive and well-documented data set for bromamine decomposition, allowing new interpretations of existing data by revealing that a previously published reaction scheme was not robust; it was not able to describe monobromamine or dibromamine decay outside of the conditions for which it was calibrated. The current research's simplified model (3 reactions, 17 constants) represented the experimental data better than the previously published model (4 reactions, 28 constants). A final model evaluation was conducted based on representative drinking water conditions to determine a minimal model (3 reactions, 8 constants) applicable for drinking water conditions.

RhoA/ROCK Signaling Pathway Mediates Shuanghuanglian Injection-Induced Pseudo-allergic Reactions.

PubMed

Han, Jiayin; Zhao, Yong; Zhang, Yushi; Li, Chunying; Yi, Yan; Pan, Chen; Tian, Jingzhuo; Yang, Yifei; Cui, Hongyu; Wang, Lianmei; Liu, Suyan; Liu, Jing; Deng, Nuo; Liang, Aihua

2018-01-01

Background: Shuanghuanglian injection (SHLI) is a famous Chinese medicine used as an intravenous preparation for the treatment of acute respiratory tract infections. In the recent years, the immediate hypersensitivity reactions induced by SHLI have attracted broad attention. However, the mechanism involved in these reactions has not yet been elucidated. The present study aims to explore the characteristics of the immediate hypersensitivity reactions induced by SHLI and deciphers the role of the RhoA/ROCK signaling pathway in these reactions. Methods: SHLI-immunized mice or naive mice were intravenously injected (i.v.) with SHLI (600 mg/kg) once, and vascular leakage in the ears was evaluated. Passive cutaneous anaphylaxis test was conducted using sera collected from SHLI-immunized mice. Naive mice were administered (i.v.) with a single dose of 150, 300, or 600 mg/kg of SHLI, and vascular leakage, histamine release, and histopathological alterations in the ears, lungs, and intestines were tested. In vitro , human umbilical vein endothelial cell (HUVEC) monolayer was incubated with SHLI (0.05, 0.1, or 0.15 mg/mL), and the changes in endothelial permeability and cytoskeleton were observed. Western blot analysis was performed and ROCK inhibitor was employed to investigate the contribution of the RhoA/ROCK signaling pathway in SHLI-induced hypersensitivity reactions, both in HUVECs and in mice. Results: Our results indicate that SHLI was able to cause immediate dose-dependent vascular leakage, edema, and exudates in the ears, lungs, and intestines, and histamine release in mice. These were pseudo-allergic reactions, as SHLI-specific IgE was not elicited during sensitization. In addition, SHLI induced reorganization of actin cytoskeleton and disrupted the endothelial barrier. The administration of SHLI directly activated the RhoA/ROCK signaling pathway both in HUVECs and in the ears, lungs, and intestines of mice. Fasudil hydrochloride, a ROCK inhibitor, ameliorated the SHLI-induced hypersensitivity reactions in both endothelial cells and mice indicating its protective effect. SHLI-induced pseudo-allergic reactions were mediated by the activation of the RhoA/ROCK signaling pathway. Conclusion : This study presents a novel mechanism of SHLI-induced immediate hypersensitivity reactions and suggests a potential therapeutic strategy to prevent the associated adverse reactions.

Thermal plasticity of growth and development varies adaptively among alternative developmental pathways.

PubMed

Kivelä, Sami M; Svensson, Beatrice; Tiwe, Alma; Gotthard, Karl

2015-09-01

Polyphenism, the expression of discrete alternative phenotypes, is often a consequence of a developmental switch. Physiological changes induced by a developmental switch potentially affect reaction norms, but the evolution and existence of alternative reaction norms remains poorly understood. Here, we demonstrate that, in the butterfly Pieris napi (Lepidoptera: Pieridae), thermal reaction norms of several life history traits vary adaptively among switch-induced alternative developmental pathways of diapause and direct development. The switch was affected both by photoperiod and temperature, ambient temperature during late development having the potential to override earlier photoperiodic cues. Directly developing larvae had higher development and growth rates than diapausing ones across the studied thermal gradient. Reaction norm shapes also differed between the alternative developmental pathways, indicating pathway-specific selection on thermal sensitivity. Relative mass increments decreased linearly with increasing temperature and were higher under direct development than diapause. Contrary to predictions, population phenology did not explain trait variation or thermal sensitivity, but our experimental design probably lacks power for finding subtle phenology effects. We demonstrate adaptive differentiation in thermal reaction norms among alternative phenotypes, and suggest that the consequences of an environmentally dependent developmental switch primarily drive the evolution of alternative thermal reaction norms in P. napi. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Toward rational design of amines for CO2 capture: Substituent effect on kinetic process for the reaction of monoethanolamine with CO2.

PubMed

Xie, Hongbin; Wang, Pan; He, Ning; Yang, Xianhai; Chen, Jingwen

2015-11-01

Amines have been considered as promising candidates for post-combustion CO2 capture. A mechanistic understanding for the chemical processes involved in the capture and release of CO2 is important for the rational design of amines. In this study, the structural effects of amines on the kinetic competition among three typical products (carbamates, carbamic acids and bicarbonate) from amines+CO2 were investigated, in contrast to previous thermodynamic studies to tune the reaction of amines with CO2 based on desirable reaction enthalpy and reaction stoichiometry. We used a quantum chemical method to calculate the activation energies (Ea) for the reactions of a range of substituted monoethanolamines with CO2 covering three pathways to the three products. The results indicate that the formation of carbamates is the most favorable, among the three considered products. In addition, we found that the Ea values for all pathways linearly correlate with pKa of amines, and more importantly, the kinetic competition between carbamate and bicarbonate absorption pathways varies with pKa of the amines, i.e. stronger basicity results in less difference in Ea. These results highlight the importance of the consideration of kinetic competition among different reaction pathways in amine design. Copyright © 2015. Published by Elsevier B.V.

Dynamics Sampling in Transition Pathway Space.

PubMed

Zhou, Hongyu; Tao, Peng

2018-01-09

The minimum energy pathway contains important information describing the transition between two states on a potential energy surface (PES). Chain-of-states methods were developed to efficiently calculate minimum energy pathways connecting two stable states. In the chain-of-states framework, a series of structures are generated and optimized to represent the minimum energy pathway connecting two states. However, multiple pathways may exist connecting two existing states and should be identified to obtain a full view of the transitions. Therefore, we developed an enhanced sampling method, named as the direct pathway dynamics sampling (DPDS) method, to facilitate exploration of a PES for multiple pathways connecting two stable states as well as addition minima and their associated transition pathways. In the DPDS method, molecular dynamics simulations are carried out on the targeting PES within a chain-of-states framework to directly sample the transition pathway space. The simulations of DPDS could be regulated by two parameters controlling distance among states along the pathway and smoothness of the pathway. One advantage of the chain-of-states framework is that no specific reaction coordinates are necessary to generate the reaction pathway, because such information is implicitly represented by the structures along the pathway. The chain-of-states setup in a DPDS method greatly enhances the sufficient sampling in high-energy space between two end states, such as transition states. By removing the constraint on the end states of the pathway, DPDS will also sample pathways connecting minima on a PES in addition to the end points of the starting pathway. This feature makes DPDS an ideal method to directly explore transition pathway space. Three examples demonstrate the efficiency of DPDS methods in sampling the high-energy area important for reactions on the PES.

Products and kinetics of the liquid-phase reaction of glyoxal catalyzed by ammonium ions (NH4(+)).

PubMed

Nozière, Barbara; Dziedzic, Pawel; Córdova, Armando

2009-01-08

Glyoxal, a common atmospheric gas, has been reported to be depleted in some regions of the atmosphere. The corresponding sink could be accounted for by reactions in or at the surface of atmospheric particles, but these reactions were not identified. Recently, we showed that inorganic ammonium ions, NH(4)(+), are efficient catalysts for reactions of carbonyl compounds, including glyoxal, in the liquid phase. To determine whether ammonium-catalyzed reactions can contribute to depletion of glyoxal in the atmosphere, the reactivity of this compound in aqueous solutions containing ammonium salts (ammonium sulfate, chloride, fluoride, and phosphate) at 298 K has been studied. The products identified by LC-HRMS and UV absorption revealed a mechanism involving two distinct pathways: a Bronsted acid pathway and an iminium pathway. The kinetics of the iminium pathway was studied by monitoring formation of a specific product. This pathway was second order in glyoxal in most of the solutions studied and should therefore be second order in most ammonium-containing aerosols in the atmosphere. The corresponding rate constant, k(II) (M(-1) s(-1)), increased strongly with ammonium ion activity, a(NH(4)(+)), and pH: k(II) (M(-1) s(-1)) = (2 +/- 1) x 10(-10) exp((1.5 +/- 0.8)aNH(4)(+)) exp((2.5 +/- 0.2)pH). This iminium pathway is a lower limit for the ammonium-catalyzed consumption of glyoxal, but the contribution of the acid pathway is expected to be small in tropospheric aerosols. With these results the reactive uptake of glyoxal on ammonium-containing aerosols was estimated and shown to be a possible explanation for depletion of this compound in Mexico City.

A parallel reaction-transport model applied to cement hydration and microstructure development

NASA Astrophysics Data System (ADS)

Bullard, Jeffrey W.; Enjolras, Edith; George, William L.; Satterfield, Steven G.; Terrill, Judith E.

2010-03-01

A recently described stochastic reaction-transport model on three-dimensional lattices is parallelized and is used to simulate the time-dependent structural and chemical evolution in multicomponent reactive systems. The model, called HydratiCA, uses probabilistic rules to simulate the kinetics of diffusion, homogeneous reactions and heterogeneous phenomena such as solid nucleation, growth and dissolution in complex three-dimensional systems. The algorithms require information only from each lattice site and its immediate neighbors, and this localization enables the parallelized model to exhibit near-linear scaling up to several hundred processors. Although applicable to a wide range of material systems, including sedimentary rock beds, reacting colloids and biochemical systems, validation is performed here on two minerals that are commonly found in Portland cement paste, calcium hydroxide and ettringite, by comparing their simulated dissolution or precipitation rates far from equilibrium to standard rate equations, and also by comparing simulated equilibrium states to thermodynamic calculations, as a function of temperature and pH. Finally, we demonstrate how HydratiCA can be used to investigate microstructure characteristics, such as spatial correlations between different condensed phases, in more complex microstructures.

BiKEGG: a COBRA toolbox extension for bridging the BiGG and KEGG databases.

PubMed

Jamialahmadi, Oveis; Motamedian, Ehsan; Hashemi-Najafabadi, Sameereh

2016-10-18

Development of an interface tool between the Biochemical, Genetic and Genomic (BiGG) and KEGG databases is necessary for simultaneous access to the features of both databases. For this purpose, we present the BiKEGG toolbox, an open source COBRA toolbox extension providing a set of functions to infer the reaction correspondences between the KEGG reaction identifiers and those in the BiGG knowledgebase using a combination of manual verification and computational methods. Inferred reaction correspondences using this approach are supported by evidence from the literature, which provides a higher number of reconciled reactions between these two databases compared to the MetaNetX and MetRxn databases. This set of equivalent reactions is then used to automatically superimpose the predicted fluxes using COBRA methods on classical KEGG pathway maps or to create a customized metabolic map based on the KEGG global metabolic pathway, and to find the corresponding reactions in BiGG based on the genome annotation of an organism in the KEGG database. Customized metabolic maps can be created for a set of pathways of interest, for the whole KEGG global map or exclusively for all pathways for which there exists at least one flux carrying reaction. This flexibility in visualization enables BiKEGG to indicate reaction directionality as well as to visualize the reaction fluxes for different static or dynamic conditions in an animated manner. BiKEGG allows the user to export (1) the output visualized metabolic maps to various standard image formats or save them as a video or animated GIF file, and (2) the equivalent reactions for an organism as an Excel spreadsheet.

Theoretical study on the reaction mechanism of CH 4 with CaO

NASA Astrophysics Data System (ADS)

Yang, Hua-Qing; Hu, Chang-Wei; Qin, Song

2006-11-01

The reaction pathways and energetics for the reaction of methane with CaO are discussed on the singlet spin state potential energy surface at the B3LYP/6-311+G(2df,2p) and QCISD/6-311++G(3df,3pd)//B3LYP/6-311+G(2df,2p) levels of theory. The reaction of methane with CaO is proposed to proceed in the following reaction pathways: CaO + CH 4 → CaOCH 4 → [TS] → CaOH + CH 3, CaO + CH 4 → OCaCH 4 → [TS] → HOCaCH 3 → CaOH + CH 3 or [TS] → CaCH 3OH → Ca + CH 3OH, and OCaCH 4 → [TS] → HCaOCH 3 → CaOCH 3 + H or [TS] → CaCH 3OH → Ca + CH 3OH. The gas-phase methane-methanol conversion by CaO is suggested to proceed via two kinds of important reaction intermediates, HOCaCH 3 and HCaOCH 3, and the reaction pathway via the hydroxy intermediate (HOCaCH 3) is energetically more favorable than the other one via the methoxy intermediate (HCaOCH 3). The hydroxy intermediate HOCaCH 3 is predicted to be the energetically most preferred configuration in the reaction of CaO + CH 4. Meanwhile, these three product channels (CaOH + CH 3, CaOCH 3 + H and Ca + CH 3OH) are expected to compete with each other, and the formation of methyl radical is the most preferable pathway energetically. On the other hand, the intermediates HCaOCH 3 and HOCaCH 3 are predicted to be the energetically preferred configuration in the reaction of Ca + CH 3OH, which is precisely the reverse reaction of methane hydroxylation.

Audio-visual integration through the parallel visual pathways.

PubMed

Kaposvári, Péter; Csete, Gergő; Bognár, Anna; Csibri, Péter; Tóth, Eszter; Szabó, Nikoletta; Vécsei, László; Sáry, Gyula; Tamás Kincses, Zsigmond

2015-10-22

Audio-visual integration has been shown to be present in a wide range of different conditions, some of which are processed through the dorsal, and others through the ventral visual pathway. Whereas neuroimaging studies have revealed integration-related activity in the brain, there has been no imaging study of the possible role of segregated visual streams in audio-visual integration. We set out to determine how the different visual pathways participate in this communication. We investigated how audio-visual integration can be supported through the dorsal and ventral visual pathways during the double flash illusion. Low-contrast and chromatic isoluminant stimuli were used to drive preferably the dorsal and ventral pathways, respectively. In order to identify the anatomical substrates of the audio-visual interaction in the two conditions, the psychophysical results were correlated with the white matter integrity as measured by diffusion tensor imaging.The psychophysiological data revealed a robust double flash illusion in both conditions. A correlation between the psychophysical results and local fractional anisotropy was found in the occipito-parietal white matter in the low-contrast condition, while a similar correlation was found in the infero-temporal white matter in the chromatic isoluminant condition. Our results indicate that both of the parallel visual pathways may play a role in the audio-visual interaction. Copyright © 2015. Published by Elsevier B.V.

Anisotropic transverse mixing and its effect on reaction rates in multi-scale, 3D heterogeneous porous media

NASA Astrophysics Data System (ADS)

Engdahl, N. B.

2016-12-01

Mixing rates in porous media have been a heavily research topic in recent years covering analytic, random, and structured fields. However, there are some persistent assumptions and common features to these models that raise some questions about the generality of the results. One of these commonalities is the orientation of the flow field with respect to the heterogeneity structure, which are almost always defined to be parallel each other if there is an elongated axis of permeability correlation. Given the vastly different tortuosities for flow parallel to bedding and flow transverse to bedding, this assumption of parallel orientation may have significant effects on reaction rates when natural flows deviate from this assumed setting. This study investigates the role of orientation on mixing and reaction rates in multi-scale, 3D heterogeneous porous media with varying degrees of anisotropy in the correlation structure. Ten realizations of a small flow field, with three anisotropy levels, were simulated for flow parallel and transverse to bedding. Transport was simulated in each model with an advective-diffusive random walk and reactions were simulated using the chemical Langevin equation. The reaction system is a vertically segregated, transverse mixing problem between two mobile reactants. The results show that different transport behaviors and reaction rates are obtained by simply rotating the direction of flow relative to bedding, even when the net flux in both directions is the same. This kind of behavior was observed for three different weightings of the initial condition: 1) uniform, 2) flux-based, and 3) travel time based. The different schemes resulted in 20-50% more mass formation in the transverse direction than the longitudinal. The greatest variability in mass was observed for the flux weights and these were proportionate to the level of anisotropy. The implications of this study are that flux or travel time weights do not provide any guarantee of a fair comparison in this kind of a mixing scenario and that the role of directional tendencies on reaction rates can be significant. Further, it may be necessary to include anisotropy in future upscaled models to create robust methods that give representative reaction rates for any flow direction relative to geologic bedding.

How Changes in White Matter Might Underlie Improved Reaction Time Due to Practice1

PubMed Central

Voelker, Pascale; Piscopo, Denise; Weible, Aldis; Lynch, Gary; Rothbart, Mary K.; Posner, Michael I.; Niell, Cristopher M.

2017-01-01

Why does training on a task reduce the reaction time for performing it? New research points to changes in white matter pathways as one likely mechanism. These pathways connect remote brain areas involved in performing the task. Genetic variations may be involved in individual differences in the extent of this improvement. If white matter change is involved in improved reaction time with training, it may point the way toward understanding where and how generalization occurs. We examine the hypothesis that brain pathways shared by different tasks may result in improved performance of cognitive tasks remote from the training. PMID:27064751

Pathway collages: personalized multi-pathway diagrams.

PubMed

Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

2016-12-13

Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

Alpha-tryptophan synthase of Isatis tinctoria: gene cloning and expression.

PubMed

Salvini, M; Boccardi, T M; Sani, E; Bernardi, R; Tozzi, S; Pugliesi, C; Durante, M

2008-07-01

Indole producing reaction is a crux in the regulation of metabolite flow through the pathways and the coordination of primary and secondary product biosynthesis in plants. Indole is yielded transiently from indole-3-glycerol phosphate and immediately condensed with serine to give tryptophan, by the enzyme tryptophan synthase (TS). There is evidence that plant TS, like the bacterial complex, functions as an alpha beta heteromer. In few species, e.g. maize, are known enzymes, related with the TS alpha-subunit (TSA), able to catalyse reaction producing indole, which is free to enter the secondary metabolite pathways. In this contest, we searched for TSA and TSA related genes in Isatis tinctoria, a species producing the natural blue dye indigo. The It-TSA cDNA and the full-length exons/introns genomic region were isolated. The phylogenetic analysis indicates that It-TSA is more closely related to Arabidopsis thaliana At-T14E10.210 TSA (95.7% identity at the amino acid level) with respect to A. thaliana At-T10P11.11 TSA1-like (63%), Zea mays indole-3-glycerol phosphate lyase (54%), Z. mays TSA (53%), and Z. mays indole synthase (50%). The It-TSA cDNA was also able to complement an Escherichia coli trpA mutant. To examine the involvement of It-TSA in the biosynthesis of secondary metabolism compounds, It-TSA expression was tested in seedling grown under different light conditions. Semi-quantitative RT-PCR showed an increase in the steady-state level of It-TSA mRNA, paralleled by an increase of indigo and its precursor isatan B. Our results appear to indicate an involvement for It-TSA in indigo precursor synthesis and/or tryptophan biosynthesis.

Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum.

PubMed

Kitamura, Takuya; Seki, Naoya; Kihara, Akio

2017-03-28

Although normal fatty acids (FAs) are degraded via β-oxidation, unusual FAs such as 2-hydroxy (2-OH) FAs and 3-methyl-branched FAs are degraded via α-oxidation. Phytosphingosine (PHS) is one of the long-chain bases (the sphingolipid components) and exists in specific tissues, including the epidermis and small intestine in mammals. In the degradation pathway, PHS is converted to 2-OH palmitic acid and then to pentadecanoic acid (C15:0-COOH) via FA α-oxidation. However, the detailed reactions and genes involved in the α-oxidation reactions of the PHS degradation pathway have yet to be determined. In the present study, we reveal the entire PHS degradation pathway: PHS is converted to C15:0-COOH via six reactions [phosphorylation, cleavage, oxidation, CoA addition, cleavage (C1 removal), and oxidation], in which the last three reactions correspond to the α-oxidation. The aldehyde dehydrogenase ALDH3A2 catalyzes both the first and second oxidation reactions (fatty aldehydes to FAs). In Aldh3a2 -deficient cells, the unmetabolized fatty aldehydes are reduced to fatty alcohols and are incorporated into ether-linked glycerolipids. We also identify HACL2 (2-hydroxyacyl-CoA lyase 2) [previous name, ILVBL; ilvB (bacterial acetolactate synthase)-like] as the major 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the FA α-oxidation of the PHS degradation pathway. HACL2 is localized in the endoplasmic reticulum. Thus, in addition to the already-known FA α-oxidation in the peroxisomes, we have revealed the existence of FA α-oxidation in the endoplasmic reticulum in mammals.

Positive and negative gustatory inputs affect Drosophila lifespan partly in parallel to dFOXO signaling

PubMed Central

Ostojic, Ivan; Boll, Werner; Waterson, Michael J.; Chan, Tammy; Chandra, Rashmi; Pletcher, Scott D.; Alcedo, Joy

2014-01-01

In Caenorhabditis elegans, a subset of gustatory neurons, as well as olfactory neurons, shortens lifespan, whereas a different subset of gustatory neurons lengthens it. Recently, the lifespan-shortening effect of olfactory neurons has been reported to be conserved in Drosophila. Here we show that the Drosophila gustatory system also affects lifespan in a bidirectional manner. We find that taste inputs shorten lifespan through inhibition of the insulin pathway effector dFOXO, whereas other taste inputs lengthen lifespan in parallel to this pathway. We also note that the gustatory influence on lifespan does not necessarily depend on food intake levels. Finally, we identify the nature of some of the taste inputs that could shorten versus lengthen lifespan. Together our data suggest that different gustatory cues can modulate the activities of distinct signaling pathways, including different insulin-like peptides, to promote physiological changes that ultimately affect lifespan. PMID:24847072

Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila

PubMed Central

Hampel, Stefanie; McKellar, Claire E

2017-01-01

A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al., 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response. PMID:28887878

Geochemical roots of autotrophic carbon fixation: hydrothermal experiments in the system citric acid, H 2O-(±FeS)-(±NiS)

NASA Astrophysics Data System (ADS)

Cody, G. D.; Boctor, N. Z.; Hazen, R. M.; Brandes, J. A.; Morowitz, Harold J.; Yoder, H. S.

2001-10-01

Recent theories have proposed that life arose from primitive hydrothermal environments employing chemical reactions analogous to the reductive citrate cycle (RCC) as the primary pathway for carbon fixation. This chemistry is presumed to have developed as a natural consequence of the intrinsic geochemistry of the young, prebiotic, Earth. There has been no experimental evidence, however, demonstrating that there exists a natural pathway into such a cycle. Toward this end, the results of hydrothermal experiments involving citric acid are used as a method of deducing such a pathway. Homocatalytic reactions observed in the citric acid-H2O experiments encompass many of the reactions found in modern metabolic systems, i.e., hydration-dehydration, retro-Aldol, decarboxylation, hydrogenation, and isomerization reactions. Three principal decomposition pathways operate to degrade citric acid under thermal and aquathermal conditions. It is concluded that the acid catalyzed βγ decarboxylation pathway, leading ultimately to propene and CO2, may provide the most promise for reaction network reversal under natural hydrothermal conditions. Increased pressure is shown to accelerate the principal decarboxylation reactions under strictly hydrothermal conditions. The effect of forcing the pH via the addition of NaOH reveals that the βγ decarboxylation pathway operates even up to intermediate pH levels. The potential for network reversal (the conversion of propene and CO2 up to a tricarboxylic acid) is demonstrated via the Koch (hydrocarboxylation) reaction promoted heterocatalytically with NiS in the presence of a source of CO. Specifically, an olefin (1-nonene) is converted to a monocarboxylic acid; methacrylic acid is converted to the dicarboxylic acid, methylsuccinic acid; and the dicarboxylic acid, itaconic acid, is converted into the tricarboxylic acid, hydroaconitic acid. A number of interesting sulfur-containing products are also formed that may provide for additional reaction. The intrinsic catalytic qualities of FeS and NiS are also explored in the absence of CO. It was shown that the addition of NiS has a minimal effect in the product distribution, whereas the addition of FeS leads to the formation of hydrogenated and sulfur-containing products (thioethers). These results point to a simple hydrothermal redox pathway for citric acid synthesis that may have provided a geochemical ignition point for the reductive citrate cycle.

Explorations into Chemical Reactions and Biochemical Pathways.

PubMed

Gasteiger, Johann

2016-12-01

A brief overview of the work in the research group of the present author on extracting knowledge from chemical reaction data is presented. Methods have been developed to calculate physicochemical effects at the reaction site. It is shown that these physicochemical effects can quite favourably be used to derive equations for the calculation of data on gas phase reactions and on reactions in solution such as aqueous acidity of alcohols or carboxylic acids or the hydrolysis of amides. Furthermore, it is shown that these physicochemical effects are quite effective for assigning reactions into reaction classes that correspond to chemical knowledge. Biochemical reactions constitute a particularly interesting and challenging task for increasing our understanding of living species. The BioPath.Database is a rich source of information on biochemical reactions and has been used for a variety of applications of chemical, biological, or medicinal interests. Thus, it was shown that biochemical reactions can be assigned by the physicochemical effects into classes that correspond to the classification of enzymes by the EC numbers. Furthermore, 3D models of reaction intermediates can be used for searching for novel enzyme inhibitors. It was shown in a combined application of chemoinformatics and bioinformatics that essential pathways of diseases can be uncovered. Furthermore, a study showed that bacterial flavor-forming pathways can be discovered. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theoretical investigation on the dimerization of the deprotonated aquo ion of Al(III) in water.

PubMed

Qian, Zhaosheng; Feng, Hui; Zhang, Zhenjiang; Yang, Wenjing; Jin, Jing; Miao, Qiang; He, Lina; Bi, Shuping

2009-01-21

Reaction pathways, solvent effects and energy barriers have been investigated for the dimerization of the deprotonated aquo ion of Al(III) in aqueous solution by performing supramolecule density functional theory calculations. Two competing reaction pathways were investigated, sharing a common first step and third step, i.e. the formation of the aggregate II of two aluminium monomers and the doubly bridged dimer. One pathway involves a nucleophilic attack to undercoordinated metal center in the first step and then the loss of a coordinated water molecule. Another pathway involves a water exchange reaction in the first step and then the formation of the hydroxo bridge. The calculated results indicate that both pathways I and II are possible in aqueous solution. The direct participation of the solvent water molecule facilitates the dimerization, but the extremely large solvent shifts of the energy barriers for each reaction are attributed mainly to the bulk effect. The computed activation energies for the water exchange reactions are in good agreement with the available experimental values, namely, the calculated value 37.5 kJ mol(-1) compared to the experimental value 36.4 (+/-5) kJ mol(-1). In agreement with experimental observations in aqueous solution, the calculated results favor the transformation of singly-bridged to doubly-bridged aluminium ion, which is helpful to understand the complicated hydrolytic polymerizaiton of Al(III).

Oncogenic KRAS and BRAF Drive Metabolic Reprogramming in Colorectal Cancer *

PubMed Central

Hutton, Josiah E.; Wang, Xiaojing; Zimmerman, Lisa J.; Slebos, Robbert J. C.; Trenary, Irina A.; Young, Jamey D.; Li, Ming; Liebler, Daniel C.

2016-01-01

Metabolic reprogramming, in which altered utilization of glucose and glutamine supports rapid growth, is a hallmark of most cancers. Mutations in the oncogenes KRAS and BRAF drive metabolic reprogramming through enhanced glucose uptake, but the broader impact of these mutations on pathways of carbon metabolism is unknown. Global shotgun proteomic analysis of isogenic DLD-1 and RKO colon cancer cell lines expressing mutant and wild type KRAS or BRAF, respectively, failed to identify significant differences (at least 2-fold) in metabolic protein abundance. However, a multiplexed parallel reaction monitoring (PRM) strategy targeting 73 metabolic proteins identified significant protein abundance increases of 1.25–twofold in glycolysis, the nonoxidative pentose phosphate pathway, glutamine metabolism, and the phosphoserine biosynthetic pathway in cells with KRAS G13D mutations or BRAF V600E mutations. These alterations corresponded to mutant KRAS and BRAF-dependent increases in glucose uptake and lactate production. Metabolic reprogramming and glucose conversion to lactate in RKO cells were proportional to levels of BRAF V600E protein. In DLD-1 cells, these effects were independent of the ratio of KRAS G13D to KRAS wild type protein. A study of 8 KRAS wild type and 8 KRAS mutant human colon tumors confirmed the association of increased expression of glycolytic and glutamine metabolic proteins with KRAS mutant status. Metabolic reprogramming is driven largely by modest (<2-fold) alterations in protein expression, which are not readily detected by the global profiling methods most commonly employed in proteomic studies. The results indicate the superiority of more precise, multiplexed, pathway-targeted analyses to study functional proteome systems. Data are available through MassIVE Accession MSV000079486 at ftp://MSV000079486@massive.ucsd.edu. PMID:27340238

Identification of the dominant photochemical pathways and mechanistic insights to the ultrafast ligand exchange of Fe(CO) 5 to Fe(CO) 4EtOH

DOE PAGES

Kunnus, K.; Josefsson, I.; Rajkovic, I.; ...

2016-02-09

We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO) 5 in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO) 4 which are observed following a charge transfer photoexcitation of Fe(CO) 5 as reported in our previous study [Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the 1A 1 state of Fe(CO) 4. A sub-picosecond time constant of themore » spin crossover from 1B 2 to 3B 2 is rationalized by the proposed 1B 2 → 1A 1 → 3B 2 mechanism. Ultrafast ligation of the 1B 2 Fe(CO) 4 state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the 3B 2 Fe(CO) 4 ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via 1B 2 → 1A 1 → 1A' Fe(CO) 4EtOH pathway and the time scale of the 1A 1 Fe(CO) 4 state ligation is governed by the solute-solvent collision frequency. In conclusion, our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution.« less

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

PubMed Central

Marcu, Oana; Lera, Matthew P.; Sanchez, Max E.; Levic, Edina; Higgins, Laura A.; Shmygelska, Alena; Fahlen, Thomas F.; Nichol, Helen; Bhattacharya, Sharmila

2011-01-01

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways. PMID:21264297

Capacitively coupled RF diamond-like-carbon reactor

DOEpatents

Devlin, David James; Coates, Don Mayo; Archuleta, Thomas Arthur; Barbero, Robert Steven

2000-01-01

A process of coating a non-conductive fiber with diamond-like carbon, including passing a non-conductive fiber between a pair of parallel metal grids within a reaction chamber, introducing a hydrocarbon gas into the reaction chamber, forming a plasma within the reaction chamber for a sufficient period of time whereby diamond-like carbon is formed upon the non-conductive fiber, is provided together with a reactor chamber for deposition of diamond-like carbon upon a non-conductive fiber, including a vacuum chamber, a cathode assembly including a pair of electrically isolated opposingly parallel metal grids spaced apart at a distance of less than about 1 centimeter, an anode, a means of introducing a hydrocarbon gas into said vacuum chamber, and a means of generating a plasma within said vacuum chamber.

Polymerase chain reaction system

DOEpatents

Benett, William J.; Richards, James B.; Stratton, Paul L.; Hadley, Dean R.; Milanovich, Fred P.; Belgrader, Phil; Meyer, Peter L.

2004-03-02

A portable polymerase chain reaction DNA amplification and detection system includes one or more chamber modules. Each module supports a duplex assay of a biological sample. Each module has two parallel interrogation ports with a linear optical system. The system is capable of being handheld.

Probabilistic pathway construction.

PubMed

Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

2011-07-01

Expression of novel synthesis pathways in host organisms amenable to genetic manipulations has emerged as an attractive metabolic engineering strategy to overproduce natural products, biofuels, biopolymers and other commercially useful metabolites. We present a pathway construction algorithm for identifying viable synthesis pathways compatible with balanced cell growth. Rather than exhaustive exploration, we investigate probabilistic selection of reactions to construct the pathways. Three different selection schemes are investigated for the selection of reactions: high metabolite connectivity, low connectivity and uniformly random. For all case studies, which involved a diverse set of target metabolites, the uniformly random selection scheme resulted in the highest average maximum yield. When compared to an exhaustive search enumerating all possible reaction routes, our probabilistic algorithm returned nearly identical distributions of yields, while requiring far less computing time (minutes vs. years). The pathways identified by our algorithm have previously been confirmed in the literature as viable, high-yield synthesis routes. Prospectively, our algorithm could facilitate the design of novel, non-native synthesis routes by efficiently exploring the diversity of biochemical transformations in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

A multi-pathway model for photosynthetic reaction center

NASA Astrophysics Data System (ADS)

Qin, M.; Shen, H. Z.; Yi, X. X.

2016-03-01

Charge separation occurs in a pair of tightly coupled chlorophylls at the heart of photosynthetic reaction centers of both plants and bacteria. Recently it has been shown that quantum coherence can, in principle, enhance the efficiency of a solar cell, working like a quantum heat engine. Here, we propose a biological quantum heat engine (BQHE) motivated by Photosystem II reaction center (PSII RC) to describe the charge separation. Our model mainly considers two charge-separation pathways which is more than that typically considered in the published literature. We explore how these cross-couplings increase the current and power of the charge separation and discuss the effects of multiple pathways in terms of current and power. The robustness of the BQHE against the charge recombination in natural PSII RC and dephasing induced by environments is also explored, and extension from two pathways to multiple pathways is made. These results suggest that noise-induced quantum coherence helps to suppress the influence of acceptor-to-donor charge recombination, and besides, nature-mimicking architectures with engineered multiple pathways for charge separations might be better for artificial solar energy devices considering the influence of environments.

FORMATION OF POLYCYCLIC AROMATIC HYDROCARBONS AND THEIR GROWTH TO SOOT -A REVIEW OF CHEMICAL REACTION PATHWAYS. (R824970)

EPA Science Inventory

The generation by combustion processes of airborne species of current health concern such as polycyclic aromatic hydrocarbons (PAH) and soot particles necessitates a detailed understanding of chemical reaction pathways responsible for their formation. The present review discus...

The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin.

PubMed

Chon, Hye Sook; Marchion, Douglas C; Xiong, Yin; Chen, Ning; Bicaku, Elona; Stickles, Xiaomang Ba; Bou Zgheib, Nadim; Judson, Patricia L; Hakam, Ardeshir; Gonzalez-Bosquet, Jesus; Wenham, Robert M; Apte, Sachin M; Lancaster, Johnathan M

2012-01-01

To identify pathways that influence endometrial cancer (EC) cell sensitivity to cisplatin and to characterize the BCL2 antagonist of cell death (BAD) pathway as a therapeutic target to increase cisplatin sensitivity. Eight EC cell lines (Ishikawa, MFE296, RL 95-2, AN3CA, KLE, MFE280, MFE319, HEC-1-A) were subjected to Affymetrix Human U133A GeneChip expression analysis of approximately 22,000 probe sets. In parallel, endometrial cell line sensitivity to cisplatin was quantified by MTS assay, and IC(50) values were calculated. Pearson's correlation test was used to identify genes associated with response to cisplatin. Genes associated with cisplatin responsiveness were subjected to pathway analysis. The BAD pathway was identified and subjected to targeted modulation, and the effect on cisplatin sensitivity was evaluated. Pearson's correlation analysis identified 1443 genes associated with cisplatin resistance (P<0.05), which included representation of the BAD-apoptosis pathway. Small interfering RNA (siRNA) knockdown of BAD pathway protein phosphatase PP2C expression was associated with increased phosphorylated BAD (serine-155) levels and a parallel increase in cisplatin resistance in Ishikawa (P=0.004) and HEC-1-A (P=0.02) cell lines. In contrast, siRNA knockdown of protein kinase A expression increased cisplatin sensitivity in the Ishikawa (P=0.02) cell line. The BAD pathway influences EC cell sensitivity to cisplatin, likely via modulation of the phosphorylation status of the BAD protein. The BAD pathway represents an appealing therapeutic target to increase EC cell sensitivity to cisplatin. Copyright © 2011 Elsevier Inc. All rights reserved.

Sum over Histories Representation for Kinetic Sensitivity Analysis: How Chemical Pathways Change When Reaction Rate Coefficients Are Varied

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Shirong; Davis, Michael J.; Skodje, Rex T.

2015-11-12

The sensitivity of kinetic observables is analyzed using a newly developed sum over histories representation of chemical kinetics. In the sum over histories representation, the concentrations of the chemical species are decomposed into the sum of probabilities for chemical pathways that follow molecules from reactants to products or intermediates. Unlike static flux methods for reaction path analysis, the sum over histories approach includes the explicit time dependence of the pathway probabilities. Using the sum over histories representation, the sensitivity of an observable with respect to a kinetic parameter such as a rate coefficient is then analyzed in terms of howmore » that parameter affects the chemical pathway probabilities. The method is illustrated for species concentration target functions in H-2 combustion where the rate coefficients are allowed to vary over their associated uncertainty ranges. It is found that large sensitivities are often associated with rate limiting steps along important chemical pathways or by reactions that control the branching of reactive flux« less

Electron-beam generated porous dextran gels: experimental and quantum chemical studies.

PubMed

Naumov, Sergej; Knolle, Wolfgang; Becher, Jana; Schnabelrauch, Matthias; Reichelt, Senta

2014-06-01

The aim of this work was to investigate the reaction mechanism of electron-beam generated macroporous dextran cryogels by quantum chemical calculation and electron paramagnetic resonance measurements. Electron-beam radiation was used to initiate the cross-linking reaction of methacrylated dextran in semifrozen aqueous solutions. The pore morphology of the resulting cryogels was visualized by scanning electron microscopy. Quantum chemical calculations and electron paramagnetic resonance studies provided information on the most probable reaction pathway and the chain growth radicals. The most probable reaction pathway was a ring opening reaction and the addition of a C-atom to the double-bond of the methacrylated dextran molecule. First detailed quantum chemical calculation on the reaction mechanism of electron-beam initiated cross-linking reaction of methacrylated dextran are presented.

Widening and Increasing Post-16 Mathematics Participation: Pathways, Pedagogies and Politics

ERIC Educational Resources Information Center

Noyes, Andrew; Wake, Geoff; Drake, Pat

2011-01-01

This paper explores the potential impact of a national pilot initiative in England aimed at increasing and widening participation in advanced mathematical study through the creation of a new qualification for 16- to 18-year-olds. This proposed qualification pathway--"Use of Mathematics"--sits in parallel with long-established,…

Parvocellular Pathway Impairment in Autism Spectrum Disorder: Evidence from Visual Evoked Potentials

ERIC Educational Resources Information Center

Fujita, Takako; Yamasaki, Takao; Kamio, Yoko; Hirose, Shinichi; Tobimatsu, Shozo

2011-01-01

In humans, visual information is processed via parallel channels: the parvocellular (P) pathway analyzes color and form information, whereas the magnocellular (M) stream plays an important role in motion analysis. Individuals with autism spectrum disorder (ASD) often show superior performance in processing fine detail, but impaired performance in…

Parallel Development of Risk Behaviors in Adolescence: Potential Pathways to Co-Occurrence

ERIC Educational Resources Information Center

Huang, David Y. C.; Lanza, H. Isabella; Murphy, Debra A.; Hser, Yih-Ing

2012-01-01

This study used data from 5,382 adolescents from the 1997 United States (US) National Longitudinal Survey of Youth (NLSY97) to investigate developmental pathways of alcohol use, marijuana use, sexual risk behaviors, and delinquency across ages 14 to 20; examine interrelationships among these risk behaviors across adolescence; and evaluate…

The Ca2+/H+ antiporter TMEM165 expression, localization in the developing, lactating and involuting mammary gland parallels the secretory pathway Ca2+ATPase (SPCA1)

USDA-ARS?s Scientific Manuscript database

Plasma membrane Ca2+-ATPase 2 (PMCA2) knockout mice showed that ~ 60 % of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca2+-ATPase’s 1 and/or 2 (SP...

Roles of different initial Maillard intermediates and pathways in meat flavor formation for cysteine-xylose-glycine model reaction systems.

PubMed

Hou, Li; Xie, Jianchun; Zhao, Jian; Zhao, Mengyao; Fan, Mengdie; Xiao, Qunfei; Liang, Jingjing; Chen, Feng

2017-10-01

To explore initial Maillard reaction pathways and mechanisms for maximal formation of meaty flavors in heated cysteine-xylose-glycine systems, model reactions with synthesized initial Maillard intermediates, Gly-Amadori, TTCA (2-threityl-thiazolidine-4-carboxylic acids) and Cys-Amadori, were investigated. Relative relativities were characterized by spectrophotometrically monitoring the development of colorless degradation intermediates and browning reaction products. Aroma compounds formed were determined by solid-phase microextraction combined with GC-MS and GC-olfactometry. Gly-Amadori showed the fastest reaction followed by Cys-Amadori then TTCA. Free glycine accelerated reaction of TTCA, whereas cysteine inhibited that of Gly-Amadori due to association forming relatively stable thiazolidines. Cys-Amadori/Gly had the highest reactivity in development of both meaty flavors and brown products. TTCA/Gly favored yielding meaty flavors, whereas Gly-Amadori/Cys favored generation of brown products. Conclusively, initial formation of TTCA and pathway involving TTCA with glycine were more applicable to efficiently produce processed-meat flavorings in a cysteine-xylose-glycine system. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Insights into Reaction Mechanisms of Ethanol Steam Reforming on Co-ZrO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Junming; Karim, Ayman M.; Mei, Donghai

2015-01-01

The reaction pathway of ethanol steam reforming on Co-ZrO2 has been identified and the active sites associated with each step are proposed. Ethanol is converted to acetaldehyde and then to acetone, followed by acetone steam reforming. More than 90% carbon was found to follow this reaction pathway. N2-Sorption, X-ray Diffraction (XRD), Temperature Programmed Reduction (TPR), in situ X-ray Photoelectron Spectroscopy (XPS), Transmission Electron Microscopy, as well as theoretical Density Functional Theory (DFT) calculations have been employed to identify the structure and functionality of the catalysts, which was further used to correlate their performance in ESR. It was found that metallicmore » cobalt is mainly responsible for the acetone steam reforming reactions; while, CoO and basic sites on the support play a key role in converting ethanol to acetone via dehydrogenation and condensation/ketonization reaction pathways. The current work provides fundamental understanding of the ethanol steam reforming reaction mechanisms on Co-ZrO2 catalysts and sheds light on the rational design of selective and durable ethanol steam reforming catalysts.« less

Exhaustive analysis of the modular structure of the spliceosomal assembly network: a petri net approach.

PubMed

Bortfeldt, Ralf H; Schuster, Stefan; Koch, Ina

2011-01-01

Spliceosomes are macro-complexes involving hundreds of proteins with many functional interactions. Spliceosome assembly belongs to the key processes that enable splicing of mRNA and modulate alternative splicing. A detailed list of factors involved in spliceosomal reactions has been assorted over the past decade, but, their functional interplay is often unknown and most of the present biological models cover only parts of the complete assembly process. It is a challenging task to build a computational model that integrates dispersed knowledge and combines a multitude of reaction schemes proposed earlier. Because for most reactions involved in spliceosome assembly kinetic parameters are not available, we propose a discrete modeling using Petri nets, through which we are enabled to get insights into the system's behavior via computation of structural and dynamic properties. In this paper, we compile and examine reactions from experimental reports that contribute to a functional spliceosome. All these reactions form a network, which describes the inventory and conditions necessary to perform the splicing process. The analysis is mainly based on system invariants. Transition invariants (T-invariants) can be interpreted as signaling routes through the network. Due to the huge number of T-invariants that arise with increasing network size and complexity, maximal common transition sets (MCTS) and T-clusters were used for further analysis. Additionally, we introduce a false color map representation, which allows a quick survey of network modules and the visual detection of single reactions or reaction sequences, which participate in more than one signaling route. We designed a structured model of spliceosome assembly, which combines the demands on a platform that i) can display involved factors and concurrent processes, ii) offers the possibility to run computational methods for knowledge extraction, and iii) is successively extendable as new insights into spliceosome function are reported by experimental reports. The network consists of 161 transitions (reactions) and 140 places (reactants). All reactions are part of at least one of the 71 T-invariants. These T-invariants define pathways, which are in good agreement with the current knowledge and known hypotheses on reaction sequences during spliceosome assembly, hence contributing to a functional spliceosome. We demonstrate that present knowledge, in particular of the initial part of the assembly process, describes parallelism and interaction of signaling routes, which indicate functional redundancy and reflect the dependency of spliceosome assembly initiation on different cellular conditions. The complexity of the network is further increased by two switches, which introduce alternative routes during A-complex formation in early spliceosome assembly and upon transition from the B-complex to the C-complex. By compiling known reactions into a complete network, the combinatorial nature of invariant computation leads to pathways that have previously not been described as connected routes, although their constituents were known. T-clusters divide the network into modules, which we interpret as building blocks in spliceosome maturation. We conclude that Petri net representations of large biological networks and system invariants, are well-suited as a means for validating the integration of experimental knowledge into a consistent model. Based on this network model, the design of further experiments is facilitated.

Exhaustive analysis of the modular structure of the spliceosomal assembly network: a Petri net approach.

PubMed

Bortfeldt, Ralf H; Schuster, Stefan; Koch, Ina

2010-01-01

Spliceosomes are macro-complexes involving hundreds of proteins with many functional interactions. Spliceosome assembly belongs to the key processes that enable splicing of mRNA and modulate alternative splicing. A detailed list of factors involved in spliceosomal reactions has been assorted over the past decade, but, their functional interplay is often unknown and most of the present biological models cover only parts of the complete assembly process. It is a challenging task to build a computational model that integrates dispersed knowledge and combines a multitude of reaction schemes proposed earlier.Because for most reactions involved in spliceosome assembly kinetic parameters are not available, we propose a discrete modeling using Petri nets, through which we are enabled to get insights into the system's behavior via computation of structural and dynamic properties. In this paper, we compile and examine reactions from experimental reports that contribute to a functional spliceosome. All these reactions form a network, which describes the inventory and conditions necessary to perform the splicing process. The analysis is mainly based on system invariants. Transition invariants (T-invariants) can be interpreted as signaling routes through the network. Due to the huge number of T-invariants that arise with increasing network size and complexity, maximal common transition sets (MCTS) and T-clusters were used for further analysis. Additionally, we introduce a false color map representation, which allows a quick survey of network modules and the visual detection of single reactions or reaction sequences, which participate in more than one signaling route. We designed a structured model of spliceosome assembly, which combines the demands on a platform that i) can display involved factors and concurrent processes, ii) offers the possibility to run computational methods for knowledge extraction, and iii) is successively extendable as new insights into spliceosome function are reported by experimental reports. The network consists of 161 transitions (reactions) and 140 places (reactants). All reactions are part of at least one of the 71 T-invariants. These T-invariants define pathways, which are in good agreement with the current knowledge and known hypotheses on reaction sequences during spliceosome assembly, hence contributing to a functional spliceosome. We demonstrate that present knowledge, in particular of the initial part of the assembly process, describes parallelism and interaction of signaling routes, which indicate functional redundancy and reflect the dependency of spliceosome assembly initiation on different cellular conditions. The complexity of the network is further increased by two switches, which introduce alternative routes during A-complex formation in early spliceosome assembly and upon transition from the B-complex to the C-complex. By compiling known reactions into a complete network, the combinatorial nature of invariant computation leads to pathways that have previously not been described as connected routes, although their constituents were known. T-clusters divide the network into modules, which we interpret as building blocks in spliceosome maturation. We conclude that Petri net representations of large biological networks and system invariants, are well-suited as a means for validating the integration of experimental knowledge into a consistent model. Based on this network model, the design of further experiments is facilitated.

Parallel processing of general and specific threat during early stages of perception

PubMed Central

2016-01-01

Differential processing of threat can consummate as early as 100 ms post-stimulus. Moreover, early perception not only differentiates threat from non-threat stimuli but also distinguishes among discrete threat subtypes (e.g. fear, disgust and anger). Combining spatial-frequency-filtered images of fear, disgust and neutral scenes with high-density event-related potentials and intracranial source estimation, we investigated the neural underpinnings of general and specific threat processing in early stages of perception. Conveyed in low spatial frequencies, fear and disgust images evoked convergent visual responses with similarly enhanced N1 potentials and dorsal visual (middle temporal gyrus) cortical activity (relative to neutral cues; peaking at 156 ms). Nevertheless, conveyed in high spatial frequencies, fear and disgust elicited divergent visual responses, with fear enhancing and disgust suppressing P1 potentials and ventral visual (occipital fusiform) cortical activity (peaking at 121 ms). Therefore, general and specific threat processing operates in parallel in early perception, with the ventral visual pathway engaged in specific processing of discrete threats and the dorsal visual pathway in general threat processing. Furthermore, selectively tuned to distinctive spatial-frequency channels and visual pathways, these parallel processes underpin dimensional and categorical threat characterization, promoting efficient threat response. These findings thus lend support to hybrid models of emotion. PMID:26412811

Reaction Force of Micro-scale Liquid Droplets Constrained Between Parallel Plates through CFD

NASA Astrophysics Data System (ADS)

Free, Robert; Hekiri, Haider; Hawa, Takumi

2012-02-01

Micro-scale liquid droplets responding to depression between parallel plates are investigated analytically and numerically. The functional dependence of the reaction force accrued in such droplets on droplet size, surface tension, depression amount, and contact angle is explored. For both the 2D and 3D case, an analytical model is developed based on first principles. Computational fluid dynamics is then utilized to evaluate the validity of these models. The reaction force is highly nonlinear, initially increasing very slowly with increasing depression of the droplet, but eventually moving asymptotically to infinity. The force scales linearly with both the droplet free radius and surface tension of the liquid, but has a much more complicated dependence on the contact angle and depression. Explicit expressions for the reaction force have been determined, showing these dependencies. The 3D model has been largely supported by the CFD results. It very accurately predicts the reaction force on the upper plate as the droplet is crushed, accounting for the effect of contact angle, surface tension, and droplet size.

Polycyclic aromatic hydrocarbon formation during the gasification of sewage sludge in sub- and supercritical water: Effect of reaction parameters and reaction pathways.

PubMed

Gong, Miao; Wang, Yulan; Fan, Yujie; Zhu, Wei; Zhang, Huiwen; Su, Ying

2018-02-01

The formation of polycyclic aromatic hydrocarbon is a widespread issue during the supercritical water gasification of sewage sludge, which directly reduces the gasification efficiency and restricts the technology practical application. The changes of the concentrations and forms as well as the synthesis rate of polycyclic aromatic hydrocarbons in the residues from supercritical water gasification of dewatered sewage sludge were investigated to understand influence factors and the reaction pathways. Results showed that the increase of reaction temperature during the heating period favours directly concentration of polycyclic aromatic hydrocarbon (especially higher-molecular-weight), especially when it raise above 300 °C. Lower heating and cooling rate essentially extend the total reaction time. Higher polycyclic aromatic hydrocarbon concentration and higher number of rings were generally promoted by lower heating and cooling rate, longer reaction time and higher reaction temperature. The lower-molecular-weight polycyclic aromatic hydrocarbons can be directly generated through the decomposition of aromatic-containing compounds in sewage sludge, as well as 3-ring and 4-ring polycyclic aromatic hydrocarbons can be formed by aromatization of steroids. Possible mechanisms of reaction pathways of supercritical water gasification of sewage sludge were also proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanistic insights into iron catalyzed dehydrogenation of formic acid: β-hydride elimination vs. direct hydride transfer.

PubMed

Yang, Xinzheng

2013-09-07

Density functional theory calculations reveal a complete reaction mechanism with detailed energy profiles and transition state structures for the dehydrogenation of formic acid catalyzed by an iron complex, [P(CH2CH2PPh2)3FeH](+). In the cationic reaction pathway, a β-hydride elimination process is confirmed to be the rate-determining step in this catalytic reaction. A potential reaction pathway starting with a direct hydride transfer from HCOO(-) to Fe is found to be possible, but slightly less favorable than the catalytic cycle with a β-hydride elimination step.

Lewis Acid Induced Toggle from Ir(II) to Ir(IV) Pathways in Photocatalytic Reactions: Synthesis of Thiomorpholines and Thiazepanes from Aldehydes and SLAP Reagents

PubMed Central

2016-01-01

Redox neutral photocatalytic transformations often require careful pairing of the substrates and photoredox catalysts in order to achieve a catalytic cycle. This can limit the range of viable transformations, as we recently observed in attempting to extend the scope of the photocatalytic synthesis of N-heterocycles using silicon amine protocol (SLAP) reagents to include starting materials that require higher oxidation potentials. We now report that the inclusion of Lewis acids in photocatalytic reactions of organosilanes allows access to a distinct reaction pathway featuring an Ir(III)*/Ir(IV) couple instead of the previously employed Ir(III)*/Ir(II) pathway, enabling the transformation of aromatic and aliphatic aldehydes to thiomorpholines and thiazepanes. The role of the Lewis acid in accepting an electron—either directly or via coordination to an imine—can be extended to other classes of photocatalysts and transformations, including oxidative cyclizations. The combination of light induced reactions and Lewis acids therefore promises access to new pathways and transformations that are not viable using the photocatalysts alone. PMID:28149955

Kinetic and energy production analysis of pyrolysis of lignocellulosic biomass using a three-parallel Gaussian reaction model.

PubMed

Chen, Tianju; Zhang, Jinzhi; Wu, Jinhu

2016-07-01

The kinetic and energy productions of pyrolysis of a lignocellulosic biomass were investigated using a three-parallel Gaussian distribution method in this work. The pyrolysis experiment of the pine sawdust was performed using a thermogravimetric-mass spectroscopy (TG-MS) analyzer. A three-parallel Gaussian distributed activation energy model (DAEM)-reaction model was used to describe thermal decomposition behaviors of the three components, hemicellulose, cellulose and lignin. The first, second and third pseudocomponents represent the fractions of hemicellulose, cellulose and lignin, respectively. It was found that the model is capable of predicting the pyrolysis behavior of the pine sawdust. The activation energy distribution peaks for the three pseudo-components were centered at 186.8, 197.5 and 203.9kJmol(-1) for the pine sawdust, respectively. The evolution profiles of H2, CH4, CO, and CO2 were well predicted using the three-parallel Gaussian distribution model. In addition, the chemical composition of bio-oil was also obtained by pyrolysis-gas chromatography/mass spectrometry instrument (Py-GC/MS). Copyright © 2016 Elsevier Ltd. All rights reserved.

Pyramidal neurovision architecture for vision machines

NASA Astrophysics Data System (ADS)

Gupta, Madan M.; Knopf, George K.

1993-08-01

The vision system employed by an intelligent robot must be active; active in the sense that it must be capable of selectively acquiring the minimal amount of relevant information for a given task. An efficient active vision system architecture that is based loosely upon the parallel-hierarchical (pyramidal) structure of the biological visual pathway is presented in this paper. Although the computational architecture of the proposed pyramidal neuro-vision system is far less sophisticated than the architecture of the biological visual pathway, it does retain some essential features such as the converging multilayered structure of its biological counterpart. In terms of visual information processing, the neuro-vision system is constructed from a hierarchy of several interactive computational levels, whereupon each level contains one or more nonlinear parallel processors. Computationally efficient vision machines can be developed by utilizing both the parallel and serial information processing techniques within the pyramidal computing architecture. A computer simulation of a pyramidal vision system for active scene surveillance is presented.

Quantifying Risks and Uncertainties Associated with Induced Seismicity due to CO2 Injection into Geologic Formations with Faults

NASA Astrophysics Data System (ADS)

Hou, Z.; Nguyen, B. N.; Bacon, D. H.; White, M. D.; Murray, C. J.

2016-12-01

A multiphase flow and reactive transport simulator named STOMP-CO2-R has been developed and coupled to the ABAQUS® finite element package for geomechanical analysis enabling comprehensive thermo-hydro-geochemical-mechanical (THMC) analyses. The coupled THMC simulator has been applied to analyze faulted CO2 reservoir responses (e.g., stress and strain distributions, pressure buildup, slip tendency factor, pressure margin to fracture) with various complexities in fault and reservoir structures and mineralogy. Depending on the geological and reaction network settings, long-term injection of CO2 can have a significant effect on the elastic stiffness and permeability of formation rocks. In parallel, an uncertainty quantification framework (UQ-CO2), which consists of entropy-based prior uncertainty representation, efficient sampling, geostatistical reservoir modeling, and effective response surface analysis, has been developed for quantifying risks and uncertainties associated with CO2 sequestration. It has been demonstrated for evaluating risks in CO2 leakage through natural pathways and wellbores, and for developing predictive reduced order models. Recently, a parallel STOMP-CO2-R has been developed and the updated STOMP/ABAQUS model has been proven to have a great scalability, which makes it possible to integrate the model with the UQ framework to effectively and efficiently explore multidimensional parameter space (e.g., permeability, elastic modulus, crack orientation, fault friction coefficient) for a more systematic analysis of induced seismicity risks.

Experiment E89-044 of quasi-elastic diffusion 3He(e,e'p) at Jefferson Laboratory: Analyze cross sections of the two body breakup in parallel kinematics; Experience E89-044 de diffusion quasi-elastique 3he(e,e'p) au Jefferson Laboratory : analyse des sections efficaces de desintegration a deux corps en cinematique parallele (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penel-Nottaris, Emilie

2004-07-01

The Jefferson Lab Hall A experiment has measured the 3He(e,e'p) reaction cross sections. The separation of the longitudinal and transverse response functions for the two-body breakup reaction in parallel kinematics allows to study the bound proton electromagnetic properties in the 3He nucleus and the involved nuclear mechanisms beyond impulse approximation. Preliminary cross sections show some disagreement with theoretical predictions for the forward angles kinematics around 0 MeV/c missing momenta, and sensitivity to final state interactions and 3He wave functions for missing momenta of 300 MeV/c.

Accurate reaction-diffusion operator splitting on tetrahedral meshes for parallel stochastic molecular simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hepburn, I.; De Schutter, E., E-mail: erik@oist.jp; Theoretical Neurobiology & Neuroengineering, University of Antwerp, Antwerp 2610

Spatial stochastic molecular simulations in biology are limited by the intense computation required to track molecules in space either in a discrete time or discrete space framework, which has led to the development of parallel methods that can take advantage of the power of modern supercomputers in recent years. We systematically test suggested components of stochastic reaction-diffusion operator splitting in the literature and discuss their effects on accuracy. We introduce an operator splitting implementation for irregular meshes that enhances accuracy with minimal performance cost. We test a range of models in small-scale MPI simulations from simple diffusion models to realisticmore » biological models and find that multi-dimensional geometry partitioning is an important consideration for optimum performance. We demonstrate performance gains of 1-3 orders of magnitude in the parallel implementation, with peak performance strongly dependent on model specification.« less

Quantitative Proteomics Reveals Temporal Proteomic Changes in Signaling Pathways during BV2 Mouse Microglial Cell Activation.

PubMed

Woo, Jongmin; Han, Dohyun; Wang, Joseph Injae; Park, Joonho; Kim, Hyunsoo; Kim, Youngsoo

2017-09-01

The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. We have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted. There are varying degrees of microglial activation, and we chose to focus on the proinflammatory reactive state that is induced by exposure to such stimuli as lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Using an improved shotgun proteomics approach, we identified 5497 proteins in the whole-cell proteome and 4938 proteins in the secretome that were associated with the activation of BV2 mouse microglia by LPS or IFN-γ. Of the differentially expressed proteins in stimulated microglia, we classified pathways that were related to immune-inflammatory responses and metabolism. Our label-free parallel reaction monitoring (PRM) approach made it possible to comprehensively measure the hyper-multiplex quantitative value of each protein by high-resolution mass spectrometry. Over 450 peptides that corresponded to pathway proteins and direct or indirect interactors via the STRING database were quantified by label-free PRM in a single run. Moreover, we performed a longitudinal quantification of secreted proteins during microglial activation, in which neurotoxic molecules that mediate neuronal cell loss in the brain are released. These data suggest that latent pathways that are associated with neurodegenerative diseases can be discovered by constructing and analyzing a pathway network model of proteins. Furthermore, this systematic quantification platform has tremendous potential for applications in large-scale targeted analyses. The proteomics data for discovery and label-free PRM analysis have been deposited to the ProteomeXchange Consortium with identifiers and , respectively.

Evaluation of parallel milliliter-scale stirred-tank bioreactors for the study of biphasic whole-cell biocatalysis with ionic liquids.

PubMed

Dennewald, Danielle; Hortsch, Ralf; Weuster-Botz, Dirk

2012-01-01

As clear structure-activity relationships are still rare for ionic liquids, preliminary experiments are necessary for the process development of biphasic whole-cell processes involving these solvents. To reduce the time investment and the material costs, the process development of such biphasic reaction systems would profit from a small-scale high-throughput platform. Exemplarily, the reduction of 2-octanone to (R)-2-octanol by a recombinant Escherichia coli in a biphasic ionic liquid/water system was studied in a miniaturized stirred-tank bioreactor system allowing the parallel operation of up to 48 reactors at the mL-scale. The results were compared to those obtained in a 20-fold larger stirred-tank reactor. The maximum local energy dissipation was evaluated at the larger scale and compared to the data available for the small-scale reactors, to verify if similar mass transfer could be obtained at both scales. Thereafter, the reaction kinetics and final conversions reached in different reactions setups were analysed. The results were in good agreement between both scales for varying ionic liquids and for ionic liquid volume fractions up to 40%. The parallel bioreactor system can thus be used for the process development of the majority of biphasic reaction systems involving ionic liquids, reducing the time and resource investment during the process development of this type of applications. Copyright © 2011. Published by Elsevier B.V.

RhoA/ROCK Signaling Pathway Mediates Shuanghuanglian Injection-Induced Pseudo-allergic Reactions

PubMed Central

Han, Jiayin; Zhao, Yong; Zhang, Yushi; Li, Chunying; Yi, Yan; Pan, Chen; Tian, Jingzhuo; Yang, Yifei; Cui, Hongyu; Wang, Lianmei; Liu, Suyan; Liu, Jing; Deng, Nuo; Liang, Aihua

2018-01-01

Background: Shuanghuanglian injection (SHLI) is a famous Chinese medicine used as an intravenous preparation for the treatment of acute respiratory tract infections. In the recent years, the immediate hypersensitivity reactions induced by SHLI have attracted broad attention. However, the mechanism involved in these reactions has not yet been elucidated. The present study aims to explore the characteristics of the immediate hypersensitivity reactions induced by SHLI and deciphers the role of the RhoA/ROCK signaling pathway in these reactions. Methods: SHLI-immunized mice or naive mice were intravenously injected (i.v.) with SHLI (600 mg/kg) once, and vascular leakage in the ears was evaluated. Passive cutaneous anaphylaxis test was conducted using sera collected from SHLI-immunized mice. Naive mice were administered (i.v.) with a single dose of 150, 300, or 600 mg/kg of SHLI, and vascular leakage, histamine release, and histopathological alterations in the ears, lungs, and intestines were tested. In vitro, human umbilical vein endothelial cell (HUVEC) monolayer was incubated with SHLI (0.05, 0.1, or 0.15 mg/mL), and the changes in endothelial permeability and cytoskeleton were observed. Western blot analysis was performed and ROCK inhibitor was employed to investigate the contribution of the RhoA/ROCK signaling pathway in SHLI-induced hypersensitivity reactions, both in HUVECs and in mice. Results: Our results indicate that SHLI was able to cause immediate dose-dependent vascular leakage, edema, and exudates in the ears, lungs, and intestines, and histamine release in mice. These were pseudo-allergic reactions, as SHLI-specific IgE was not elicited during sensitization. In addition, SHLI induced reorganization of actin cytoskeleton and disrupted the endothelial barrier. The administration of SHLI directly activated the RhoA/ROCK signaling pathway both in HUVECs and in the ears, lungs, and intestines of mice. Fasudil hydrochloride, a ROCK inhibitor, ameliorated the SHLI-induced hypersensitivity reactions in both endothelial cells and mice indicating its protective effect. SHLI-induced pseudo-allergic reactions were mediated by the activation of the RhoA/ROCK signaling pathway. Conclusion: This study presents a novel mechanism of SHLI-induced immediate hypersensitivity reactions and suggests a potential therapeutic strategy to prevent the associated adverse reactions. PMID:29487527

Surface Proton Transfer Promotes Four-Electron Oxygen Reduction on Gold Nanocrystal Surfaces in Alkaline Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Fang; Zhang, Yu; Liu, Shizhong

Four-electron oxygen reduction reaction (4e-ORR), as a key pathway in energy conversion, is preferred over the two-electron reduction pathway that falls short in dissociating dioxygen molecules. Gold (Au) surfaces exhibit high sensitivity of the ORR pathway to its atomic structures. The long-standing puzzle remains unsolved why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze the 4e-ORR in alkaline solution, though limited within a narrow potential window. Herein we report the discovery of a dominant 4e-ORR over the whole potential range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism (TDP). In contrast, ORR pathways onmore » single-crystalline facets of shaped nanoparticles, including {111} on nano-octahedra and {100} on nano-cubes, are similar to their single-crystal counterparts. Combining our experimental results with density functional theory calculations, we elucidate the key role of surface proton transfers from co-adsorbed H 2O molecules in activating the facet- and potential-dependent 4e ORR on Au in alkaline solutions. These results elucidate how surface atomic structures determine the reaction pathways via bond scission and formation among weakly adsorbed water and reaction intermediates. The new insight helps in developing facet-specific nanocatalysts for various reactions.« less

Thermal decomposition pathways of hydroxylamine: theoretical investigation on the initial steps.

PubMed

Wang, Qingsheng; Wei, Chunyang; Pérez, Lisa M; Rogers, William J; Hall, Michael B; Mannan, M Sam

2010-09-02

Hydroxylamine (NH(2)OH) is an unstable compound at room temperature, and it has been involved in two tragic industrial incidents. Although experimental studies have been carried out to study the thermal stability of hydroxylamine, the detailed decomposition mechanism is still in debate. In this work, several density functional and ab initio methods were used in conjunction with several basis sets to investigate the initial thermal decomposition steps of hydroxylamine, including both unimolecular and bimolecular reaction pathways. The theoretical investigation shows that simple bond dissociations and unimolecular reactions are unlikely to occur. The energetically favorable initial step of decomposition pathways was determined as a bimolecular isomerization of hydroxylamine into ammonia oxide with an activation barrier of approximately 25 kcal/mol at the MPW1K level of theory. Because hydroxylamine is available only in aqueous solutions, solvent effects on the initial decomposition pathways were also studied using water cluster methods and the polarizable continuum model (PCM). In water, the activation barrier of the bimolecular isomerization reaction decreases to approximately 16 kcal/mol. The results indicate that the bimolecular isomerization pathway of hydroxylamine is more favorable in aqueous solutions. However, the bimolecular nature of this reaction means that more dilute aqueous solution will be more stable.

Surface Proton Transfer Promotes Four-Electron Oxygen Reduction on Gold Nanocrystal Surfaces in Alkaline Solution

DOE PAGES

Lu, Fang; Zhang, Yu; Liu, Shizhong; ...

2017-05-11

Four-electron oxygen reduction reaction (4e-ORR), as a key pathway in energy conversion, is preferred over the two-electron reduction pathway that falls short in dissociating dioxygen molecules. Gold (Au) surfaces exhibit high sensitivity of the ORR pathway to its atomic structures. The long-standing puzzle remains unsolved why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze the 4e-ORR in alkaline solution, though limited within a narrow potential window. Herein we report the discovery of a dominant 4e-ORR over the whole potential range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism (TDP). In contrast, ORR pathways onmore » single-crystalline facets of shaped nanoparticles, including {111} on nano-octahedra and {100} on nano-cubes, are similar to their single-crystal counterparts. Combining our experimental results with density functional theory calculations, we elucidate the key role of surface proton transfers from co-adsorbed H 2O molecules in activating the facet- and potential-dependent 4e ORR on Au in alkaline solutions. These results elucidate how surface atomic structures determine the reaction pathways via bond scission and formation among weakly adsorbed water and reaction intermediates. The new insight helps in developing facet-specific nanocatalysts for various reactions.« less

Development of linear free energy relationships for aqueous phase radical-involved chemical reactions.

PubMed

Minakata, Daisuke; Mezyk, Stephen P; Jones, Jace W; Daws, Brittany R; Crittenden, John C

2014-12-02

Aqueous phase advanced oxidation processes (AOPs) produce hydroxyl radicals (HO•) which can completely oxidize electron rich organic compounds. The proper design and operation of AOPs require that we predict the formation and fate of the byproducts and their associated toxicity. Accordingly, there is a need to develop a first-principles kinetic model that can predict the dominant reaction pathways that potentially produce toxic byproducts. We have published some of our efforts on predicting the elementary reaction pathways and the HO• rate constants. Here we develop linear free energy relationships (LFERs) that predict the rate constants for aqueous phase radical reactions. The LFERs relate experimentally obtained kinetic rate constants to quantum mechanically calculated aqueous phase free energies of activation. The LFERs have been applied to 101 reactions, including (1) HO• addition to 15 aromatic compounds; (2) addition of molecular oxygen to 65 carbon-centered aliphatic and cyclohexadienyl radicals; (3) disproportionation of 10 peroxyl radicals, and (4) unimolecular decay of nine peroxyl radicals. The LFERs correlations predict the rate constants within a factor of 2 from the experimental values for HO• reactions and molecular oxygen addition, and a factor of 5 for peroxyl radical reactions. The LFERs and the elementary reaction pathways will enable us to predict the formation and initial fate of the byproducts in AOPs. Furthermore, our methodology can be applied to other environmental processes in which aqueous phase radical-involved reactions occur.

Employing Content-Based Curricula in Nursing at Illinois Central College to Improve Equity and Outcomes for Students. Pathways to Results: Implementation Partnerships Strategy Brief

ERIC Educational Resources Information Center

Graham, Edmund

2016-01-01

Since the creation of Pathways to Results (PTR) in 2009, Illinois Central College (ICC) has participated in all but one year, working to improve outcomes across a number of different pathways. ICC has been innovative in its use of PTR over the years, and the 2014/2015 PTR project was no different. The ICC team worked to identify parallels between…

Solution-phase parallel synthesis of hexahydro-1H-isoindolone libraries via tactical combination of Cu-catalyzed three-component coupling and Diels-Alder reactions.

PubMed

Zhang, Lei; Lushington, Gerald H; Neuenswander, Benjamin; Hershberger, John C; Malinakova, Helena C

2008-01-01

Parallel solution-phase synthesis of combinatorial libraries of hexahydro-1 H-isoindolones exploiting a novel "tactical combination" of Cu-catalyzed three-component coupling and Diels-Alder reactions was accomplished. Three distinct libraries consisting of 24 members (library I), 60 members (library II), and 32 members (library III) were constructed. Variation of three substituents on the isoindolone scaffold in library I was exclusively achieved by the choice of the building blocks. In the syntheses of libraries II and III, sublibraries of isoindolone scaffolds were prepared initially in a one-pot/two-step process and were further diversified via Pd-catalyzed Suzuki cross-coupling reaction with boronic acids at two different diversification points. The Lipinski profiles and calculated ADME properties of the compounds are also reported.

ReactionPredictor: prediction of complex chemical reactions at the mechanistic level using machine learning.

PubMed

Kayala, Matthew A; Baldi, Pierre

2012-10-22

Proposing reasonable mechanisms and predicting the course of chemical reactions is important to the practice of organic chemistry. Approaches to reaction prediction have historically used obfuscating representations and manually encoded patterns or rules. Here we present ReactionPredictor, a machine learning approach to reaction prediction that models elementary, mechanistic reactions as interactions between approximate molecular orbitals (MOs). A training data set of productive reactions known to occur at reasonable rates and yields and verified by inclusion in the literature or textbooks is derived from an existing rule-based system and expanded upon with manual curation from graduate level textbooks. Using this training data set of complex polar, hypervalent, radical, and pericyclic reactions, a two-stage machine learning prediction framework is trained and validated. In the first stage, filtering models trained at the level of individual MOs are used to reduce the space of possible reactions to consider. In the second stage, ranking models over the filtered space of possible reactions are used to order the reactions such that the productive reactions are the top ranked. The resulting model, ReactionPredictor, perfectly ranks polar reactions 78.1% of the time and recovers all productive reactions 95.7% of the time when allowing for small numbers of errors. Pericyclic and radical reactions are perfectly ranked 85.8% and 77.0% of the time, respectively, rising to >93% recovery for both reaction types with a small number of allowed errors. Decisions about which of the polar, pericyclic, or radical reaction type ranking models to use can be made with >99% accuracy. Finally, for multistep reaction pathways, we implement the first mechanistic pathway predictor using constrained tree-search to discover a set of reasonable mechanistic steps from given reactants to given products. Webserver implementations of both the single step and pathway versions of ReactionPredictor are available via the chemoinformatics portal http://cdb.ics.uci.edu/.

Rapid Optimization of Engineered Metabolic Pathways with Serine Integrase Recombinational Assembly (SIRA).

PubMed

Merrick, C A; Wardrope, C; Paget, J E; Colloms, S D; Rosser, S J

2016-01-01

Metabolic pathway engineering in microbial hosts for heterologous biosynthesis of commodity compounds and fine chemicals offers a cheaper, greener, and more reliable method of production than does chemical synthesis. However, engineering metabolic pathways within a microbe is a complicated process: levels of gene expression, protein stability, enzyme activity, and metabolic flux must be balanced for high productivity without compromising host cell viability. A major rate-limiting step in engineering microbes for optimum biosynthesis of a target compound is DNA assembly, as current methods can be cumbersome and costly. Serine integrase recombinational assembly (SIRA) is a rapid DNA assembly method that utilizes serine integrases, and is particularly applicable to rapid optimization of engineered metabolic pathways. Using six pairs of orthogonal attP and attB sites with different central dinucleotide sequences that follow SIRA design principles, we have demonstrated that ΦC31 integrase can be used to (1) insert a single piece of DNA into a substrate plasmid; (2) assemble three, four, and five DNA parts encoding the enzymes for functional metabolic pathways in a one-pot reaction; (3) generate combinatorial libraries of metabolic pathway constructs with varied ribosome binding site strengths or gene orders in a one-pot reaction; and (4) replace and add DNA parts within a construct through targeted postassembly modification. We explain the mechanism of SIRA and the principles behind designing a SIRA reaction. We also provide protocols for making SIRA reaction components and practical methods for applying SIRA to rapid optimization of metabolic pathways. © 2016 Elsevier Inc. All rights reserved.

Fusion yield: Guderley model and Tsallis statistics

NASA Astrophysics Data System (ADS)

Haubold, H. J.; Kumar, D.

2011-02-01

The reaction rate probability integral is extended from Maxwell-Boltzmann approach to a more general approach by using the pathway model introduced by Mathai in 2005 (A pathway to matrix-variate gamma and normal densities. Linear Algebr. Appl. 396, 317-328). The extended thermonuclear reaction rate is obtained in the closed form via a Meijer's G-function and the so-obtained G-function is represented as a solution of a homogeneous linear differential equation. A physical model for the hydrodynamical process in a fusion plasma-compressed and laser-driven spherical shock wave is used for evaluating the fusion energy integral by integrating the extended thermonuclear reaction rate integral over the temperature. The result obtained is compared with the standard fusion yield obtained by Haubold and John in 1981 (Analytical representation of the thermonuclear reaction rate and fusion energy production in a spherical plasma shock wave. Plasma Phys. 23, 399-411). An interpretation for the pathway parameter is also given.

Pathways for Ethanol Dehydrogenation and Dehydration Catalyzed by Ceria (111) and (100) Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beste, Ariana; Steven Overbury

2015-01-08

We have performed computations to better understand how surface structure affects selectivity in dehydrogenation and dehydration reactions of alcohols. Ethanol reactions on the (111) and (100) ceria surfaces were studied starting from the dominant surface species, ethoxy. We used DFT (PBE+U) to explore reaction pathways leading to ethylene and acetaldehyde and calculated estimates of rate constants employing transition state theory. To assess pathway contributions, we carried out kinetic analysis. Our results show that intermediate and transition state structures are stabilized on the (100) surface compared to the (111) surface. Formation of acetaldehyde over ethylene is kinetically and thermodynamically preferred onmore » both surfaces. Our results are consistent with temperature programmed surface reaction and steady-state experiments, where acetaldehyde was found as the main product and evidence was presented that ethylene formation at higher temperature originates from changes in adsorbate and surface structure.« less

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis.

PubMed

Sang-aroon, Wichien; Amornkitbamrung, Vittaya; Ruangpornvisuti, Vithaya

2013-12-01

In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

Sono-activated persulfate oxidation of diclofenac: Degradation, kinetics, pathway and contribution of the different radicals involved.

PubMed

Monteagudo, J M; El-Taliawy, H; Durán, A; Caro, G; Bester, K

2018-06-20

Degradation of a diclofenac aqueous solution was performed using persulfate anions activated by ultrasound. The objective of this study was to analyze different parameters affecting the diclofenac (DCF) removal reaction by the ultrasonic persulfate (US/PS) process and to evaluate the role played by various intermediate oxidative species such as hydroxyl- and sulfate radicals, superoxide radical anion or singlet oxygen in the removal process as well as to determine a possible reaction pathway. The effects of pH, initial persulfate anion concentration, ultrasonic amplitude and temperature on DCF degradation were examined. Sulfate and hydroxyl radicals were involved in the main reaction pathway of diclofenac. Diclofenac amide and three hydroxy-diclofenac isomers (3´-hydroxy diclofenac, 4´-hydroxy diclofenac and 5-hydroxy diclofenac) were identified as reaction intermediates. Copyright © 2018 Elsevier B.V. All rights reserved.

Metabolite damage and repair in metabolic engineering design.

PubMed

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Metabolite damage and repair in metabolic engineering design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields,more » and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.« less

Minimum Energy Pathways for Chemical Reactions

NASA Technical Reports Server (NTRS)

Walch, S. P.; Langhoff, S. R. (Technical Monitor)

1995-01-01

Computed potential energy surfaces are often required for computation of such parameters as rate constants as a function of temperature, product branching ratios, and other detailed properties. We have found that computation of the stationary points/reaction pathways using CASSCF/derivative methods, followed by use of the internally contracted CI method to obtain accurate energetics, gives useful results for a number of chemically important systems. The talk will focus on a number of applications to reactions leading to NOx and soot formation in hydrocarbon combustion.

Phosphorylation Reaction in cAPK Protein Kinase - Free Energy Quantum Mechanic/Molecular Mechanics Simulations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valiev, Marat; Yang, Jie; Adams, Joseph

2007-11-29

Protein kinases catalyze the transfer of the γ-phosphoryl group from ATP, a key regulatory process governing signalling pathways in eukaryotic cells. The structure of the active site in these enzymes is highly conserved implying common catalytic mechanism. In this work we investigate the reaction process in cAPK protein kinase (PKA) using a combined quantum mechanics and molecular mechanics approach. The novel computational features of our work include reaction pathway determination with nudged elastic band methodology and calculation of free energy profiles of the reaction process taking into account finite temperature fluctuations of the protein environment. We find that the transfermore » of the γ-phosphoryl group in the protein environment is an exothermic reaction with the reaction barrier of 15 kcal/mol.« less

Reactivity of seventeen- and nineteen-valence electron complexes in organometallic chemistry

NASA Technical Reports Server (NTRS)

Stiegman, Albert E.; Tyler, David R.

1986-01-01

A guideline to the reactivity of 17- and 19-valence electron species in organometallic chemistry is proposed which the authors believe will supersede all others. The thesis holds that the reactions of 17-electron metal radicals are associatively activated with reactions proceeding through a 19-valence electron species. The disparate reaction chemistry of the 17-electron metal radicals are unified in terms of this associative reaction pathway, and the intermediacy of 19-valence electron complexes in producing the observed products is discussed. It is suggested that related associatively activated pathways need to be considered in some reactions that are thought to occur by more conventional routes involving 16- and 18-electron intermediates. The basic reaction chemistry and electronic structures of these species are briefly discussed.

DEOP: a database on osmoprotectants and associated pathways

PubMed Central

Bougouffa, Salim; Radovanovic, Aleksandar; Essack, Magbubah; Bajic, Vladimir B.

2014-01-01

Microorganisms are known to counteract salt stress through salt influx or by the accumulation of osmoprotectants (also called compatible solutes). Understanding the pathways that synthesize and/or breakdown these osmoprotectants is of interest to studies of crops halotolerance and to biotechnology applications that use microbes as cell factories for production of biomass or commercial chemicals. To facilitate the exploration of osmoprotectants, we have developed the first online resource, ‘Dragon Explorer of Osmoprotection associated Pathways’ (DEOP) that gathers and presents curated information about osmoprotectants, complemented by information about reactions and pathways that use or affect them. A combined total of 141 compounds were confirmed osmoprotectants, which were matched to 1883 reactions and 834 pathways. DEOP can also be used to map genes or microbial genomes to potential osmoprotection-associated pathways, and thus link genes and genomes to other associated osmoprotection information. Moreover, DEOP provides a text-mining utility to search deeper into the scientific literature for supporting evidence or for new associations of osmoprotectants to pathways, reactions, enzymes, genes or organisms. Two case studies are provided to demonstrate the usefulness of DEOP. The system can be accessed at. Database URL: http://www.cbrc.kaust.edu.sa/deop/ PMID:25326239

A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G-quadruplexes

PubMed Central

Wang, Zi-Fu; Li, Ming-Hao; Chen, Wei-Wen; Hsu, Shang-Te Danny; Chang, Ta-Chau

2016-01-01

The folding topology of DNA G-quadruplexes (G4s) depends not only on their nucleotide sequences but also on environmental factors and/or ligand binding. Here, a G4 ligand, 3,6-bis(1-methyl-4-vinylpyridium iodide)-9-(1-(1-methyl-piperidinium iodide)-3,6,9-trioxaundecane) carbazole (BMVC-8C3O), can induce topological conversion of non-parallel to parallel forms in human telomeric DNA G4s. Nuclear magnetic resonance (NMR) spectroscopy with hydrogen-deuterium exchange (HDX) reveals the presence of persistent imino proton signals corresponding to the central G-quartet during topological conversion of Tel23 and Tel25 G4s from hybrid to parallel forms, implying that the transition pathway mainly involves local rearrangements. In contrast, rapid HDX was observed during the transition of 22-CTA G4 from an anti-parallel form to a parallel form, resulting in complete disappearance of all the imino proton signals, suggesting the involvement of substantial unfolding events associated with the topological transition. Site-specific imino proton NMR assignments of Tel23 G4 enable determination of the interconversion rates of individual guanine bases and detection of the presence of intermediate states. Since the rate of ligand binding is much higher than the rate of ligand-induced topological conversion, a three-state kinetic model was evoked to establish the associated energy diagram for the topological conversion of Tel23 G4 induced by BMVC-8C3O. PMID:26975658

Dissecting Germ Cell Metabolism through Network Modeling.

PubMed

Whitmore, Leanne S; Ye, Ping

2015-01-01

Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health.

Parallel steady state studies on a milliliter scale accelerate fed-batch bioprocess design for recombinant protein production with Escherichia coli.

PubMed

Schmideder, Andreas; Cremer, Johannes H; Weuster-Botz, Dirk

2016-11-01

In general, fed-batch processes are applied for recombinant protein production with Escherichia coli (E. coli). However, state of the art methods for identifying suitable reaction conditions suffer from severe drawbacks, i.e. direct transfer of process information from parallel batch studies is often defective and sequential fed-batch studies are time-consuming and cost-intensive. In this study, continuously operated stirred-tank reactors on a milliliter scale were applied to identify suitable reaction conditions for fed-batch processes. Isopropyl β-d-1-thiogalactopyranoside (IPTG) induction strategies were varied in parallel-operated stirred-tank bioreactors to study the effects on the continuous production of the recombinant protein photoactivatable mCherry (PAmCherry) with E. coli. Best-performing induction strategies were transferred from the continuous processes on a milliliter scale to liter scale fed-batch processes. Inducing recombinant protein expression by dynamically increasing the IPTG concentration to 100 µM led to an increase in the product concentration of 21% (8.4 g L -1 ) compared to an implemented high-performance production process with the most frequently applied induction strategy by a single addition of 1000 µM IPGT. Thus, identifying feasible reaction conditions for fed-batch processes in parallel continuous studies on a milliliter scale was shown to be a powerful, novel method to accelerate bioprocess design in a cost-reducing manner. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1426-1435, 2016. © 2016 American Institute of Chemical Engineers.

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

PubMed Central

LIU, BINGSHAN; LI, GUOJUN; WANG, XIAO; LIU, YANG

2014-01-01

This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1-antitrypsin Portland (α1-PDX). Wound-healing and Transwell assays were used for the detection of the effects of α1-PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription-polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1-MMP), Wnt and β-catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1-MMP gene transcription activity. The results showed that α1-PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1-MMP decreased evidently upon α1-PDX treatment, paralleled with reductions in the expression levels of Wnt and β-catenin. Further analysis of the transcriptional activity of MT1-MMP revealed that the α1-PDX-induced downregulation of the levels of MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that α1-PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway. PMID:24944664

A Novel Role for Cytochrome c: Efficient Catalysis of S-Nitrosothiol Formation

PubMed Central

Basu, Swati; Keszler, Agnes; Azarova, Natalia A.; Nwanze, Nneka; Perlegas, Andreas; Shiva, Sruti; Broniowska, Katarzyna A.; Hogg, Neil; Kim-Shapiro, Daniel B.

2009-01-01

While S-nitrosothiols are regarded as important elements of many NO-dependent signal transduction pathways, the physiological mechanism of their formation remains elusive. Here, we demonstrate a novel mechanism by which cytochrome c may represent an efficient catalyst of S-nitrosation in vivo. In this mechanism, initial binding of GSH to ferric cytochrome c is followed by reaction of NO with this complex, yielding ferrous cytochrome c and GSNO. We show that when submitochondrial particles or cell lysates are exposed to NO in the presence of cytochrome c, there is a robust formation of protein S-nitrosothiols. In the case of submitochondrial particles protein S-nitrosation is paralleled with an inhibition of mitochondrial complex I. These observations raise the possibility that cytochrome c is a mediator of S-nitrosation in biological systems, particularly during hypoxia, and that release of cytochrome c in to the cytosol during apoptosis potentially releases a GSNO synthase activity which could modulate apoptotic signaling. PMID:19879353

Comparative Transcriptomic Analysis in Paddy Rice under Storage and Identification of Differentially Regulated Genes in Response to High Temperature and Humidity.

PubMed

Zhao, Chanjuan; Xie, Junqi; Li, Li; Cao, Chongjiang

2017-09-20

The transcriptomes of paddy rice in response to high temperature and humidity were studied using a high-throughput RNA sequencing approach. Effects of high temperature and humidity on the sucrose and starch contents and α/β-amylase activity were also investigated. Results showed that 6876 differentially expressed genes (DEGs) were identified in paddy rice under high temperature and humidity storage. Importantly, 12 DEGs that were downregulated fell into the "starch and sucrose pathway". The quantitative real-time polymerase chain reaction assays indicated that expression of these 12 DEGs was significantly decreased, which was in parallel with the reduced level of enzyme activities and the contents of sucrose and starch in paddy rice stored at high temperature and humidity conditions compared to the control group. Taken together, high temperature and humidity influence the quality of paddy rice at least partially by downregulating the expression of genes encoding sucrose transferases and hydrolases, which might result in the decrease of starch and sucrose contents.

Assessing the utility of the willingness/prototype model in predicting help-seeking decisions.

PubMed

Hammer, Joseph H; Vogel, David L

2013-01-01

Prior research on professional psychological help-seeking behavior has operated on the assumption that the decision to seek help is based on intentional and reasoned processes. However, research on the dual-process prototype/willingness model (PWM; Gerrard, Gibbons, Houlihan, Stock, & Pomery, 2008) suggests health-related decisions may also involve social reaction processes that influence one's spontaneous willingness (rather than planned intention) to seek help, given conducive circumstances. The present study used structural equation modeling to evaluate the ability of these 2 information-processing pathways (i.e., the reasoned pathway and the social reaction pathway) to predict help-seeking decisions among 182 college students currently experiencing clinical levels of psychological distress. Results indicated that when both pathways were modeled simultaneously, only the social reaction pathway independently accounted for significant variance in help-seeking decisions. These findings argue for the utility of the PWM framework in the context of professional psychological help seeking and hold implications for future counseling psychology research, prevention, and practice. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Solvent friction changes the folding pathway of the tryptophan zipper TZ2.

PubMed

Narayanan, Ranjani; Pelakh, Leslie; Hagen, Stephen J

2009-07-17

Because the rate of a diffusional process such as protein folding is controlled by friction encountered along the reaction pathway, the speed of folding is readily tunable through adjustment of solvent viscosity. The precise relationship between solvent viscosity and the rate of diffusion is complex and even conformation-dependent, however, because both solvent friction and protein internal friction contribute to the total reaction friction. The heterogeneity of the reaction friction along the folding pathway may have subtle consequences. For proteins that fold on a multidimensional free-energy surface, an increase in solvent friction may drive a qualitative change in folding trajectory. Our time-resolved experiments on the rapidly and heterogeneously folding beta-hairpin TZ2 show a shift in the folding pathway as viscosity increases, even though the energetics of folding is unaltered. We also observe a nonlinear or saturating behavior of the folding relaxation time with rising solvent viscosity, potentially an experimental signature of the shifting pathway for unfolding. Our results show that manipulations of solvent viscosity in folding experiments and simulations may have subtle and unexpected consequences on the folding dynamics being studied.

Dynamics of NAD-metabolism: everything but constant.

PubMed

Opitz, Christiane A; Heiland, Ines

2015-12-01

NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG. In metabolic pathway analysis, the total amount of NAD is usually assumed to be constant. That means that changes in the redox state might be considered, but concentration changes of the NAD moiety are usually neglected. However, a growing number of NAD-consuming reactions have been identified, showing that this assumption does not hold true in general. NAD-consuming reactions are common characteristics of NAD(+)-dependent signalling pathways and include mono- and poly-ADP-ribosylation of proteins, NAD(+)-dependent deacetylation by sirtuins and the formation of messenger molecules such as cyclic ADP-ribose (cADPR) and nicotinic acid (NA)-ADP (NAADP). NAD-consuming reactions are thus involved in major signalling and gene regulation pathways such as DNA-repair or regulation of enzymes central in metabolism. All known NAD(+)-dependent signalling processes include the release of nicotinamide (Nam). Thus cellular NAD pools need to be constantly replenished, mostly by recycling Nam to NAD(+). This process is, among others, regulated by the circadian clock, causing complex dynamic changes in NAD concentration. As disturbances in NAD homoeostasis are associated with a large number of diseases ranging from cancer to diabetes, it is important to better understand the dynamics of NAD metabolism to develop efficient pharmacological invention strategies to target this pathway. © 2015 Authors; published by Portland Press Limited.

A PC parallel port button box provides millisecond response time accuracy under Linux.

PubMed

Stewart, Neil

2006-02-01

For psychologists, it is sometimes necessary to measure people's reaction times to the nearest millisecond. This article describes how to use the PC parallel port to receive signals from a button box to achieve millisecond response time accuracy. The workings of the parallel port, the corresponding port addresses, and a simple Linux program for controlling the port are described. A test of the speed and reliability of button box signal detection is reported. If the reader is moderately familiar with Linux, this article should provide sufficient instruction for him or her to build and test his or her own parallel port button box. This article also describes how the parallel port could be used to control an external apparatus.

Gas-Phase Reaction Pathways and Rate Coefficients for the Dichlorosilane-Hydrogen and Trichlorosilane-Hydrogen Systems

NASA Technical Reports Server (NTRS)

Dateo, Christopher E.; Walch, Stephen P.

2002-01-01

As part of NASA Ames Research Center's Integrated Process Team on Device/Process Modeling and Nanotechnology our goal is to create/contribute to a gas-phase chemical database for use in modeling microelectronics devices. In particular, we use ab initio methods to determine chemical reaction pathways and to evaluate reaction rate coefficients. Our initial studies concern reactions involved in the dichlorosilane-hydrogen (SiCl2H2--H2) and trichlorosilane-hydrogen (SiCl2H-H2) systems. Reactant, saddle point (transition state), and product geometries and their vibrational harmonic frequencies are determined using the complete-active-space self-consistent-field (CASSCF) electronic structure method with the correlation consistent polarized valence double-zeta basis set (cc-pVDZ). Reaction pathways are constructed by following the imaginary frequency mode of the saddle point to both the reactant and product. Accurate energetics are determined using the singles and doubles coupled-cluster method that includes a perturbational estimate of the effects of connected triple excitations (CCSD(T)) extrapolated to the complete basis set limit. Using the data from the electronic structure calculations, reaction rate coefficients are obtained using conventional and variational transition state and RRKM theories.

Pharmacological modulators of autophagy activate a parallel noncanonical pathway driving unconventional LC3 lipidation.

PubMed

Jacquin, Elise; Leclerc-Mercier, Stéphanie; Judon, Celine; Blanchard, Emmanuelle; Fraitag, Sylvie; Florey, Oliver

2017-05-04

The modulation of canonical macroautophagy/autophagy for therapeutic benefit is an emerging strategy of medical and pharmaceutical interest. Many drugs act to inhibit autophagic flux by targeting lysosome function, while others were developed to activate the pathway. Here, we report the surprising finding that many therapeutically relevant autophagy modulators with lysosomotropic and ionophore properties, classified as inhibitors of canonical autophagy, are also capable of activating a parallel noncanonical autophagy pathway that drives MAP1LC3/LC3 lipidation on endolysosomal membranes. Further, we provide the first evidence supporting drug-induced noncanonical autophagy in vivo using the local anesthetic lidocaine and human skin biopsies. In addition, we find that several published inducers of autophagy and mitophagy are also potent activators of noncanonical autophagy. Together, our data raise important issues regarding the interpretation of LC3 lipidation data and the use of autophagy modulators, and highlight the need for a greater understanding of the functional consequences of noncanonical autophagy.

Dual element (CCl) isotope approach to distinguish abiotic reactions of chlorinated methanes by Fe(0) and by Fe(II) on iron minerals at neutral and alkaline pH.

PubMed

Rodríguez-Fernández, Diana; Heckel, Benjamin; Torrentó, Clara; Meyer, Armin; Elsner, Martin; Hunkeler, Daniel; Soler, Albert; Rosell, Mònica; Domènech, Cristina

2018-05-07

A dual element CCl isotopic study was performed for assessing chlorinated methanes (CMs) abiotic transformation reactions mediated by iron minerals and Fe(0) to further distinguish them in natural attenuation monitoring or when applying remediation strategies in polluted sites. Isotope fractionation was investigated during carbon tetrachloride (CT) and chloroform (CF) degradation in anoxic batch experiments with Fe(0), with FeCl 2 (aq), and with Fe-bearing minerals (magnetite, Mag and pyrite, Py) amended with FeCl 2 (aq), at two different pH values (7 and 12) representative of field and remediation conditions. At pH 7, only CT batches with Fe(0) and Py underwent degradation and CF accumulation evidenced hydrogenolysis. With Py, thiolytic reduction was revealed by CS 2 yield and is a likely reason for different Λ value (Δδ 13 C/Δδ 37 Cl) comparing with Fe(0) experiments at pH 7 (2.9 ± 0.5 and 6.1 ± 0.5, respectively). At pH 12, all CT experiments showed degradation to CF, again with significant differences in Λ values between Fe(0) (5.8 ± 0.4) and Fe-bearing minerals (Mag, 2 ± 1, and Py, 3.7 ± 0.9), probably evidencing other parallel pathways (hydrolytic and thiolytic reduction). Variation of pH did not significantly affect the Λ values of CT degradation by Fe(0) nor Py. CF degradation by Fe(0) at pH 12 showed a Λ (8 ± 1) similar to that reported at pH 7 (8 ± 2), suggesting CF hydrogenolysis as the main reaction and that CF alkaline hydrolysis (13.0 ± 0.8) was negligible. Our data establish a base for discerning the predominant or combined pathways of CMs natural attenuation or for assessing the effectiveness of remediation strategies using recycled minerals or Fe(0). Copyright © 2018 Elsevier Ltd. All rights reserved.

Pump-shaped dump optimal control reveals the nuclear reaction pathway of isomerization of a photoexcited cyanine dye.

PubMed

Dietzek, Benjamin; Brüggemann, Ben; Pascher, Torbjörn; Yartsev, Arkady

2007-10-31

Using optimal control as a spectroscopic tool we decipher the details of the molecular dynamics of the essential multidimensional excited-state photoisomerization - a fundamental chemical reaction of key importance in biology. Two distinct nuclear motions are identified in addition to the overall bond-twisting motion: Initially, the reaction is dominated by motion perpendicular to the torsion coordinate. At later times, a second optically active vibration drives the system along the reaction path to the bottom of the excited-state potential. The time scales of the wavepacket motion on a different part of the excited-state potential are detailed by pump-shaped dump optimal control. This technique offers new means to control a chemical reaction far from the Franck-Condon point of absorption and to map details of excited-state reaction pathways revealing unique insights into the underlying reaction mechanism.

Divergent reaction pathways for one-pot, three-component synthesis of novel 4H-pyrano[3,2-h]quinolines under ultrasound irradiation.

PubMed

Al-Bogami, Abdullah S; Saleh, Tamer S; Zayed, Ehab M

2013-09-01

The present paper deal with the multi-component condensation of 8-hydroxy quinoline, aromatic aldehydes, and sulfone derivatives catalyzed by p-toluenesulfonic acid for the synthesis of a series of 4H-pyrano[3,2-h]quinoline derivatives in ethanol under ultrasonic irradiations. We provide a series of quinoline derivatives containing sulfone moiety interesting for biological screening tests. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with classical silent conditions. Also, also, sonochemical reaction give different reaction pathway other than silent reaction. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms of acoustic cavitation phenomenon. Structures of the products were established on analytical and spectral data. Copyright © 2013 Elsevier B.V. All rights reserved.

One-step simultaneous differential scanning calorimetry-FTIR microspectroscopy to quickly detect continuous pathways in the solid-state glucose/asparagine Maillard reaction.

PubMed

Hwang, Deng-Fwu; Hsieh, Tzu-Feng; Lin, Shan-Yang

2013-01-01

The stepwise reaction pathway of the solid-state Maillard reaction between glucose (Glc) and asparagine (Asn) was investigated using simultaneous differential scanning calorimetry (DSC)-FTIR microspectroscopy. The color change and FTIR spectra of Glc-Asn physical mixtures (molar ratio = 1:1) preheated to different temperatures followed by cooling were also examined. The successive reaction products such as Schiff base intermediate, Amadori product, and decarboxylated Amadori product in the solid-state Glc-Asn Maillard reaction were first simultaneously evidenced by this unique DSC-FTIR microspectroscopy. The color changed from white to yellow-brown to dark brown, and appearance of new IR peaks confirmed the formation of Maillard reaction products. The present study clearly indicates that this unique DSC-FTIR technique not only accelerates but also detects precursors and products of the Maillard reaction in real time.

14 CFR 25.507 - Reversed braking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... must be in a three point static ground attitude. Horizontal reactions parallel to the ground and... must be equal to 0.55 times the vertical load at each wheel or to the load developed by 1.2 times the... ground reactions must pass through the center of gravity of the airplane. ...

14 CFR 25.507 - Reversed braking.

Code of Federal Regulations, 2014 CFR

2014-01-01

... must be in a three point static ground attitude. Horizontal reactions parallel to the ground and... must be equal to 0.55 times the vertical load at each wheel or to the load developed by 1.2 times the... ground reactions must pass through the center of gravity of the airplane. ...

14 CFR 25.507 - Reversed braking.

Code of Federal Regulations, 2011 CFR

2011-01-01

... must be in a three point static ground attitude. Horizontal reactions parallel to the ground and... must be equal to 0.55 times the vertical load at each wheel or to the load developed by 1.2 times the... ground reactions must pass through the center of gravity of the airplane. ...

14 CFR 25.507 - Reversed braking.

Code of Federal Regulations, 2012 CFR

2012-01-01

... must be in a three point static ground attitude. Horizontal reactions parallel to the ground and... must be equal to 0.55 times the vertical load at each wheel or to the load developed by 1.2 times the... ground reactions must pass through the center of gravity of the airplane. ...

14 CFR 25.507 - Reversed braking.

Code of Federal Regulations, 2013 CFR

2013-01-01

... must be in a three point static ground attitude. Horizontal reactions parallel to the ground and... must be equal to 0.55 times the vertical load at each wheel or to the load developed by 1.2 times the... ground reactions must pass through the center of gravity of the airplane. ...

Mixed Potentials: Experimental Illustrations of an Important Concept in Practical Electrochemistry.

ERIC Educational Resources Information Center

Power, G. P.; Ritchie, I. M.

1983-01-01

Presents a largely experimental approach to the concept of mixed potentials, pointing out the close parallel that exists between equilibrium potentials. Describes several important examples of mixed potentials, providing current-voltage and polarization curves and half reactions as examples. Includes a discussion of corrosion reactions and…

Reaction rates of graphite with ozone measured by etch decoration

NASA Technical Reports Server (NTRS)

Hennig, G. R.; Montet, G. L.

1968-01-01

Etch-decoration technique of detecting vacancies in graphite has been used to determine the reaction rates of graphite with ozone in the directions parallel and perpendicular to the layer planes. It consists essentially of peeling single atom layers off graphite crystals without affecting the remainder of the crystal.

Kinetically-Driven Phase Transformation during Lithiation in Copper Sulfide Nanoflakes

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Kai; Yao, Zhenpeng; Hwang, Sooyeon

Two-dimensional (2D) transition metal chalcogenides have been widely studied and utilized as electrode materials for lithium ion batteries due to their unique layered structures to accommodate reversible lithium insertion. Real-time observation and mechanistic understanding of the phase transformations during lithiation of these materials are critically important for improving battery performance by controlling structures and reaction pathways. Here, we use in situ transmission electron microscopy methods to study the structural, morphological, and chemical evolutions in individual copper sulfide (CuS) nanoflakes during lithiation. We report a highly kinetically driven phase transformation in which lithium ions rapidly intercalate into the 2D van dermore » Waals-stacked interlayers in the initial stage, and further lithiation induces the Cu extrusion via a displacement reaction mechanism that is different from the typical conversion reactions. Density functional theory calculations have confirmed both the thermodynamically favored and the kinetically driven reaction pathways. Lastly, our findings elucidate the reaction pathways of the Li/CuS system under nonequilibrium conditions and provide valuable insight into the atomistic lithiation mechanisms of transition metal sulfides in general.« less

Kinetically-Driven Phase Transformation during Lithiation in Copper Sulfide Nanoflakes

DOE PAGES

He, Kai; Yao, Zhenpeng; Hwang, Sooyeon; ...

2017-08-11

Two-dimensional (2D) transition metal chalcogenides have been widely studied and utilized as electrode materials for lithium ion batteries due to their unique layered structures to accommodate reversible lithium insertion. Real-time observation and mechanistic understanding of the phase transformations during lithiation of these materials are critically important for improving battery performance by controlling structures and reaction pathways. Here, we use in situ transmission electron microscopy methods to study the structural, morphological, and chemical evolutions in individual copper sulfide (CuS) nanoflakes during lithiation. We report a highly kinetically driven phase transformation in which lithium ions rapidly intercalate into the 2D van dermore » Waals-stacked interlayers in the initial stage, and further lithiation induces the Cu extrusion via a displacement reaction mechanism that is different from the typical conversion reactions. Density functional theory calculations have confirmed both the thermodynamically favored and the kinetically driven reaction pathways. Lastly, our findings elucidate the reaction pathways of the Li/CuS system under nonequilibrium conditions and provide valuable insight into the atomistic lithiation mechanisms of transition metal sulfides in general.« less

Interleukin-6 Induced "Acute" Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics.

PubMed

Xue, Ting; Liu, Ping; Zhou, Yong; Liu, Kun; Yang, Li; Moritz, Robert L; Yan, Wei; Xu, Lisa X

2016-01-01

Cryo-thermal therapy has been emerged as a promising novel therapeutic strategy for advanced breast cancer, triggering higher incidence of tumor regression and enhanced remission of metastasis than routine treatments. To better understand its anti-tumor mechanism, we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare N-glycoproteome changes in 94 serum samples with and without treatment. We quantified 231 highly confident N-glycosylated proteins using iTRAQ shotgun proteomics. Among them, 53 showed significantly discriminated regulatory patterns over the time course, in which the acute phase response emerged as the most enhanced pathway. The anti-tumor feature of the acute response was further investigated using parallel reaction monitoring target proteomics and flow cytometry on 23 of the 53 significant proteins. We found that cryo-thermal therapy reset the tumor chronic inflammation to an "acute" phenotype, with up-regulation of acute phase proteins including IL-6 as a key regulator. The IL-6 mediated "acute" phenotype transformed IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN-γ and IL-12 production, augmented complement system activation and CD86(+)MHCII(+) dendritic cells maturation and enhanced the proliferation of Th1 memory cells. In addition, we found an increased production of tumor progression and metastatic inhibitory proteins under such "acute" environment, favoring the anti-metastatic effect. Moreover, cryo-thermal on tumors induced the strongest "acute" response compared to cryo/hyperthermia alone or cryo-thermal on healthy tissues, accompanying by the most pronounced anti-tumor immunological effect. In summary, we demonstrated that cryo-thermal therapy induced, IL-6 mediated "acute" microenvironment shifted the tumor chronic microenvironment from Th2 immunosuppressive and pro-tumorigenic to Th1 immunostimulatory and tumoricidal state. Moreover, the magnitude of "acute" and "danger" signals play a key role in determining the efficacy of anti-tumor activity.

Stimulation of the Lateral Geniculate, Superior Colliculus, or Visual Cortex is Sufficient for Eyeblink Conditioning in Rats

ERIC Educational Resources Information Center

Halverson, Hunter E.; Hubbard, Erin M.; Freeman, John H.

2009-01-01

The role of the cerebellum in eyeblink conditioning is well established. Less work has been done to identify the necessary conditioned stimulus (CS) pathways that project sensory information to the cerebellum. A possible visual CS pathway has been hypothesized that consists of parallel inputs to the pontine nuclei from the lateral geniculate…

Sparse Partial Equilibrium Tables in Chemically Resolved Reactive Flow

NASA Astrophysics Data System (ADS)

Vitello, Peter; Fried, Laurence E.; Pudliner, Brian; McAbee, Tom

2004-07-01

The detonation of an energetic material is the result of a complex interaction between kinetic chemical reactions and hydrodynamics. Unfortunately, little is known concerning the detailed chemical kinetics of detonations in energetic materials. CHEETAH uses rate laws to treat species with the slowest chemical reactions, while assuming other chemical species are in equilibrium. CHEETAH supports a wide range of elements and condensed detonation products and can also be applied to gas detonations. A sparse hash table of equation of state values is used in CHEETAH to enhance the efficiency of kinetic reaction calculations. For large-scale parallel hydrodynamic calculations, CHEETAH uses parallel communication to updates to the cache. We present here details of the sparse caching model used in the CHEETAH coupled to an ALE hydrocode. To demonstrate the efficiency of modeling using a sparse cache model we consider detonations in energetic materials.

Evolution of amino acid metabolism inferred through cladistic analysis.

PubMed

Cunchillos, Chomin; Lecointre, Guillaume

2003-11-28

Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

PubMed Central

Ueki, Iori

2010-01-01

Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions. PMID:20162368

Oscillations and patterns in a model of simultaneous CO and C2H2 oxidation and NO(x) reduction in a cross-flow reactor.

PubMed

Hadač, Otto; Kohout, Martin; Havlica, Jaromír; Schreiber, Igor

2015-03-07

A model describing simultaneous catalytic oxidation of CO and C2H2 and reduction of NOx in a cross-flow tubular reactor is explored with the aim of relating spatiotemporal patterns to specific pathways in the mechanism. For that purpose, a detailed mechanism proposed for three-way catalytic converters is split into two subsystems, (i) simultaneous oxidation of CO and C2H2, and (ii) oxidation of CO combined with NOx reduction. The ability of these two subsystems to display mechanism-specific dynamical effects is studied initially by neglecting transport phenomena and applying stoichiometric network and bifurcation analyses. We obtain inlet temperature - inlet oxygen concentration bifurcation diagrams, where each region possessing specific dynamics - oscillatory, bistable and excitable - is associated with a dominant reaction pathway. Next, the spatiotemporal behaviour due to reaction kinetics combined with transport processes is studied. The observed spatiotemporal patterns include phase waves, travelling fronts, pulse waves and spatiotemporal chaos. Although these types of pattern occur generally when the kinetic scheme possesses autocatalysis, we find that some of their properties depend on the underlying dominant reaction pathway. The relation of patterns to specific reaction pathways is discussed.

Effects of a Protic Ionic Liquid on the Reaction Pathway during Non-Aqueous Sol–Gel Synthesis of Silica: A Raman Spectroscopic Investigation

PubMed Central

Martinelli, Anna

2014-01-01

The reaction pathway during the formation of silica via a two-component “non-aqueou” sol-gel synthesis is studied by in situ time-resolved Raman spectroscopy. This synthetic route is followed with and without the addition of the protic ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide (C2HImTFSI) in order to investigate its effect on the reaction pathway. We demonstrate that Raman spectroscopy is suitable to discriminate between different silica intermediates, which are produced and consumed at different rates with respect to the point of gelation. We find that half-way to gelation monomers and shorter chains are the most abundant silica species, while the formation of silica rings strongly correlates to the sol-to-gel transition. Thus, curling up of linear chains is here proposed as a plausible mechanism for the formation of small rings. These in turn act as nucleation sites for the condensation of larger rings and thus the formation of the open and polymeric silica network. We find that the protic ionic liquid does not change the reaction pathway per se, but accelerates the cyclization process, intermediated by the faster inclusion of monomeric species. PMID:24743891

Chemical failure modes of AlQ3-based OLEDs: AlQ3 hydrolysis.

PubMed

Knox, John E; Halls, Mathew D; Hratchian, Hrant P; Schlegel, H Bernhard

2006-03-28

Tris(8-hydroxyquinoline)aluminum(III), AlQ3, is used in organic light-emitting diodes (OLEDs) as an electron-transport material and emitting layer. The reaction of AlQ3 with trace H2O has been implicated as a major failure pathway for AlQ3-based OLEDs. Hybrid density functional calculations have been carried out to characterize the hydrolysis of AlQ3. The thermochemical and atomistic details for this important reaction are reported for both the neutral and oxidized AlQ3/AlQ3+ systems. In support of experimental conclusions, the neutral hydrolysis reaction pathway is found to be a thermally activated process, having a classical barrier height of 24.2 kcal mol(-1). First-principles infrared and electronic absorption spectra are compared to further characterize AlQ3 and the hydrolysis pathway product, AlQ2OH. The activation energy for the cationic AlQ3 hydrolysis pathway is found to be 8.5 kcal mol(-1) lower than for the neutral reaction, which is significant since it suggests a role for charge imbalance in promoting chemical failure modes in OLED devices.

Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity ?

PubMed Central

Herskind, Carsten; Talbot, Christopher J.; Kerns, Sarah L.; Veldwijk, Marlon R.; Rosenstein, Barry S.; West, Catharine M. L.

2016-01-01

Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy. PMID:26944314

A Detailed Chemical Kinetic Reaction Mechanism for n-Alkane Hydrocarbons from n-Octane to n-Hexadecane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westbrook, C K; Pitz, W J; Herbinet, O

2007-09-25

Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of the n-alkanes, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on previous mechanisms for n-heptane, using the same reaction class mechanism construction developed initially for n-heptane. Individual reaction class rules are as simple as possible in order to focus onmore » the parallelism between all of the n-alkane fuels included in the mechanisms, and there is an intent to develop these mechanisms further in the future to incorporate greater levels of accuracy and predictive capability. Several of these areas for improvement are identified and explained in detail. These mechanisms are validated through comparisons between computed and experimental data from as many different sources as possible. In addition, numerical experiments are carried out to examine features of n-alkane combustion in which the detailed mechanisms can be used to compare processes in all of the n-alkane fuels. The mechanisms for all of these n-alkanes are presented as a single detailed mechanism, which can be edited to produce efficient mechanisms for any of the n-alkanes included, and the entire mechanism, with supporting thermochemical and transport data, together with an explanatory glossary explaining notations and structural details, will be available on our web page when the paper is accepted for publication.« less

A Detailed Chemical Kinetic Reaction Mechanism for n-Alkane Hydrocarbons From n-Octane to n-Hexadecane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westbrook, C K; Pitz, W J; Herbinet, O

2008-02-08

Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of nine n-alkanes larger than n-heptane, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on our previous mechanisms for the primary reference fuels n-heptane and iso-octane, using the reaction class mechanism construction first developed for n-heptane. Individual reaction class rules aremore » as simple as possible in order to focus on the parallelism between all of the n-alkane fuels included in the mechanisms, and these mechanisms will be refined further in the future to incorporate greater levels of accuracy and predictive capability. These mechanisms are validated through extensive comparisons between computed and experimental data from a wide variety of different sources. In addition, numerical experiments are carried out to examine features of n-alkane combustion in which the detailed mechanisms can be used to compare reactivities of different n-alkane fuels. The mechanisms for all of these n-alkanes are presented as a single detailed mechanism, which can be edited to produce efficient mechanisms for any of the n-alkanes included, and the entire mechanism, with supporting thermochemical and transport data, together with an explanatory glossary explaining notations and structural details, will be available for download from our web page.« less

High-resolution mineralogical characterization and biogeochemical modeling of uranium reaction pathways at the FRC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Zhu

2006-06-15

High-Resolution Mineralogical Characterization and Biogeochemical Modeling of Uranium Reduction Pathways at the Oak Ridge Field-Research Center (FRC) Chen Zhu, Indiana University, David R. Veblen, Johns Hopkins University We have successfully completed a proof-of-concept, one-year grant on a three-year proposal from the former NABIR program, and here we seek additional two-year funding to complete and publish the research. Using a state-of-the-art 300-kV, atomic resolution, Field Emission Gun Transmission Electron Microscope (TEM), we have successfully identified three categories of mineral hosts for uranium in contaminated soils: (1) iron oxides; (2) mixed manganese-iron oxides; and (3) uranium phosphates. Method development using parallel electronmore » energy loss spectroscopy (EELS) associated with the TEM shows great promise for characterizing the valence states of immobilized U during bioremediation. We have also collected 27 groundwater samples from two push-pull field biostimulation tests, which form two time series from zero to approximately 600 hours. The temporal evolution in major cations, anions, trace elements, and the stable isotopes 34S, 18O in sulfate, 15N in nitrate, and 13C in dissolved inorganic carbon (DIC) clearly show that biostimulation resulted in reduction of nitrate, Mn(IV), Fe(III), U(VI), sulfate, and Tc(VII), and these reduction reactions were intimately coupled with a complex network of inorganic reactions evident from alkalinity, pH, Na, K, Mg, and Ca concentrations. From these temporal trends, apparent zero order rates were regressed. However, our extensive suite of chemical and isotopic data sets, perhaps the first and only comprehensive data set available at the FRC, show that the derived rates from these field biostimulation experiments are composite and lump-sum rates. There were several reactions that were occurring at the same time but were masked by these pseudo-zero order rates. A reaction-path model comprising a total of nine redox couples (NO3–/NH4+, MnO2(s)/Mn2+, Fe(OH)3(s) /Fe2+, TcO4–/TcO2(s), UO22+/UO2(s), SO42–/HS–, CO2/CH4, ethanol/acetate, and H+/H2.) is used to simulate the temporal biogeochemical evolution observed in the field tests. Preliminary results show that the models based on thermodynamics and more complex rate laws can generate the apparent zero order rates when several concurrent or competing reactions occur. Professor Alex Halliday of Oxford University, UK, and his postdoctoral associates are measuring the uranium isotopes in our groundwater samples. Newly developed state-of-the-art analytical techniques in measuring variability in 235U/238U offer the potential to distinguish biotic and abiotic uranium reductive mechanisms.« less

Meta-All: a system for managing metabolic pathway information.

PubMed

Weise, Stephan; Grosse, Ivo; Klukas, Christian; Koschützki, Dirk; Scholz, Uwe; Schreiber, Falk; Junker, Björn H

2006-10-23

Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed. We have designed META-ALL, an information system that allows the management of metabolic pathways, including reaction kinetics, detailed locations, environmental factors and taxonomic information. Data can be stored together with quality tags and in different parallel versions. META-ALL uses Oracle DBMS and Oracle Application Express. We provide the META-ALL information system for download and use. In this paper, we describe the database structure and give information about the tools for submitting and accessing the data. As a first application of META-ALL, we show how the information contained in a detailed kinetic model can be stored and accessed. META-ALL is a system for managing information about metabolic pathways. It facilitates the handling of pathway-related data and is designed to help biochemists and molecular biologists in their daily research. It is available on the Web at http://bic-gh.de/meta-all and can be downloaded free of charge and installed locally.

Meta-All: a system for managing metabolic pathway information

PubMed Central

Weise, Stephan; Grosse, Ivo; Klukas, Christian; Koschützki, Dirk; Scholz, Uwe; Schreiber, Falk; Junker, Björn H

2006-01-01

Background Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed. Results We have designed META-ALL, an information system that allows the management of metabolic pathways, including reaction kinetics, detailed locations, environmental factors and taxonomic information. Data can be stored together with quality tags and in different parallel versions. META-ALL uses Oracle DBMS and Oracle Application Express. We provide the META-ALL information system for download and use. In this paper, we describe the database structure and give information about the tools for submitting and accessing the data. As a first application of META-ALL, we show how the information contained in a detailed kinetic model can be stored and accessed. Conclusion META-ALL is a system for managing information about metabolic pathways. It facilitates the handling of pathway-related data and is designed to help biochemists and molecular biologists in their daily research. It is available on the Web at and can be downloaded free of charge and installed locally. PMID:17059592

The "parallel pathway": a novel nutritional and metabolic approach to cancer patients.

PubMed

Muscaritoli, Maurizio; Molfino, Alessio; Gioia, Gianfranco; Laviano, Alessandro; Rossi Fanelli, Filippo

2011-04-01

Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia-cachexia syndrome. This condition has a negative impact upon patients' nutritional status. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients' nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named "parallel pathway", has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The "parallel pathway" implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey.

Computed Potential Energy Surfaces and Minimum Energy Pathway for Chemical Reactions

NASA Technical Reports Server (NTRS)

Walch, Stephen P.; Langhoff, S. R. (Technical Monitor)

1994-01-01

Computed potential energy surfaces are often required for computation of such observables as rate constants as a function of temperature, product branching ratios, and other detailed properties. We have found that computation of the stationary points/reaction pathways using CASSCF/derivative methods, followed by use of the internally contracted CI method with the Dunning correlation consistent basis sets to obtain accurate energetics, gives useful results for a number of chemically important systems. Applications to complex reactions leading to NO and soot formation in hydrocarbon combustion are discussed.

New challenges for text mining: mapping between text and manually curated pathways

PubMed Central

Oda, Kanae; Kim, Jin-Dong; Ohta, Tomoko; Okanohara, Daisuke; Matsuzaki, Takuya; Tateisi, Yuka; Tsujii, Jun'ichi

2008-01-01

Background Associating literature with pathways poses new challenges to the Text Mining (TM) community. There are three main challenges to this task: (1) the identification of the mapping position of a specific entity or reaction in a given pathway, (2) the recognition of the causal relationships among multiple reactions, and (3) the formulation and implementation of required inferences based on biological domain knowledge. Results To address these challenges, we constructed new resources to link the text with a model pathway; they are: the GENIA pathway corpus with event annotation and NF-kB pathway. Through their detailed analysis, we address the untapped resource, ‘bio-inference,’ as well as the differences between text and pathway representation. Here, we show the precise comparisons of their representations and the nine classes of ‘bio-inference’ schemes observed in the pathway corpus. Conclusions We believe that the creation of such rich resources and their detailed analysis is the significant first step for accelerating the research of the automatic construction of pathway from text. PMID:18426550

Comprehensive speciation of low-molecular weight selenium metabolites in mustard seeds using HPLC-electrospray linear trap/Orbitrap tandem mass spectrometry.

PubMed

Ouerdane, Laurent; Aureli, Federica; Flis, Paulina; Bierla, Katarzyna; Preud'homme, Hugues; Cubadda, Francesco; Szpunar, Joanna

2013-09-01

An analytical methodology based on high-resolution high mass accuracy electrospray ionization (ESI) tandem MS assisted by Se-specific detection using inductively coupled plasma mass spectrometry (ICP MS) was developed for speciation of selenium (Se) in seeds of black mustard (Brassica nigra) grown on Se-rich soil. Size-exclusion LC-ICP MS allowed the determination of the Se distribution according to the molecular mass and the control of the species stability during extraction. The optimization of hydrophilic interaction of LC and cation-exchange HPLC resulted in analytical conditions making it possible to detect and characterize over 30 Se species using ESI MS, including a number of minor (<0.5%) metabolites. Selenoglucosinolates were found to be the most important class of species accounting for at least 15% of the total Se present and over 50% of all the metabolites. They were found particularly unstable during aqueous extraction leading to the loss of Se by volatilization as methylselenonitriles and methylselenoisothiocyanates identified using gas chromatography (GC) with the parallel ICP MS and atmospheric pressure chemical ionization (APCI) MS/MS detection. However, selenoglucosinolates could be efficiently recovered by extraction with 70% methanol. Other classes of identified species included selenoamino acids, selenosugars, selenosinapine and selenourea derivatives. The three types of reactions leading to the formation of selenometabolites were: the Se-S substitution in the metabolic pathway, oxidative reactions of -SeH groups with endogenous biomolecules, and chemical reactions, e.g., esterification, of Se-containing molecules and other biomolecules through functional groups not involving Se.

UV/chlorine treatment of carbamazepine: Transformation products and their formation kinetics.

PubMed

Pan, Yanheng; Cheng, ShuangShuang; Yang, Xin; Ren, Jingyue; Fang, Jingyun; Shang, Chii; Song, Weihua; Lian, Lushi; Zhang, Xinran

2017-06-01

Carbamazepine (CBZ) is one of the pharmaceuticals most frequently detected in the aqueous environment. This study investigated the transformation products when CBZ is degraded by chlorine under ultraviolet (UV) irradiation (the UV/chlorine process). Detailed pathways for the degradation of CBZ were elucidated using ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry (QTOF-MS). CBZ is readily degraded by hydroxyl radicals (HO) and chlorine radicals (Cl) in the UV/chlorine process, and 24 transformation products were identified. The products indicate that the 10,11-double bond and aromatic ring in CBZ are the sites most susceptible to attack by HO and Cl. Subsequent reaction produces hydroxylated and chlorinated aromatic ring products. Four specific products were quantified and their evolution was related with the chlorine dose, pH, and natural organic matter concentration. Their yields showed an increase followed by a decreasing trend with prolonged reaction time. CBZ-10,11-epoxide (I), the main quantified transformation product from HO oxidation, was observed with a peak transformation yield of 3-32% depending on the conditions. The more toxic acridine (IV) was formed involving both HO and Cl with peak transformation yields of 0.4-1%. All four quantified products together amounted to a peak transformation yield of 34.5%. The potential toxicity of the transformation products was assayed by evaluating their inhibition of the bioluminescence of the bacterium Vibrio Fischeri. The inhibition increased at first and the decreased at longer reaction times, which was in parallel with the evolution of transformation products. Copyright © 2017 Elsevier Ltd. All rights reserved.

How Living Things Obtain Energy: A Simpler Explanation.

ERIC Educational Resources Information Center

Igelsrud, Donald E.

1989-01-01

Examines five basic reactions which describe the biochemical pathways for living things obtaining energy. Shows the reactions that occur in respiration after glycolysis, the dehydrogenation reaction, decarboxylation, and two kinds of make-ready reactions which prepare molecules for further dehydrogenation and decarboxylation. Diagrams are…

Greener Pathways to Organics and Nanomaterials: Sustainable Applications of Nano-Catalysts(South Korea)

EPA Science Inventory

Sustainable chemical synthetic activity involving alternate energy input, and greener reaction medium in aqueous or solvent-free conditions will be summarized for heterocyclic compounds, coupling reactions, and a variety of name reactions; these reactions are catalyzed by basic w...

Parallel Distributed Processing and Lexical-Semantic Effects in Visual Word Recognition: Are a Few Stages Necessary?

ERIC Educational Resources Information Center

Borowsky, Ron; Besner, Derek

2006-01-01

D. C. Plaut and J. R. Booth presented a parallel distributed processing model that purports to simulate human lexical decision performance. This model (and D. C. Plaut, 1995) offers a single mechanism account of the pattern of factor effects on reaction time (RT) between semantic priming, word frequency, and stimulus quality without requiring a…

Electrophysiological evidence for parallel and serial processing during visual search.

PubMed

Luck, S J; Hillyard, S A

1990-12-01

Event-related potentials were recorded from young adults during a visual search task in order to evaluate parallel and serial models of visual processing in the context of Treisman's feature integration theory. Parallel and serial search strategies were produced by the use of feature-present and feature-absent targets, respectively. In the feature-absent condition, the slopes of the functions relating reaction time and latency of the P3 component to set size were essentially identical, indicating that the longer reaction times observed for larger set sizes can be accounted for solely by changes in stimulus identification and classification time, rather than changes in post-perceptual processing stages. In addition, the amplitude of the P3 wave on target-present trials in this condition increased with set size and was greater when the preceding trial contained a target, whereas P3 activity was minimal on target-absent trials. These effects are consistent with the serial self-terminating search model and appear to contradict parallel processing accounts of attention-demanding visual search performance, at least for a subset of search paradigms. Differences in ERP scalp distributions further suggested that different physiological processes are utilized for the detection of feature presence and absence.

PFLOTRAN: Reactive Flow & Transport Code for Use on Laptops to Leadership-Class Supercomputers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammond, Glenn E.; Lichtner, Peter C.; Lu, Chuan

PFLOTRAN, a next-generation reactive flow and transport code for modeling subsurface processes, has been designed from the ground up to run efficiently on machines ranging from leadership-class supercomputers to laptops. Based on an object-oriented design, the code is easily extensible to incorporate additional processes. It can interface seamlessly with Fortran 9X, C and C++ codes. Domain decomposition parallelism is employed, with the PETSc parallel framework used to manage parallel solvers, data structures and communication. Features of the code include a modular input file, implementation of high-performance I/O using parallel HDF5, ability to perform multiple realization simulations with multiple processors permore » realization in a seamless manner, and multiple modes for multiphase flow and multicomponent geochemical transport. Chemical reactions currently implemented in the code include homogeneous aqueous complexing reactions and heterogeneous mineral precipitation/dissolution, ion exchange, surface complexation and a multirate kinetic sorption model. PFLOTRAN has demonstrated petascale performance using 2{sup 17} processor cores with over 2 billion degrees of freedom. Accomplishments achieved to date include applications to the Hanford 300 Area and modeling CO{sub 2} sequestration in deep geologic formations.« less

Characterization of phenol and cresol biodegradation by compound-specific stable isotope analysis.

PubMed

Wei, Xi; Gilevska, Tetyana; Wetzig, Felix; Dorer, Conrad; Richnow, Hans-Hermann; Vogt, Carsten

2016-03-01

Microbial degradation of phenol and cresols can occur under oxic and anoxic conditions by different degradation pathways. One recent technique to take insight into reaction mechanisms is compound-specific isotope analysis (CSIA). While enzymes and reaction mechanisms of several degradation pathways have been characterized in (bio)chemical studies, associated isotope fractionation patterns have been rarely reported, possibly due to constraints in current analytical methods. In this study, carbon enrichment factors and apparent kinetic isotope effects (AKIEc) of the initial steps of different aerobic and anaerobic phenol and cresols degradation pathways were analyzed by isotope ratio mass spectrometry connected with liquid chromatography (LC-IRMS). Significant isotope fractionation was detected for aerobic ring hydroxylation, anoxic side chain hydroxylation, and anoxic fumarate addition, while anoxic carboxylation reactions produced small and inconsistent fractionation. The results suggest that several microbial degradation pathways of phenol and cresols are detectable in the environment by CSIA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism insight into the cyanide-catalyzed benzoin condensation: a density functional theory study.

PubMed

He, Yunqing; Xue, Ying

2010-09-02

The reaction mechanism of the cyanide-catalyzed benzoin condensation without protonic solvent assistance has been studied computationally for the first time employing the density functional theory (B3LYP) method in conjunction with 6-31+G(d,p) basis set. Four possible pathways have been investigated. A new proposed pathway on the basis of the Lapworth mechanism is determined to be the dominant pathway in aprotic solvent, in which the formation of the Lapworth's cyanohydrin intermediate is a sequence including three steps assisted by benzaldehyde, clearly manifesting that the reaction can take place in aprotic solvents such as DMSO. In this favorable pathway with six possible transition states located along the potential energy surface, the reaction of the cyanide/benzaldehyde complex with another benzaldehyde to afford an alpha-hydroxy ether is the rate-determining dynamically with the activation free energy barrier of 26.9 kcal/mol, and the step to form cyanohydrin intermediate from alpha-hydroxy ether is partially rate-determining for its relatively significant barrier 20.0 kcal/mol.

Hemoglobin as a nitrite anhydrase: modeling methemoglobin-mediated N2O3 formation.

PubMed

Hopmann, Kathrin H; Cardey, Bruno; Gladwin, Mark T; Kim-Shapiro, Daniel B; Ghosh, Abhik

2011-05-27

Nitrite has recently been recognized as a storage form of NO in blood and as playing a key role in hypoxic vasodilation. The nitrite ion is readily reduced to NO by hemoglobin in red blood cells, which, as it happens, also presents a conundrum. Given NO's enormous affinity for ferrous heme, a key question concerns how it escapes capture by hemoglobin as it diffuses out of the red cells and to the endothelium, where vasodilation takes place. Dinitrogen trioxide (N(2)O(3)) has been proposed as a vehicle that transports NO to the endothelium, where it dissociates to NO and NO(2). Although N(2)O(3) formation might be readily explained by the reaction Hb-Fe(3+)+NO(2)(-)+NO⇌Hb-Fe(2+)+N(2)O(3), the exact manner in which methemoglobin (Hb-Fe(3+)), nitrite and NO interact with one another is unclear. Both an "Hb-Fe(3+)-NO(2)(-)+NO" pathway and an "Hb-Fe(3+)-NO+NO(2)(-) " pathway have been proposed. Neither pathway has been established experimentally. Nor has there been any attempt until now to theoretically model N(2)O(3) formation, the so-called nitrite anhydrase reaction. Both pathways have been examined here in a detailed density functional theory (DFT, B3LYP/TZP) study and both have been found to be feasible based on energetics criteria. Modeling the "Hb-Fe(3+)-NO(2)(-)+NO" pathway proved complex. Not only are multiple linkage-isomeric (N- and O-coordinated) structures conceivable for methemoglobin-nitrite, multiple isomeric forms are also possible for N(2)O(3) (the lowest-energy state has an N-N-bonded nitronitrosyl structure, O(2)N-NO). We considered multiple spin states of methemoglobin-nitrite as well as ferromagnetic and antiferromagnetic coupling of the Fe(3+) and NO spins. Together, the isomerism and spin variables result in a diabolically complex combinatorial space of reaction pathways. Fortunately, transition states could be successfully calculated for the vast majority of these reaction channels, both M(S)=0 and M(S)=1. For a six-coordinate Fe(3+)-O-nitrito starting geometry, which is plausible for methemoglobin-nitrite, we found that N(2)O(3) formation entails barriers of about 17-20 kcal mol(-1) , which is reasonable for a physiologically relevant reaction. For the "Hb-Fe(3+) -NO+NO(2) (-) " pathway, which was also found to be energetically reasonable, our calculations indicate a two-step mechanism. The first step involves transfer of an electron from NO(2)(-) to the Fe(3+)-heme-NO center ({FeNO}(6)) , resulting in formation of nitrogen dioxide and an Fe(2+)-heme-NO center ({FeNO}(7)). Subsequent formation of N(2)O(3) entails a barrier of only 8.1 kcal mol(-1) . From an energetics point of view, the nitrite anhydrase reaction thus is a reasonable proposition. Although it is tempting to interpret our results as favoring the "{FeNO}(6)+NO(2)(-) " pathway over the "Fe(3+)-nitrite+NO" pathway, both pathways should be considered energetically reasonable for a biological reaction and it seems inadvisable to favor a unique reaction channel based solely on quantum chemical modeling. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bridge-bonded formate: active intermediate or spectator species in formic acid oxidation on a Pt film electrode?

PubMed

Chen, Y-X; Heinen, M; Jusys, Z; Behm, R J

2006-12-05

We present and discuss the results of an in situ IR study on the mechanism and kinetics of formic acid oxidation on a Pt film/Si electrode, performed in an attenuated total reflection (ATR) flow cell configuration under controlled mass transport conditions, which specifically aimed at elucidating the role of the adsorbed bridge-bonded formates in this reaction. Potentiodynamic measurements show a complex interplay between formation and desorption/oxidation of COad and formate species and the total Faradaic current. The notably faster increase of the Faradaic current compared to the coverage of bridge-bonded formate in transient measurements at constant potential, but with different formic acid concentrations, reveals that adsorbed formate decomposition is not rate-limiting in the dominant reaction pathway. If being reactive intermediate at all, the contribution of formate adsorption/decomposition to the reaction current decreases with increasing formic acid concentration, accounting for at most 15% for 0.2 M DCOOH at 0.7 VRHE. The rapid build-up/removal of the formate adlayer and its similarity with acetate or (bi-)sulfate adsorption/desorption indicate that the formate adlayer coverage is dominated by a fast dynamic adsorption-desorption equilibrium with the electrolyte, and that formate desorption is much faster than its decomposition. The results corroborate the proposal of a triple pathway reaction mechanism including an indirect pathway, a formate pathway, and a dominant direct pathway, as presented previously (Chen, Y. X.; et al. Angew. Chem. Int. Ed. 2006, 45, 981), in which adsorbed formates act as a site-blocking spectator in the dominant pathway rather than as an active intermediate.

FragariaCyc: A Metabolic Pathway Database for Woodland Strawberry Fragaria vesca

PubMed Central

Naithani, Sushma; Partipilo, Christina M.; Raja, Rajani; Elser, Justin L.; Jaiswal, Pankaj

2016-01-01

FragariaCyc is a strawberry-specific cellular metabolic network based on the annotated genome sequence of Fragaria vesca L. ssp. vesca, accession Hawaii 4. It was built on the Pathway-Tools platform using MetaCyc as the reference. The experimental evidences from published literature were used for supporting/editing existing entities and for the addition of new pathways, enzymes, reactions, compounds, and small molecules in the database. To date, FragariaCyc comprises 66 super-pathways, 488 unique pathways, 2348 metabolic reactions, 3507 enzymes, and 2134 compounds. In addition to searching and browsing FragariaCyc, researchers can compare pathways across various plant metabolic networks and analyze their data using Omics Viewer tool. We view FragariaCyc as a resource for the community of researchers working with strawberry and related fruit crops. It can help understanding the regulation of overall metabolism of strawberry plant during development and in response to diseases and abiotic stresses. FragariaCyc is available online at http://pathways.cgrb.oregonstate.edu. PMID:26973684

KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats.

PubMed

Wrzodek, Clemens; Dräger, Andreas; Zell, Andreas

2011-08-15

The KEGG PATHWAY database provides a widely used service for metabolic and nonmetabolic pathways. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses KGML, a proprietary XML-format. Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g. MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator is freely available as a Java(™) Web Start application and for download at http://www.cogsys.cs.uni-tuebingen.de/software/KEGGtranslator/. KGML files can be downloaded from within the application. clemens.wrzodek@uni-tuebingen.de Supplementary data are available at Bioinformatics online.

Completion of biosynthetic pathways for bacteriochlorophyll g in Heliobacterium modesticaldum: The C8-ethylidene group formation.

PubMed

Tsukatani, Yusuke; Yamamoto, Haruki; Mizoguchi, Tadashi; Fujita, Yuichi; Tamiaki, Hitoshi

2013-10-01

Heliobacteria have the simplest photosynthetic apparatus, i.e., a type-I reaction center lacking a peripheral light-harvesting complex. Bacteriochlorophyll (BChl) g molecules are bound to the reaction center complex and work both as special-pair and antenna pigments. The C8-ethylidene group formation for BChl g is the last missing link in biosynthetic pathways for bacterial special-pair pigments, which include BChls a and b as well. Here, we report that chlorophyllide a oxidoreductase (COR) of Heliobacterium modesticaldum catalyzes the C8-ethylidene formation from 8-vinyl-chlorophyllide a, producing bacteriochlorophyllide g, the direct precursor for BChl g without the farnesyl tail. The finding led to plausible biosynthetic pathways for 8(1)-hydroxy-chlorophyll a, a primary electron acceptor from the special pair in heliobacterial reaction centers. Proposed catalytic mechanisms on hydrogenation reaction of the ethylidene synthase-type CORs are also discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Automated Discovery of Elementary Chemical Reaction Steps Using Freezing String and Berny Optimization Methods.

PubMed

Suleimanov, Yury V; Green, William H

2015-09-08

We present a simple protocol which allows fully automated discovery of elementary chemical reaction steps using in cooperation double- and single-ended transition-state optimization algorithms--the freezing string and Berny optimization methods, respectively. To demonstrate the utility of the proposed approach, the reactivity of several single-molecule systems of combustion and atmospheric chemistry importance is investigated. The proposed algorithm allowed us to detect without any human intervention not only "known" reaction pathways, manually detected in the previous studies, but also new, previously "unknown", reaction pathways which involve significant atom rearrangements. We believe that applying such a systematic approach to elementary reaction path finding will greatly accelerate the discovery of new chemistry and will lead to more accurate computer simulations of various chemical processes.

Catalytic Chemistry of Hydrocarbon Conversion Reactions on Metallic Single Crystals

NASA Astrophysics Data System (ADS)

Tysoe, Wilfred T.

The ability to be able to follow the chemistry of adsorbates on model catalyst surfaces has, in principle, allowed us to peer inside the “black box” of a catalytic reaction and understand the pathway. Such a strategy is most simply implemented for well-ordered single crystal model catalysts for which the catalytic reaction proceeds in ultrahigh vacuum. Thus, in order to be a good model for the supported catalyst, the single crystal should catalyze the reactions with kinetics identical to those for the supported system. This chapter focuses on catalytic systems that fulfill these criteria, namely alkene and alkyne hydrogenation and acetylene cyclotrimerization on Pd(111). The surface chemistry and geometries of the reactants in ultrahigh vacuum are explored in detail allowing fundamental insights into the catalytic reaction pathways to be obtained.

Ab initio study on the 1:2 reaction of CO 2 with dimethylamine

NASA Astrophysics Data System (ADS)

Jamróz, MichałH.; Dobrowolski, Jan Cz.; Borowiak, Marek A.

1997-02-01

The reaction between CO 2 and the dimethylamine molecule in the presence of a second dimethylamine molecule is modeled by the ab initio RHF/3-21G method. Starting from the most stable 1:2 complex, the most effective reaction pathway turned out to be proton transfer between amine molecules followed by immediate proton transfer from one of the amine molecules to the CO 2 moiety. The activation barrier for this pathway (9.54 kcal mol -1 with respect to the 1:2 complex) is within the range of activation energy values found in kinetic studies for similar reactions with different hydroxylamines (from 9.2 to 13.0 kcal mol -1). The reaction product is the cyclic hydrogen bonded complex of dimethylcarbamic acid with dimethylamine.

A toolbox model of evolution of metabolic pathways on networks of arbitrary topology.

PubMed

Pang, Tin Yau; Maslov, Sergei

2011-05-01

In prokaryotic genomes the number of transcriptional regulators is known to be proportional to the square of the total number of protein-coding genes. A toolbox model of evolution was recently proposed to explain this empirical scaling for metabolic enzymes and their regulators. According to its rules, the metabolic network of an organism evolves by horizontal transfer of pathways from other species. These pathways are part of a larger "universal" network formed by the union of all species-specific networks. It remained to be understood, however, how the topological properties of this universal network influence the scaling law of functional content of genomes in the toolbox model. Here we answer this question by first analyzing the scaling properties of the toolbox model on arbitrary tree-like universal networks. We prove that critical branching topology, in which the average number of upstream neighbors of a node is equal to one, is both necessary and sufficient for quadratic scaling. We further generalize the rules of the model to incorporate reactions with multiple substrates/products as well as branched and cyclic metabolic pathways. To achieve its metabolic tasks, the new model employs evolutionary optimized pathways with minimal number of reactions. Numerical simulations of this realistic model on the universal network of all reactions in the KEGG database produced approximately quadratic scaling between the number of regulated pathways and the size of the metabolic network. To quantify the geometrical structure of individual pathways, we investigated the relationship between their number of reactions, byproducts, intermediate, and feedback metabolites. Our results validate and explain the ubiquitous appearance of the quadratic scaling for a broad spectrum of topologies of underlying universal metabolic networks. They also demonstrate why, in spite of "small-world" topology, real-life metabolic networks are characterized by a broad distribution of pathway lengths and sizes of metabolic regulons in regulatory networks.

Acceleration and sensitivity analysis of lattice kinetic Monte Carlo simulations using parallel processing and rate constant rescaling

NASA Astrophysics Data System (ADS)

Núñez, M.; Robie, T.; Vlachos, D. G.

2017-10-01

Kinetic Monte Carlo (KMC) simulation provides insights into catalytic reactions unobtainable with either experiments or mean-field microkinetic models. Sensitivity analysis of KMC models assesses the robustness of the predictions to parametric perturbations and identifies rate determining steps in a chemical reaction network. Stiffness in the chemical reaction network, a ubiquitous feature, demands lengthy run times for KMC models and renders efficient sensitivity analysis based on the likelihood ratio method unusable. We address the challenge of efficiently conducting KMC simulations and performing accurate sensitivity analysis in systems with unknown time scales by employing two acceleration techniques: rate constant rescaling and parallel processing. We develop statistical criteria that ensure sufficient sampling of non-equilibrium steady state conditions. Our approach provides the twofold benefit of accelerating the simulation itself and enabling likelihood ratio sensitivity analysis, which provides further speedup relative to finite difference sensitivity analysis. As a result, the likelihood ratio method can be applied to real chemistry. We apply our methodology to the water-gas shift reaction on Pt(111).

Reactive Transport Modeling of Induced Calcite Precipitation Reaction Fronts in Porous Media Using A Parallel, Fully Coupled, Fully Implicit Approach

NASA Astrophysics Data System (ADS)

Guo, L.; Huang, H.; Gaston, D.; Redden, G. D.; Fox, D. T.; Fujita, Y.

2010-12-01

Inducing mineral precipitation in the subsurface is one potential strategy for immobilizing trace metal and radionuclide contaminants. Generating mineral precipitates in situ can be achieved by manipulating chemical conditions, typically through injection or in situ generation of reactants. How these reactants transport, mix and react within the medium controls the spatial distribution and composition of the resulting mineral phases. Multiple processes, including fluid flow, dispersive/diffusive transport of reactants, biogeochemical reactions and changes in porosity-permeability, are tightly coupled over a number of scales. Numerical modeling can be used to investigate the nonlinear coupling effects of these processes which are quite challenging to explore experimentally. Many subsurface reactive transport simulators employ a de-coupled or operator-splitting approach where transport equations and batch chemistry reactions are solved sequentially. However, such an approach has limited applicability for biogeochemical systems with fast kinetics and strong coupling between chemical reactions and medium properties. A massively parallel, fully coupled, fully implicit Reactive Transport simulator (referred to as “RAT”) based on a parallel multi-physics object-oriented simulation framework (MOOSE) has been developed at the Idaho National Laboratory. Within this simulator, systems of transport and reaction equations can be solved simultaneously in a fully coupled, fully implicit manner using the Jacobian Free Newton-Krylov (JFNK) method with additional advanced computing capabilities such as (1) physics-based preconditioning for solution convergence acceleration, (2) massively parallel computing and scalability, and (3) adaptive mesh refinements for 2D and 3D structured and unstructured mesh. The simulator was first tested against analytical solutions, then applied to simulating induced calcium carbonate mineral precipitation in 1D columns and 2D flow cells as analogs to homogeneous and heterogeneous porous media, respectively. In 1D columns, calcium carbonate mineral precipitation was driven by urea hydrolysis catalyzed by urease enzyme, and in 2D flow cells, calcium carbonate mineral forming reactants were injected sequentially, forming migrating reaction fronts that are typically highly nonuniform. The RAT simulation results for the spatial and temporal distributions of precipitates, reaction rates and major species in the system, and also for changes in porosity and permeability, were compared to both laboratory experimental data and computational results obtained using other reactive transport simulators. The comparisons demonstrate the ability of RAT to simulate complex nonlinear systems and the advantages of fully coupled approaches, over de-coupled methods, for accurate simulation of complex, dynamic processes such as engineered mineral precipitation in subsurface environments.

Ceramic membrane reactor with two reactant gases at different pressures

DOEpatents

Balachandran, Uthamalingam; Mieville, Rodney L.

2001-01-01

The invention is a ceramic membrane reactor for syngas production having a reaction chamber, an inlet in the reactor for natural gas intake, a plurality of oxygen permeating ceramic slabs inside the reaction chamber with each slab having a plurality of passages paralleling the gas flow for transporting air through the reaction chamber, a manifold affixed to one end of the reaction chamber for intake of air connected to the slabs, a second manifold affixed to the reactor for removing the oxygen depleted air, and an outlet in the reaction chamber for removing syngas.

What is adaptive about adaptive decision making? A parallel constraint satisfaction account.

PubMed

Glöckner, Andreas; Hilbig, Benjamin E; Jekel, Marc

2014-12-01

There is broad consensus that human cognition is adaptive. However, the vital question of how exactly this adaptivity is achieved has remained largely open. Herein, we contrast two frameworks which account for adaptive decision making, namely broad and general single-mechanism accounts vs. multi-strategy accounts. We propose and fully specify a single-mechanism model for decision making based on parallel constraint satisfaction processes (PCS-DM) and contrast it theoretically and empirically against a multi-strategy account. To achieve sufficiently sensitive tests, we rely on a multiple-measure methodology including choice, reaction time, and confidence data as well as eye-tracking. Results show that manipulating the environmental structure produces clear adaptive shifts in choice patterns - as both frameworks would predict. However, results on the process level (reaction time, confidence), in information acquisition (eye-tracking), and from cross-predicting choice consistently corroborate single-mechanisms accounts in general, and the proposed parallel constraint satisfaction model for decision making in particular. Copyright © 2014 Elsevier B.V. All rights reserved.

Resistance to awareness of the supervisor's transferences with special reference to the parallel process.

PubMed

Stimmel, B

1995-06-01

Supervision is an essential part of psychoanalytic education. Although not taken for granted, it is not studied with the same critical eye as is the analytic process. This paper examines the supervision specifically with a focus on the supervisor's transference towards the supervisee. The point is made, in the context of clinical examples, that one of the ways these transference reactions may be rationalised is within the setting of the parallel process so often encountered in supervision. Parallel process, a very familiar term, is used frequently and easily when discussing supervision. It may be used also as a resistance to awareness of transference phenomena within the supervisor in relation to the supervisee, particularly because of its clinical presentation. It is an enactment between supervisor and supervisee, thus ripe with possibilities for disguise, displacement and gratification. While transference reactions of the supervisee are often discussed, those of the supervisor are notably missing in our literature.

Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome

PubMed Central

Milacic, Marija; Haw, Robin; Rothfels, Karen; Wu, Guanming; Croft, David; Hermjakob, Henning; D’Eustachio, Peter; Stein, Lincoln

2012-01-01

Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of “cancer” pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics. PMID:24213504

Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism

PubMed Central

García-Cabezas, Miguel Ángel; Barbas, Helen

2018-01-01

Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans. An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to understand connections in humans. We addressed this question within a theoretical framework of systematic cortical variation and used identical high-resolution methods to compare the architecture of cortical gray matter and the white matter beneath, which gives rise to short- and long-distance pathways in humans and rhesus monkeys. We used the prefrontal cortex as a model system because of its key role in attention, emotions, and executive function, which are processes often affected in brain diseases. We found striking parallels and consistent trends in the gray and white matter architecture in humans and monkeys and between the architecture and actual connections mapped with neural tracers in rhesus monkeys and, by extension, in humans. Using the novel architectonic portrait as a base, we found significant changes in pathways between nearby prefrontal and distant areas in autism. Our findings reveal that a theoretical framework allows study of normal neural communication in humans at high resolution and specific disruptions in diverse psychiatric and neurodegenerative diseases. PMID:29401206

Bipolar cell gap junctions serve major signaling pathways in the human retina.

PubMed

Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

Computational Study of a Model System of Enzyme-Mediated [4+2] Cycloaddition Reaction

PubMed Central

2015-01-01

A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reac-tion was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation. PMID:25853669

A barrier-free atomic radical-molecule reaction: N (2D) NO2 (2A1) mechanistic study

NASA Astrophysics Data System (ADS)

Zuo, Ming-Hui; Liu, Hui-Ling; Huang, Xu-Ri; Zhan, Jin-Hui; Sun, Chia-Chung

The reaction of N (2D) radical with NO2 molecule has been studied theoretically using density functional theory and ab initio quantum chemistry method. Singlet electronic state [N2O2] potential energy surfaces (PES) are calculated at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-311+G(d) + ZPE and G3B3 levels of theory. All the involved transition states for generation of (2NO) and (O2 + N2) lie much lower than the reactants. Thus, the novel reaction N + NO2 can proceed effectively even at low temperatures and it is expected to play a role in both combustion and interstellar processes. On the basis of the analysis of the kinetics of all pathways through which the reactions proceed, we expect that the competitive power of reaction pathways may vary with experimental conditions for the title reaction.

Analyses of bifurcation of reaction pathways on a global reaction route map: A case study of gold cluster Au5

NASA Astrophysics Data System (ADS)

Harabuchi, Yu; Ono, Yuriko; Maeda, Satoshi; Taketsugu, Tetsuya

2015-07-01

A global reaction route map is generated for Au5 by the anharmonic downward distortion following method in which 5 minima and 14 transition states (TSs) are located. Through vibrational analyses in the 3N - 7 (N = 5) dimensional space orthogonal to the intrinsic reaction coordinate (IRC), along all the IRCs, four IRCs are found to have valley-ridge transition (VRT) points on the way where a potential curvature changes its sign from positive to negative in a direction orthogonal to the IRC. The detailed mechanisms of bifurcations related to the VRTs are discussed by surveying a landscape of the global reaction route map, and the connectivity of VRT points and minima is clarified. Branching of the products through bifurcations is confirmed by ab initio molecular dynamics simulations starting from the TSs. A new feature of the reaction pathways, unification, is found and discussed.

Theoretical investigation of the gas-phase reactions of CrO(+) with ethylene.

PubMed

Scupp, Thomas M; Dudley, Timothy J

2010-01-21

The potential energy surfaces associated with the reactions of chromium oxide cation (CrO(+)) with ethylene have been characterized using density functional, coupled-cluster, and multireference methods. Our calculations show that the most probable reaction involves the formation of acetaldehyde and Cr(+) via a hydride transfer involving the metal center. Our calculations support previous experimental hypotheses that a four-membered ring intermediate plays an important role in the reactivity of the system. We have also characterized a number of viable reaction pathways that lead to other products, including ethylene oxide. Due to the experimental observation that CrO(+) can activate carbon-carbon bonds, a reaction pathway involving C-C bond cleavage has also been characterized. Since many of the reactions involve a change in the spin state in going from reactants to products, locations of these spin surface crossings are presented and discussed. The applicability of methods based on Hartree-Fock orbitals is also discussed.

Conditional iron and pH-dependent activity of a non-enzymatic glycolysis and pentose phosphate pathway.

PubMed

Keller, Markus A; Zylstra, Andre; Castro, Cecilia; Turchyn, Alexandra V; Griffin, Julian L; Ralser, Markus

2016-01-01

Little is known about the evolutionary origins of metabolism. However, key biochemical reactions of glycolysis and the pentose phosphate pathway (PPP), ancient metabolic pathways central to the metabolic network, have non-enzymatic pendants that occur in a prebiotically plausible reaction milieu reconstituted to contain Archean sediment metal components. These non-enzymatic reactions could have given rise to the origin of glycolysis and the PPP during early evolution. Using nuclear magnetic resonance spectroscopy and high-content metabolomics that allowed us to measure several thousand reaction mixtures, we experimentally address the chemical logic of a metabolism-like network constituted from these non-enzymatic reactions. Fe(II), the dominant transition metal component of Archean oceanic sediments, has binding affinity toward metabolic sugar phosphates and drives metabolism-like reactivity acting as both catalyst and cosubstrate. Iron and pH dependencies determine a metabolism-like network topology and comediate reaction rates over several orders of magnitude so that the network adopts conditional activity. Alkaline pH triggered the activity of the non-enzymatic PPP pendant, whereas gentle acidic or neutral conditions favored non-enzymatic glycolytic reactions. Fe(II)-sensitive glycolytic and PPP-like reactions thus form a chemical network mimicking structural features of extant carbon metabolism, including topology, pH dependency, and conditional reactivity. Chemical networks that obtain structure and catalysis on the basis of transition metals found in Archean sediments are hence plausible direct precursors of cellular metabolic networks.

Conditional iron and pH-dependent activity of a non-enzymatic glycolysis and pentose phosphate pathway

PubMed Central

Keller, Markus A.; Zylstra, Andre; Castro, Cecilia; Turchyn, Alexandra V.; Griffin, Julian L.; Ralser, Markus

2016-01-01

Little is known about the evolutionary origins of metabolism. However, key biochemical reactions of glycolysis and the pentose phosphate pathway (PPP), ancient metabolic pathways central to the metabolic network, have non-enzymatic pendants that occur in a prebiotically plausible reaction milieu reconstituted to contain Archean sediment metal components. These non-enzymatic reactions could have given rise to the origin of glycolysis and the PPP during early evolution. Using nuclear magnetic resonance spectroscopy and high-content metabolomics that allowed us to measure several thousand reaction mixtures, we experimentally address the chemical logic of a metabolism-like network constituted from these non-enzymatic reactions. Fe(II), the dominant transition metal component of Archean oceanic sediments, has binding affinity toward metabolic sugar phosphates and drives metabolism-like reactivity acting as both catalyst and cosubstrate. Iron and pH dependencies determine a metabolism-like network topology and comediate reaction rates over several orders of magnitude so that the network adopts conditional activity. Alkaline pH triggered the activity of the non-enzymatic PPP pendant, whereas gentle acidic or neutral conditions favored non-enzymatic glycolytic reactions. Fe(II)-sensitive glycolytic and PPP-like reactions thus form a chemical network mimicking structural features of extant carbon metabolism, including topology, pH dependency, and conditional reactivity. Chemical networks that obtain structure and catalysis on the basis of transition metals found in Archean sediments are hence plausible direct precursors of cellular metabolic networks. PMID:26824074

High Throughput Engineering to Revitalize a Vestigial Electron Transfer Pathway in Bacterial Photosynthetic Reaction Centers*

PubMed Central

Faries, Kaitlyn M.; Kressel, Lucas L.; Wander, Marc J.; Holten, Dewey; Laible, Philip D.; Kirmaier, Christine; Hanson, Deborah K.

2012-01-01

Photosynthetic reaction centers convert light energy into chemical energy in a series of transmembrane electron transfer reactions, each with near 100% yield. The structures of reaction centers reveal two symmetry-related branches of cofactors (denoted A and B) that are functionally asymmetric; purple bacterial reaction centers use the A pathway exclusively. Previously, site-specific mutagenesis has yielded reaction centers capable of transmembrane charge separation solely via the B branch cofactors, but the best overall electron transfer yields are still low. In an attempt to better realize the architectural and energetic factors that underlie the directionality and yields of electron transfer, sites within the protein-cofactor complex were targeted in a directed molecular evolution strategy that implements streamlined mutagenesis and high throughput spectroscopic screening. The polycistronic approach enables efficient construction and expression of a large number of variants of a heteroligomeric complex that has two intimately regulated subunits with high sequence similarity, common features of many prokaryotic and eukaryotic transmembrane protein assemblies. The strategy has succeeded in the discovery of several mutant reaction centers with increased efficiency of the B pathway; they carry multiple substitutions that have not been explored or linked using traditional approaches. This work expands our understanding of the structure-function relationships that dictate the efficiency of biological energy-conversion reactions, concepts that will aid the design of bio-inspired assemblies capable of both efficient charge separation and charge stabilization. PMID:22247556

Exploring reaction pathways in the hydrothermal growth of phase-pure bismuth ferrites

NASA Astrophysics Data System (ADS)

Goldman, Abby R.; Fredricks, Jeremy L.; Estroff, Lara A.

2017-06-01

Phase-pure bismuth ferrites (BiFeO3 and Bi2Fe4O9) are grown using hydrothermal synthesis. In addition to varying the KOH, bismuth, and iron salt concentrations to tune which crystalline phases are formed, we identified that a 48 h, pre-furnace, room temperature reaction is critical for the formation of phase-pure BiFeO3. To understand the reaction pathways leading to the different bismuth ferrite phases, we investigate the changes in composition of the intermediate products as a function of reagent concentrations and room temperature reaction times. During the syntheses that included a room temperature reaction, Bi25FeO40 is formed in the intermediate products, and BiFeO3 is the majority phase of the final products. The BiFeO3 crystals grown using this method are clusters of faceted subunits. These results indicate that forming Bi25FeO40 is a productive route to the formation of BiFeO3. Bi2Fe4O9 is formed via an alternate reaction pathway that proceeded via an amorphous precursor. This improved understanding of how hydrothermal synthesis can be used to control the phase-purity and morphology of bismuth ferrites opens doors to explore the multiferroic properties of BiFeO3 with complex morphologies.

Three Rate-Constant Kinetic Model for Permanganate Reactions Autocatalyzed by Colloidal Manganese Dioxide: The Oxidation of L-Phenylalanine.

PubMed

Perez-Benito, Joaquin F; Ferrando, Jordi

2014-12-26

The reduction of permanganate ion to MnO(2)-Mn(2)O(3) soluble colloidal mixed oxide by l-phenylalanine in aqueous phosphate-buffered neutral solutions has been followed by a spectrophotometric method, monitoring the decay of permanganate ion at 525 nm and the formation of the colloidal oxide at 420 nm. The reaction is autocatalyzed by the manganese product, and three rate constants have been required to fit the experimental absorbance-time kinetic data. The reaction shows base catalysis, and the values of the activation parameters at different pHs have been determined. A mechanism including both the nonautocatalytic and the autocatalytic reaction pathways, and in agreement with the available experimental data, has been proposed. Some key features of this mechanism are the following: (i) of the two predominant forms of the amino acid, the anionic form exhibits a stronger reducing power than the zwitterionic form; (ii) the nonautocatalytic reaction pathway starts with the transfer of the hydrogen atom in the α position of the amino acid to permanganate ion; and (iii) the autocatalytic reaction pathway involves the reduction of Mn(IV) to Mn(II) by the amino acid and the posterior reoxidation of Mn(II) to Mn(IV) by permanganate ion.

Fragmentation Pathways of Lithiated Hexose Monosaccharides

NASA Astrophysics Data System (ADS)

Abutokaikah, Maha T.; Frye, Joseph W.; Tschampel, John; Rabus, Jordan M.; Bythell, Benjamin J.

2018-05-01

We characterize the primary fragmentation reactions of three isomeric lithiated D-hexose sugars (glucose, galactose, and mannose) utilizing tandem mass spectrometry, regiospecific labeling, and theory. We provide evidence that these three isomers populate similar fragmentation pathways to produce the abundant cross-ring cleavage peaks (0,2A1 and 0,3A1). These pathways are highly consistent with the prior literature (Hofmeister et al. J. Am. Chem. Soc. 113, 5964-5970, 1991, Bythell et al. J. Am. Soc. Mass Spectrom. 28, 688-703, 2017, Rabus et al. Phys. Chem. Chem. Phys. 19, 25643-25652, 2017) and the present labeling data. However, the structure-specific energetics and rate-determining steps of these reactions differ as a function of precursor sugar and anomeric configuration. The lowest energy water loss pathways involve loss of the anomeric oxygen to furnish B1 ions. For glucose and galactose, the lithiated α-anomers generate ketone structures at C2 in a concerted reaction involving a 1,2-migration of the C2-H to the anomeric carbon (C1). In contrast, the β-anomers are predicted to form 1,3-anhydroglucose/galactose B1 ion structures. Initiation of the water loss reactions from each anomeric configuration requires distinct reactive conformers, resulting in different product ion structures. Inversion of the stereochemistry at C2 has marked consequences. Both lithiated mannose forms expel water to form 1,2-anhydromannose B1 ions with the newly formed epoxide group above the ring. Additionally, provided water loss is not instantaneous, the α-anomer can also isomerize to generate a ketone structure at C2 in a concerted reaction involving a 1,2-migration of the C2-H to C1. This product is indistinguishable to that from α-glucose. The energetics and interplay of these pathways are discussed. [Figure not available: see fulltext.

A Theoretical Study of 8-Chloro-9-Hydroxy-Aflatoxin B₁, the Conversion Product of Aflatoxin B₁ by Neutral Electrolyzed Water.

PubMed

Escobedo-González, René; Méndez-Albores, Abraham; Villarreal-Barajas, Tania; Aceves-Hernández, Juan Manuel; Miranda-Ruvalcaba, René; Nicolás-Vázquez, Inés

2016-07-21

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B₁ (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B₁ (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated-the first one considering only ionic species (Cl⁺ and OH(-)) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C₉ atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays.

The Glycerate and Phosphorylated Pathways of Serine Synthesis in Plants: The Branches of Plant Glycolysis Linking Carbon and Nitrogen Metabolism.

PubMed

Igamberdiev, Abir U; Kleczkowski, Leszek A

2018-01-01

Serine metabolism in plants has been studied mostly in relation to photorespiration where serine is formed from two molecules of glycine. However, two other pathways of serine formation operate in plants and represent the branches of glycolysis diverging at the level of 3-phosphoglyceric acid. One branch (the glycerate - serine pathway) is initiated in the cytosol and involves glycerate formation from 3-phosphoglycerate, while the other (the phosphorylated serine pathway) operates in plastids and forms phosphohydroxypyruvate as an intermediate. Serine formed in these pathways becomes a precursor of glycine, formate and glycolate accumulating in stress conditions. The pathways can be linked to GABA shunt via transamination reactions and via participation of the same reductase for both glyoxylate and succinic semialdehyde. In this review paper we present a hypothesis of the regulation of redox balance in stressed plant cells via participation of the reactions associated with glycerate and phosphorylated serine pathways. We consider these pathways as important processes linking carbon and nitrogen metabolism and maintaining cellular redox and energy levels in stress conditions.

Simulating the reactions of CO2 in aqueous monoethanolamine solution by reaction ensemble Monte Carlo using the continuous fractional component method.

PubMed

Balaji, Sayee Prasaad; Gangarapu, Satesh; Ramdin, Mahinder; Torres-Knoop, Ariana; Zuilhof, Han; Goetheer, Earl L V; Dubbeldam, David; Vlugt, Thijs J H

2015-06-09

Molecular simulations were used to compute the equilibrium concentrations of the different species in CO2/monoethanolamine solutions for different CO2 loadings. Simulations were performed in the Reaction Ensemble using the continuous fractional component Monte Carlo method at temperatures of 293, 333, and 353 K. The resulting computed equilibrium concentrations are in excellent agreement with experimental data. The effect of different reaction pathways was investigated. For a complete understanding of the equilibrium speciation, it is essential to take all elementary reactions into account because considering only the overall reaction of CO2 with MEA is insufficient. The effects of electrostatics and intermolecular van der Waals interactions were also studied, clearly showing that solvation of reactants and products is essential for the reaction. The Reaction Ensemble Monte Carlo using the continuous fractional component method opens the possibility of investigating the effects of the solvent on CO2 chemisorption by eliminating the need to study different reaction pathways and concentrate only on the thermodynamics of the system.

Modeling chemical reactions for drug design.

PubMed

Gasteiger, Johann

2007-01-01

Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

Gas-Phase Anionic σ-Adduct (Trans)formations in Heteroaromatic Systems1

NASA Astrophysics Data System (ADS)

Zimnicka, Magdalena; Danikiewicz, Witold

2015-07-01

Anions of nitroderivatives of thiophene and furan were subjected to the reactions with selected C-H acids in the gas phase. Various structures and reaction pathways were proposed for the observed ionic products. In general, the reactions of heteroaromatic anions with C-H acids may be divided into three groups, depending on the proton affinity difference between C-H acid's conjugate base and heteroaromatic anion (ΔPA). The proton transfer from C-H acid to heteroaromatic anion is a dominant process in the reactions for which ΔPA < 0 kcal mol-1, whereas the reactions with high ΔPA (ΔPA > 16 kcal mol-1) do not lead to any ionic products. The formation of σ-adducts and products of their further transformations according to the VNS, SNAr, cine, and tele substitution mechanisms have been proposed for reactions with moderate ΔPA. The other possible mechanisms as SN2 reaction, nucleophilic addition to the cyano group, ring-opening pathway, and halogenophilic reaction have also been discussed to contribute in the reactions between heteroaromatic anions and C-H acids.

The RNA world and the origin of metabolic enzymes

PubMed Central

Ralser, Markus

2014-01-01

An RNA world has been placed centre stage for explaining the origin of life. Indeed, RNA is the most plausible molecule able to form both a (self)-replicator and to inherit information, necessities for initiating genetics. However, in parallel with self-replication, the proto-organism had to obtain the ability to catalyse supply of its chemical constituents, including the ribonucleotide metabolites required to replicate RNA. Although the possibility of an RNA-catalysed metabolic network has been considered, it is to be questioned whether RNA molecules, at least on their own, possess the required catalytic capacities. An alternative scenario for the origin of metabolism involves chemical reactions that are based on environmental catalysts. Recently, we described a non-enzymatic glycolysis and pentose phosphate pathway-like reactions catalysed by metal ions [mainly Fe(II)] and phosphate, simple inorganic molecules abundantly found in Archaean sediments. While the RNA world can serve to explain the origin of genetics, the origin of the metabolic network might thus date back to constraints of environmental chemistry. Interestingly, considering a metal-catalysed origin of metabolism gives rise to an attractive hypothesis about how the first enzymes could have formed: simple RNA or (poly)peptide molecules could have bound the metal ions, and thus increased their solubility, concentration and accessibility. In a second step, this would have allowed substrate specificity to evolve. PMID:25109990

Adenine radicals generated in alternating AT duplexes by direct absorption of low-energy UV radiation.

PubMed

Banyasz, Akos; Ketola, Tiia; Martínez-Fernández, Lara; Improta, Roberto; Markovitsi, Dimitra

2018-04-17

There is increasing evidence that the direct absorption of photons with energies that are lower than the ionization potential of nucleobases may result in oxidative damage to DNA. The present work, which combines nanosecond transient absorption spectroscopy and quantum mechanical calculations, studies this process in alternating adenine-thymine duplexes (AT)n. We show that the one-photon ionization quantum yield of (AT)10 at 266 nm (4.66 eV) is (1.5 ± 0.3) × 10-3. According to our PCM/TD-DFT calculations carried out on model duplexes composed of two base pairs, (AT)1 and (TA)1, simultaneous base pairing and stacking does not induce important changes in the absorption spectra of the adenine radical cation and deprotonated radical. The adenine radicals, thus identified in the time-resolved spectra, disappear with a lifetime of 2.5 ms, giving rise to a reaction product that absorbs at 350 nm. In parallel, the fingerprint of reaction intermediates other than radicals, formed directly from singlet excited states and assigned to AT/TA dimers, is detected at shorter wavelengths. PCM/TD-DFT calculations are carried out to map the pathways leading to such species and to characterize their absorption spectra; we find that, in addition to the path leading to the well-known TA* photoproduct, an AT photo-dimerization path may be operative in duplexes.

Emotional reactivity and awareness of task performance in Alzheimer's disease.

PubMed

Mograbi, Daniel C; Brown, Richard G; Salas, Christian; Morris, Robin G

2012-07-01

Lack of awareness about performance in tasks is a common feature of Alzheimer's disease. Nevertheless, clinical anecdotes have suggested that patients may show emotional or behavioural responses to the experience of failure despite reporting limited awareness, an aspect which has been little explored experimentally. The current study investigated emotional reactions to success or failure in tasks despite unawareness of performance in Alzheimer's disease. For this purpose, novel computerised tasks which expose participants to systematic success or failure were used in a group of Alzheimer's disease patients (n=23) and age-matched controls (n=21). Two experiments, the first with reaction time tasks and the second with memory tasks, were carried out, and in each experiment two parallel tasks were used, one in a success condition and one in a failure condition. Awareness of performance was measured comparing participant estimations of performance with actual performance. Emotional reactivity was assessed with a self-report questionnaire and rating of filmed facial expressions. In both experiments the results indicated that, relative to controls, Alzheimer's disease patients exhibited impaired awareness of performance, but comparable differential reactivity to failure relative to success tasks, both in terms of self-report and facial expressions. This suggests that affective valence of failure experience is processed despite unawareness of task performance, which might indicate implicit processing of information in neural pathways bypassing awareness. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Feasibility of Studying 44Ti(α, p)47V Reaction at Astrophysical Energies

NASA Astrophysics Data System (ADS)

Al-Abdullah, Tariq; Bemmerer, D.; Elekes, Z.; Schumann, D.

2018-01-01

The gamma-ray lines from the decay of 44Ti have been observed by space-based gamma-ray telescopes from two supernova remnants. It is believed that the 44Ti(α, p)47V reaction dominates the destruction of 44Ti. This work presents a possible technique to determine its reaction rate in forward kinematics at astrophysically relevant energies. Several online and offline measurements in parallel with Monte Carlo simulations were performed to illustrate the feasibility of performing this reaction. The results will be discussed.

Mass action at the single-molecule level.

PubMed

Shon, Min Ju; Cohen, Adam E

2012-09-05

We developed a system to reversibly encapsulate small numbers of molecules in an array of nanofabricated "dimples". This system enables highly parallel, long-term, and attachment-free studies of molecular dynamics via single-molecule fluorescence. In studies of bimolecular reactions of small numbers of confined molecules, we see phenomena that, while expected from basic statistical mechanics, are not observed in bulk chemistry. Statistical fluctuations in the occupancy of sealed reaction chambers lead to steady-state fluctuations in reaction equilibria and rates. These phenomena are likely to be important whenever reactions happen in confined geometries.

Real-time elucidation of catalytic pathways in CO hydrogenation on Ru

DOE PAGES

LaRue, Jerry; Krejci, Ondrej; Yu, Liang; ...

2017-07-31

Here, the direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast timescales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO 2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time x-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

Hypothesis: Hemolytic Transfusion Reactions Represent an Alternative Type of Anaphylaxis

PubMed Central

Hod, Eldad A.; Sokol, Set A.; Zimring, James C.; Spitalnik, Steven L.

2009-01-01

Classical anaphylaxis is the most severe, and potentially fatal, type of allergic reaction, manifested by hypotension, bronchoconstriction, and vascular permeability. Similarly, a hemolytic transfusion reaction (HTR) is the most feared consequence of blood transfusion. Evidence for the existence of an alternative, IgG-mediated pathway of anaphylaxis may be relevant for explaining the pathophysiology of IgG-mediated-HTRs. The purpose of this review is to summarize the evidence for this alternative pathway of anaphylaxis and to present the hypothesis that an IgG-mediated HTR is one example of this type of anaphylaxis. PMID:18830382

Hydrogen bonding effects on the reorganization energy for photoinduced charge separation reaction between porphyrin and quinone studied by nanosecond laser flash photolysis.

PubMed

Yago, Tomoaki; Gohdo, Masao; Wakasa, Masanobu

2010-02-25

Alcohol concentration dependences of photoinduced charge separation (CS) reaction of zinc tetraphenyl-porphyrin (ZnTPP) and duroquinone (DQ) were investigated in benzonitrile by a nanosecond laser flash photolysis technique. The photoinduced CS reaction was accelerated by the addition of alcohols, whereas the addition of acetonitrile caused little effect on the CS reactions. The simple theory was developed to calculate an increase in reorganization energies induced by the hydrogen bonding interactions between DQ and alcohols using the chemical equilibrium constants for the hydrogen bonding complexes through the concerted pathway and the stepwise one. The experimental results were analyzed by using the Marcus equation where we took into account the hydrogen bonding effects on the reorganization energy and the reaction free energy for the CS reaction. The observed alcohol concentration dependence of the CS reaction rates was well explained by the formation of the hydrogen bonding complexes through the concerted pathway, demonstrating the increase in the reorganization energy by the hydrogen bonding interactions.

Revealing a double-inversion mechanism for the F⁻+CH₃Cl SN2 reaction.

PubMed

Szabó, István; Czakó, Gábor

2015-01-19

Stereo-specific reaction mechanisms play a fundamental role in chemistry. The back-side attack inversion and front-side attack retention pathways of the bimolecular nucleophilic substitution (SN2) reactions are the textbook examples for stereo-specific chemical processes. Here, we report an accurate global analytic potential energy surface (PES) for the F(-)+CH₃Cl SN2 reaction, which describes both the back-side and front-side attack substitution pathways as well as the proton-abstraction channel. Moreover, reaction dynamics simulations on this surface reveal a novel double-inversion mechanism, in which an abstraction-induced inversion via a FH···CH₂Cl(-) transition state is followed by a second inversion via the usual [F···CH₃···Cl](-) saddle point, thereby opening a lower energy reaction path for retention than the front-side attack. Quasi-classical trajectory computations for the F(-)+CH₃Cl(ν1=0, 1) reactions show that the front-side attack is a fast direct, whereas the double inversion is a slow indirect process.

Gaseous species as reaction tracers in the solvothermal synthesis of the zinc oxide terephthalate MOF-5.

PubMed

Hausdorf, Steffen; Baitalow, Felix; Seidel, Jürgen; Mertens, Florian O R L

2007-05-24

Gaseous species emitted during the zinc oxide/zinc hydroxide 1,4-benzenedicarboxylate metal organic framework synthesis (MOF-5, MOF-69c) have been used to investigate the reaction scheme that leads to the framework creation. Changes of the gas-phase composition over time indicate that the decomposition of the solvent diethylformamide occurs at least via two competing reaction pathways that can be linked to the reaction's overall water and pH management. From isotope exchange experiments, we deduce that one of the decomposition pathways leads to the removal of water from the reaction mixture, which sets the conditions when the synthesis of an oxide-based (MOF-5) instead of an hydroxide-based MOF (MOF-69c) occurs. A quantitative account of most reactants and byproducts before and after the MOF-5/MOF-69c synthesis is presented. From the investigation of the reaction intermediates and byproducts, we derive a proposal of a basic reaction scheme for the standard synthesis zinc oxide carboxylate MOFs.

Photofragmentation of Gas-Phase Lanthanide Cyclopentadienyl Complexes: Experimental and Time-Dependent Excited-State Molecular Dynamics

PubMed Central

2015-01-01

Unimolecular gas-phase laser-photodissociation reaction mechanisms of open-shell lanthanide cyclopentadienyl complexes, Ln(Cp)3 and Ln(TMCp)3, are analyzed from experimental and computational perspectives. The most probable pathways for the photoreactions are inferred from photoionization time-of-flight mass spectrometry (PI-TOF-MS), which provides the sequence of reaction intermediates and the distribution of final products. Time-dependent excited-state molecular dynamics (TDESMD) calculations provide insight into the electronic mechanisms for the individual steps of the laser-driven photoreactions for Ln(Cp)3. Computational analysis correctly predicts several key reaction products as well as the observed branching between two reaction pathways: (1) ligand ejection and (2) ligand cracking. Simulations support our previous assertion that both reaction pathways are initiated via a ligand-to-metal charge-transfer (LMCT) process. For the more complex chemistry of the tetramethylcyclopentadienyl complexes Ln(TMCp)3, TMESMD is less tractable, but computational geometry optimization reveals the structures of intermediates deduced from PI-TOF-MS, including several classic “tuck-in” structures and products of Cp ring expansion. The results have important implications for metal–organic catalysis and laser-assisted metal–organic chemical vapor deposition (LCVD) of insulators with high dielectric constants. PMID:24910492

Simulation studies in biochemical signaling and enzyme reactions

NASA Astrophysics Data System (ADS)

Nelatury, Sudarshan R.; Vagula, Mary C.

2014-06-01

Biochemical pathways characterize various biochemical reaction schemes that involve a set of species and the manner in which they are connected. Determination of schematics that represent these pathways is an important task in understanding metabolism and signal transduction. Examples of these Pathways are: DNA and protein synthesis, and production of several macro-molecules essential for cell survival. A sustained feedback mechanism arises in gene expression and production of mRNA that lead to protein synthesis if the protein so synthesized serves as a transcription factor and becomes a repressor of the gene expression. The cellular regulations are carried out through biochemical networks consisting of reactions and regulatory proteins. Systems biology is a relatively new area that attempts to describe the biochemical pathways analytically and develop reliable mathematical models for the pathways. A complete understanding of chemical reaction kinetics is prohibitively hard thanks to the nonlinear and highly complex mechanisms that regulate protein formation, but attempting to numerically solve some of the governing differential equations seems to offer significant insight about their biochemical picture. To validate these models, one can perform simple experiments in the lab. This paper introduces fundamental ideas in biochemical signaling and attempts to take first steps into the understanding of biochemical oscillations. Initially, the two-pool model of calcium is used to describe the dynamics behind the oscillations. Later we present some elementary results showing biochemical oscillations arising from solving differential equations of Elowitz and Leibler using MATLAB software.

A Radical-Mediated Pathway for the Formation of [M + H](+) in Dielectric Barrier Discharge Ionization.

PubMed

Wolf, Jan-Christoph; Gyr, Luzia; Mirabelli, Mario F; Schaer, Martin; Siegenthaler, Peter; Zenobi, Renato

2016-09-01

Active capillary plasma ionization is a highly efficient ambient ionization method. Its general principle of ion formation is closely related to atmospheric pressure chemical ionization (APCI). The method is based on dielectric barrier discharge ionization (DBDI), and can be constructed in the form of a direct flow-through interface to a mass spectrometer. Protonated species ([M + H](+)) are predominantly formed, although in some cases radical cations are also observed. We investigated the underlying ionization mechanisms and reaction pathways for the formation of protonated analyte ([M + H](+)). We found that ionization occurs in the presence and in the absence of water vapor. Therefore, the mechanism cannot exclusively rely on hydronium clusters, as generally accepted for APCI. Based on isotope labeling experiments, protons were shown to originate from various solvents (other than water) and, to a minor extent, from gaseous impurities and/or self-protonation. By using CO2 instead of air or N2 as plasma gas, additional species like [M + OH](+) and [M - H](+) were observed. These gas-phase reaction products of CO2 with the analyte (tertiary amines) indicate the presence of a radical-mediated ionization pathway, which proceeds by direct reaction of the ionized plasma gas with the analyte. The proposed reaction pathway is supported with density functional theory (DFT) calculations. These findings add a new ionization pathway leading to the protonated species to those currently known for APCI. Graphical Abstract ᅟ.

Quantitative assessment on the contribution of direct photolysis and radical oxidation in photochemical degradation of 4-chlorophenol and oxytetracycline.

PubMed

Liu, Yiqing; He, Xuexiang; Fu, Yongsheng; Dionysiou, Dionysios D

2016-07-01

In UV-254 nm/H2O2 advanced oxidation process (AOP), the potential degradation pathways for organic pollutants include (1) hydrolysis, (2) direct H2O2 oxidation, (3) UV direct photolysis, and (4) hydroxyl radical (HO(•)) reaction. In this study, the contribution of these pathways was quantitatively assessed in the photochemical destruction of 4-chlorophenol (4-CP), demonstrating pathways (3) and (4) to be predominantly responsible for the removal of 4-CP by UV/H2O2 in 50 mM phosphate buffer solution. Increasing reaction pH could significantly enhance the contribution of direct photolysis in UV/H2O2 process. The contribution of HO(•) oxidation was improved with increasing initial H2O2 concentration probably due to the increased formation of HO(•). Presence of sodium carbonate (Na2CO3) as in UV/H2O2/Na2CO3 system promoted the degradation of 4-CP, with carbonate radical (CO3 (•-)) reaction and direct photolysis identified to be the main contributing pathways. The trends in the contribution of each factor were further evaluated and validated on the degradation of the antibiotic compound oxytetracycline (OTC). This study provides valuable information on the relative importance of different reaction pathways on the photochemical degradation of organic contaminants such as 4-CP and OTC in the presence and absence of a CO3 (•-) precursor.

A Synthetic Alternative to Canonical One-Carbon Metabolism.

PubMed

Bouzon, Madeleine; Perret, Alain; Loreau, Olivier; Delmas, Valérie; Perchat, Nadia; Weissenbach, Jean; Taran, Frédéric; Marlière, Philippe

2017-08-18

One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO 2 . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.

Network design and analysis for multi-enzyme biocatalysis.

PubMed

Blaß, Lisa Katharina; Weyler, Christian; Heinzle, Elmar

2017-08-10

As more and more biological reaction data become available, the full exploration of the enzymatic potential for the synthesis of valuable products opens up exciting new opportunities but is becoming increasingly complex. The manual design of multi-step biosynthesis routes involving enzymes from different organisms is very challenging. To harness the full enzymatic potential, we developed a computational tool for the directed design of biosynthetic production pathways for multi-step catalysis with in vitro enzyme cascades, cell hydrolysates and permeabilized cells. We present a method which encompasses the reconstruction of a genome-scale pan-organism metabolic network, path-finding and the ranking of the resulting pathway candidates for proposing suitable synthesis pathways. The network is based on reaction and reaction pair data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the thermodynamics calculator eQuilibrator. The pan-organism network is especially useful for finding the most suitable pathway to a target metabolite from a thermodynamic or economic standpoint. However, our method can be used with any network reconstruction, e.g. for a specific organism. We implemented a path-finding algorithm based on a mixed-integer linear program (MILP) which takes into account both topology and stoichiometry of the underlying network. Unlike other methods we do not specify a single starting metabolite, but our algorithm searches for pathways starting from arbitrary start metabolites to a target product of interest. Using a set of biochemical ranking criteria including pathway length, thermodynamics and other biological characteristics such as number of heterologous enzymes or cofactor requirement, it is possible to obtain well-designed meaningful pathway alternatives. In addition, a thermodynamic profile, the overall reactant balance and potential side reactions as well as an SBML file for visualization are generated for each pathway alternative. We present an in silico tool for the design of multi-enzyme biosynthetic production pathways starting from a pan-organism network. The method is highly customizable and each module can be adapted to the focus of the project at hand. This method is directly applicable for (i) in vitro enzyme cascades, (ii) cell hydrolysates and (iii) permeabilized cells.

CMPF: class-switching minimized pathfinding in metabolic networks.

PubMed

Lim, Kevin; Wong, Limsoon

2012-01-01

The metabolic network is an aggregation of enzyme catalyzed reactions that converts one compound to another. Paths in a metabolic network are a sequence of enzymes that describe how a chemical compound of interest can be produced in a biological system. As the number of such paths is quite large, many methods have been developed to score paths so that the k-shortest paths represent the set of paths that are biologically meaningful or efficient. However, these approaches do not consider whether the sequence of enzymes can be manufactured in the same pathway/species/localization. As a result, a predicted sequence might consist of groups of enzymes that operate in distinct pathway/species/localization and may not truly reflect the events occurring within cell. We propose a path weighting method CMPF (Class-switching Minimized Pathfinder) to search for routes in a metabolic network which minimizes pathway switching. In biological terms, a pathway is a series of chemical reactions which define a specific function (e.g. glycolysis). We conjecture that routes that cross many pathways are inefficient since different pathways define different metabolic functions. In addition, native routes are also well characterized within pathways, suggesting that reasonable paths should not involve too many pathway switches. Our method can be generalized when reactions participate in a class set (e.g., pathways, species or cellular localization) so that the paths predicted have minimal class crossings. We show that our method generates k-paths that involve the least number of class switching. In addition, we also show that native paths are recoverable and alternative paths deviates less from native paths compared to other methods. This suggests that paths ranked by our method could be a way to predict paths that are likely to occur in biological systems.

Characterization of the Minimum Energy Paths and Energetics for the Reaction of Vinylidene with Acetylene

NASA Technical Reports Server (NTRS)

Walch, Stephen P.; Taylor, Peter R.

1995-01-01

The reaction of vinylidene (CH2C) with acetylene may be an initiating reaction in soot formation. We report minimum energy paths and accurate energetics for a pathway leading to vinyl-acetylene and for a number of isomers of C4H4. The calculations use complete active space self-consistent field (CASSCF) derivative methods to characterize the stationary points and internally contacted configuration interaction (ICCI) and/or coupled cluster singles and doubles with a perturbational estimate of triple excitations (CCSD(T)) to determine the energetics. We find an entrance channel barrier of about 5 kcal/mol for the addition of vinylidene to acetylene, but no barriers above reactants for the reaction pathway leading to vinyl-acetylene.

Characterization of the Minimum Energy Paths and Energetics for the reaction of Vinylidene with Acetylene

NASA Technical Reports Server (NTRS)

Walch, Stephen P.; Taylor, Peter R.

1995-01-01

The reaction of vinylidene (CH2C) with acetylene may be an initiating reaction in soot formation. We report minimum energy paths and accurate energetics for a pathway leading to vinylacetylene and for a number of isomers Of C4H4. The calculations use complete active space self-consistent field (CASSCF) derivative methods to characterize the stationary points and internally contacted configuration interaction (ICCI) and/or coupled cluster singles and doubles with a perturbational estimate of triple excitations (CCSD(T)) to determine the energetics. We find an entrance channel barrier of about 5 kcal/mol for the addition of vinylidene to acetylene, but no barriers above reactants for the reaction pathway leading to vinylacetylene.

Mixing enhancement of reacting parallel fuel jets in a supersonic combustor

NASA Technical Reports Server (NTRS)

Drummond, J. P.

1991-01-01

Pursuant to a NASA-Langley development program for a scramjet HST propulsion system entailing the optimization of the scramjet combustor's fuel-air mixing and reaction characteristics, a numerical study has been conducted of the candidate parallel fuel injectors. Attention is given to a method for flow mixing-process and combustion-efficiency enhancement in which a supersonic circular hydrogen jet coflows with a supersonic air stream. When enhanced by a planar oblique shock, the injector configuration exhibited a substantial degree of induced vorticity in the fuel stream which increased mixing and chemical reaction rates, relative to the unshocked configuration. The resulting heat release was effective in breaking down the stable hydrogen vortex pair that had inhibited more extensive fuel-air mixing.

Method for measuring pollutant formation

NASA Technical Reports Server (NTRS)

Stickler, David B. (Inventor); Annen, Kurt (Inventor)

2001-01-01

Diagnostic methods for determining an instantaneous rate of pollutant formation in a combustion system are based on measurement of chemiluminescence intensity generated simultaneously with the formation of the pollutant. The chemiluminescent signal is generated by an analog reaction which occurs in parallel with a key step in the formation of a specific pollutant of interest. The connection between the analog reaction and the pollution reaction is such that the chemiluminescent signal indicates the local, instantaneous formation rate of the pollutant of interest.

Experiment E89-044 on the Quasielastic 3He(e,e'p) Reaction at Jefferson Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penel-Nottaris, Emilie

The Jefferson Lab Hall A E89-044 experiment has measured the 3He(e,e'p) reaction cross-sections. The extraction of the longitudinal and transverse response functions for the two-body break-up 3He(e,e'p)d reaction in parallel kinematics allows the study of the bound proton electromagnetic properties inside the 3He nucleus and the involved nuclear mechanisms beyond plane wave approximations.

The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases

PubMed Central

Caspi, Ron; Altman, Tomer; Dale, Joseph M.; Dreher, Kate; Fulcher, Carol A.; Gilham, Fred; Kaipa, Pallavi; Karthikeyan, Athikkattuvalasu S.; Kothari, Anamika; Krummenacker, Markus; Latendresse, Mario; Mueller, Lukas A.; Paley, Suzanne; Popescu, Liviu; Pujar, Anuradha; Shearer, Alexander G.; Zhang, Peifen; Karp, Peter D.

2010-01-01

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. With more than 1400 pathways, MetaCyc is the largest collection of metabolic pathways currently available. Pathways reactions are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than 500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs also contain additional features, such as predicted operons, transport systems, and pathway hole-fillers. The BioCyc Web site offers several tools for the analysis of the PGDBs, including Omics Viewers that enable visualization of omics datasets on two different genome-scale diagrams and tools for comparative analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party interested in curation of metabolic, regulatory, and genome-related information about an organism. PMID:19850718

Parallel evolution of Nitric Oxide signaling: Diversity of synthesis & memory pathways

PubMed Central

Moroz, Leonid L.; Kohn, Andrea B.

2014-01-01

The origin of NO signaling can be traceable back to the origin of life with the large scale of parallel evolution of NO synthases (NOSs). Inducible-like NOSs may be the most basal prototype of all NOSs and that neuronal-like NOS might have evolved several times from this prototype. Other enzymatic and non-enzymatic pathways for NO synthesis have been discovered using reduction of nitrites, an alternative source of NO. Diverse synthetic mechanisms can co-exist within the same cell providing a complex NO-oxygen microenvironment tightly coupled with cellular energetics. The dissection of multiple sources of NO formation is crucial in analysis of complex biological processes such as neuronal integration and learning mechanisms when NO can act as a volume transmitter within memory-forming circuits. In particular, the molecular analysis of learning mechanisms (most notably in insects and gastropod molluscs) opens conceptually different perspectives to understand the logic of recruiting evolutionarily conserved pathways for novel functions. Giant uniquely identified cells from Aplysia and related species precent unuque opportunities for integrative analysis of NO signaling at the single cell level. PMID:21622160

Recovering metabolic pathways via optimization.

PubMed

Beasley, John E; Planes, Francisco J

2007-01-01

A metabolic pathway is a coherent set of enzyme catalysed biochemical reactions by which a living organism transforms an initial (source) compound into a final (target) compound. Some of the different metabolic pathways adopted within organisms have been experimentally determined. In this paper, we show that a number of experimentally determined metabolic pathways can be recovered by a mathematical optimization model.

Gadolinium photoionization process

DOEpatents

Paisner, J.A.; Comaskey, B.J.; Haynam, C.A.; Eggert, J.H.

1993-04-13

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Gadolinium photoionization process

DOEpatents

Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

1993-01-01

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Er-Wen; Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou; Xue, Sheng-Jiang

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation,more » facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.« less

Protein biomarker discovery and fast monitoring for the identification and detection of Anisakids by parallel reaction monitoring (PRM) mass spectrometry.

PubMed

Carrera, Mónica; Gallardo, José M; Pascual, Santiago; González, Ángel F; Medina, Isabel

2016-06-16

Anisakids are fish-borne parasites that are responsible for a large number of human infections and allergic reactions around the world. World health organizations and food safety authorities aim to control and prevent this emerging health problem. In the present work, a new method for the fast monitoring of these parasites is described. The strategy is divided in three steps: (i) purification of thermostable proteins from fish-borne parasites (Anisakids), (ii) in-solution HIFU trypsin digestion and (iii) monitoring of several peptide markers by parallel reaction monitoring (PRM) mass spectrometry. This methodology allows the fast detection of Anisakids in <2h. An affordable assay utilizing this methodology will facilitate testing for regulatory and safety applications. The work describes for the first time, the Protein Biomarker Discovery and the Fast Monitoring for the identification and detection of Anisakids in fishery products. The strategy is based on the purification of thermostable proteins, the use of accelerated in-solution trypsin digestions under an ultrasonic field provided by High-Intensity Focused Ultrasound (HIFU) and the monitoring of several peptide biomarkers by Parallel Reaction Monitoring (PRM) Mass Spectrometry in a linear ion trap mass spectrometer. The workflow allows the unequivocal detection of Anisakids, in <2h. The present strategy constitutes the fastest method for Anisakids detection, whose application in the food quality control area, could provide to the authorities an effective and rapid method to guarantee the safety to the consumers. Copyright © 2016 Elsevier B.V. All rights reserved.

It takes two-coincidence coding within the dual olfactory pathway of the honeybee.

PubMed

Brill, Martin F; Meyer, Anneke; Rössler, Wolfgang

2015-01-01

To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code).

Mechanisms for the inversion of chirality: global reaction route mapping of stereochemical pathways in a probable chiral extraterrestrial molecule, 2-aminopropionitrile.

PubMed

Kaur, Ramanpreet; Vikas

2015-02-21

2-Aminopropionitrile (APN), a probable candidate as a chiral astrophysical molecule, is a precursor to amino-acid alanine. Stereochemical pathways in 2-APN are explored using Global Reaction Route Mapping (GRRM) method employing high-level quantum-mechanical computations. Besides predicting the conventional mechanism for chiral inversion that proceeds through an achiral intermediate, a counterintuitive flipping mechanism is revealed for 2-APN through chiral intermediates explored using the GRRM. The feasibility of the proposed stereochemical pathways, in terms of the Gibbs free-energy change, is analyzed at the temperature conditions akin to the interstellar medium. Notably, the stereoinversion in 2-APN is observed to be more feasible than the dissociation of 2-APN and intermediates involved along the stereochemical pathways, and the flipping barrier is observed to be as low as 3.68 kJ/mol along one of the pathways. The pathways proposed for the inversion of chirality in 2-APN may provide significant insight into the extraterrestrial origin of life.

Radiochemical study of reactions of alkyl cations with amines. I. Reactions of methyl and sec-butyl cations with diethylamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ignat`ev, I.S.; Kochina, T.A.; Nefedov, V.D.

1995-08-10

Ion-molecular gas-phase reactions of free methyl and sec-butyl cations with diethylamine were studied. These reactions proceed via two competing pathways involving formation of a condensation complex or a proton-transfer complex, the latter process predominating. 32 refs., 1 tab.

TEMPO-promoted Pauson-Khand reaction. Single-electron activation of cobalt-carbonyl bonds?

PubMed

Lagunas, Anna; Mairata I Payeras, Antoni; Jimeno, Ciril; Pericàs, Miquel A

2005-07-07

[reaction: see text] The Pauson-Khand reaction is notably accelerated by TEMPO. According to DFT calculations, TEMPO could trigger a radical, low-energy pathway for the reaction by facilitating the decarbonylation of doublet complexes arising either from a CO/nitroxide exchange or from nitroxide addition to a CO ligand.

The concern of emergence of multi-station reaction pathways that might make stepwise the mechanism of the 1,3-dipolar cycloadditions of azides and alkynes

NASA Astrophysics Data System (ADS)

Mohtat, Bita; Siadati, Seyyed Amir; Khalilzadeh, Mohammad Ali; Zareyee, Daryoush

2018-03-01

After hot debates on the concerted or stepwise nature of the mechanism of the catalyst-free 1,3-dipolar cycloadditions (DC)s, nowadays, it is being believed that for the reaction of each dipole and dipolarophile, there is a possibility that the reaction mechanism becomes stepwise, intermediates emerge, and the reaction becomes non-stereospecific. Yield of even minimal amounts of unwanted side products or stereoisomers as impurities could bring many troubles like difficult purification steps. In this project, we have made attempts to study all probable reaction channels of the azide cycloadditions with two functionalized alkynes, in order to answer this question: "is there any possibility that intermediates evolve in the catalyst-free click 1,3-DC reaction of azide-alkynes?". During the calculations, several multi-station reaction pathways supporting the stepwise and concerted mechanisms were detected. Also, the born-oppenheimer molecular dynamic (BOMD) simulation was used to find trustable geometries which could be emerged during the reaction coordinate.

Dynamic exit-channel pathways of the microsolvated HOO-(H2O) + CH3Cl SN2 reaction: Reaction mechanisms at the atomic level from direct chemical dynamics simulations

NASA Astrophysics Data System (ADS)

Yu, Feng

2018-01-01

Microsolvated bimolecular nucleophilic substitution (SN2) reaction of monohydrated hydrogen peroxide anion [HOO-(H2O)] with methyl chloride (CH3Cl) has been investigated with direct chemical dynamics simulations at the M06-2X/6-31+G(d,p) level of theory. Dynamic exit-channel pathways and corresponding reaction mechanisms at the atomic level are revealed in detail. Accordingly, a product distribution of 0.85:0.15 is obtained for Cl-:Cl-(H2O), which is consistent with a previous experiment [D. L. Thomsen et al. J. Am. Chem. Soc. 135, 15508 (2013)]. Compared with the HOO- + CH3Cl SN2 reaction, indirect dynamic reaction mechanisms are enhanced by microsolvation for the HOO-(H2O) + CH3Cl SN2 reaction. On the basis of our simulations, further crossed molecular beam imaging experiments are highly suggested for the SN2 reactions of HOO- + CH3Cl and HOO-(H2O) + CH3Cl.

Dynamic exit-channel pathways of the microsolvated HOO-(H2O) + CH3Cl SN2 reaction: Reaction mechanisms at the atomic level from direct chemical dynamics simulations.

PubMed

Yu, Feng

2018-01-07

Microsolvated bimolecular nucleophilic substitution (S N 2) reaction of monohydrated hydrogen peroxide anion [HOO - (H 2 O)] with methyl chloride (CH 3 Cl) has been investigated with direct chemical dynamics simulations at the M06-2X/6-31+G(d,p) level of theory. Dynamic exit-channel pathways and corresponding reaction mechanisms at the atomic level are revealed in detail. Accordingly, a product distribution of 0.85:0.15 is obtained for Cl - :Cl - (H 2 O), which is consistent with a previous experiment [D. L. Thomsen et al. J. Am. Chem. Soc. 135, 15508 (2013)]. Compared with the HOO - + CH 3 Cl S N 2 reaction, indirect dynamic reaction mechanisms are enhanced by microsolvation for the HOO - (H 2 O) + CH 3 Cl S N 2 reaction. On the basis of our simulations, further crossed molecular beam imaging experiments are highly suggested for the S N 2 reactions of HOO - + CH 3 Cl and HOO - (H 2 O) + CH 3 Cl.

Fluorescent probes for tracking the transfer of iron–sulfur cluster and other metal cofactors in biosynthetic reaction pathways

DOE PAGES

Vranish, James N.; Russell, William K.; Yu, Lusa E.; ...

2014-12-05

Iron–sulfur (Fe–S) clusters are protein cofactors that are constructed and delivered to target proteins by elaborate biosynthetic machinery. Mechanistic insights into these processes have been limited by the lack of sensitive probes for tracking Fe–S cluster synthesis and transfer reactions. Here we present fusion protein- and intein-based fluorescent labeling strategies that can probe Fe–S cluster binding. The fluorescence is sensitive to different cluster types ([2Fe–2S] and [4Fe–4S] clusters), ligand environments ([2Fe–2S] clusters on Rieske, ferredoxin (Fdx), and glutaredoxin), and cluster oxidation states. The power of this approach is highlighted with an extreme example in which the kinetics of Fe–S clustermore » transfer reactions are monitored between two Fdx molecules that have identical Fe–S spectroscopic properties. This exchange reaction between labeled and unlabeled Fdx is catalyzed by dithiothreitol (DTT), a result that was confirmed by mass spectrometry. DTT likely functions in a ligand substitution reaction that generates a [2Fe–2S]–DTT species, which can transfer the cluster to either labeled or unlabeled Fdx. The ability to monitor this challenging cluster exchange reaction indicates that real-time Fe–S cluster incorporation can be tracked for a specific labeled protein in multicomponent assays that include several unlabeled Fe–S binding proteins or other chromophores. Such advanced kinetic experiments are required to untangle the intricate networks of transfer pathways and the factors affecting flux through branch points. High sensitivity and suitability with high-throughput methodology are additional benefits of this approach. Lastly, we anticipate that this cluster detection methodology will transform the study of Fe–S cluster pathways and potentially other metal cofactor biosynthetic pathways.« less

Reconstruction of biological pathways and metabolic networks from in silico labeled metabolites.

PubMed

Hadadi, Noushin; Hafner, Jasmin; Soh, Keng Cher; Hatzimanikatis, Vassily

2017-01-01

Reaction atom mappings track the positional changes of all of the atoms between the substrates and the products as they undergo the biochemical transformation. However, information on atom transitions in the context of metabolic pathways is not widely available in the literature. The understanding of metabolic pathways at the atomic level is of great importance as it can deconvolute the overlapping catabolic/anabolic pathways resulting in the observed metabolic phenotype. The automated identification of atom transitions within a metabolic network is a very challenging task since the degree of complexity of metabolic networks dramatically increases when we transit from metabolite-level studies to atom-level studies. Despite being studied extensively in various approaches, the field of atom mapping of metabolic networks is lacking an automated approach, which (i) accounts for the information of reaction mechanism for atom mapping and (ii) is extendable from individual atom-mapped reactions to atom-mapped reaction networks. Hereby, we introduce a computational framework, iAM.NICE (in silico Atom Mapped Network Integrated Computational Explorer), for the systematic atom-level reconstruction of metabolic networks from in silico labelled substrates. iAM.NICE is to our knowledge the first automated atom-mapping algorithm that is based on the underlying enzymatic biotransformation mechanisms, and its application goes beyond individual reactions and it can be used for the reconstruction of atom-mapped metabolic networks. We illustrate the applicability of our method through the reconstruction of atom-mapped reactions of the KEGG database and we provide an example of an atom-level representation of the core metabolic network of E. coli. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

PubMed

Kim, Ju Han; Ha, Il Soo; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang

2004-11-01

Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

Reactivity index based on orbital energies.

PubMed

Tsuneda, Takao; Singh, Raman K

2014-05-30

This study shows that the chemical reactivities depend on the orbital energy gaps contributing to the reactions. In the process where a reaction only makes progress through charge transfer with the minimal structural transformation of the reactant, the orbital energy gap gradient (OEGG) between the electron-donating and electron-accepting orbitals is proven to be very low. Using this relation, a normalized reaction diagram is constructed by plotting the normalized orbital energy gap with respect to the normalized intrinsic reaction coordinate. Application of this reaction diagram to 43 fundamental reactions showed that the majority of the forward reactions provide small OEGGs in the initial stages, and therefore, the initial processes of the forward reactions are supposed to proceed only through charge transfer. Conversely, more than 60% of the backward reactions are found to give large OEGGs implying very slow reactions associated with considerable structural transformations. Focusing on the anti-activation-energy reactions, in which the forward reactions have higher barriers than those of the backward ones, most of these reactions are shown to give large OEGGs for the backward reactions. It is also found that the reactions providing large OEGGs in the forward directions inconsistent with the reaction rate constants are classified into SN 2, symmetric, and methyl radical reactions. Interestingly, several large-OEGG reactions are experimentally established to get around the optimum pathways. This indicates that the reactions can take significantly different pathways from the optimum ones provided no charge transfer proceeds spontaneously without the structural transformations of the reactants. Copyright © 2014 Wiley Periodicals, Inc.

In silico and in vitro studies of the reduction of unsaturated α,β bonds of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid – Important steps towards biobased production of adipic acid

PubMed Central

Westman, Gunnar; Eriksson, Leif A.; Mapelli, Valeria

2018-01-01

The biobased production of adipic acid, a precursor in the production of nylon, is of great interest in order to replace the current petrochemical production route. Glucose-rich lignocellulosic raw materials have high potential to replace the petrochemical raw material. A number of metabolic pathways have been proposed for the microbial conversion of glucose to adipic acid, but achieved yields and titers remain to be improved before industrial applications are feasible. One proposed pathway starts with lysine, an essential metabolite industrially produced from glucose by microorganisms. However, the drawback of this pathway is that several reactions are involved where there is no known efficient enzyme. By changing the order of the enzymatic reactions, we were able to identify an alternative pathway with one unknown enzyme less compared to the original pathway. One of the reactions lacking known enzymes is the reduction of the unsaturated α,β bond of 6-amino-trans-2-hexenoic acid and trans-2-hexenedioic acid. To identify the necessary enzymes, we selected N-ethylmaleimide reductase from Escherichia coli and Old Yellow Enzyme 1 from Saccharomyces pastorianus. Despite successful in silico docking studies, where both target substrates could fit in the enzyme pockets, and hydrogen bonds with catalytic residues of both enzymes were predicted, no in vitro activity was observed. We hypothesize that the lack of activity is due to a difference in electron withdrawing potential between the naturally reduced aldehyde and the carboxylate groups of our target substrates. Suggestions for protein engineering to induce the reactions are discussed, as well as the advantages and disadvantages of the two metabolic pathways from lysine. We have highlighted bottlenecks associated with the lysine pathways, and proposed ways of addressing them. PMID:29474495

On-surface synthesis on a bulk insulator surface

NASA Astrophysics Data System (ADS)

Richter, Antje; Floris, Andrea; Bechstein, Ralf; Kantorovich, Lev; Kühnle, Angelika

2018-04-01

On-surface synthesis has rapidly emerged as a most promising approach to prepare functional molecular structures directly on a support surface. Compared to solution synthesis, performing chemical reactions on a surface offers several exciting new options: due to the absence of a solvent, reactions can be envisioned that are otherwise not feasible due to the insolubility of the reaction product. Perhaps even more important, the confinement to a two-dimensional surface might enable reaction pathways that are not accessible otherwise. Consequently, on-surface synthesis has attracted great attention in the last decade, with an impressive number of classical reactions transferred to a surface as well as new reactions demonstrated that have no classical analogue. So far, the majority of the work has been carried out on conducting surfaces. However, when aiming for electronic decoupling of the resulting structures, e.g. for the use in future molecular electronic devices, non-conducting surfaces are highly desired. Here, we review the current status of on-surface reactions demonstrated on the (10.4) surface of the bulk insulator calcite. Besides thermally induced C-C coupling of halogen-substituted aryls, photochemically induced [2  +  2] cycloaddition has been proven possible on this surface. Moreover, experimental evidence exists for coupling of terminal alkynes as well as diacetylene polymerization. While imaging of the resulting structures with dynamic atomic force microscopy provides a direct means of reaction verification, the detailed reaction pathway often remains unclear. Especially in cases where the presence of metal atoms is known to catalyze the corresponding solution chemistry reaction (e.g. in the case of the Ullmann reaction), disclosing the precise reaction pathway is of importance to understand and generalize on-surface reactivity on a bulk insulator surface. To this end, density-functional theory calculations have proven to provide atomic-scale insights that have greatly contributed to unravelling the details of on-surface synthesis on a bulk insulator surface.

Degradation of Nicotine in Chlorinated Water: Pathways and ...

EPA Pesticide Factsheets

Report The objective of the study is to illustrate how drinking water would affect alkaloid pesticides, and to address the issue by (a) investigating the fate of nicotine in chlorinated drinking water and deionized water, (b) determining the reaction rate and pathway of the reaction between nicotine and aqueous chlorine, (c) identifying nicotine’s degradation products, and (d) providing data that can be used to assess the potential threat from nicotine in drinking water.

In Situ Treatment of Chlorinated Ethene-Contaminated Groundwater Using horizontal Flow Treatment Wells.

DTIC Science & Technology

2000-03-01

groundwater, Environmental Science and Technology, 30 (12): 536A-539A, 1996. Arnold, W. A. and A. L. Roberts, Pathways of chlorinated ethylene and...chlorinated acetylene reaction with Zn(0), Environmental Science and Technology, 32 (19): 3017-3025, 1998. Arnold, W. A. and A. L. Roberts, Pathways and...kinetics of chlorinated ethylene and chlorinated acetylene reaction with Fe(0) particles, Environmental Science and Technology, in press, 2000

Preface: Special Topic on Reaction Pathways

NASA Astrophysics Data System (ADS)

Clementi, Cecilia; Henkelman, Graeme

2017-10-01

This Special Topic Issue on Reaction Pathways collects original research articles illustrating the state of the art in the development and application of methods to describe complex chemical systems in terms of relatively simple mechanisms and collective coordinates. A broad range of applications is presented, spanning the sub-fields of biophysics and material science, in an attempt to showcase the similarities in the formulation of the approaches and highlight the different needs of the different application domains.

Role of APOE Isoforms in the Pathogenesis of TBI induced Alzheimer’s Disease

DTIC Science & Technology

2016-10-01

deletion, APOE targeted replacement, complex breeding, CCI model optimization, mRNA library generation, high throughput massive parallel sequencing...demonstrate that the lack of Abca1 increases amyloid plaques and decreased APOE protein levels in AD-model mice. In this proposal we will test the hypothesis...injury, inflammatory reaction, transcriptome, high throughput massive parallel sequencing, mRNA-seq., behavioral testing, memory impairment, recovery 3

HCN and chromophore formation on Jupiter

NASA Technical Reports Server (NTRS)

Ferris, James P.; Ishikawa, Yoji

1987-01-01

Reaction paths for the formation of HCN and chromophores on Jupiter are suggested. The reactions involve photolysis of ammonia/acetylene mixtures. Experimental data supporting these pathways are reported.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hay, J.; Schwender, J.

Computational simulation of large-scale biochemical networks can be used to analyze and predict the metabolic behavior of an organism, such as a developing seed. Based on the biochemical literature, pathways databases and decision rules defining reaction directionality we reconstructed bna572, a stoichiometric metabolic network model representing Brassica napus seed storage metabolism. In the highly compartmentalized network about 25% of the 572 reactions are transport reactions interconnecting nine subcellular compartments and the environment. According to known physiological capabilities of developing B. napus embryos, four nutritional conditions were defined to simulate heterotrophy or photoheterotrophy, each in combination with the availability of inorganicmore » nitrogen (ammonia, nitrate) or amino acids as nitrogen sources. Based on mathematical linear optimization the optimal solution space was comprehensively explored by flux variability analysis, thereby identifying for each reaction the range of flux values allowable under optimality. The range and variability of flux values was then categorized into flux variability types. Across the four nutritional conditions, approximately 13% of the reactions have variable flux values and 10-11% are substitutable (can be inactive), both indicating metabolic redundancy given, for example, by isoenzymes, subcellular compartmentalization or the presence of alternative pathways. About one-third of the reactions are never used and are associated with pathways that are suboptimal for storage synthesis. Fifty-seven reactions change flux variability type among the different nutritional conditions, indicating their function in metabolic adjustments. This predictive modeling framework allows analysis and quantitative exploration of storage metabolism of a developing B. napus oilseed.« less

Modeling the Reaction of Fe Atoms with CCl4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camaioni, Donald M.; Ginovska, Bojana; Dupuis, Michel

2009-01-05

The reaction of zero-valent iron with carbon tetrachloride (CCl4) in gas phase was studied using density functional theory. Temperature programmed desorption experiments over a range of Fe and CCl4 coverages on a FeO(111) surface, demonstrate a rich surface chemistry with several reaction products (C2Cl4, C2Cl6, OCCl2, CO, FeCl2, FeCl3) observed. The reactivity of Fe and CCl4 was studied under three stoichiometries, one Fe with one CCl4, one Fe with two CCl4 molecules and two Fe with one CCl4, modeling the environment of the experimental work. The electronic structure calculations give insight into the reactions leading to the experimentally observed productsmore » and suggest that novel Fe-C-Cl containing species are important intermediates in these reactions. The intermediate complexes are formed in highly exothermic reactions, in agreement with the experimentally observed reactivity with the surface at low temperature (30 K). This initial survey of the reactivity of Fe with CCl4 identifies some potential reaction pathways that are important in the effort to use Fe nano-particles to differentiate harmful pathways that lead to the formation of contaminants like chloroform (CHCl3) from harmless pathways that lead to products such as formate (HCO2-) or carbon oxides in water and soil. The Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Reaction pathways of model compounds of biomass-derived oxygenates on Fe/Ni bimetallic surfaces

NASA Astrophysics Data System (ADS)

Yu, Weiting; Chen, Jingguang G.

2015-10-01

Controlling the activity and selectivity of converting biomass-derivatives to fuels and valuable chemicals is critical for the utilization of biomass feedstocks. There are primarily three classes of non-food competing biomass, cellulose, hemicellulose and lignin. In the current work, glycolaldehyde, furfural and acetaldehyde are studied as model compounds of the three classes of biomass-derivatives. Monometallic Ni(111) and monolayer (ML) Fe/Ni(111) bimetallic surfaces are studied for the reaction pathways of the three biomass surrogates. The ML Fe/Ni(111) surface is identified as an efficient surface for the conversion of biomass-derivatives from the combined results of density functional theory (DFT) calculations and temperature programmed desorption (TPD) experiments. A correlation is also established between the optimized adsorption geometry and experimental reaction pathways. These results should provide helpful insights in catalyst design for the upgrading and conversion of biomass.

Impact of the Valence Charge of Transition Metals on the Cobalt- and Rhodium-Catalyzed Synthesis of Indenamines, Indenols, and Isoquinolinium Salts: A Catalytic Cycle Involving MIII/MV [M = Co, Rh] for [4+2] Annulation.

PubMed

Chiou, Mong-Feng; Jayakumar, Jayachandran; Cheng, Chien-Hong; Chuang, Shih-Ching

2018-06-13

Reaction mechanisms for the synthesis of indenamines, indenols, and isoquinolinium salts through cobalt- and rhodium-catalysis were investigated using density functional theory calculations. We found that the valence charge of transition metals dramatically influences the reaction pathways. Catalytic reactions involving lower-oxidation-state transition metals (M I /M III , M = Co and Rh) generally favor a [3+2] cyclization pathway, whereas those involving higher oxidation states (M III /M V ) proceed through a [4+2] cyclization pathway. A catalytic cycle with novel M III /M V as a crucial species was successfully revealed for isoquinolinium salts synthesis, which highly valent M V was not only encountered in the [RhCp*]-catalysis but also in the [CoCp*]-catalysis.

Exploratory tests of two strut fuel injectors for supersonic combustion

NASA Technical Reports Server (NTRS)

Anderson, G. Y.; Gooderum, P. B.

1974-01-01

Results of supersonic mixing and combustion tests performed with two simple strut injector configurations, one with parallel injectors and one with perpendicular injectors, are presented and analyzed. Good agreement is obtained between static pressure measured on the duct wall downstream of the strut injectors and distributions obtained from one-dimensional calculations. Measured duct heat load agrees with results of the one-dimensional calculations for moderate amounts of reaction, but is underestimated when large separated regions occur near the injection location. For the parallel injection strut, good agreement is obtained between the shape of the injected fuel distribution inferred from gas sample measurements at the duct exit and the distribution calculated with a multiple-jet mixing theory. The overall fraction of injected fuel reacted in the multiple-jet calculation closely matches the amount of fuel reaction necessary to match static pressure with the one-dimensional calculation. Gas sample measurements with the perpendicular injection strut also give results consistent with the amount of fuel reaction in the one-dimensional calculation.

A comparative DFT study on the dehydrogenation of methanol on Rh(100) and Rh(110)

NASA Astrophysics Data System (ADS)

Zhang, Minhua; Wu, Xingyu; Yu, Yingzhe

2018-04-01

Numerous density functional theory calculations have been performed to investigate the complete mechanisms of methanol dehydrogenation on Rh(100) and Rh(110) surfaces. The adsorption properties of relevant species were discussed in details. In addition, a comprehensive reaction network including four reaction pathways was built and analyzed. It is found that the initial Osbnd H bond scission of CH3OH seems to be more favorable than Csbnd H bond cleavage on both Rh(100) and Rh(110) surfaces from the perspective of activation barriers. It is also concluded that path1 (CH3OH → CH3O → CH2O → CHO → CO) is the predominant pathway on both Rh(100) and Rh (110) surfaces. On the whole, in most of the dehydrogenation reactions investigated, the energy barriers on Rh(100) are lower than those on Rh (110). Remarkable differences in the activity and predominant reaction pathway on Rh(100), Rh(110) and Rh(111) indicate that the dehydrogenation of methanol might be structure-sensitive.

Reaction pathways and free energy profiles for cholinesterase-catalyzed hydrolysis of 6-monoacetylmorphine

PubMed Central

Qiao, Yan; Han, Keli; Zhan, Chang-Guo

2014-01-01

As the most active metabolite of heroin, 6-monoacetylmorphine (6-MAM) can penetrate into the brain for the rapid onset of heroin effects. The primary enzymes responsible for the metabolism of 6-MAM to the less potent morphine in humans are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The detailed reaction pathways for AChE- and BChE-catalyzed hydrolysis of 6-MAM to morphine have been explored, for the first time, in the present study by performing first-principles quantum mechanical/molecular mechanical free energy calculations. It has been demonstrated that the two enzymatic reaction processes follow the similar catalytic reaction mechanism, and the whole catalytic reaction pathway for each enzyme consists of four reaction steps. According to the calculated results, the second reaction step associated with the transition state TS2a/TS2b should be rate-determining for the AChE/BChE-catalyzed hydrolysis, and the free energy barrier calculated for the AChE-catalyzed hydrolysis (18.3 kcal/mol) is 2.5 kcal/mol lower than that for the BChE-catalyzed hydrolysis (20.8 kcal/mol). The free energy barriers calculated for the AChE- and BChE-catalyzed reactions are in good agreement with the experimentally derived activation free energies (17.5 and 20.7 kcal/mol for the AChE- and BChE-catalyzed reactions, respectively). Further structural analysis reveals that the aromatic residues Phe295 and Phe297 in the acyl pocket of AChE (corresponding to Leu286 and Val288 in BChE) contribute to the lower energy of TS2a relative to TS2b. The obtained structural and mechanistic insights could be valuable for use in future rational design of a novel therapeutic treatment of heroin abuse. PMID:24595354

Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

NASA Astrophysics Data System (ADS)

Boland, Nathan E.; Stone, Alan T.

2017-09-01

Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive pathway or adjunctive pathway to multidentate ligand exchange reactions, our results indicate that a third "semijunctive" pathway is necessary to account for slow reactions progressing through Lsbnd Nisbnd Y ternary complexes. Ligand exchange pathways with NTA-type chelating agents are assigned a disjunctive pathway, while pathways with EDDA-type chelating agents are assigned a semijunctive pathway. Based upon operative mechanism(s), magnitudes of exchange rates and effects of ambient geochemical conditions can be predicted.

The role of grain boundaries and transient porosity increase as fluid pathways for reaction front propagation

NASA Astrophysics Data System (ADS)

Jonas, Laura; John, Timm; Geisler, Thorsten; Putnis, Andrew

2013-04-01

The pseudomorphic replacement of Carrara marble by calcium phosphates was studied as a model system to examine the influence of different fluid pathways for reaction front propagation induced by fluid-rock interaction. In this model system, the grain boundaries present in the rock and the transient porosity structures developing throughout the replacement reaction enable the reaction front to progress further into the rock as well as to the center of each single grain until complete transformation. Hydrothermal treatment of the marble using phosphate bearing solutions at temperature levels of 150° C and 200° C for different durations lead to the formation of two product phases which were identified as hydroxyapatite [Ca5(PO4)3OH] as well as β-tricalcium phosphate [β-Ca3(PO4)2] (β-TCP). The formation of β-TCP was probably favored by the presence of ~0.6wt.% of Mg in the parent phase. Completely transformed single grains show a distinctive zoning, both in composition and texture. Whereas areas next to the grain boundary consist of nearly pure hydroxyapatite and show a coarse porosity, areas close to the center of the single grains show a high amount of β-TCP and a very fine porous microstructure. If F was added as an additional solution component, the formation of β-TCP was avoided and up to 3wt.% of F were incorporated into the product apatite. The use of the isotope 18O as a chronometer for the replacement reaction makes it possible to reconstruct the chronological development of the calcium phosphate reaction front. Raman analysis revealed that the incorporation of 18O in the PO4 tetrahedron of hydroxyapatite results in the development of distinct profiles in the calcium phosphate reaction front perpendicular to the grain boundaries of the marble. Through the use of the 18O chronometer, it is possible to estimate and compare the time effectiveness of the different fluid pathways in this model system. The results show that the grain boundaries serve as a very effective pathway that enable the fluid to penetrate the rock more than one order of magnitude faster compared to the newly developing channel-like porosity structures which act as pathways towards the center of single mineral grains. Thus, it may be possible for the fluid to progress relatively large distances along the grain boundaries after only short reaction durations without producing broad reaction fronts along the path.

Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways

PubMed Central

Mitsche, Matthew A; McDonald, Jeffrey G; Hobbs, Helen H; Cohen, Jonathan C

2015-01-01

Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K–R pathway. Rather, a hybrid pathway was identified that we call the modified K–R (MK–R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK–R pathway. Thus, relative use of the Bloch and MK–R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol. DOI: http://dx.doi.org/10.7554/eLife.07999.001 PMID:26114596

Annotation-based inference of transporter function.

PubMed

Lee, Thomas J; Paulsen, Ian; Karp, Peter

2008-07-01

We present a method for inferring and constructing transport reactions for transporter proteins based primarily on the analysis of the names of individual proteins in the genome annotation of an organism. Transport reactions are declarative descriptions of transporter activities, and thus can be manipulated computationally, unlike free-text protein names. Once transporter activities are encoded as transport reactions, a number of computational analyses are possible including database queries by transporter activity; inclusion of transporters into an automatically generated metabolic-map diagram that can be painted with omics data to aid in their interpretation; detection of anomalies in the metabolic and transport networks, such as substrates that are transported into the cell but are not inputs to any metabolic reaction or pathway; and comparative analyses of the transport capabilities of different organisms. On randomly selected organisms, the method achieves precision and recall rates of 0.93 and 0.90, respectively in identifying transporter proteins by name within the complete genome. The method obtains 67.5% accuracy in predicting complete transport reactions; if allowance is made for predictions that are overly general yet not incorrect, reaction prediction accuracy is 82.5%. The method is implemented as part of PathoLogic, the inference component of the Pathway Tools software. Pathway Tools is freely available to researchers at non-commercial institutions, including source code; a fee applies to commercial institutions. Supplementary data are available at Bioinformatics online.

Catalytic wet air oxidation of phenol with functionalized carbon materials as catalysts: reaction mechanism and pathway.

PubMed

Wang, Jianbing; Fu, Wantao; He, Xuwen; Yang, Shaoxia; Zhu, Wanpeng

2014-08-01

The development of highly active carbon material catalysts in catalytic wet air oxidation (CWAO) has attracted a great deal of attention. In this study different carbon material catalysts (multi-walled carbon nanotubes, carbon fibers and graphite) were developed to enhance the CWAO of phenol in aqueous solution. The functionalized carbon materials exhibited excellent catalytic activity in the CWAO of phenol. After 60 min reaction, the removal of phenol was nearly 100% over the functionalized multi-walled carbon, while it was only 14% over the purified multi-walled carbon under the same reaction conditions. Carboxylic acid groups introduced on the surface of the functionalized carbon materials play an important role in the catalytic activity in CWAO. They can promote the production of free radicals, which act as strong oxidants in CWAO. Based on the analysis of the intermediates produced in the CWAO reactions, a new reaction pathway for the CWAO of phenol was proposed in this study. There are some differences between the proposed reaction pathway and that reported in the literature. First, maleic acid is transformed directly into malonic acid. Second, acetic acid is oxidized into an unknown intermediate, which is then oxidized into CO2 and H2O. Finally, formic acid and oxalic acid can mutually interconvert when conditions are favorable. Copyright © 2014. Published by Elsevier B.V.

Dry (CO2) reforming of methane over Pt catalysts studied by DFT and kinetic modeling

NASA Astrophysics Data System (ADS)

Niu, Juntian; Du, Xuesen; Ran, Jingyu; Wang, Ruirui

2016-07-01

Dry reforming of methane (DRM) is a well-studied reaction that is of both scientific and industrial importance. In order to design catalysts that minimize the deactivation and improve the selectivity and activity for a high H2/CO yield, it is necessary to understand the elementary reaction steps involved in activation and conversion of CO2 and CH4. In our present work, a microkinetic model based on density functional theory (DFT) calculations is applied to explore the reaction mechanism for methane dry reforming on Pt catalysts. The adsorption energies of the reactants, intermediates and products, and the activation barriers for the elementary reactions involved in the DRM process are calculated over the Pt(1 1 1) surface. In the process of CH4 direct dissociation, the kinetic results show that CH dissociative adsorption on Pt(1 1 1) surface is the rate-determining step. CH appears to be the most abundant species on the Pt(1 1 1) surface, suggesting that carbon deposition is not easy to form in CH4 dehydrogenation on Pt(1 1 1) surface. In the process of CO2 activation, three possible reaction pathways are considered to contribute to the CO2 decomposition: (I) CO2* + * → CO* + O*; (II) CO2* + H* → COOH* + * → CO* + OH*; (III) CO2* + H* → mono-HCOO* + * → bi-HCOO* + * [CO2* + H* → bi-HCOO* + *] → CHO* + O*. Path I requires process to overcome the activation barrier of 1.809 eV and the forward reaction is calculated to be strongly endothermic by 1.430 eV. In addition, the kinetic results also indicate this process is not easy to proceed on Pt(1 1 1) surface. While the CO2 activation by H adsorbed over the catalyst surface to form COOH intermediate (Path II) is much easier to be carried out with the lower activation barrier of 0.746 eV. The Csbnd O bond scission is the rate-determining step along this pathway and the process needs to overcome the activation barrier of 1.522 eV. Path III reveals the CO2 activation through H adsorbed over the catalyst surface to form HCOO intermediate firstly. This reaction requires a quite high activation barrier and is a strongly endothermic process leading to a very low forward rate constant. In conclusion, Path II is the dominant reaction pathway in CO2 activation. Additionally, there are two pathways of CH oxidation by O: (A) CH* + O* → CHO* + * → CO* + H*; (B) CH* + O* → COH* + * → CO* + H*. Both the activation barriers and kinetic results demonstrate that Path A is the prior reaction pathway. Furthermore, in the two pathways of CH oxidation by OH: (C) CH* + OH* → CHOH* + * → CHO* + H*; (D) CH* + OH* → CHOH* + * → COH* + H*. Path C is easier to proceed. In conclusion, the main reaction pathway in CH oxidation according to the mechanism: CH* + OH* → CHOH* + * → CHO* + H* → CO* + 2H*. These results could provide some useful information for the operation of DRM over Pt catalysts, and are helpful to understand the mechanisms of DRM from the atomic scale.

Pathways to agility in the production of neutron generators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoltz, R.E.; Beavis, L.C.; Cutchen, J.T.

1994-02-01

This report is the result of a study team commissioned to explore pathways for increased agility in the manufacture of neutron generators. As a part of Sandia`s new responsibility for generator production, the goal of the study was to identify opportunities to reduce costs and increase flexibility in the manufacturing operation. Four parallel approaches (or pathways) were recommended: (1) Know the goal, (2) Use design leverage effectively, (3) Value simplicity, and (4) Configure for flexibility. Agility in neutron generator production can be enhanced if all of these pathways are followed. The key role of the workforce in achieving agility wasmore » also noted, with emphasis on ownership, continuous learning, and a supportive environment.« less

An autonomous organic reaction search engine for chemical reactivity.

PubMed

Dragone, Vincenza; Sans, Victor; Henson, Alon B; Granda, Jaroslaw M; Cronin, Leroy

2017-06-09

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.

An autonomous organic reaction search engine for chemical reactivity

NASA Astrophysics Data System (ADS)

Dragone, Vincenza; Sans, Victor; Henson, Alon B.; Granda, Jaroslaw M.; Cronin, Leroy

2017-06-01

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.

Reaction Mechanisms on Multiwell Potential Energy Surfaces in Combustion (and Atmospheric) Chemistry

DOE PAGES

Osborn, David L.

2017-03-15

Chemical reactions occurring on a potential energy surface with multiple wells are ubiquitous in low temperature combustion and the oxidation of volatile organic compounds in earth’s atmosphere. The rich variety of structural isomerizations that compete with collisional stabilization make characterizing such complex-forming reactions challenging. This review describes recent experimental and theoretical advances that deliver increasingly complete views of their reaction mechanisms. New methods for creating reactive intermediates coupled with multiplexed measurements provide many experimental observables simultaneously. Automated methods to explore potential energy surfaces can uncover hidden reactive pathways, while master equation methods enable a holistic treatment of both sequential andmore » well-skipping pathways. Our ability to probe and understand nonequilibrium effects and reaction sequences is increasing. These advances provide the fundamental science base for predictive models of combustion and the atmosphere that are crucial to address global challenges.« less

Mapping the Complete Reaction Path of a Complex Photochemical Reaction.

PubMed

Smith, Adam D; Warne, Emily M; Bellshaw, Darren; Horke, Daniel A; Tudorovskya, Maria; Springate, Emma; Jones, Alfred J H; Cacho, Cephise; Chapman, Richard T; Kirrander, Adam; Minns, Russell S

2018-05-04

We probe the dynamics of dissociating CS_{2} molecules across the entire reaction pathway upon excitation. Photoelectron spectroscopy measurements using laboratory-generated femtosecond extreme ultraviolet pulses monitor the competing dissociation, internal conversion, and intersystem crossing dynamics. Dissociation occurs either in the initially excited singlet manifold or, via intersystem crossing, in the triplet manifold. Both product channels are monitored and show that, despite being more rapid, the singlet dissociation is the minor product and that triplet state products dominate the final yield. We explain this by a consideration of accurate potential energy curves for both the singlet and triplet states. We propose that rapid internal conversion stabilizes the singlet population dynamically, allowing for singlet-triplet relaxation via intersystem crossing and the efficient formation of spin-forbidden dissociation products on longer timescales. The study demonstrates the importance of measuring the full reaction pathway for defining accurate reaction mechanisms.

Mapping the Complete Reaction Path of a Complex Photochemical Reaction

NASA Astrophysics Data System (ADS)

Smith, Adam D.; Warne, Emily M.; Bellshaw, Darren; Horke, Daniel A.; Tudorovskya, Maria; Springate, Emma; Jones, Alfred J. H.; Cacho, Cephise; Chapman, Richard T.; Kirrander, Adam; Minns, Russell S.

2018-05-01

We probe the dynamics of dissociating CS2 molecules across the entire reaction pathway upon excitation. Photoelectron spectroscopy measurements using laboratory-generated femtosecond extreme ultraviolet pulses monitor the competing dissociation, internal conversion, and intersystem crossing dynamics. Dissociation occurs either in the initially excited singlet manifold or, via intersystem crossing, in the triplet manifold. Both product channels are monitored and show that, despite being more rapid, the singlet dissociation is the minor product and that triplet state products dominate the final yield. We explain this by a consideration of accurate potential energy curves for both the singlet and triplet states. We propose that rapid internal conversion stabilizes the singlet population dynamically, allowing for singlet-triplet relaxation via intersystem crossing and the efficient formation of spin-forbidden dissociation products on longer timescales. The study demonstrates the importance of measuring the full reaction pathway for defining accurate reaction mechanisms.

Reaction Mechanisms on Multiwell Potential Energy Surfaces in Combustion (and Atmospheric) Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osborn, David L.

Chemical reactions occurring on a potential energy surface with multiple wells are ubiquitous in low temperature combustion and the oxidation of volatile organic compounds in earth’s atmosphere. The rich variety of structural isomerizations that compete with collisional stabilization make characterizing such complex-forming reactions challenging. This review describes recent experimental and theoretical advances that deliver increasingly complete views of their reaction mechanisms. New methods for creating reactive intermediates coupled with multiplexed measurements provide many experimental observables simultaneously. Automated methods to explore potential energy surfaces can uncover hidden reactive pathways, while master equation methods enable a holistic treatment of both sequential andmore » well-skipping pathways. Our ability to probe and understand nonequilibrium effects and reaction sequences is increasing. These advances provide the fundamental science base for predictive models of combustion and the atmosphere that are crucial to address global challenges.« less

An autonomous organic reaction search engine for chemical reactivity

PubMed Central

Dragone, Vincenza; Sans, Victor; Henson, Alon B.; Granda, Jaroslaw M.; Cronin, Leroy

2017-01-01

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways. PMID:28598440

Successful removal of hyperkeratotic-lichenoid reaction to red ink tattoo with preservation of the whole tattoo using a skin grafting knife.

PubMed

Mlakar, Boštjan

2015-01-01

With the increasing popularity of tattoo body decorations, reports of medical complications with tattoos have increased in parallel. Although tattoo reactions can resolve spontaneously, they often last for months or even years, despite the various treatment methods. In our case, we present the successful removal of hyperkeratotic-lichenoid reaction to red ink using a simple and cheap skin grafting knife. The entire tattoo was preserved with a good aesthetic result with minimal scarring.

Metabolic PathFinding: inferring relevant pathways in biochemical networks.

PubMed

Croes, Didier; Couche, Fabian; Wodak, Shoshana J; van Helden, Jacques

2005-07-01

Our knowledge of metabolism can be represented as a network comprising several thousands of nodes (compounds and reactions). Several groups applied graph theory to analyse the topological properties of this network and to infer metabolic pathways by path finding. This is, however, not straightforward, with a major problem caused by traversing irrelevant shortcuts through highly connected nodes, which correspond to pool metabolites and co-factors (e.g. H2O, NADP and H+). In this study, we present a web server implementing two simple approaches, which circumvent this problem, thereby improving the relevance of the inferred pathways. In the simplest approach, the shortest path is computed, while filtering out the selection of highly connected compounds. In the second approach, the shortest path is computed on the weighted metabolic graph where each compound is assigned a weight equal to its connectivity in the network. This approach significantly increases the accuracy of the inferred pathways, enabling the correct inference of relatively long pathways (e.g. with as many as eight intermediate reactions). Available options include the calculation of the k-shortest paths between two specified seed nodes (either compounds or reactions). Multiple requests can be submitted in a queue. Results are returned by email, in textual as well as graphical formats (available in http://www.scmbb.ulb.ac.be/pathfinding/).

Theoretical study of the decomposition pathways and products of C5- perfluorinated ketone (C5 PFK)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Yuwei; Wang, Xiaohua, E-mail: xhw@mail.xjtu.edu.cn, E-mail: mzrong@mail.xjtu.edu.cn; Li, Xi

Due to the high global warming potential (GWP) and increasing environmental concerns, efforts on searching the alternative gases to SF{sub 6}, which is predominantly used as insulating and interrupting medium in high-voltage equipment, have become a hot topic in recent decades. Overcoming the drawbacks of the existing candidate gases, C5- perfluorinated ketone (C5 PFK) was reported as a promising gas with remarkable insulation capacity and the low GWP of approximately 1. Experimental measurements of the dielectric strength of this novel gas and its mixtures have been carried out, but the chemical decomposition pathways and products of C5 PFK during breakdownmore » are still unknown, which are the essential factors in evaluating the electric strength of this gas in high-voltage equipment. Therefore, this paper is devoted to exploring all the possible decomposition pathways and species of C5 PFK by density functional theory (DFT). The structural optimizations, vibrational frequency calculations and energy calculations of the species involved in a considered pathway were carried out with DFT-(U)B3LYP/6-311G(d,p) method. Detailed potential energy surface was then investigated thoroughly by the same method. Lastly, six decomposition pathways of C5 PFK decomposition involving fission reactions and the reactions with a transition states were obtained. Important intermediate products were also determined. Among all the pathways studied, the favorable decomposition reactions of C5 PFK were found, involving C-C bond ruptures producing Ia and Ib in pathway I, followed by subsequent C-C bond ruptures and internal F atom transfers in the decomposition of Ia and Ib presented in pathways II + III and IV + V, respectively. Possible routes were pointed out in pathway III and lead to the decomposition of IIa, which is the main intermediate product found in pathway II of Ia decomposition. We also investigated the decomposition of Ib, which can undergo unimolecular reactions to give the formation of IV a, IV b and products of CF{sub 3} + CF-CF{sub 3} in pathway IV. Although IV a is dominant to a lesser extent due to its relative high energy barrier, its complicated decomposition pathway V was also studied and CF{sub 3}, C = CF{sub 2} as well as C-CF{sub 3} species were found as the ultimate products. To complete the decomposition of C5 PFK, pathway V I of Ic decomposition was fully explored and the final products were obtained. Therefore, the integrate decomposition scheme of C5 PFK was proposed, which contains six pathways and forty-eight species (including all the reactants, products and transition states). This work is hopeful to lay a theoretical basis for the insulating properties of C5 PFK.« less

Conservation of direct dynamics in sterically hindered SN2/E2 reactions.

PubMed

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin; Wester, Roland

2018-01-21

Nucleophilic substitution (S N 2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl - and CN - with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct S N 2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern S N 2 and E2 pathways even in sterically hindered exchange reaction systems.

Conservation of direct dynamics in sterically hindered SN2/E2 reactions

PubMed Central

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin

2017-01-01

Nucleophilic substitution (SN2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl– and CN– with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct SN2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern SN2 and E2 pathways even in sterically hindered exchange reaction systems. PMID:29629138

Phosphatase Complex Pph3/Psy2 Is Involved in Regulation of Efficient Non-Homologous End-Joining Pathway in the Yeast Saccharomyces cerevisiae

PubMed Central

Omidi, Katayoun; Hooshyar, Mohsen; Jessulat, Matthew; Samanfar, Bahram; Sanders, Megan; Burnside, Daniel; Pitre, Sylvain; Schoenrock, Andrew; Xu, Jianhua; Babu, Mohan; Golshani, Ashkan

2014-01-01

One of the main mechanisms for double stranded DNA break (DSB) repair is through the non-homologous end-joining (NHEJ) pathway. Using plasmid and chromosomal repair assays, we showed that deletion mutant strains for interacting proteins Pph3p and Psy2p had reduced efficiencies in NHEJ. We further observed that this activity of Pph3p and Psy2p appeared linked to cell cycle Rad53p and Chk1p checkpoint proteins. Pph3/Psy2 is a phosphatase complex, which regulates recovery from the Rad53p DNA damage checkpoint. Overexpression of Chk1p checkpoint protein in a parallel pathway to Rad53p compensated for the deletion of PPH3 or PSY2 in a chromosomal repair assay. Double mutant strains Δpph3/Δchk1 and Δpsy2/Δchk1 showed additional reductions in the efficiency of plasmid repair, compared to both single deletions which is in agreement with the activity of Pph3p and Psy2p in a parallel pathway to Chk1p. Genetic interaction analyses also supported a role for Pph3p and Psy2p in DNA damage repair, the NHEJ pathway, as well as cell cycle progression. Collectively, we report that the activity of Pph3p and Psy2p further connects NHEJ repair to cell cycle progression. PMID:24498054

Phosphatase complex Pph3/Psy2 is involved in regulation of efficient non-homologous end-joining pathway in the yeast Saccharomyces cerevisiae.

PubMed

Omidi, Katayoun; Hooshyar, Mohsen; Jessulat, Matthew; Samanfar, Bahram; Sanders, Megan; Burnside, Daniel; Pitre, Sylvain; Schoenrock, Andrew; Xu, Jianhua; Babu, Mohan; Golshani, Ashkan

2014-01-01

One of the main mechanisms for double stranded DNA break (DSB) repair is through the non-homologous end-joining (NHEJ) pathway. Using plasmid and chromosomal repair assays, we showed that deletion mutant strains for interacting proteins Pph3p and Psy2p had reduced efficiencies in NHEJ. We further observed that this activity of Pph3p and Psy2p appeared linked to cell cycle Rad53p and Chk1p checkpoint proteins. Pph3/Psy2 is a phosphatase complex, which regulates recovery from the Rad53p DNA damage checkpoint. Overexpression of Chk1p checkpoint protein in a parallel pathway to Rad53p compensated for the deletion of PPH3 or PSY2 in a chromosomal repair assay. Double mutant strains Δpph3/Δchk1 and Δpsy2/Δchk1 showed additional reductions in the efficiency of plasmid repair, compared to both single deletions which is in agreement with the activity of Pph3p and Psy2p in a parallel pathway to Chk1p. Genetic interaction analyses also supported a role for Pph3p and Psy2p in DNA damage repair, the NHEJ pathway, as well as cell cycle progression. Collectively, we report that the activity of Pph3p and Psy2p further connects NHEJ repair to cell cycle progression.

Measuring protection of aromatic wine thiols from oxidation by competitive reactions vs wine preservatives with ortho-quinones.

PubMed

Nikolantonaki, Maria; Magiatis, Prokopios; Waterhouse, Andrew L

2014-11-15

Quinones are central intermediates in wine oxidation that can degrade the quality of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione, ascorbic acid and model tannin, phloroglucinol) was assessed by competitive sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and identification by NMR spectroscopy. Nucleophilic addition reactions compete with two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both routes serve as effective quenching pathways, but minor secondary products from coupled redox reactions between the products and reactants are also observed. The wine preservatives were all highly reactive and thus all very protective against 3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant effects. Confirmation of these reaction rates and pathways in wine is needed to assess the actual protective action of each tested preservative. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intracellular signal propagation in a two-dimensional autocatalytic reaction model.

PubMed

Castiglione, F; Bernaschi, M; Succi, S; Heinrich, R; Kirschner, M W

2002-09-01

We study a simple reaction scheme in a two-dimensional lattice of particles or molecules with a refractory state. We analyze the dynamics of the propagating front as a function of physical-chemical properties of the host medium. The anisotropy of the medium significantly affects the smoothness of the wave front. Similarly, if particles or molecules may diffuse slowly to neighboring sites, then the front wave is more likely to be irregular. Both situations affect the ability of the whole system to relax to the original state, which is a required feature in the biological cells. Attempts to map this simple reaction scheme to reactions involved in the intracellular pathways suggest that, in some cases, signal transduction might take both connotation of a random walk and a propagating wave, depending on the local density of the medium. In particular, a sufficient condition for the appearance of waves in high-density regions of the media, is the existence of at least one autocatalytic reaction in the chain of reactions characterizing the pathway.

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

PubMed Central

Byers, Jeffery A.; Jamison, Timothy F.

2013-01-01

Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. PMID:24046369

Visualizing non-equilibrium lithiation of spinel oxide via in situ transmission electron microscopy

PubMed Central

He, Kai; Zhang, Sen; Li, Jing; Yu, Xiqian; Meng, Qingping; Zhu, Yizhou; Hu, Enyuan; Sun, Ke; Yun, Hongseok; Yang, Xiao-Qing; Zhu, Yimei; Gan, Hong; Mo, Yifei; Stach, Eric A.; Murray, Christopher B.; Su, Dong

2016-01-01

Spinel transition metal oxides are important electrode materials for lithium-ion batteries, whose lithiation undergoes a two-step reaction, whereby intercalation and conversion occur in a sequential manner. These two reactions are known to have distinct reaction dynamics, but it is unclear how their kinetics affects the overall electrochemical response. Here we explore the lithiation of nanosized magnetite by employing a strain-sensitive, bright-field scanning transmission electron microscopy approach. This method allows direct, real-time, high-resolution visualization of how lithiation proceeds along specific reaction pathways. We find that the initial intercalation process follows a two-phase reaction sequence, whereas further lithiation leads to the coexistence of three distinct phases within single nanoparticles, which has not been previously reported to the best of our knowledge. We use phase-field theory to model and describe these non-equilibrium reaction pathways, and to directly correlate the observed phase evolution with the battery's discharge performance. PMID:27157119

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matz, Dallas L.; Schalnat, Matthew C.; Pemberton, Jeanne E.

The reaction between small organic molecules and low work function metals is of interest in organometallic, astronomical, and optoelectronic device chemistry. Here, thin, solid-state, amorphous benzene and pyridine films are reacted with Ca at 30 K under ultrahigh vacuum with the reaction progress monitored by Raman spectroscopy. Although both films react with Ca to produce product species identifiable by their vibrational spectroscopic signatures, benzene is less reactive with Ca than pyridine. Benzene reacts by electron transfer from Ca to benzene producing multiple species including the phenyl radical anion, the phenyl radical, and the benzyne diradical. Pyridine initially reacts along amore » similar electron transfer pathway as indicated by the presence of the corresponding pyridyl radical and pyridyne diradical species, but these pyridyl radicals are less stable and subject to further ring-opening reactions that lead to a complex array of smaller molecule reaction products and ultimately amorphous carbon. The elucidation of this reaction pathway provides insight into the reactions of aromatics with Ca that are relevant in the areas of catalysis, astrochemistry, and organic optoelectronics.« less

Hydroxyacetone production from C 3 Criegee intermediates

DOE PAGES

Taatjes, Craig A.; Liu, Fang; Rotavera, Brandon; ...

2016-12-21

Hydroxyacetone (CH 3C(O)CH 2OH) is observed as a stable end product from reactions of the (CH 3) 2COO Criegee intermediate, acetone oxide, in a flow tube coupled with multiplexed photoionization mass spectrometer detection. In the experiment, the isomers at m/z = 74 are distinguished by their different photoionization spectra and reaction times. Hydroxyacetone is observed as a persistent signal at longer reaction times at a higher photoionization threshold of ca. 9.7 eV than Criegee intermediate and definitively identified by comparison with the known photoionization spectrum. Complementary electronic structure calculations reveal multiple possible reaction pathways for hydroxyacetone formation, including unimolecular isomerizationmore » via hydrogen atom transfer and –OH group migration as well as self-reaction of Criegee intermediates. Varying the concentration of Criegee intermediates suggests contributions from both unimolecular and self-reaction pathways to hydroxyacetone. As a result, the hydroxyacetone end product can provide an effective, stable marker for the production of transient Criegee intermediates in future studies of alkene ozonolysis.« less

Unraveling reaction pathways and specifying reaction kinetics for complex systems.

PubMed

Vinu, R; Broadbelt, Linda J

2012-01-01

Many natural and industrial processes involve a complex set of competing reactions that include several different species. Detailed kinetic modeling of such systems can shed light on the important pathways involved in various transformations and therefore can be used to optimize the process conditions for the desired product composition and properties. This review focuses on elucidating the various components involved in modeling the kinetics of pyrolysis and oxidation of polymers. The elementary free radical steps that constitute the chain reaction mechanism of gas-phase/nonpolar liquid-phase processes are outlined. Specification of the rate coefficients of the various reaction families, which is central to the theme of kinetics, is described. Construction of the reaction network on the basis of the types of end groups and reactive moieties in a polymer chain is discussed. Modeling frameworks based on the method of moments and kinetic Monte Carlo are evaluated using illustrations. Finally, the prospects and challenges in modeling biomass conversion are addressed.

Class and Home Problems: Modeling of an Industrial Anaerobic Digester: A Case Study for Undergraduate Students

ERIC Educational Resources Information Center

Durruty, Ignacio; Ayude, María A.

2014-01-01

The case study discussed in this work is used at the chemical reaction engineering course, offered in fifth-year of the chemical engineering undergraduate program at National University of Mar del Plata (UNMdP). A serial-parallel reaction system based on the anaerobic degradation of particulate-containing potato processing wastewater is presented.…

The Oxidation of Iron: Experiment, Simulation, and Analysis in Introductory Chemistry

ERIC Educational Resources Information Center

Schubert, Frederic E.

2015-01-01

In this exercise, an actual chemical reaction, oxidation of iron in air, is studied along with a related analogue simulation of that reaction. The rusting of steel wool is carried out as a class effort. The parallel simulation is performed by students working in small groups. The analogue for the reacting gas is a countable set of discrete marble…

CO2 Reduction Catalyzed by Nitrogenase: Pathways to Formate, Carbon Monoxide, and Methane.

PubMed

Khadka, Nimesh; Dean, Dennis R; Smith, Dayle; Hoffman, Brian M; Raugei, Simone; Seefeldt, Lance C

2016-09-06

The reduction of N2 to NH3 by Mo-dependent nitrogenase at its active-site metal cluster FeMo-cofactor utilizes reductive elimination of Fe-bound hydrides with obligatory loss of H2 to activate the enzyme for binding/reduction of N2. Earlier work showed that wild-type nitrogenase and a nitrogenase with amino acid substitutions in the MoFe protein near FeMo-cofactor can catalytically reduce CO2 by two or eight electrons/protons to carbon monoxide (CO) and methane (CH4) at low rates. Here, it is demonstrated that nitrogenase preferentially reduces CO2 by two electrons/protons to formate (HCOO(-)) at rates >10 times higher than rates of CO2 reduction to CO and CH4. Quantum mechanical calculations on the doubly reduced FeMo-cofactor with a Fe-bound hydride and S-bound proton (E2(2H) state) favor a direct reaction of CO2 with the hydride ("direct hydride transfer" reaction pathway), with facile hydride transfer to CO2 yielding formate. In contrast, a significant barrier is observed for reaction of Fe-bound CO2 with the hydride ("associative" reaction pathway), which leads to CO and CH4. Remarkably, in the direct hydride transfer pathway, the Fe-H behaves as a hydridic hydrogen, whereas in the associative pathway it acts as a protic hydrogen. MoFe proteins with amino acid substitutions near FeMo-cofactor (α-70(Val→Ala), α-195(His→Gln)) are found to significantly alter the distribution of products between formate and CO/CH4.

Electrophysiological evidence of cerebellar fiber system involvement in the Miller Fisher syndrome.

PubMed

Lo, Y L; Fook-Chong, S; Chan, L L; Ong, W Y; Ratnagopal, P

2010-01-15

In the Miller Fisher syndrome (MFS), ataxia may be due involvement of Ia afferents and the cerebellum. Transcranial magnetic stimulation (TMS) over the cerebellum is known to interfere transiently with normal function. In this study, we utilized a previously described TMS protocol over the cerebellum in combination with ballistic movements to investigate cerebellar dysfunction in MFS patients. The agonist (biceps) reaction time in MFS patients during a motor cancellation task was not significantly reduced during the initial TMS study. However, during the repeat TMS study, significant reduction was seen for all patients, in tandem with clinical recovery. There was significant correlation between anti-GQ1b IgG titers and change in agonist reaction time between the initial and repeat TMS studies. TMS likely affected horizontally orientated parallel fibers in the cerebellar molecular layer. During disease onset, antibody binding may have interfered with facilitation of reaction time during motor cancellation tasks seen in normal subjects. Normalization of reaction time facilitation corresponded to resolution of antibody-mediated interference in the molecular layer. Our study has provided evidence suggesting parallel fiber involvement in MFS, and suggested a role of anti-GQ1b IgG antibody in these changes.

Visual reaction times during prolonged angular acceleration parallel the subjective perception of rotation

NASA Technical Reports Server (NTRS)

Mattson, D. L.

1975-01-01

The effect of prolonged angular acceleration on choice reaction time to an accelerating visual stimulus was investigated, with 10 commercial airline pilots serving as subjects. The pattern of reaction times during and following acceleration was compared with the pattern of velocity estimates reported during identical trials. Both reaction times and velocity estimates increased at the onset of acceleration, declined prior to the termination of acceleration, and showed an aftereffect. These results are inconsistent with the torsion-pendulum theory of semicircular canal function and suggest that the vestibular adaptation is of central origin.

Multinucleon transfer reactions – a pathway to new heavy and superheavy nuclei?

NASA Astrophysics Data System (ADS)

Heinz, Sophie

2018-05-01

Recently, we reported the observation of several new neutron-deficient isotopes with proton numbers Z ≥ 92 in collisions of 48Ca + 248Cm at the Coulomb barrier. The peculiarity is that these nuclei were produced in deep inelastic multinucleon transfer reactions, a method which is presently discussed as a possible new pathway to enter so far unknown regions in the upper part of the Chart of Nuclides. Of particular interest are multinucleon transfer reactions as a possible means to produce neutron-rich superheavy nuclei and nuclei along the magic neutron shell N = 126. Based on present-day physical and technical state-of-the art, we will discuss the question how big are our chances to enter these regions by applying multinucleon transfer reactions.

Kinetic and mechanisms of methanimine reactions with singlet and triplet molecular oxygen: Substituent and catalyst effects

NASA Astrophysics Data System (ADS)

Asgharzadeh, Somaie; Vahedpour, Morteza

2018-06-01

Methanimine reaction with O2 on singlet and triplet potential energy surfaces are investigated using B3PW91, M06-2X, MP2 and CCSD(T) methods. Thermodynamic and kinetic parameters are calculated at M06-2X method. The most favorable channel involves H-abstraction of CH2NH+O2 to the formation of HCN + H2O2 products via low level energy barrier. The catalytic effect of water molecule on HCN + H2O2 products pathway are investigated. Result shows that contribution of water molecule using complex formation with methanimine can decreases barrier energy of transition state and the reaction rate increases. Also, substituent effect of fluorine atom as deactivating group are investigated on the main reaction pathway.

Modeling evolution of crosstalk in noisy signal transduction networks

NASA Astrophysics Data System (ADS)

Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

2018-02-01

Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

Pyrolysis reaction networks for lignin model compounds: unraveling thermal deconstruction of β-O-4 and α-O-4 compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yong S.; Singh, Rahul; Zhang, Jing

2016-01-01

Although lignin is one of the main components of biomass, its pyrolysis chemistry is not well understood due to complex heterogeneity. To gain insights into this chemistry, the pyrolysis of seven lignin model compounds (five ..beta..-O-4 and two ..alpha..-O-4 linked molecules) was investigated in a micropyrolyzer connected to GC-MS/FID. According to quantitative product mole balance for the reaction networks, concerted retro-ene fragmentation and homolytic dissociation were strongly suggested as the initial reaction step for ..beta..-O-4 compounds and ..alpha..-O-4 compounds, respectively. The difference in reaction pathway between compounds with different linkages was believed to result from thermodynamics of the radical initiation.more » The rate constants for the different reaction pathways were predicted from ab initio density functional theory calculations and pre-exponential literature values. The computational findings were consistent with the experiment results, further supporting the different pyrolysis mechanisms for the ..beta..-ether linked and ..alpha..-ether linked compounds. A combination of the two pathways from the dimeric model compounds was able to describe qualitatively the pyrolysis of a trimeric lignin model compound containing both ..beta..-O-4 and ..alpha..-O-4 linkages.« less

Ferrate(VI) oxidation of polychlorinated diphenyl sulfides: Kinetics, degradation, and oxidized products.

PubMed

Chen, Jing; Xu, Xinxin; Zeng, Xiaolan; Feng, Mingbao; Qu, Ruijuan; Wang, Zunyao; Nesnas, Nasri; Sharma, Virender K

2018-06-13

This paper presents oxidation of polychlorinated diphenyl sulfides (PCDPSs), dioxin-like compounds, by ferrate(VI) (Fe VI O 4 2- , Fe(VI)). Kinetics of the reactions of Fe(VI) with seventeen PCDPSs, differ in number and positions of chlorine atoms (from 2 to 7), were investigated at pH 8.0. The second-order rate constants (k, M -1 s -1 ) of the reactions varied with the numbers and positions of chlorine atoms and appeared to be related with standard Gibbs free energy of formation (Δ f G 0 ) of PCDPSs. Degradation experiments in the presence of ions and humic acid demonstrated complete removal of PeCDPS by Fe(VI) in minutes. Pathways of the reaction were investigated by identifying oxidized products (OPs) of the reaction between Fe(VI) and 2,2',3',4,5-pentachlorodiphenyl sulfide (PeCDPS) at pH 8.0. Pathways of oxidation involved major pathway of attack on sulfur(II) by Fe(VI) in steps to yield sulfoxide type products, and subsequent breakage of C-S bond with the formation of sulfonic acid-containing trichloro compound. Minor pathways were hydroxylation of benzene ring and substitution of chlorine atom with hydroxyl group. Estimation of toxicity of OPs of the oxidation of PeCDPS by Fe(VI) suggested the decreased toxicity from the parent contaminant. Copyright © 2018. Published by Elsevier Ltd.

Lower limb joint angles and ground reaction forces in forefoot strike and rearfoot strike runners during overground downhill and uphill running.

PubMed

Kowalski, Erik; Li, Jing Xian

2016-11-01

This study investigated the normal and parallel ground reaction forces during downhill and uphill running in habitual forefoot strike and habitual rearfoot strike (RFS) runners. Fifteen habitual forefoot strike and 15 habitual RFS recreational male runners ran at 3 m/s ± 5% during level, uphill and downhill overground running on a ramp mounted at 6° and 9°. Results showed that forefoot strike runners had no visible impact peak in all running conditions, while the impact peaks only decreased during the uphill conditions in RFS runners. Active peaks decreased during the downhill conditions in forefoot strike runners while active loading rates increased during downhill conditions in RFS runners. Compared to the level condition, parallel braking peaks were larger during downhill conditions and parallel propulsive peaks were larger during uphill conditions. Combined with previous biomechanics studies, our findings suggest that forefoot strike running may be an effective strategy to reduce impacts, especially during downhill running. These findings may have further implications towards injury management and prevention.

STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB.

PubMed

Klingbeil, Guido; Erban, Radek; Giles, Mike; Maini, Philip K

2011-04-15

The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new software tool STOCHSIMGPU that exploits graphics processing units (GPUs) for parallel stochastic simulations of biological/chemical reaction systems and show that significant gains in efficiency can be made. It is integrated into MATLAB and works with the Systems Biology Toolbox 2 (SBTOOLBOX2) for MATLAB. The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU). Using our software does not require any changes to the user's models, since it acts as a direct replacement of the stochastic simulation software of the SBTOOLBOX2. The software is open source under the GPL v3 and available at http://www.maths.ox.ac.uk/cmb/STOCHSIMGPU. The web site also contains supplementary information. klingbeil@maths.ox.ac.uk Supplementary data are available at Bioinformatics online.

Rapid determination of enantiomeric excess: a focus on optical approaches.

PubMed

Leung, Diana; Kang, Sung Ok; Anslyn, Eric V

2012-01-07

High-throughput screening (HTS) methods are becoming increasingly essential in discovering chiral catalysts or auxiliaries for asymmetric transformations due to the advent of parallel synthesis and combinatorial chemistry. Both parallel synthesis and combinatorial chemistry can lead to the exploration of a range of structural candidates and reaction conditions as a means to obtain the highest enantiomeric excess (ee) of a desired transformation. One current bottleneck in these approaches to asymmetric reactions is the determination of ee, which has led researchers to explore a wide range of HTS techniques. To be truly high-throughput, it has been proposed that a technique that can analyse a thousand or more samples per day is needed. Many of the current approaches to this goal are based on optical methods because they allow for a rapid determination of ee due to quick data collection and their parallel analysis capabilities. In this critical review these techniques are reviewed with a discussion of their respective advantages and drawbacks, and with a contrast to chromatographic methods (180 references). This journal is © The Royal Society of Chemistry 2012

Reaction of Cl- ions in electrolyte solution induced electrical discharge plasma in the presence of argon fine bubbles

NASA Astrophysics Data System (ADS)

Hayashi, Yui; Takada, Noriharu; Wahyudiono, Kanda, Hideki; Goto, Motonobu

2017-05-01

Active chlorine species such as chlorine molecules and hypochlorous acid have been known as high performance sanitizers. They would act more reactive on chemical and biological substances when an electrical discharge was introduced in water containing an electrolyte substance. Here, the reaction of chloride (Cl-) ions were examined by introducing of a pulsed discharge plasma in sodium chloride (NaCl) solution as an electrolyte solution at room temperature. The results show that a large electrical current generated by the pulsed discharge plasma affected the reaction of Cl- ions to result available chlorine. The reaction pathway for available chlorine production was assumed similar with the reaction pathway as electrolysis. A pulsed discharge plasma in NaCl solution in the presence of argon (Ar) fine bubbles exhibited intense emissions and high electron density compared to when no Ar fine bubbles were introduced. At these conditions, the dissociation reaction rate of water increased drastically leads to the formation of 0 atoms. As a result, the reaction of Cl- ions and the available chlorine generation were also increased.

Synaptic vesicle recycling: steps and principles.

PubMed

Rizzoli, Silvio O

2014-04-16

Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle.

GAS-PHASE OXIDATION PRODUCTS OF BIPHENYL AND POLYCHLORINATED BIPHENYLS (R825377)

EPA Science Inventory

Our laboratory recently measured the gas-phase reaction rate constants of
polychlorinated biphenyls (PCBs) with the hydroxyl radical (OH) and concluded
that OH reactions are the primary removal pathway of PCBs from the atmosphere.
With the reaction system previousl...

Dissociative double-photoionization of butadiene in the 25-45 eV energy range using 3-D multi-coincidence ion momentum imaging spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oghbaie, Shabnam; Gisselbrecht, Mathieu; Laksman, Joakim

Dissociative double-photoionization of butadiene in the 25-45 eV energy range has been studied with tunable synchrotron radiation using full three-dimensional ion momentum imaging. Using ab initio calculations, the electronic states of the molecular dication below 33 eV are identified. The results of the measurement and calculation show that double ionization from π orbitals selectively triggers twisting about the terminal or central C–C bonds. We show that this conformational rearrangement depends upon the dication electronic state, which effectively acts as a gateway for the dissociation reaction pathway. For photon energies above 33 eV, three-body dissociation channels where neutral H-atom evaporation precedesmore » C–C charge-separation in the dication species appear in the correlation map. The fragment angular distributions support a model where the dication species is initially aligned with the molecular backbone parallel to the polarization vector of the light, indicating a high probability for double-ionization to the “gateway states” for molecules with this orientation.« less

Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding.

PubMed

Ponce, Carlos R; Lomber, Stephen G; Livingstone, Margaret S

2017-05-10

In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells contribute to visual object recognition. They receive concurrent inputs from visual areas V4, V3, and V2. We asked how these different anatomical pathways shape PIT response properties by deactivating them while monitoring PIT activity in two male macaques. We found that cooling of V4 or V2|3 did not lead to consistent changes in population excitatory drive; however, population pattern analyses showed that V4-based pathways were more important than V2|3-based pathways. We did not find any image features that predicted decoding accuracy differences between both interventions. Using the HMAX hierarchical model of visual recognition, we found that different groups of simulated "PIT" units with different input histories (lacking "V2|3" or "V4" input) allowed for comparable levels of object-decoding performance and that removing a large fraction of "PIT" activity resulted in similar drops in performance as in the cooling experiments. We conclude that distinct input pathways to PIT relay similar types of shape information, with V1-dependent V4 cells providing more quantitatively useful information for overall encoding than cells in V2 projecting directly to PIT. SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of the visual system, but most emphasize input transformations across a serial hierarchy akin to the primary "ventral stream" (V1 → V2 → V4 → IT). However, the ventral stream also comprises parallel "bypass" pathways: V1 also connects to V4, and V2 to IT. To explore the advantages of mixing long and short pathways in the macaque brain, we used cortical cooling to silence inputs to posterior IT and compared the findings with an HMAX model with parallel pathways. Copyright © 2017 the authors 0270-6474/17/375019-16$15.00/0.

Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding

PubMed Central

2017-01-01

In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells contribute to visual object recognition. They receive concurrent inputs from visual areas V4, V3, and V2. We asked how these different anatomical pathways shape PIT response properties by deactivating them while monitoring PIT activity in two male macaques. We found that cooling of V4 or V2|3 did not lead to consistent changes in population excitatory drive; however, population pattern analyses showed that V4-based pathways were more important than V2|3-based pathways. We did not find any image features that predicted decoding accuracy differences between both interventions. Using the HMAX hierarchical model of visual recognition, we found that different groups of simulated “PIT” units with different input histories (lacking “V2|3” or “V4” input) allowed for comparable levels of object-decoding performance and that removing a large fraction of “PIT” activity resulted in similar drops in performance as in the cooling experiments. We conclude that distinct input pathways to PIT relay similar types of shape information, with V1-dependent V4 cells providing more quantitatively useful information for overall encoding than cells in V2 projecting directly to PIT. SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of the visual system, but most emphasize input transformations across a serial hierarchy akin to the primary “ventral stream” (V1 → V2 → V4 → IT). However, the ventral stream also comprises parallel “bypass” pathways: V1 also connects to V4, and V2 to IT. To explore the advantages of mixing long and short pathways in the macaque brain, we used cortical cooling to silence inputs to posterior IT and compared the findings with an HMAX model with parallel pathways. PMID:28416597

Investigating the Relationship Between Posttraumatic Stress Symptoms and Posttraumatic Growth Following Community Violence: The Role of Anger.

PubMed

Strasshofer, David R; Peterson, Zoë D; Beagley, Marin C; Galovski, Tara E

2017-10-05

Past research has revealed that posttraumatic stress disorder (PTSD) is characterized by disturbances in emotional reactivity, including anger reactions. In turn, posttraumatic stress symptoms (PTSS) and anger reactions have been shown to be independently associated with posttraumatic growth (PTG). As such, anger reactions may serve as a pathway of influence through which PTSS lead to PTG in trauma-exposed adults. The current study examined cross-sectional relationships among PTSS, anger reactions, and PTG in 318 participants who were exposed to the violent political protests in Ferguson, Missouri after the officer-involved shooting of Michael Brown. Specifically, anger reactions were examined as a pathway of influence through which PTSS contribute to PTG. PTSS positively predicted anger reactions and PTG. Further anger reactions were associated with PTG. Anger reactions were found to partially account for the relationship between PTSS and PTG; thus, PTSS affect PTG, in part, through anger reactions to traumatic events. These results indicate a more direct role of anger reactions in facilitating growth after the associated distress of community violence. On the basis of these findings, anger may be useful in galvanizing individuals to make positive change after traumatic events. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Investigation of the chemical pathway of gaseous nitrogen dioxide formation during flue gas desulfurization with dry sodium bicarbonate injection

NASA Astrophysics Data System (ADS)

Stein, Antoinette Weil

The chemical reaction pathway for the viable flue gas desulfurization process, dry sodium bicarbonate injection, was investigated to mitigate undesirable plume discoloration. Based on a foundation of past findings, a simplified three-step reaction pathway was hypothesized for the formation of the plume-discoloring constituent, NO2. As the first step, it was hypothesized that sodium sulfite formed by sodium bicarbonate reaction with flue gas SO 2. As the second step, it was hypothesized that sodium nitrate formed by sodium sulfite reaction with flue gas NO. And as the third step, it was hypothesized that NO2 and sodium sulfate formed by sodium nitrate reaction with SO2. The second and third hypothesized steps were experimentally investigated using an isothermal fixed bed reactor. As reported in the past, technical grade sodium sulfite was found to be un-reactive with NO and O2. Freshly prepared sodium sulfite, maintained unexposed to moist air, was shown to react with NO and O2 resulting in a mixture of sodium nitrite and sodium nitrate together with a significant temperature rise. This reaction was found to proceed only when oxygen was present in the flue gas. As reported in the past, technical grade sodium nitrate was shown to be un-reactive with SO2. But freshly formed sodium nitrate kept unexposed to humidity was found to be reactive with SO2 and O 2 resulting in the formation of NO2 and sodium sulfate polymorphic Form I. The NO2 formation by this reaction was shown to be temperature dependent with maximum formation at 175°C. Plume mitigation methods were studied based on the validated three-step reaction pathway. Mitigation of NO2 was exhibited by limiting oxygen concentration in the flue gas to a level below 5%. It was also shown that significant NO2 mitigation was achieved by operating below 110°C or above 250°C. An innovative NO2 mitigation method was patented as a result of the findings of this study. The patented process incorporated a process step of sodium sulfite injection to remove flue gas NO prior to sodium bicarbonate injection.

Mechanism for the Coupled Photochemistry of Ammonia and Acetylene: Implications for Giant Planets, Comets and Interstellar Organic Synthesis

NASA Astrophysics Data System (ADS)

Keane, Thomas C.

2017-09-01

Laboratory studies provide a fundamental understanding of photochemical processes in planetary atmospheres. Photochemical reactions taking place on giant planets like Jupiter and possibly comets and the interstellar medium are the subject of this research. Reaction pathways are proposed for the coupled photochemistry of NH3 (ammonia) and C2H2 (acetylene) within the context Jupiter's atmosphere. We then extend the discussion to the Great Red Spot, Extra-Solar Giant Planets, Comets and Interstellar Organic Synthesis. Reaction rates in the form of quantum yields were measured for the decomposition of reactants and the formation of products and stable intermediates: HCN (hydrogen cyanide), CH3CN (acetonitrile), CH3CH = N-N = CHCH3 (acetaldazine), CH3CH = N-NH2 (acetaldehyde hydrazone), C2H5NH2 (ethylamine), CH3NH2 (methylamine) and C2H4 (ethene) in the photolysis of NH3/C2H2 mixtures. Some of these compounds, formed in our investigation of pathways for HCN synthesis, were not encountered previously in observational, theoretical or laboratory photochemical studies. The quantum yields obtained allowed for the formulation of a reaction mechanism that attempts to explain the observed results under varying experimental conditions. In general, the results of this work are consistent with the initial observations of Ferris and Ishikawa (1988). However, their proposed reaction pathway which centers on the photolysis of CH3CH = N-N = CHCH3 does not explain all of the results obtained in this study. The formation of CH3CH = N-N = CHCH3 by a radical combination reaction of CH3CH = N• was shown in this work to be inconsistent with other experiments where the CH3CH = N• radical is thought to form but where no CH3CH = N-N = CHCH3 was detected. The importance of the role of H atom abstraction reactions was demonstrated and an alternative pathway for CH3CH = N-N = CHCH3 formation involving nucleophilic reaction between N2H4 and CH3CH = NH is advanced.

Mechanism for the Coupled Photochemistry of Ammonia and Acetylene: Implications for Giant Planets, Comets and Interstellar Organic Synthesis.

PubMed

Keane, Thomas C

2017-09-01

Laboratory studies provide a fundamental understanding of photochemical processes in planetary atmospheres. Photochemical reactions taking place on giant planets like Jupiter and possibly comets and the interstellar medium are the subject of this research. Reaction pathways are proposed for the coupled photochemistry of NH 3 (ammonia) and C 2 H 2 (acetylene) within the context Jupiter's atmosphere. We then extend the discussion to the Great Red Spot, Extra-Solar Giant Planets, Comets and Interstellar Organic Synthesis. Reaction rates in the form of quantum yields were measured for the decomposition of reactants and the formation of products and stable intermediates: HCN (hydrogen cyanide), CH 3 CN (acetonitrile), CH 3 CH = N-N = CHCH 3 (acetaldazine), CH 3 CH = N-NH 2 (acetaldehyde hydrazone), C 2 H 5 NH 2 (ethylamine), CH 3 NH 2 (methylamine) and C 2 H 4 (ethene) in the photolysis of NH 3 /C 2 H 2 mixtures. Some of these compounds, formed in our investigation of pathways for HCN synthesis, were not encountered previously in observational, theoretical or laboratory photochemical studies. The quantum yields obtained allowed for the formulation of a reaction mechanism that attempts to explain the observed results under varying experimental conditions. In general, the results of this work are consistent with the initial observations of Ferris and Ishikawa (1988). However, their proposed reaction pathway which centers on the photolysis of CH 3 CH = N-N = CHCH 3 does not explain all of the results obtained in this study. The formation of CH 3 CH = N-N = CHCH 3 by a radical combination reaction of CH 3 CH = N• was shown in this work to be inconsistent with other experiments where the CH 3 CH = N• radical is thought to form but where no CH 3 CH = N-N = CHCH 3 was detected. The importance of the role of H atom abstraction reactions was demonstrated and an alternative pathway for CH 3 CH = N-N = CHCH 3 formation involving nucleophilic reaction between N 2 H 4 and CH 3 CH = NH is advanced.

Porous AgPt@Pt Nanooctahedra as an Efficient Catalyst toward Formic Acid Oxidation with Predominant Dehydrogenation Pathway.

PubMed

Jiang, Xian; Yan, Xiaoxiao; Ren, Wangyu; Jia, Yufeng; Chen, Jianian; Sun, Dongmei; Xu, Lin; Tang, Yawen

2016-11-16

For direct formic acid fuel cells (DFAFCs), the dehydrogenation pathway is a desired reaction pathway, to boost the overall cell efficiency. Elaborate composition tuning and nanostructure engineering provide two promising strategies to design efficient electrocatalysts for DFAFCs. Herein, we present a facile synthesis of porous AgPt bimetallic nanooctahedra with enriched Pt surface (denoted as AgPt@Pt nanooctahedra) by a selective etching strategy. The smart integration of geometric and electronic effect confers a substantial enhancement of desired dehydrogenation pathway as well as electro-oxidation activity for the formic acid oxidation reaction (FAOR). We anticipate that the obtained nanocatalyst may hold great promises in fuel cell devices, and furthermore, the facile synthetic strategy demonstrated here can be extendable for the fabrication of other multicomponent nanoalloys with desirable morphologies and enhanced electrocatalytic performances.

Reversible Parallel Discrete-Event Execution of Large-scale Epidemic Outbreak Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perumalla, Kalyan S; Seal, Sudip K

2010-01-01

The spatial scale, runtime speed and behavioral detail of epidemic outbreak simulations together require the use of large-scale parallel processing. In this paper, an optimistic parallel discrete event execution of a reaction-diffusion simulation model of epidemic outbreaks is presented, with an implementation over themore » $$\\mu$$sik simulator. Rollback support is achieved with the development of a novel reversible model that combines reverse computation with a small amount of incremental state saving. Parallel speedup and other runtime performance metrics of the simulation are tested on a small (8,192-core) Blue Gene / P system, while scalability is demonstrated on 65,536 cores of a large Cray XT5 system. Scenarios representing large population sizes (up to several hundred million individuals in the largest case) are exercised.« less

Parallel synthesis of a series of potentially brain penetrant aminoalkyl benzoimidazoles.

PubMed

Micco, Iolanda; Nencini, Arianna; Quinn, Joanna; Bothmann, Hendrick; Ghiron, Chiara; Padova, Alessandro; Papini, Silvia

2008-03-01

Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist binding site of an alpha7 homology model and a series of aminoalkyl benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a selection of diamines, followed by reduction of the nitro group to obtain a series of monoalkylated phenylene diamines. N,N'-Carbonyldiimidazole (CDI) mediated acylation, followed by a parallel automated work-up procedure, afforded the monoacylated phenylenediamines which were cyclised under acidic conditions. Parallel work-up and purification afforded the array products in good yields and purities with a robust parallel methodology which will be useful for other libraries. Screening for alpha7 activity revealed compounds with agonist activity for the receptor.

A Theoretical Study of 8-Chloro-9-Hydroxy-Aflatoxin B1, the Conversion Product of Aflatoxin B1 by Neutral Electrolyzed Water

PubMed Central

Escobedo-González, René; Méndez-Albores, Abraham; Villarreal-Barajas, Tania; Aceves-Hernández, Juan Manuel; Miranda-Ruvalcaba, René; Nicolás-Vázquez, Inés

2016-01-01

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B1 (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B1 (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated—the first one considering only ionic species (Cl+ and OH−) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C9 atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays. PMID:27455324

Photochemical Reactions of Particulate Organic Matter: Deciphering the Role of Direct and Indirect Processes

NASA Astrophysics Data System (ADS)

Carrasquillo, A. J.; Gelfond, C. E.; Kocar, B. D.

2016-12-01

Photochemical reactions of natural organic matter (NOM) represent potentially important pathways for biologically recalcitrant material to be chemically altered in aquatic systems. Irradiation can alter the physical state of organic matter by facilitating the cycling between the particulate (POM) and dissolved (DOM) pools, however, a molecular level understanding of this chemically dynamic system is currently lacking. Photochemical reactions of a target molecule proceed by the direct absorption of a photon, or through reaction with a second photolytically generated species (i.e. the hydroxyl radical, singlet oxygen, excited triplet state NOM, hydrogen peroxide, etc.). Here, we isolate the major direct and indirect photochemical reactions of a lignocellulose-rich POM material (Phragmites australis) to determine their relative importance in changing the the chemical structure of the parent POM, and in the production of DOM. We measured POM molecular structure using a combination of NMR and FTIR for bulk analyses and scanning transmission x-ray microscopy (STXM) for spatially resolved chemistry, while the chemical composition of photo-produced DOM was measured using ultra-high resolution mass spectrometry. Results are discussed in the context of the differences in chemical composition of both NOM pools resulting from the isolated photochemical pathways. All treatments result in an increase in DOM with reaction time, indicating that the larger POM matrix is likely fragmenting into smaller more soluble species. Spectroscopic measurements, on the other hand, point to functionalization reactions which increase the abundance of alcohol, acid, and carbonyl moieties in both carbon pools. This unique dataset provides new insight into how photochemical reactions alter the chemical composition of NOM while highlighting the relative importance of indirect pathways.

Reaction pathways of propene pyrolysis.

PubMed

Qu, Yena; Su, Kehe; Wang, Xin; Liu, Yan; Zeng, Qingfeng; Cheng, Laifei; Zhang, Litong

2010-05-01

The gas-phase reaction pathways in preparing pyrolytic carbon with propene pyrolysis have been investigated in detail with a total number of 110 transition states and 50 intermediates. The structure of the species was determined with density functional theory at B3PW91/6-311G(d,p) level. The transition states and their linked intermediates were confirmed with frequency and the intrinsic reaction coordinates analyses. The elementary reactions were explored in the pathways of both direct and the radical attacking decompositions. The energy barriers and the reaction energies were determined with accurate model chemistry method at G3(MP2) level after an examination of the nondynamic electronic correlations. The heat capacities and entropies were obtained with statistical thermodynamics. The Gibbs free energies at 298.15 K for all the reaction steps were reported. Those at any temperature can be developed with classical thermodynamics by using the fitted (as a function of temperature) heat capacities. It was found that the most favorable paths are mainly in the radical attacking chain reactions. The chain was proposed with 26 reaction steps including two steps of the initialization of the chain to produce H and CH(3) radicals. For a typical temperature (1200 K) adopted in the experiments, the highest energy barriers were found in the production of C(3) to be 203.4 and 193.7 kJ/mol. The highest energy barriers for the production of C(2) and C were found 174.1 and 181.4 kJ/mol, respectively. These results are comparable with the most recent experimental observation of the apparent activation energy 201.9 +/- 0.6 or 137 +/- 25 kJ/mol. Copyright 2010 Wiley Periodicals, Inc.

Accelerating research into bio-based FDCA-polyesters by using small scale parallel film reactors.

PubMed

Gruter, Gert-Jan M; Sipos, Laszlo; Adrianus Dam, Matheus

2012-02-01

High Throughput experimentation has been well established as a tool in early stage catalyst development and catalyst and process scale-up today. One of the more challenging areas of catalytic research is polymer catalysis. The main difference with most non-polymer catalytic conversions is the fact that the product is not a well defined molecule and the catalytic performance cannot be easily expressed only in terms of catalyst activity and selectivity. In polymerization reactions, polymer chains are formed that can have various lengths (resulting in a molecular weight distribution rather than a defined molecular weight), that can have different compositions (when random or block co-polymers are produced), that can have cross-linking (often significantly affecting physical properties), that can have different endgroups (often affecting subsequent processing steps) and several other variations. In addition, for polyolefins, mass and heat transfer, oxygen and moisture sensitivity, stereoregularity and many other intrinsic features make relevant high throughput screening in this field an incredible challenge. For polycondensation reactions performed in the melt often the viscosity becomes already high at modest molecular weights, which greatly influences mass transfer of the condensation product (often water or methanol). When reactions become mass transfer limited, catalyst performance comparison is often no longer relevant. This however does not mean that relevant experiments for these application areas cannot be performed on small scale. Relevant catalyst screening experiments for polycondensation reactions can be performed in very efficient small scale parallel equipment. Both transesterification and polycondensation as well as post condensation through solid-stating in parallel equipment have been developed. Next to polymer synthesis, polymer characterization also needs to be accelerated without making concessions to quality in order to draw relevant conclusions.

24 and 48 h allergen exposure in patch testing. Comparative study with 11 common contact allergens and NiCl2.

PubMed

Kalimo, K; Lammintausta, K

1984-01-01

Patch test reactions to 11 common contact allergens were studied after 24 h and 48 h occlusion with Finn Chambers in 390 patients. Concordant allergic results were found in 96 cases (74%). In 22 patients (17%), the reaction was positive only after 48 h and in 11 cases (8.5%) only after 24 h exposure. Most of the discordant reactions were to nickel, cobalt, neomycin, formaldehyde and perfume mix. Irritant reactions were found in 55 cases, the majority occurring after 48 h occlusion. Nickel chloride tested in parallel with 48 h exposure lead to more positive allergic and toxic reactions than nickel sulphate.

Isolation and characterization of lipid rafts in Emiliania huxleyi: a role for membrane microdomains in host-virus interactions.

PubMed

Rose, Suzanne L; Fulton, James M; Brown, Christopher M; Natale, Frank; Van Mooy, Benjamin A S; Bidle, Kay D

2014-04-01

Coccolithoviruses employ a suite of glycosphingolipids (GSLs) to successfully infect the globally important coccolithophore Emiliania huxleyi. Lipid rafts, chemically distinct membrane lipid microdomains that are enriched in GSLs and are involved in sensing extracellular stimuli and activating signalling cascades through protein-protein interactions, likely play a fundamental role in host-virus interactions. Using combined lipidomics, proteomics and bioinformatics, we isolated and characterized the lipid and protein content of lipid rafts from control E. huxleyi cells and those infected with EhV86, the type strain for Coccolithovirus. Lipid raft-enriched fractions were isolated and purified as buoyant, detergent-resistant membranes (DRMs) in OptiPrep density gradients. Transmission electron microscopy of vesicle morphology, polymerase chain reaction amplification of the EhV major capsid protein gene and immunoreactivity to flotillin antisera served as respective physical, molecular and biochemical markers. Subsequent lipid characterization of DRMs via high performance liquid chromatography-triple quadrapole mass spectrometry revealed four distinct GSL classes. Parallel proteomic analysis confirmed flotillin as a major lipid raft protein, along with a variety of proteins affiliated with host defence, programmed cell death and innate immunity pathways. The detection of an EhV86-encoded C-type lectin-containing protein confirmed that infection occurs at the interface between lipid rafts and cellular stress/death pathways via specific GSLs and raft-associated proteins. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

A thermosensory pathway that controls body temperature

PubMed Central

Nakamura, Kazuhiro; Morrison, Shaun F.

2008-01-01

Defending body temperature against environmental thermal challenges is one of the most fundamental homeostatic functions governed by the nervous system. Here we show a novel somatosensory pathway, which essentially constitutes the afferent arm of the thermoregulatory reflex triggered by cutaneous sensation of environmental temperature changes. Using rat in vivo electrophysiological and anatomical approaches, we revealed that lateral parabrachial neurons play a pivotal role in this pathway by glutamatergically transmitting cutaneous thermosensory signals received from spinal somatosensory neurons directly to the thermoregulatory command center, preoptic area. This feedforward pathway mediates not only sympathetic and shivering thermogenic responses but also metabolic and cardiac responses to skin cooling challenges. Notably, this ‘thermoregulatory afferent’ pathway exists in parallel with the spinothalamocortical somatosensory pathway mediating temperature perception. These findings make an important contribution to our understanding of both the somatosensory system and thermal homeostasis—two mechanisms fundamental to the nervous system and to our survival. PMID:18084288

A thermosensory pathway that controls body temperature.

PubMed

Nakamura, Kazuhiro; Morrison, Shaun F

2008-01-01

Defending body temperature against environmental thermal challenges is one of the most fundamental homeostatic functions that are governed by the nervous system. Here we describe a somatosensory pathway that essentially constitutes the afferent arm of the thermoregulatory reflex that is triggered by cutaneous sensation of environmental temperature changes. Using in vivo electrophysiological and anatomical approaches in the rat, we found that lateral parabrachial neurons are pivotal in this pathway by glutamatergically transmitting cutaneous thermosensory signals received from spinal somatosensory neurons directly to the thermoregulatory command center, the preoptic area. This feedforward pathway mediates not only sympathetic and shivering thermogenic responses but also metabolic and cardiac responses to skin cooling challenges. Notably, this 'thermoregulatory afferent' pathway exists in parallel with the spinothalamocortical somatosensory pathway that mediates temperature perception. These findings make an important contribution to our understanding of both the somatosensory system and thermal homeostasis -- two mechanisms that are fundamental to the nervous system and to our survival.

Metabolic assessment of E. coli as a Biofactory for commercial products.

PubMed

Zhang, Xiaolin; Tervo, Christopher J; Reed, Jennifer L

2016-05-01

Metabolic engineering uses microorganisms to synthesize chemicals from renewable resources. Given the thousands of known metabolites, it is unclear what valuable chemicals could be produced by a microorganism and what native and heterologous reactions are needed for their synthesis. To answer these questions, a systematic computational assessment of Escherichia coli's potential ability to produce different chemicals was performed using an integrated metabolic model that included native E.coli reactions and known heterologous reactions. By adding heterologous reactions, a total of 1777 non-native products could theoretically be produced in E. coli under glucose minimal medium conditions, of which 279 non-native products have commercial applications. Synthesis pathways involving native and heterologous reactions were identified from eight central metabolic precursors to the 279 non-native commercial products. These pathways were used to evaluate the dependence on, and diversity of, native and heterologous reactions to produce each non-native commercial product, as well as to identify each product׳s closest central metabolic precursor. Analysis of the synthesis pathways (with 5 or fewer reaction steps) to non-native commercial products revealed that isopentenyl diphosphate, pyruvate, and oxaloacetate are the closest central metabolic precursors to the most non-native commercial products. Additionally, 4-hydroxybenzoate, tyrosine, and phenylalanine were found to be common precursors to a large number of non-native commercial products. Strains capable of producing high levels of these precursors could be further engineered to create strains capable of producing a variety of commercial non-native chemicals. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

PubMed Central

Dailey, Tamara A.; Gerdes, Svetlana; Jahn, Dieter; O'Brian, Mark R.; Warren, Martin J.

2017-01-01

SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized. PMID:28123057

Mechanisms for the inversion of chirality: Global reaction route mapping of stereochemical pathways in a probable chiral extraterrestrial molecule, 2-aminopropionitrile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, Ramanpreet; Vikas, E-mail: qlabspu@pu.ac.in, E-mail: qlabspu@yahoo.com

2015-02-21

2-Aminopropionitrile (APN), a probable candidate as a chiral astrophysical molecule, is a precursor to amino-acid alanine. Stereochemical pathways in 2-APN are explored using Global Reaction Route Mapping (GRRM) method employing high-level quantum-mechanical computations. Besides predicting the conventional mechanism for chiral inversion that proceeds through an achiral intermediate, a counterintuitive flipping mechanism is revealed for 2-APN through chiral intermediates explored using the GRRM. The feasibility of the proposed stereochemical pathways, in terms of the Gibbs free-energy change, is analyzed at the temperature conditions akin to the interstellar medium. Notably, the stereoinversion in 2-APN is observed to be more feasible than themore » dissociation of 2-APN and intermediates involved along the stereochemical pathways, and the flipping barrier is observed to be as low as 3.68 kJ/mol along one of the pathways. The pathways proposed for the inversion of chirality in 2-APN may provide significant insight into the extraterrestrial origin of life.« less

[Traffic-related PM2.5 regulates IL-2 releasing in Jurkat T cells by calcium signaling pathway].

PubMed

Tong, Guoqiang; Zhang, Zhihong; Han, Jianbiao; Qiu, Yong; Xu, Jianjun

2013-09-01

To explore the effects of traffic-related PM2.5 on interleukin-2 (IL-2) in Jurkat T cells and the regulatory action of calcium signaling pathway. The cells were exposed to 100 microg/ml of PM2.5 for 3, 6 and 24 h. Normal saline group, blank filter group, calcium chelating agent EGTA group and the calcineurin antagonist cyclosporine A (CSA) group were as parallel control. The level of IL-2 was detected by ELISA kits, the mRNA expression of CaN, NFAT were determined by QRT-PCR. The nuclear distribution of NFAT was observed by immunofluorescence microscopy. The level of IL-2 in Jurkat T cells exposed to 100 microg/ml PM2.5 was significantly lower than parallel groups, but higher than PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). With the increase of time, the releasing level of IL-2 appeared reducing trend in 100 microg/ml of PM2.5 group. The mRNA expression level of NFAT and CaN were higher than parallel groups, PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). PM2.5 can induce NFAT protein with dephosphorylation and be activated, and NFAT protein can shift into nuclear. The level of IL-2 was negatively associated with the expression level of NFAT and CaN gene (P < 0.05). Traffic-related PM2.5 may inhibit the releasing of IL-2, Ca(2+)-CaN-NFAT signal pathway may involve in the regulation of IL-2.

Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

DTIC Science & Technology

2010-11-15

denitrosation of MNX by DN22 did not involve direct participation of either oxygen or water, but both played major roles in subsequent secondary chemical and... secondary reactions and products distributions would pro- vide new insights into the degradation pathway of RDX and thus help in the development of...not involve direct participation of either oxygen or water, but both played major roles in subsequent secondary chemical and biochemical reactions of

The Reactome pathway knowledgebase

PubMed Central

Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R.; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

2014-01-01

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation. PMID:24243840

The Reactome pathway knowledgebase.

PubMed

Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

2014-01-01

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.

General low-temperature reaction pathway from precursors to monomers before nucleation of compound semiconductor nanocrystals

PubMed Central

Yu, Kui; Liu, Xiangyang; Qi, Ting; Yang, Huaqing; Whitfield, Dennis M.; Y. Chen, Queena; Huisman, Erik J. C.; Hu, Changwei

2016-01-01

Little is known about the molecular pathway to monomers of semiconductor nanocrystals. Here we report a general reaction pathway, which is based on hydrogen-mediated ligand loss for the precursor conversion to ‘monomers' at low temperature before nucleation. We apply 31P nuclear magnetic resonance spectroscopy to monitor the key phosphorous-containing products that evolve from MXn+E=PPh2H+HY mixtures, where MXn, E=PPh2H, and HY are metal precursors, chalcogenide precursors, and additives, respectively. Surprisingly, the phosphorous-containing products detected can be categorized into two groups, Ph2P–Y and Ph2P(E)–Y. On the basis of our experimental and theoretical results, we propose two competing pathways to the formation of M2En monomers, each of which is accompanied by one of the two products. Our study unravels the pathway of precursor evolution into M2En monomers, the stoichiometry of which directly correlates with the atomic composition of the final compound nanocrystals. PMID:27531507

Replacement of Calcite (CaCO 3) by Cerussite (PbCO 3)

DOE PAGES

Yuan, Ke; Lee, Sang Soo; De Andrade, Vincent; ...

2016-10-21

The mobility of toxic elements, such as lead (Pb) can be attenuated by adsorption, incorporation, and precipitation on carbonate minerals in subsurface environments. Here in this paper, we report a study of the bulk transformation of single-crystal calcite (CaCO 3) into polycrystalline cerussite (PbCO 3) through reaction with acidic Pb-bearing solutions. This reaction began with the growth of a cerussite shell on top of calcite surfaces followed by the replacement of the remaining calcite core. The external shape of the original calcite was preserved by a balance between calcite dissolution and cerussite growth controlled by adjusting the Pb 2+ concentration and pH. The relation between the rounded calcite core and the surrounding lath-shaped cerussite aggregates was imaged by transmission X-ray microscopy, which revealed preferentially elongated cerussite crystals parallel to the surface and edge directions of calcite. The replacement reaction involved concurrent development ~100 nm wide pores parallel to calcite c-glide or (1more » $$\\overline{20}$$) planes, which may have provided permeability for chemical exchange during the reaction. X-ray reflectivity measurements showed no clear epitaxial relation of cerussite to the calcite (104) surface. These results demonstrate Pb sequestration through mineral replacement reactions and the critical role of nanoporosity (3% by volume) on the solid phase transformation through a dissolution-recrystallization mechanism.« less

The Function of the Glutamate-Nitric Oxide-cGMP Pathway in Brain in Vivo and Learning Ability Decrease in Parallel in Mature Compared with Young Rats

ERIC Educational Resources Information Center

Piedrafita, Blanca; Cauli, Omar; Montoliu, Carmina; Felipo, Vicente

2007-01-01

Aging is associated with cognitive impairment, but the underlying mechanisms remain unclear. We have recently reported that the ability of rats to learn a Y-maze conditional discrimination task depends on the function of the glutamate-nitric oxide-cGMP pathway in brain. The aims of the present work were to assess whether the ability of rats to…

Chaperonin GroEL-GroES Functions as both Alternating and Non-Alternating Engines.

PubMed

Yamamoto, Daisuke; Ando, Toshio

2016-07-31

A double ring-shaped GroEL consisting of 14 ATPase subunits assists protein folding, together with co-chaperonin GroES. The dynamic GroEL-GroES interaction is actively involved in the chaperonin reaction. Therefore, revealing this dynamic interaction is a key to understanding the operation principle of GroEL. Nevertheless, how this interaction proceeds in the reaction cycle has long been controversial. Here, we directly imaged GroEL-GroES interaction in the presence of disulfide-reduced α-lactalbumin as a substrate protein using high-speed atomic force microscopy. This real-time imaging revealed the occurrence of primary, symmetric GroEL:GroES2 and secondary, asymmetric GroEL:GroES1 complexes. Remarkably, the reaction was observed to often branch into main and side pathways. In the main pathway, alternate binding and release of GroES occurs at the two rings, indicating tight cooperation between the two rings. In the side pathway, however, this cooperation is disrupted, resulting in the interruption of alternating rhythm. From various properties observed for both pathways, we provide mechanistic insight into the alternate and non-alternate operations of the two-engine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcriptome analysis reveals candidate genes involved in luciferin metabolism in Luciola aquatilis (Coleoptera: Lampyridae)

PubMed Central

Vongsangnak, Wanwipa; Chumnanpuen, Pramote

2016-01-01

Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system. PMID:27761329

C/EBPα induces adipogenesis through PPARγ: a unified pathway

PubMed Central

Rosen, Evan D.; Hsu, Chung-Hsin; Wang, Xinzhong; Sakai, Shuichi; Freeman, Mason W.; Gonzalez, Frank J.; Spiegelman, Bruce M.

2002-01-01

PPARγ and C/EBPα are critical transcription factors in adipogenesis, but the precise role of these proteins has been difficult to ascertain because they positively regulate each other's expression. Questions remain about whether these factors operate independently in separate, parallel pathways of differentiation, or whether a single pathway exists. PPARγ can promote adipogenesis in C/EBPα-deficient cells, but the converse has not been tested. We have created an immortalized line of fibroblasts lacking PPARγ, which we use to show that C/EBPα has no ability to promote adipogenesis in the absence of PPARγ. These results indicate that C/EBPα and PPARγ participate in a single pathway of fat cell development with PPARγ being the proximal effector of adipogenesis. PMID:11782441

Linear free energy relationships between aqueous phase hydroxyl radical reaction rate constants and free energy of activation.

PubMed

Minakata, Daisuke; Crittenden, John

2011-04-15

The hydroxyl radical (HO(•)) is a strong oxidant that reacts with electron-rich sites on organic compounds and initiates complex radical chain reactions in aqueous phase advanced oxidation processes (AOPs). Computer based kinetic modeling requires a reaction pathway generator and predictions of associated reaction rate constants. Previously, we reported a reaction pathway generator that can enumerate the most important elementary reactions for aliphatic compounds. For the reaction rate constant predictor, we develop linear free energy relationships (LFERs) between aqueous phase literature-reported HO(•) reaction rate constants and theoretically calculated free energies of activation for H-atom abstraction from a C-H bond and HO(•) addition to alkenes. The theoretical method uses ab initio quantum mechanical calculations, Gaussian 1-3, for gas phase reactions and a solvation method, COSMO-RS theory, to estimate the impact of water. Theoretically calculated free energies of activation are found to be within approximately ±3 kcal/mol of experimental values. Considering errors that arise from quantum mechanical calculations and experiments, this should be within the acceptable errors. The established LFERs are used to predict the HO(•) reaction rate constants within a factor of 5 from the experimental values. This approach may be applied to other reaction mechanisms to establish a library of rate constant predictions for kinetic modeling of AOPs.

Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two methyluridine derivatives at tRNA wobble positions

PubMed Central

Moukadiri, Ismaïl; Prado, Silvia; Piera, Julio; Velázquez-Campoy, Adrián; Björk, Glenn R.; Armengod, M.-Eugenia

2009-01-01

The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE and GidA proteins. The resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons and reading frame maintenance during mRNA translation. The lack of this tRNA modification produces a pleiotropic phenotype in bacteria and has been associated with mitochondrial encephalomyopathies in humans. In this work, we use in vitro and in vivo approaches to characterize the enzymatic pathway controlled by the Escherichia coli MnmE•GidA complex. Surprisingly, this complex catalyzes two different GTP- and FAD-dependent reactions, which produce 5-aminomethyluridine and 5-carboxymethylamino-methyluridine using ammonium and glycine, respectively, as substrates. In both reactions, methylene-tetrahydrofolate is the most probable source to form the C5-methylene moiety, whereas NADH is dispensable in vitro unless FAD levels are limiting. Our results allow us to reformulate the bacterial MnmE•GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins. PMID:19767610

Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations

PubMed Central

Lee, In-Ho; Kim, Seung-Yeon; Lee, Jooyoung

2013-01-01

We propose a protocol that provides a systematic definition of reaction coordinate and related free-energy profile as the function of temperature for the protein-folding simulation. First, using action-derived molecular dynamics (ADMD), we investigate the dynamic folding pathway model of a protein between a fixed extended conformation and a compact conformation. We choose the pathway model to be the reaction coordinate, and the folding and unfolding processes are characterized by the ADMD step index, in contrast to the common a priori reaction coordinate as used in conventional studies. Second, we calculate free-energy profile as the function of temperature, by employing the replica-exchange molecular dynamics (REMD) method. The current method provides efficient exploration of conformational space and proper characterization of protein folding/unfolding dynamics from/to an arbitrary extended conformation. We demonstrate that combination of the two simulation methods, ADMD and REMD, provides understanding on molecular conformational changes in proteins. The protocol is tested on a small protein, penta-peptide of met-enkephalin. For the neuropeptide met-enkephalin system, folded, extended, and intermediate sates are well-defined through the free-energy profile over the reaction coordinate. Results are consistent with those in the literature. PMID:23917881

Explore the reaction mechanism of the Maillard reaction: a density functional theory study.

PubMed

Ren, Ge-Rui; Zhao, Li-Jiang; Sun, Qiang; Xie, Hu-Jun; Lei, Qun-Fang; Fang, Wen-Jun

2015-05-01

The mechanism of Maillard reaction has been investigated by means of density functional theory calculations in the gaseous phase and aqueous solution. The Maillard reaction is a cascade of consecutive and parallel reaction. In the present model system study, glucose and glycine were taken as the initial reactants. On the basis of previous experimental results, the mechanisms of Maillard reaction have been proposed, and the possibility for the formation of different compounds have been evaluated through calculating the relative energy changes for different steps of reaction under different pH conditions. Our calculations reveal that the TS3 in Amadori rearrangement reaction is the rate-determining step of Maillard reaction with the activation barriers of about 66.7 and 68.8 kcal mol(-1) in the gaseous phase and aqueous solution, respectively. The calculation results are in good agreement with previous studies and could provide insights into the reaction mechanism of Maillard reaction, since experimental evaluation of the role of intermediates in the Maillard reaction is quite complicated.

Lithiation Thermodynamics and Kinetics of the TiO 2 (B) Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, Xiao; Liu, Zheng; Fischer, Michael G.

TiO2 (B) has attracted a lot of attention in recent years because it exhibits the largest capacity among all studied titania polymorphs with high rate performance for Li intercalation achieved when this material is nanostructured. However, due to the complex nature of its lithiation mechanism and practical challenges in probing Li local environments in nanostructured materials, a definitive understanding of the lithiation thermodynamics has yet to be established. A comprehensive mechanistic investigation of the TiO2 (B) nanoparticles is therefore presented using a combination of in situ / operando X-ray pair distribution function (PDF) and electrochemical techniques. The discharge begins withmore » surface reactions involving surface hydroxyl groups. Such reactions contribute to the capacity loss and take place in parallel with Li insertion into the near-surface region of the nanoparticles. The Li bulk insertion starts with a single-phase reaction into the A2 site, a position adjacent to the b channel. A change of the Li diffusion pathway from that along this open channel to that along the c-direction is likely to occur at the composition of Li0.25TiO2 until Li0.5TiO2 is attained, leading to a two-step A2-site incorporation with one step kinetically distinct from the other. Subsequent Li insertion involves C’ site, a position situated inside the channel, and follows a rapid two-phase reaction to form Li0.75TiO2. Due to the high diffusion barrier associated with the further lithiation, Li insertion into the A1 site, another position adjacent to the channel neighboring the A2 sites, is kinetically restricted. It can be promoted by either nanostructuring or raising the operating temperature, the latter however triggering concurrent electrolyte decomposition giving rise to additional capacity loss. This study not only provides compelling experimental evidence for the unresolved reaction thermodynamics of nanoparticulate TiO2 (B), but also serves as a strong reference for future studies of the bulk phase, and for future calculations to study the kinetic properties of TiO2 (B).« less

Zeolite catalysis in the synthesis of isobutylene from hydrous ethanol

NASA Astrophysics Data System (ADS)

Phillips, Cory Bernard

1999-11-01

This work deals with the synthesis of isobutylene from a hydrous ethanol feedstock over zeolites. The synthesis is accomplished in three steps: (1) low-temperature direct ethanol conversion to ethylene on H-ZSM-5 zeolite, (2) ethylene conversion to butene products over metal-exchanged zeolites, and (3) butene skeletal rearrangement to isobutylene over FER zeolites. The key to understanding and optimizing each synthesis step lies in the ability to control and regulate the zeolite acidity (Bronsted and Lewis)---both strength and number. Therefore, the continuous temperature programmed amine desorption (CTPAD) technique was further developed to simultaneously count the Bronsted acid sites and quantitatively characterize their strength. The adsorption of ethanol, reaction products, amines, coke and ethanol-derived residue (EDR) were monitored gravimetrically using the highly sensitive, novel Tapered Element Oscillating Microreactor (TEOM) apparatus. The TEOM was also used also in conjunction with CTPAD to characterize Bronsted acidity which is a new application for the instrument. For the first synthesis step, a parallel reaction exists which simultaneously produces diethyl ether and ethylene directly over H-ZSM-5. The reaction rates for each pathway were measured directly using a differential reactor operating at low temperatures (<473 K). Water in the ethanol feed enhances the rate of ethylene formation. A mechanism and kinetic expression are proposed for this reaction over H-ZSM-5, with diethyl-ether desorption and ethylene formation as the rate limiting steps. Heat of adsorption values measured from the independent microcalorimetry work reported in the literature are incorporated into the kinetic analysis which reduces the number of regressed parameters. For the remaining synthesis steps, several zeolite structures (ZSM-5, Y, FER) partially exchanged with Pd, Ti, Ni and Au were prepared and tested. It was determined from this screening study that the zeolites containing Pd are the most efficient catalysts for the dimerization reaction. Characterization results from x-ray diffraction (XRD), electron paramagnetic resonance (EPR) spectroscopy, and CTPAD suggest a stable, Pd species with a low oxidation state as part of the active site in Pd-exchanged zeolites. Isobutylene was present in the C4 fraction at reasonable quantities for most of the catalyst candidates, especially those containing an alkali metal co-cation.

Smoldyn on graphics processing units: massively parallel Brownian dynamics simulations.

PubMed

Dematté, Lorenzo

2012-01-01

Space is a very important aspect in the simulation of biochemical systems; recently, the need for simulation algorithms able to cope with space is becoming more and more compelling. Complex and detailed models of biochemical systems need to deal with the movement of single molecules and particles, taking into consideration localized fluctuations, transportation phenomena, and diffusion. A common drawback of spatial models lies in their complexity: models can become very large, and their simulation could be time consuming, especially if we want to capture the systems behavior in a reliable way using stochastic methods in conjunction with a high spatial resolution. In order to deliver the promise done by systems biology to be able to understand a system as whole, we need to scale up the size of models we are able to simulate, moving from sequential to parallel simulation algorithms. In this paper, we analyze Smoldyn, a widely diffused algorithm for stochastic simulation of chemical reactions with spatial resolution and single molecule detail, and we propose an alternative, innovative implementation that exploits the parallelism of Graphics Processing Units (GPUs). The implementation executes the most computational demanding steps (computation of diffusion, unimolecular, and bimolecular reaction, as well as the most common cases of molecule-surface interaction) on the GPU, computing them in parallel on each molecule of the system. The implementation offers good speed-ups and real time, high quality graphics output

Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

PubMed

Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

2014-01-01

The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

Probing soil C metabolism in response to temperature: results from experiments and modeling

NASA Astrophysics Data System (ADS)

Dijkstra, P.; Dalder, J.; Blankinship, J.; Selmants, P. C.; Schwartz, E.; Koch, G. W.; Hart, S.; Hungate, B. A.

2010-12-01

C use efficiency (CUE) is one of the least understood aspects of soil C cycling, has a very large effect on soil respiration and C sequestration, and decreases with elevated temperature. CUE is directly related to substrate partitioning over energy production and biosynthesis. The production of energy and metabolic precursors occurs in well-known processes such as glycolysis and Krebs cycle. We have developed a new stable isotope approach using position-specific 13C-labeled metabolic tracers to measure these fundamental metabolic processes in intact soil communities (1). We use this new approach, combined with models of soil metabolic flux patterns, to analyze the response of microbial energy production, biosynthesis, and CUE to temperature. The method consists of adding small but precise amounts of position-specific 13C -labeled metabolic tracers to parallel soil incubations, in this case 1-13C and 2,3-13C pyruvate and 1-13C and U-13C glucose. The measurement of CO2 released from the labeled tracers is used to calculate the C flux rates through various metabolic pathways. A simplified metabolic model consisting of 23 reactions is iteratively solved using results of the metabolic tracer experiments and information on microbial precursor demand under different temperatures. This new method enables direct study of fundamental aspects of microbial energy production, C use efficiency, and soil organic matter formation in response to temperature. (1) Dijkstra P, Blankinship JC, Selmants PC, Hart SC, Koch GW, Schwarz E and Hungate BA. Probing metabolic flux patterns of soil microbial communities using parallel position-specific tracer labeling. Soil Biology and Biochemistry (accepted)

Can serpentinization induce fracturing? Fluid pathway development and the volume increase enigma

NASA Astrophysics Data System (ADS)

Plümper, Oliver; Jamtveit, Bjørn; Røyne, Anja

2013-04-01

Serpentinization of ultramafic rocks has first-order effects on global element cycles, the rheology of the oceanic lithosphere, plays a key role in plate tectonics by lubricating subduction zones and has been linked to the origin of life due to the creation of abiogenic hydrocarbons. In addition, the capability of ultramafic rocks to safely store enormous amounts of carbon dioxide through mineral reactions may provide a unique solution to fight global warming. However, all the aforementioned processes are reliant on the creation and maintenance of fluid pathways to alter an originally impermeable rock. Although the forces that move tectonic plates can produce these fluid pathways by mechanical fracturing, there is ample evidence that serpentinization reactions can 'eat' their way through a rock. This process is facilitated by solid volume changes during mineral reactions that cause expansion, fracturing the rock to generate fluid pathways. Natural observations of serpentinization/carbonation in ultramafic rocks indicate that the associated positive solid volume change alone exerts enough stress on the surrounding rock to build up a fracture network and that the influence of external tectonic forces is not necessary. Through various feedbacks these systems can either become self-sustaining, when an interconnected fracture network is formed, or self-limiting due to fluid pathway obstruction. However, extensively serpentinized outcrops suggest that although crystal growth in newly opened spaces would reduce permeability, serpentinization is not always self-limiting as porosity generation can occur concomitantly, maintaining or even increasing permeability. This is consistent with theory and demonstrates that fluids transported through fracture networks can alter vast amounts of originally impermeable rock. Nevertheless, whether serpentinization can actually generate these fracture networks is still a matter of debate and only a few scientific investigations have focused on this topic so far. Here, we investigate the feasibility of reaction-induced fracturing and pore space evolution during serpentinization by combining microstructural investigations using scanning/transmission electron microscopy and synchrotron micro-tomography of natural samples with theoretical considerations on the forces exerted during solid volume increasing reactions. We particularly focus on the interface-scale mechanism of reaction-induced fracturing (Plümper et al. 2012) and the establishment of microstructural markers (e.g., inert exsolutions in olivine) to identify volume changes and estimate crystallization pressures (Kelemen and Hirth 2012). Our investigations suggest that reaction-induced fracturing during serpentinization is possible and during certain physico-chemical circumstances a positive feedback to alter vast amounts of originally impermeable rock is established. Plümper O., Røyne A., Magraso A., Jamtveit B. (2012) The interface-scale mechanism of reaction-induced fracturing during serpentinization. Geology. 40, 1103-1106. Kelemen, P. B. & Hirth, G. (2012) Reaction-driven cracking during retrograde metamorphism: Olivine hydration and carbonation. Earth and Planetary Science Letters 345, 81-89.

Biotransformation of Hydroxylaminobenzene and Aminophenol by Pseudomonas putida 2NP8 Cells Grown in the Presence of 3-Nitrophenol

PubMed Central

Zhao, Jian-Shen; Singh, Ajay; Huang, Xiao-Dong; Ward, Owen P.

2000-01-01

Biotransformation products of hydroxylaminobenzene and aminophenol produced by 3-nitrophenol-grown cells of Pseudomonas putida 2NP8, a strain grown on 2- and 3-nitrophenol, were characterized. Ammonia, 2-aminophenol, 4-aminophenol, 4-benzoquinone, N-acetyl-4-aminophenol, N-acetyl-2-aminophenol, 2-aminophenoxazine-3-one, 4-hydroquinone, and catechol were produced from hydroxylaminobenzene. Ammonia, N-acetyl-2-aminophenol, and 2-aminophenoxazine-3-one were produced from 2-aminophenol. All of these metabolites were also found in the nitrobenzene transformation medium, and this demonstrated that they were metabolites of nitrobenzene transformation via hydroxylaminobenzene. Production of 2-aminophenoxazine-3-one indicated that oxidation of 2-aminophenol via imine occurred. Rapid release of ammonia from 2-aminophenol transformation indicated that hydrolysis of the imine intermediate was the dominant reaction. The low level of 2-aminophenoxazine-3-one indicated that formation of this compound was probably due to a spontaneous reaction accompanying oxidation of 2-aminophenol via imine. 4-Hydroquinone and catechol were reduction products of 2- and 4-benzoquinones. Based on these transformation products, we propose a new ammonia release pathway via oxidation of aminophenol to benzoquinone monoimine and subsequent hydrolysis for transformation of nitroaromatic compounds by 3-nitrophenol-grown cells of P. putida 2NP8. We propose a parallel mechanism for 3-nitrophenol degradation in P. putida 2NP8, in which all of the possible intermediates are postulated. PMID:10831408

Biotransformation of hydroxylaminobenzene and aminophenol by Pseudomonas putida 2NP8 cells grown in the presence of 3-nitrophenol.

PubMed

Zhao, J S; Singh, A; Huang, X D; Ward, O P

2000-06-01

Biotransformation products of hydroxylaminobenzene and aminophenol produced by 3-nitrophenol-grown cells of Pseudomonas putida 2NP8, a strain grown on 2- and 3-nitrophenol, were characterized. Ammonia, 2-aminophenol, 4-aminophenol, 4-benzoquinone, N-acetyl-4-aminophenol, N-acetyl-2-aminophenol, 2-aminophenoxazine-3-one, 4-hydroquinone, and catechol were produced from hydroxylaminobenzene. Ammonia, N-acetyl-2-aminophenol, and 2-aminophenoxazine-3-one were produced from 2-aminophenol. All of these metabolites were also found in the nitrobenzene transformation medium, and this demonstrated that they were metabolites of nitrobenzene transformation via hydroxylaminobenzene. Production of 2-aminophenoxazine-3-one indicated that oxidation of 2-aminophenol via imine occurred. Rapid release of ammonia from 2-aminophenol transformation indicated that hydrolysis of the imine intermediate was the dominant reaction. The low level of 2-aminophenoxazine-3-one indicated that formation of this compound was probably due to a spontaneous reaction accompanying oxidation of 2-aminophenol via imine. 4-Hydroquinone and catechol were reduction products of 2- and 4-benzoquinones. Based on these transformation products, we propose a new ammonia release pathway via oxidation of aminophenol to benzoquinone monoimine and subsequent hydrolysis for transformation of nitroaromatic compounds by 3-nitrophenol-grown cells of P. putida 2NP8. We propose a parallel mechanism for 3-nitrophenol degradation in P. putida 2NP8, in which all of the possible intermediates are postulated.

Manipulating the Energetics and Rates of Electron Transfer in Rhodobacter capsulatus Reaction Centers with Asymmetric Pigment Content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faries, Kaitlyn M.; Dylla, Nicholas P.; Hanson, Deborah K.

2017-07-17

Seemingly redundant parallel pathways for electron transfer (ET), composed of identical sets of cofactors, are a cornerstone feature of photosynthetic reaction centers (RCs) involved in light-energy conversion. In native bacterial RCs, both A and B branches house one bacteriochlorophyll (BChl) and one bacteriopheophytin (BPh), but the A branch is used exclusively. Described herein are the results-obtained for two Rhodobacter capsulatus RCs with an unnaturally high degree of cofactor asymmetry, two BPh on the RC's B side and two BChl on the A side. These pigment changes derive, respectively, from the His(M180)Leu mutation [a BPh ((Phi(B)) replaces the B-side BChl (BB)],more » and the Leu(M212)His mutation [a BChl (beta(A))) replaces the A-side BPh (H-A)]. Additionally, Tyr(M208)Phe was employed to disfavor ET to the A branch; in one mutant, Val(M131)Glu creates a hydrogen bond to H-B to enhance ET to H-B. In both Phi(B) mutants, the decay kinetics of the excited primary ET donor (P*) resolve three populations with lifetimes of similar to 9 ps (50-60%), similar to 40 ps (10-20%), and similar to 200 ps (20-30%), with P+Phi(-)(B) formed predominantly from the 9 ps fraction. The 50-60% yield of P+Phi(B)- is the highest yet observed for a Phi(B)-containing RC. The results provide insight into factors needed for efficient multistep ET.« less

Probing Complex Free-Radical Reaction Pathways of Fuel Model Compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchanan III, A C; Kidder, Michelle; Beste, Ariana

2012-01-01

Fossil (e.g. coal) and renewable (e.g. woody biomass) organic energy resources have received considerable attention as possible sources of liquid transportation fuels and commodity chemicals. Knowledge of the reactivity of these complex materials has been advanced through fundamental studies of organic compounds that model constituent substructures. In particular, an improved understanding of thermochemical reaction pathways involving free-radical intermediates has arisen from detailed experimental kinetic studies and, more recently, advanced computational investigations. In this presentation, we will discuss our recent investigations of the fundamental pyrolysis pathways of model compounds that represent key substructures in the lignin component of woody biomass withmore » a focus on molecules representative of the dominant beta-O-4 aryl ether linkages. Additional mechanistic insights gleaned from DFT calculations on the kinetics of key elementary reaction steps will also be presented, as well as a few thoughts on the significant contributions of Jim Franz to this area of free radical chemistry.« less

Coupling of Fast and Slow Modes in the Reaction Pathway of the Minimal Hammerhead Ribozyme Cleavage

PubMed Central

Radhakrishnan, Ravi

2007-01-01

By employing classical molecular dynamics, correlation analysis of coupling between slow and fast dynamical modes, and free energy (umbrella) sampling using classical as well as mixed quantum mechanics molecular mechanics force fields, we uncover a possible pathway for phosphoryl transfer in the self-cleaving reaction of the minimal hammerhead ribozyme. The significance of this pathway is that it initiates from the minimal hammerhead crystal structure and describes the reaction landscape as a conformational rearrangement followed by a covalent transformation. The delineated mechanism is catalyzed by two metal (Mg2+) ions, proceeds via an in-line-attack by CYT 17 O2′ on the scissile phosphorous (ADE 1.1 P), and is therefore consistent with the experimentally observed inversion configuration. According to the delineated mechanism, the coupling between slow modes involving the hammerhead backbone with fast modes in the cleavage site appears to be crucial for setting up the in-line nucleophilic attack. PMID:17545240

A global reaction route mapping-based kinetic Monte Carlo algorithm

NASA Astrophysics Data System (ADS)

Mitchell, Izaac; Irle, Stephan; Page, Alister J.

2016-07-01

We propose a new on-the-fly kinetic Monte Carlo (KMC) method that is based on exhaustive potential energy surface searching carried out with the global reaction route mapping (GRRM) algorithm. Starting from any given equilibrium state, this GRRM-KMC algorithm performs a one-step GRRM search to identify all surrounding transition states. Intrinsic reaction coordinate pathways are then calculated to identify potential subsequent equilibrium states. Harmonic transition state theory is used to calculate rate constants for all potential pathways, before a standard KMC accept/reject selection is performed. The selected pathway is then used to propagate the system forward in time, which is calculated on the basis of 1st order kinetics. The GRRM-KMC algorithm is validated here in two challenging contexts: intramolecular proton transfer in malonaldehyde and surface carbon diffusion on an iron nanoparticle. We demonstrate that in both cases the GRRM-KMC method is capable of reproducing the 1st order kinetics observed during independent quantum chemical molecular dynamics simulations using the density-functional tight-binding potential.

Nitrosation of melatonin by nitric oxide: a computational study.

PubMed

Turjanski, A G; Sáenz, D A; Doctorovich, F; Estrin, D A; Rosenstein, R E

2001-09-01

Melatonin is being increasingly promoted as a therapeutic agent for the treatment of jet lag and insomnia, and is an efficient free radical scavenger. We have recently characterized a product for the reaction of melatonin with nitric oxide (NO), N-nitrosomelatonin. In the present work, reaction pathways with N1, C2, C4, C6 and C7 as possible targets for its reaction with NO that yield the respective nitroso derivatives have been investigated using semiempirical AM1 computational tools, both in vacuo and aqueous solution. Specifically, two different pathways were studied: a radical mechanism involving the hydrogen atom abstraction to yield a neutral radical followed by NO addition, and an ionic mechanism involving addition of nitrosonium ion to the indolic moiety. Our results show that the indolic nitrogen is the most probable site for nitrosation by the radical mechanism, whereas different targets are probable considering the ionic pathway. These results are in good agreement with previous experimental findings and provide a coherent picture for the interaction of melatonin with NO.

A global reaction route mapping-based kinetic Monte Carlo algorithm.

PubMed

Mitchell, Izaac; Irle, Stephan; Page, Alister J

2016-07-14

We propose a new on-the-fly kinetic Monte Carlo (KMC) method that is based on exhaustive potential energy surface searching carried out with the global reaction route mapping (GRRM) algorithm. Starting from any given equilibrium state, this GRRM-KMC algorithm performs a one-step GRRM search to identify all surrounding transition states. Intrinsic reaction coordinate pathways are then calculated to identify potential subsequent equilibrium states. Harmonic transition state theory is used to calculate rate constants for all potential pathways, before a standard KMC accept/reject selection is performed. The selected pathway is then used to propagate the system forward in time, which is calculated on the basis of 1st order kinetics. The GRRM-KMC algorithm is validated here in two challenging contexts: intramolecular proton transfer in malonaldehyde and surface carbon diffusion on an iron nanoparticle. We demonstrate that in both cases the GRRM-KMC method is capable of reproducing the 1st order kinetics observed during independent quantum chemical molecular dynamics simulations using the density-functional tight-binding potential.

Characterization of galactomannan derivatives in roasted coffee beverages.

PubMed

Nunes, Fernando M; Reis, Ana; Domingues, M Rosário M; Coimbra, Manuel A

2006-05-03

In this work, the galactomannans from roasted coffee infusions were purified by 50% ethanol precipitation, anion exchange chromatography, and phenylboronic acid-immobilized Sepharose chromatography. Specific enzymatic hydrolysis of the beta-(1-->4)-D-mannan backbone allowed us to conclude that the galactomannans of roasted coffee infusions are high molecular weight supports of low molecular weight brown compounds. Also, the molecular weight of the brown compounds linked to the galactomannan increases with the increase of the coffee degree of roast. The reaction pathways of galactomannans during the coffee roasting process were inferred from the detection of specific chemical markers by gas chromatography-electron impact mass spectrometry and/or electrospray ionization tandem mass spectrometry. Maillard reaction, caramelization, isomerization, oxidation, and decarboxylation pathways were identified by detection of Amadori compounds, 1,6-beta-anhydromannose, fructose, glucose, mannonic acid, 2-ketogluconic acid, and arabinonic acid in the reducing end of the obtained oligosaccharides. The implication of the several competitive reaction pathways is discussed and related to the structural changes of the galactomannans present in the roasted coffee infusions.

On-the-Fly Kinetic Monte Carlo Simulation of Aqueous Phase Advanced Oxidation Processes.

PubMed

Guo, Xin; Minakata, Daisuke; Crittenden, John

2015-08-04

We have developed an on-the-fly kinetic Monte Carlo (KMC) model to predict the degradation mechanisms and fates of intermediates and byproducts that are produced during aqueous-phase advanced oxidation processes (AOPs). The on-the-fly KMC model is composed of a reaction pathway generator, a reaction rate constant estimator, a mechanistic reduction module, and a KMC solver. The novelty of this work is that we develop the pathway as we march forward in time rather than developing the pathway before we use the KMC method to solve the equations. As a result, we have fewer reactions to consider, and we have greater computational efficiency. We have verified this on-the-fly KMC model for the degradation of polyacrylamide (PAM) using UV light and titanium dioxide (i.e., UV/TiO2). Using the on-the-fly KMC model, we were able to predict the time-dependent profiles of the average molecular weight for PAM. The model provided detailed and quantitative insights into the time evolution of the molecular weight distribution and reaction mechanism. We also verified our on-the-fly KMC model for the destruction of (1) acetone, (2) trichloroethylene (TCE), and (3) polyethylene glycol (PEG) for the ultraviolet light and hydrogen peroxide AOP. We demonstrated that the on-the-fly KMC model can achieve the same accuracy as the computer-based first-principles KMC (CF-KMC) model, which has already been validated in our earlier work. The on-the-fly KMC is particularly suitable for molecules with large molecular weights (e.g., polymers) because the degradation mechanisms for large molecules can result in hundreds of thousands to even millions of reactions. The ordinary differential equations (ODEs) that describe the degradation pathways cannot be solved using traditional numerical methods, but the KMC can solve these equations.