Liberation Of Carbon Monoxide Research Articles

Mechanism of Carbon Monoxide (CO) Generation and Potential Human Health Hazard during Mechanized Tunnel Driving in Organic-Rich Rocks: Field and Laboratory Study

The monitoring of carbon emissions is increasingly becoming a sustainability issue worldwide. Despite being largely unnoticed, the toxic gas carbon monoxide (CO) is ubiquitous in mechanized tunnel driving, but the individual sources, release and enrichment mechanisms are often unknown. In this study, the generation of CO from organic matter containing sedimentary rocks was investigated during mechanized tunnel driving and by reacting claystone and sandstone with 10 mM NaCl solutions for 2 months at 70 °C and 140 °C. The mineralogical and geochemical evolution of the solids and fluids was assessed by CO measurements and the XRD, DTA, TOC, IC and ICP-OES methods. The CO concentration in the atmosphere reached up to 1920 ppm (100 ppm on average) during tunnel driving, which is more than three times higher than the legal daily average dose for tunnellers, thus requiring occupational safety operations. Mineral-specific dissolution processes and the rapid decomposition of labile organic matter upon thermal alteration contributed to the liberation of CO and also carbon dioxide (CO2) from the host rocks. In mechanized tunnel driving, frictional heat and ‘cold’ combustion with temperatures reaching 50–70 °C at the drill head is an important mechanism for increased CO and CO2 generation, especially during drilling in sedimentary rocks containing significant amounts of OM and when the ventilation of the tunnel atmosphere and air mixing are limited. Under such conditions, human health damage due to CO exposure (HHDCO) can be 30 times higher compared to tunnel outlets, where CO is emitted from traffic.

Liberation of carbon monoxide from formic acid mediated by molybdenum oxyanions.

Multistage mass spectrometry experiments, isotope labelling and DFT calculations were used to explore whether selective decarbonylation of formic acid could be mediated by molybdate anions [(MoO3)x(OH)]- (x = 1 and 2) via a formal catalytic cycle involving two steps. In step 1, both molybdate anions undergo gas-phase ion-molecule reactions (IMR) with formic acid to produce the coordinated formates [(MoO3)x(O2CH)]- and H2O. In step 2, both coordinated formates [(MoO3)x(O2CH)]- undergo decarbonylation under collision-induced dissociation (CID) conditions to reform the molybdate anions [(MoO3)x(OH)]- (x = 1 and 2), thus closing a formal catalytic cycle. In the case of [MoO3(O2CH)]- an additional decarboxylation channel also occurs to yield [MoO3(H)]-, which is unreactive towards formic acid. The reaction between [Mo18O3(18OH)]- and formic acid gives rise to [Mo18O3(O2CH)]- highlighting that ligand substitution occurs without 18O/16O exchange between the coordinated 18OH ligand and HC16O2H. The reaction between [(MoO3)x(OD)]- (x = 1 and 2) and DCO2H initially produces [(MoO3)x(OH)]- (x = 1 and 2), indicating that D/H exchange occurs. DFT calculations were carried out to investigate the reaction mechanisms and energetics associated with both steps of the formal catalytic cycle and to better understand the competition between decarbonylation and decarboxylation, which is crucial in developing a selective catalyst. The CO and CO2 loss channels from the monomolybdate anion [MoO3(O2CH)]- have similar barrier heights which is in agreement with experimental results where both fragmentation channels are observed. In contrast, the dimolybdate anion is more selective, since the decarbonylation pathway of [(MoO3)2(O2CH)]- is both kinetically and thermodynamically favoured, which agrees with experimental observations where the CO loss channel is solely observed.

Multiple complexation of CO and related ligands to a main-group element.

The ability of an atom or molecular fragment to bind multiple carbon monoxide (CO) molecules to form multicarbonyl adducts is a fundamental trait of transition metals. Transition-metal carbonyl complexes are vital to industry, appear naturally in the active sites of a number of enzymes (such as hydrogenases), are promising therapeutic agents, and have even been observed in interstellar dust clouds. Despite the wealth of established transition-metal multicarbonyl complexes, no elements outside groups 4 to 12 of the periodic table have yet been shown to react directly with two or more CO units to form stable multicarbonyl adducts. Here we present the synthesis of a borylene dicarbonyl complex, the first multicarbonyl complex of a main-group element prepared using CO. The compound is additionally stable towards ambient air and moisture. The synthetic strategy used--liberation of a borylene ligand from a transition metal using donor ligands--is broadly applicable, leading to a number of unprecedented monovalent boron species with different Lewis basic groups. The similarity of these compounds to conventional transition-metal carbonyl complexes is demonstrated by photolytic liberation of CO and subsequent intramolecular carbon-carbon bond activation.

Novel lead structures and activation mechanisms for CO-releasing molecules (CORMs).

Carbon monoxide (CO) is an endogenous small signalling molecule in the human body, produced by the action of haem oxygenase on haem. Since it is very difficult to apply safely as a gas, solid storage and delivery forms for CO are now explored. Most of these CO-releasing molecules (CORMs) are based on the inactivation of the CO by coordinating it to a transition metal centre in a prodrug approach. After a brief look at the potential cellular target structures of CO, an overview of the design principles and activation mechanisms for CO release from a metal coordination sphere is given. Endogenous and exogenous triggers discussed include ligand exchange reactions with medium, enzymatically-induced CO release and photoactivated liberation of CO. Furthermore, the attachment of CORMs to hard and soft nanomaterials to confer additional target specificity to such systems is critically assessed. A survey of analytical methods for the study of the stoichiometry and kinetics of CO release, as well as the tracking of CO in living systems by using fluorescent probes, concludes this review. CORMs are very valuable tools for studying CO bioactivity and might lead to new drug candidates; however, in the design of future generations of CORMs, particular attention has to be paid to their drug-likeness and the tuning of the peripheral 'drug sphere' for specific biomedical applications. Further progress in this field will thus critically depend on a close interaction between synthetic chemists and researchers exploring the physiological effects and therapeutic applications of CO.

Analytical Methods for Determination of CO and CO2 and their Applicability in Biological Studies

Although there are many different methods for measuring the carbon monoxide and carbon dioxide content under biological conditions, not all of them are appropriate for detecting the very low concentrations. This review discusses the principles of the most commonly used methods for the detection and quantitative determination of these species, as well as the advantages and limitations of the methods described. The considered analytical methods are discussed in relation to their accuracy, precision and sensitivity together with the extent to which any interference can occur. The described methods for measuring carbon monoxide content under biological conditions fall into six main groups, while in the case of the quantitative determination of carbon dioxide the use of ten techniques is discussed. Keywords: Analytical methods, carbon monoxide, liberation of carbon monoxide, carbon dioxide, molecular biosensors, stopped-flow spectrophotometry, comparison of methods

Carbon Monoxide-Releasing Molecules: A Pharmacological Expedient to Counteract Inflammation

Carbon monoxide (CO) mediates many of the biological effects that are attributed to heme oxygenase (HO), the enzyme responsible for CO production in mammals. Antioxidant and anti-inflammatory activities of HO-1, the inducible isoform of heme oxygenase, have been demonstrated in a variety of disease models and a therapeutic exploitation of this pathway is currently under scrutiny. In this context, the liberation of CO from CO-releasing molecules (CO-RMs) is extremely attractive as these compounds may form the basis of a new class of pharmaceuticals. Recent investigations indicate that HO-1 and CO modulate important processes in chronic inflammation; these include the control of immune responses, the production of inflammatory mediators and the mitigation of cartilage or bone destruction. As HO-1 is highly expressed in the joint tissues of patients affected by arthritic diseases, it is plausible to suggest that this pathway may play a protective role against joint degenerative diseases. Studies aimed at identifying the signaling pathways responsive to endogenous CO and CO-RMs in rheumatoid arthritis and other inflammatory states are currently in progress. This research will help to elucidate the molecular mechanisms underlying the pharmacological effects of CO-RMs and may lead to the development of novel therapeutic strategies for the treatment of acute and chronic inflammatory conditions.

Novel pathway for N1‐acetyl‐5‐methoxykynuramine: UVB‐induced liberation of carbon monoxide from precursor N 1‐acetyl‐N 2‐formyl‐5‐methoxykynuramine

Irradiation of the melatonin metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) with UV light of 254 nm causes the release of carbon monoxide (CO) and, thus, deformylation to N(1)-acetyl-5-methoxykynuramine (AMK). Liberation of CO was demonstrated by reduction of PdCl(2) to metallic palladium, under avoidance of actions by other reductants. Photochemical AMK formation was not due to UV-induced hydroxyl radicals, because the reaction also took place with high efficiency in ethanol and 2-propanol. Moreover, AMK was generated from AFMK by UVB on a dry thin layer chromatographic plate. Although AMK seems to be the major primary product generated by UVB radiation, prolonged exposure of AFMK led to various other products, especially formed by destruction of AMK, as shown by irradiation of this latter compound. With regard to the demonstration of melatonin in skin and substantial amounts of AFMK in keratinocytes, these findings may be of dermatologic relevance.

Carbon monoxide‐releasing molecules (CO‐RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages

The enzyme heme oxygenase-1 (HO-1) is a cytoprotective and anti-inflammatory protein that degrades heme to produce biliverdin/bilirubin, ferrous iron and carbon monoxide (CO). The anti-inflammatory properties of HO-1 are related to inhibition of adhesion molecule expression and reduction of oxidative stress, while exogenous CO gas treatment decreases the production of inflammatory mediators such as cytokines and nitric oxide (NO). CO-releasing molecules (CO-RMs) are a novel group of substances identified by our group that are capable of modulating physiological functions via the liberation of CO. We aimed in this study to examine the potential anti-inflammatory characteristics of CORM-2 and CORM-3 in an in vitro model of lipopolysaccharide (LPS)-stimulated murine macrophages. Stimulation of RAW264.7 macrophages with LPS resulted in increased expression of inducible NO synthase (iNOS) and production of nitrite. CORM-2 or CORM-3 (10-100 microM) reduced nitrite generation in a concentration-dependent manner but did not affect the protein levels of iNOS. CORM-3 also decreased nitrite levels when added 3 or 6 h after LPS exposure. CORM-2 or CORM-3 did not cause any evident cytotoxicity and produced an increase in HO-1 expression and heme oxygenase activity; this effect was completely prevented by the thiol donor N-acetylcysteine. CORM-3 also considerably reduced the levels of tumor necrosis factor-alpha, another mediator of the inflammatory response. The inhibitory effects of CORM-2 and CORM-3 were not observed when the inactive compounds, which do not release CO, were coincubated with LPS. These results indicate that CO liberated by CORM-2 and CORM-3 significantly suppresses the inflammatory response elicited by LPS in cultured macrophages and suggest that CO carriers can be used as an effective strategy to modulate inflammation.

Carbon monoxide and metabotropic glutamate receptors in rat nucleus tractus solitarii: participation in cardiovascular effect

Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to biliverdin and CO. Recent studies have demonstrated that CO is involved in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii of rats. The purpose of the present study was to investigate the possible interaction of CO and excitatory amino acids in the nucleus tractus solitarii. In anesthetized male Sprague–Dawley rats, unilateral intranucleus tractus solitarii microinjection of hematin, a heme molecule cleaved by heme oxygenase to yield CO, or excitatory amino acids l-glutamate produced depressor and bradycardiac effects. Similar cardiovascular effects were observed with several agonists for ionotropic glutamate receptors such as N-methyl- d-aspartate (NMDA), (±)-α-amino-3-hydroxyl-5-methylisoxazole-4-propanoic acid (AMPA), kainic acid and for metabotropic glutamate (mGlu) receptors, trans-(±)-1-amino-(1 S,3 R)-cyclopentanedicarboxylic acid (ACPD). Among these agonists, prior administration of the heme oxygenase inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) (1 nmol), significantly attenuated the cardiovascular effects of hematin, l-glutamate and ACPD. Furthermore, the cardiovascular effects of ACPD were prevented by the selective mGlu receptors antagonist l-2-amino-3-phosphonoprionate ( l-AP3). However, pretreatment with ZnDPBG failed to prevent the cardiovascular responses to microinjection of NMDA, AMPA and kainic acid. On the other hand, prior administration of the NMDA receptor antagonist, diazocilpine (MK-801), or (±)-2-amino-5-phosphonopentanoic acid (APV) attenuated the depressor and bradycardiac effect of hematin. These results demonstrated that mGlu receptors may couple to the activation of heme oxygenase via the liberation of CO to participate in central cardiovascular regulation. They also suggested that CO and excitatory amino acids may interact in the nucleus tractus solitarii of rats.

Heme Oxygenase-1 Protects the Heart

The seminal discovery of nitric oxide (NO) in the 1980s unraveled the novel concept that an endogenous production of a gaseous substance such as NO can impart diverse and critical functional effects on a wide spectrum of biological and pathological processes. Intense investigations in the chemistry and biology of NO have led to numerous fruitful discoveries, enhancing our understanding of many disease processes including cardiovascular disorders. Interestingly, though, we have known for a longer period of time that there exists another gaseous molecule, carbon monoxide (CO), which can be generated endogenously. The heme oxygenase (HO) enzyme system generates the majority of endogenous CO.1,2 Since the biochemical isolation of the HO enzyme in 1968, much of the focus of HO research has been in the study of HO in heme metabolism based on the known fact that the HO enzyme serves as the rate-limiting enzyme in the degradation of heme. However, in recent years, as a result of the emerging role of HO in a variety of biological processes, interest in HO has continued to grow beyond its role in heme metabolism and has expanded into many scientific disciplines. The recent characterization of the HO enzyme system in yeast, prokaryotic bacterial system, and plants further highlights the functional importance of a highly conserved enzyme throughout the evolution of living organisms. HO catalyzes the first and rate-limiting step in the degradation of heme to yield equimolar quantities of biliverdin IXa, CO, and iron1,2 (Figure). Biliverdin is subsequently converted to bilirubin via the action of biliverdin reductase, and free iron is promptly sequestered into ferritin. Three isoforms of HO exist; HO-1 is highly inducible whereas HO-2 and HO-3 are constitutively expressed.1,2 Heme, a major substrate of HO-1, and a variety of nonheme agents including heavy metals, cytokines, hormones, endotoxin, and …

The Effects of Thermal Degradation Products of Hydraulic Fluids Type C on the Carboxyhaemoglobin Level in Wistar SPF Rats

The carboxyhaemoglobin (COHb) levels of Wistar SPF rats were measured after exposure to a thermal decomposition mixture of hydraulic fluids type C. The evaluation of the obtained results was realised by using a mathematical carbon monoxide loading model. Significant lower COHb levels than expected were seen. This can be explained by a reduction of the respira tory minute volume due to the presence of sensory irritating products in the decomposition mixture. The COHb levels after liberation of carbon monoxide (CO) from the blood and the CO levels in the inhalation chamber of the thermal decomposition apparatus were measured by a capillary gas chromatographic method.

Synthesis, structure and properties of dimethyl(alkoxycarbonyl)gold(III) complexes having a triphenylphosphine ligand

cis-Dimethyl(alkoxycarbonyl)(triphenylphosphine)gold(III) ( cis-AuMe 2(COOR)(PPh 3); R  Me ( 1), Et ( 2), iPr ( 3)) has been synthesized by the reaction of carbon monoxide with dimethyl(methoxo)(triphenylphosphine)gold(III) prepared in situ from cis-dimethyliodo(triphenylphosphine)gold(III) and sodium methoxide in methanol. Thermolysis of 1 in benzene leads to a reductive elimination of both methyl acetate and ethane. Protonolysis of 1 with acids such as hydrogen chloride and acetic acid gives cis-dimethyl(aniono)(triphenylphosphine)gold(III) accompanied by liberation of carbon monoxide and methanol. Reaction of 1 with acetyl chloride liberates methyl acetate and carbon monoxide. The square planar structure of 1 is unequivocally confirmed by an X-ray diffraction study. Related gold(I) complex, (methoxycarbonyl)(triphenylphosphine)gold(I) is also isolated by a similar reaction of chloro(triphenylphosphine)gold(I) with carbon monoxide in the presence of sodium methoxide.

ChemInform Abstract: Synthesis and Biological Activity of Aroylpyruvoylaminobenzonitriles and 3‐Phenacylidene‐6(7)‐cyano‐3,4‐dihydro‐2‐quinoxalones.

AbstractThe dihydrofurandiones (I) are coupled with the aminobenzonitriles (II), (IV), and (VI) to give the amides (III) and (V) or the 7‐cyanoquinoxalones (VII).

Synthesis and biological activity of aroylpyruvoylaminobenzonitriles and 3-phenacylidene-6(7)-cyano-3,4-dihydro-2-quinoxalones

It was found earlier that the reaction of 5-aryl-2,3-dihydrofuran-2,3-diones (I) with aminobenzonitriles may proceed by two different paths, depending on the structure of the latter compounds: either with the liberation of carbon monoxide and formation of aroylketenes, which undergo a [4~ + 2~]-cycloaddition reaction with the participation of the cyano group of the reagent, or with the opening of the furandione ring by the amino group of the reagent. In the first case, cyclic products -6-aryl-2-amino-l,3-oxazin-4-ones are formed, and in the second acyclic products -2-cyanophenylamides of aroylpyruvic acids are obtained [6]. Among the two types of compounds, compounds were discovered with a broad spectrum of biological activity [I, 2, 8]. In continuation of these investigations, it was of interest to study the reaction of compounds I with aminobenzonitriles containing one or two amino or cyano groups, variously positioned in the benzene ring relative to one another, and to examine the biological activity of the reaction products.

Adsorption of carbonyl sulfide on nickel and tungsten films

The interaction of carbonyl sulfide with evaporated nickel and tungsten films has been investigated in the temperature range 195-450 K using gas pressures ranging from 1 to 13 N m/sup -2/. Rapid but mainly associative chemisorption of COS occurred on both metals at 195 K. Further adsorption of COS on W at temperatures 293-450 K was extremely slow and accompanied by more CO desorption than COS adsorbed. Sulfidation of Ni film by COS occurred at temperatures greater than or equal to 293 K with the liberation of carbon monoxide. The rate of adsorption increased with temperature but was independent of COS pressure. The activation energy (E/sub x/) increased with extent (X) of sulfidation to a limiting value of 97 kJ mol/sup -1/. A linear relationship was obtained from the plot of E/sub x/ against 1/X, suggesting the applicability of Cabrera-Mott theory to the sulfidation of Ni film by COS. 20 references, 2 figures, 1 table.

Photsensitized oxygenation of the enol forms of 1,2-cyclohexanediones

The enols of 1,2-cyclohexanediones have been found to undergo a photosensitized oxygenation in methanol to afford 5-oxoalkanoic acids and methyl 5-carboxyl-2-hydroxypentanoates with liberation of carbon monoxide with a remarkable temperature dependency of the product distribution, which is best accounted for in terms of trapping of a five-membered endoperoxide intermediate by methanol.

Chemical Reactions of Organic Compounds with X-Ray Activated Water

Gas free solutions of carbon monoxide, alcohols, aldehydes, ketones and acids were irradiated in the concentration range 10 μM to 1 M, between pH=1 to 13 and the reactions studied principally by gas analysis and potentiometric acid analysis. One organic component systems and, to a more limited extent, two organic component systems were investigated. To obtain significant results, foreign organic matter must be strictly excluded from the low concentration solutions and the methods used to accomplish this are described. Organic impurities in the water can be detected by irradiating the water with x‐rays and measuring the evolved hydrogen and carbon dioxide. The reactions cannot be briefly abstracted, but oxidation and condensation reactions with the evolvement of gaseous hydrogen are important in the effect of the rays. Carbon dioxide was produced from certain acids, particularly strongly from those having an oxygen containing group in the α‐position. No liberation of carbon monoxide, hydrocarbons or oxygen...

Uptake of Molecular Oxygen by Ferrous Complexes

DURING the course of a deliberate study of models for iron porphyrin complexes of biological importance we have shown that ferrous dimethylglyoxime, Fe(DMG)2, is capable of combining reversibly with molecular oxygen. The reaction occurs in a mixed solvent, 50 per cent aqueous dioxan, in which the complex is appreciably soluble in the presence of various added bases such as pyridine, ammonia, histidine and imidazole. The pH of the solution must be in the range 7–11 if the reaction is to be observed. We consider the reversible reaction to be Fe(DMG)2(base)2 + O2 ⇌ Fe(DMG)2(base) O2 + base The forward reaction can be followed by the changes in absorption spectrum as oxygen is bubbled through the solution of the Fe(DMG)2(base)2 complex and the back reaction can be followed by observing similar changes bubbling pure nitrogen through a solution of the oxygenated complex. The spectrophotometric measurements show that the reaction is completely reversible for some of the complexes but that some autoxidation occurs with others. The changes in absorption spectrum with uptake of oxygen are very similar to those which occur on the uptake of carbon monoxide or cyanide by the complex. Both the liberation of oxygen and the liberation of carbon monoxide from the complexes have been studied manometrically. There would appear to be two complexes in one of which two molecules of oxygen or carbon monoxide are bound to the cation and, in the other, one molecule is bound as in the above equation. Comparison of the manometric and spectrophotometric measurements indicates that the first molecule of oxygen or carbon monoxide is picked up slowly but the second molecule is picked up so very slowly that the two stages of the reaction can be followed.

Chemical Reactions of Organic Compounds with X-Ray Activated Water

Gas free solutions of carbon monoxide, alcohols, aldehydes, ketones and acids were irradiated in the concentration range 10 μM to 1 M, between pH=1 to 13 and the reactions studied principally by gas analysis and potentiometric acid analysis. One organic component systems and, to a more limited extent, two organic component systems were investigated. To obtain significant results, foreign organic matter must be strictly excluded from the low concentration solutions and the methods used to accomplish this are described. Organic impurities in the water can be detected by irradiating the water with x-rays and measuring the evolved hydrogen and carbon dioxide. The reactions cannot be briefly abstracted, but oxidation and condensation reactions with the evolvement of gaseous hydrogen are important in the effect of the rays. Carbon dioxide was produced from certain acids, particularly strongly from those having an oxygen containing group in the α-position. No liberation of carbon monoxide, hydrocarbons or oxygen was found. The effect of the rays on all the compounds studied depends on the hydrogen ion concentration, this factor affecting reaction rates as well as the nature of the reactions. The relation of reaction rate to pH can in some cases be represented by [P]=A(1+10−pH+α/1+10−pH+α).The rates of the reactions are in many cases independent of concentration, at high concentrations, but generally the rates decrease at low concentrations. The reason for this decrease may be the deactivation of the activated water, although this interpretation would, because of the form of the reaction product concentration curves, lead to the conclusion that the deactivation is approximately monomolecular (rather than bimolecular) during its initial stage. The same conclusion is indicated since the reaction rates are independent of x-ray intensity down to the lowest concentrations used. The x-ray reactions show some similarity to, but they are generally more complex than, the reactions produced by water activated with light inside the absorption band at 1900A. The irradiation of formic acid in the presence of oxygen at pH=3, results in a smaller decomposition of the formic acid than is produced in the absence of oxygen and a higher production of hydrogen peroxide than is obtained when oxygen is irradiated alone. This increased hydrogen peroxide production can be accounted for as resulting from the reaction of the oxygen with the nascent hydrogen liberated in the organic reaction.

Oxidation of Anthracite: Liberation of Carbon Monoxide and Its Relation to Ignition Temperature

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of Anthracite: Liberation of Carbon Monoxide and Its Relation to Ignition TemperatureG. S. Scott and G. W. JonesCite this: Ind. Eng. Chem. 1937, 29, 1, 106–108Publication Date (Print):January 1, 1937Publication History Published online1 May 2002Published inissue 1 January 1937https://doi.org/10.1021/ie50325a022RIGHTS & PERMISSIONSArticle Views16Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (349 KB) Get e-Alerts