Formulation studies for eliminating saliva carcinogenic acetaldehyde with L-cysteine containing chewing gum

Tobacco smoke is a major risk factor for the development of cancers in the upper parts of gastrointestinal tract. It has been estimated that the risk of oral cancer among smokers is 7 10 times higher than for never-smokers. Acetaldehyde is formed during the tobacco smoking burning process and may be one of the most toxic compounds in tobacco smoke. According to the International Agency for Research on Cancer (IARC), in 2004 acetaldehyde was classified as a possible carcinogen in humans (Group 2B). In 2009, acetaldehyde was classified in Group 1, as a carcinogen to humans. A non-essential-amino acid such as L-cysteine, is able to bind acetaldehyde and form 2-methylthiziolidine-4-carboxylic acid (MTCA). The general aim of this study was to through formulation studies to explore the ability of L-cysteine to eliminate carcinogenic acetaldehyde present in saliva. In addition, the aim was to develop user-friendly L-cysteine containing chewing gum to reduce acetaldehyde formed during tobacco smoking. The main variables were the chemical form of L-cysteine used (L-cysteine or L-cysteine hydrochloride) and the chewing gum preparation method (traditional and novel direct compression method). Furthermore, the aim was to obtain more information on the optimal formulation properties, using approaches such as stability studies and possible interactions between cysteine and used excipients. Caco-2 cell lines were used to access the ability of L-cysteine and MTCA to absorb from the gastrointestinal tract. A computational model was developed to analyse the effects of different physiological factors and effect of formulation parameters on tobacco smoke acetaldehyde. The combined results of these studies suggested that tobacco smoke carcinogenic acetaldehyde can be successfully eliminated with prepared L-cysteine chewing gums. Compared to the traditional manufacturing process the directly compressed gum formulation can offer an alternative method to traditional chewing gum production. Due to the slower dissolution rate, better compatibility with excipients, and better stability under higher temperature and humidity, L-cysteine as a free base is a better candidate for chewing gum formulation than cysteine hydrochloride. The Caco-2 permeability studies indicate no significant risk of the locally administered L-cysteine being absorbed before binding to acetaldehyde. Permeability results also indicated that MTCA is not absorbed locally from the gastrointestinal tract, which reduces the risk of systemic effects. An MTT assay, a widely used cytotoxicity test, demonstrated that neither L-cysteine nor MTCA was toxic to the Caco-2 cells. A computational model that was developed was able to show how sensitive acetaldehyde is to changes in the amount of L-cysteine as well as in saliva excretion rates. The model can be used as a tool for the prediction of drug amount and the local effect in the mouth of water-soluble compounds, such as L-cysteine. In conclusion, elimination of acetaldehyde, not only carcinogen, but also agent which possibly increases the addictive potential of tobacco, might help in the fight against smoking and make smoking cessation programs more efficient. L-cysteine, a non-essential amino acid, is able to prevent the harmful effects of acetaldehyde by binding acetaldehyde and forming MTCA. It should be kept in mind that acetaldehyde elimination does not make smoking completely harmless and tobacco smoke contains other carcinogens and addictives. The best way to protect from tobacco induced diseases is to refrain from smoking. However, besides the fact that most smokers want to quit but most attempts fail and since tobacco smoke contains many carcinogenic compounds, in the future, developed computational models can offer a new view in eliminating or reducing not only one toxic compound from tobacco smoke but also many other compounds using only one formulation containing various active compounds.Asetaldehydiä syntyy tupakoidessa, ja se on yksi tupakansavun toksisimmista yhdisteistä. Kansainvälinen syöväntutkimuslaitos (International Agency for Research on Cancer, IARC) totesi vuonna 2009, että asetaldehydi on I-luokan karsinogeeni eli ihmiselle syöpää aiheuttava aine. Tätä ennen asetaldehydi oli luokitettu ryhmään 2B-ihmiselle mahdollisesti karsinogeeninen aine. Eräissä tutkimuksissa on saatu viitteitä siitä, että tupakansavun asetaldehydillä on nikotiinin riippuvuutta vahvistava vaikutus. Tämän väitöskirjatutkimuksen tavoitteena oli kehittää käyttäjäystävällinen lääkepurukumivalmiste, jolla kemiallisesti sidotaan tupakasta syntyvä asetaldehydi L-kysteiinin avulla. L-kysteiini on toksiton monoaminohappo, joka reagoi kovalentisti asetaldehydin kanssa muodostaen 2-metyylidiatsolidiini-4-karboksyylihappoa (MTCA). Näin ehkäistään asetaldehydin karsinogeeninen vaikutus ruoansulatuskanavassa. Tärkeimmät muuttujat tässä tutkimuksessa olivat L-kysteiinin kemiallinen muoto (L-kysteiini/L-kysteiini-hydrokloridi) ja purukumin valmistusmenetelmä (perinteinen/suorapuristus menetelmä). Lisäksi tavoitteena oli saada lisää tietoa lääkemuodon säilyvyydestä, kuten myös yhteensopivuudesta vaikuttavan aineen ja koostumuksessa käytettävien apuaineiden kanssa. L-kysteiinin ja MTCA:n läpäisevyyttä tutkittiin CaCo-2 soluviljelmien avulla. Tietokonemalli rakennettiin mallintamaan eri muuttajien vaikutusta tupakoinnin aikana muodostuvaan asetaldehydiin. Tutkimustulokset osoittivat, että L-kysteiiniä sisältävällä purukumilla, voidaan poistaa lähes kokonaan tupakoinnin yhteydessä sylkeen muodostuva asetaldehydi. Caco-2 solulinjalla tehdyt läpäisevyystutkimukset osoittivat, että sekä L-kysteiini että MTCA eivät imeydy merkittävästi mahasta. Näin voidaan olettaa, että systeemihaittavaikutusten riski on pieni. Rakennetulla tietokonemallilla osoitettiin miten herkkä asetaldehydi on L-kysteiinin määrille ja syljen erityksen muutoksille. Mallia voidaan käyttää välineenä ennustamaan lääkeaineen määrää ja vesiliukoisten yhdisteiden, kuten L-kysteiini, paikallista vaikutusta suussa. Karsinogeenisen asetaldehydin poistaminen L-kysteiiniä sisältävien valmisteiden avulla samalla mahdollisesti vähentäisi myös nikotiinin riippuvuutta tehostavan aineen vaikutusta. Tämä auttaisi taistelussa tupakointia vastaan. On kuitenkin pidettävä mielessä, että asetaldehydin poistaminen ei tee tupakoinnista täysin vaaratonta ja tupakansavu sisältää myös monia muita karsinogeenisia ja riippuvuutta aiheuttavia aineita. Paras tapa suojautua tupakoinnin aiheuttamista sairauksista on pidättyä tupakoinnista

Advanced Manufacturing: Polymer & Composites Science-The First Issue

Dear Authors and Readers,It is my great pleasure to write the editorial for the second issue of the AMPCS Journal. To begin, I would like to introduce Dr. Carwyn Ward, recently appointed as Assista..

Effect of laminin, polylysine and cell medium components on the attachment of human hepatocellular carcinoma cells to cellulose nanofibrils analyzed by surface plasmon resonance

The development of in vitro cell models that mimic cell behavior in organs and tissues is an approach that may have remarkable impact on drug testing and tissue engineering applications in the future. Plant based, chemically unmodified cellulose nanofibrils (CNF) hydrogel is a natural, abundant, and biocompatible material that has attracted great attention for biomedical applications, in particular for threedimensional cell cultures. However, the mechanisms of cell-CNF interactions and factors that affect these interactions are not yet fully understood. In this work, multi-parametric surface plasmon resonance (SPR) was used to study how the adsorption of human hepatocellular carcinoma (HepG2) cells on CNF films is affected by the different proteins and components of the cell medium. Both human recombinant laminin 521 (LN-521, a natural protein of the extracellular matrix) and poly -L-lysine (PLL) adsorbed on CNF films and enhanced the attachment of HepG2 cells. Cell medium components (glucose and amino acids) and serum proteins (fetal bovine serum, FBS) also adsorbed on both bare CNF and on protein-coated CNF substrates. However, the adsorption of FBS hindered the attachment of HepG2 cells to LN-521and PLLcoated CNF substrates, suggesting that serum proteins blocked the formation of laminin-integrin bonds and decreased favorable PLL-cell electrostatic interactions. This work sheds light on the effect of different factors on cell attachment to CNF, paving the way for the utilization and optimization of CNF-based materials for different tissue engineering applications. (C) 2020 The Authors. Published by Elsevier Inc.Peer reviewe

Future changes in isoprene-epoxydiol-derived secondary organic aerosol (IEPOX SOA) under the Shared Socioeconomic Pathways: the importance of physicochemical dependency

Secondary organic aerosol (SOA) is a dominant contributor of fine particulate matter in the atmosphere, but the complexity of SOA formation chemistry hinders the accurate representation of SOA in models. Volatility-based SOA parameterizations have been adopted in many recent chemistry modeling studies and have shown a reasonable performance compared to observations. However, assumptions made in these empirical parameterizations can lead to substantial errors when applied to future climatic conditions as they do not include the mechanistic understanding of processes but are rather fitted to laboratory studies of SOA formation. This is particularly the case for SOA derived from isoprene epoxydiols (IEPOX SOA), for which we have a higher level of understanding of the fundamental processes than is currently parameterized in most models. We predict future SOA concentrations using an explicit mechanism and compare the predictions with the empirical parameterization based on the volatility basis set (VBS) approach. We then use the Community Earth System Model 2 (CESM2.1.0) with detailed isoprene chemistry and reactive uptake processes for the middle and end of the 21st century under four Shared Socioeconomic Pathways (SSPs): SSP1&ndash;2.6, SSP2&ndash;4.5, SSP3&ndash;7.0, and SSP5&ndash;8.5. With the explicit chemical mechanism, we find that IEPOX SOA is predicted to increase on average under all future SSP scenarios but with some variability in the results depending on regions and the scenario chosen. Isoprene emissions are the main driver of IEPOX SOA changes in the future climate, but the IEPOX SOA yield from isoprene emissions also changes by up to 50&thinsp;% depending on the SSP scenario, in particular due to different sulfur emissions. We conduct sensitivity simulations with and without CO2 inhibition of isoprene emissions that is highly uncertain, which results in factor of&nbsp;2 differences in the predicted IEPOX SOA global burden, especially for the high-CO2 scenarios (SSP3&ndash;7.0 and SSP5&ndash;8.5). Aerosol pH also plays a critical role in the IEPOX SOA formation rate, requiring accurate calculation of aerosol pH in chemistry models. On the other hand, isoprene SOA calculated with the VBS scheme predicts a nearly constant SOA yield from isoprene emissions across all SSP scenarios; as a result, it mostly follows isoprene emissions regardless of region and scenario. This is because the VBS scheme does not consider heterogeneous chemistry; in other words, there is no dependency on aerosol properties. The discrepancy between the explicit mechanism and VBS parameterization in this study is likely to occur for other SOA components as well, which may also have dependencies that cannot be captured by VBS parameterizations. This study highlights the need for more explicit chemistry or for parameterizations that capture the dependence on key physicochemical drivers when predicting SOA concentrations for climate studies. </div

Environmental impact assessment of aviation emission reduction through the implementation of composite materials

© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Carbon-fibre-reinforced polymers (CFRP) have been developed by the aviation industry to reduce aircraft fuel burn and emissions of greenhouse gases. This study presents a life cycle assessment (LCA) of an all-composite airplane, based on a Boeing 787 Dreamliner. The global transition of aircraft to those of composite architecture is estimated to contribute 20–25 % of industry CO2 reduction targets. A secondary stage of the cradle-to-grave analysis expands the study from an individual aircraft to the global fleet.Methods: An LCA was undertaken utilising SimaPro 7.2 in combination with Ecoinvent. Eco-indicator 99 (E) V2.05 Europe EI 99 E/E was the chosen method to calculate the environmental impact of the inventory data. The previously developed aviation integrated model was utilised to construct a scenario analysis of the introduction of composite aircraft against a baseline projection, through to 2050, to model CO2 emissions due to their particular relevance in the aviation sector.Results and discussion: The analysis demonstrated CFRP structure results in a reduced single score environmental impact, despite the higher environmental impact in the manufacturing phase, due to the increased fossil fuel use. Of particular importance is that CFRP scenario quickly achieved a reduction in CO2 and NOx atmospheric emissions over its lifetime, due to the reduced fuel consumption. The modelled fleet-wide CO2 reduction of 14–15 % is less than the quoted emission savings of an individual aircraft (20 %) because of the limited fleet penetration by 2050 and the increased demand for air travel due to lower operating costs.Conclusions: The introduction of aircraft based on composite material architecture has significant environmental benefits over their lifetime compared to conventional aluminium-based architecture, particularly with regards to CO2 and NOx a result of reduced fuel burn. The constructed scenario analyses the interactions of technology and the markets they are applied in, expanding on the LCA, in this case, an observed fleet-wide reduction of CO2 emission of 14–15 % compared to an individual aircraft of 20 %

Aerosol pH indicator and organosulfate detectability from aerosol mass spectrometry measurements

Aerosol sulfate is a major component of submicron particulate matter (PM1). Sulfate can be present as inorganic (mainly ammonium sulfate, AS) or organosulfate (OS). Although OS is thought to be a smaller fraction of total sulfate in most cases, recent literature argues that this may not be the case in more polluted environments. Aerodyne aerosol mass spectrometers (AMSs) measure total submicron sulfate, but it has been difficult to apportion AS vs. OS as the detected ion fragments are similar. Recently, two new methods have been proposed to quantify OS separately from AS with AMS data. We use observations collected during several airborne field campaigns covering a wide range of sources and air mass ages (spanning the continental US, marine remote troposphere, and Korea) and targeted laboratory experiments to investigate the performance and validity of the proposed OS methods. Four chemical regimes are defined to categorize the factors impacting sulfate fragmentation. In polluted areas with high ammonium nitrate concentrations and in remote areas with high aerosol acidity, the decomposition and fragmentation of sulfate in the AMS is influenced by multiple complex effects, and estimation of OS does not seem possible with current methods. In regions with lower acidity (pH \u3e 0) and ammonium nitrate (fraction of total mass \u3c 0.3), the proposed OS methods might be more reliable, although application of these methods often produced nonsensical results. However, the fragmentation of ambient neutralized sulfate varies somewhat within studies, adding uncertainty, possibly due to variations in the effect of organics. Under highly acidic conditions (when calculated pH \u3c 0 and ammonium balance \u3c 0.65), sulfate fragment ratios show a clear relationship with acidity. The measured ammonium balance (and to a lesser extent, the HySO+x / SO+x AMS ratio) is a promising indicator of rapid estimation of aerosol pH \u3c 0, including when gas-phase NH3 and HNO3 are not available. These results allow an improved understanding of important intensive properties of ambient aerosols

CAM6-chem with very short-lived halogen chemistry: evaluation with the whole air sampler aircraft data from multiple seasons and locations

A new version of the Community Atmosphere Model with chemistry (CAM6-chem) has recently been released to the atmospheric science community (June 2018). CAM6-chem has updated boundary layer processes, shallow convection and liquid cloud macrophysics, and two-moment cloud microphysics with prognostic cloud mass andconcentration. A 4-mode prognostic aerosol representation (MAM4) has been added that includes a representation of dust, sea-salt black carbon, organic carbon, and sulfate in three size categories (Gettelman et al., 2019). CAM6-Chem has a detailed representation of both tropospheric and stratospheric chemistry. The tropospheric chemistry includes updates to the representation the organic nitrates, isoprene oxidization, and the speciation of the aromaticand terpenes (Emmons et al., 2019). This mechanism also includes a comprehensive secondary organic aerosol parameterization based on the Volatility Basic Set (VBS) model framework (Hodzic et al. 2016; Tilmes et al., 2019). The stratospheric halogen chemistry represents the distribution of CH3Cl, CFCs, HCFCs, CH3Br, and halons (Kinnison et al., 2007). For this study, the emissions, wet and dry depositions, and chemical processes that represent Very Short-Lived Halogens (VSLH) were added (e.g., Saiz-Lopez et al., 2016). Evaluation of the organic VSLH distributions are to compare with trace gas measurements collected during seven field campaigns, two withmultiple deployments, to evaluate the model performance over multiple years. The campaigns include HIPPO (2009-2011) pole to pole observations in the Pacific on the NSF/NCAR GV over multiple seasons; SEAC4RS (Aug./Sept., 2013) in the central and southern U.S. and western Gulf of Mexico on the NASA ER-2 and DC8; ATTREX (2011-2015) on the NASA Global Hawk over multiple seasons and locations; CONTRAST (Jan/Feb, 2014) in the western Pacific on the NSF/NCAR GV; VIRGAS (Oct., 2015) in the south central US and western Gulf of Mexico on the NASA WB-57; ORCAS (Jan/Feb, 2016) over the southern ocean on the NSF/NCAR GV; and POSIDON (Oct, 2016) in the western Pacific on the NASA WB-57. The model was ?nudged? to NASA Modern-Era Retrospective analysis for Research and Applications, version 2 meteorological fields to represent the synoptic meteorology for each mission. The analysis will focus on along the flight tracks comparisons with the model and will also examine comparisons of vertical distributions and various tracer-tracer correlations. Implications of this new model version on estimated input of inorganic bromine and iodine into the lower stratosphere will be discussed.Fil: Kinnisson, Douglas E.. National Center for Atmospheric Research; Estados UnidosFil: Saiz Lopez, Alfonso. Consejo Superior de Investigaciones Científicas. Instituto de Química Física "Rocasolano"; EspañaFil: Cuevas, Carlos Alberto. Consejo Superior de Investigaciones Científicas. Instituto de Química Física "Rocasolano"; EspañaFil: Fernandez, Rafael Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Tecnológica Nacional; ArgentinaFil: Lamarque, Jean Francoise. National Center for Atmospheric Research; Estados UnidosFil: Tilmes, Simone. National Center for Atmospheric Research; Estados UnidosFil: Emmons, Louisa K.. National Center for Atmospheric Research; Estados UnidosFil: Hodzic, Alma. National Center for Atmospheric Research; Estados UnidosFil: Wang, Siyuan. National Center for Atmospheric Research; Estados UnidosFil: Schauffler, Sue M.. National Center for Atmospheric Research; Estados UnidosFil: Navarro, María. University Of Miami. Rosenstiel School Of Marine Atmospheric Science; Estados UnidosFil: Atlas, Elliot. University Of Miami. Rosenstiel School Of Marine Atmospheric Science; Estados UnidosEGU General Assembly 2019VienaAustriaEuropean Geociences Unio

Neural Network Emulation of the Formation of Organic Aerosols Based on the Explicit GECKO-A Chemistry Model

Secondary organic aerosols (SOA) are formed from oxidation of hundreds of volatile organic compounds (VOCs) emitted from anthropogenic and natural sources. Accurate predictions of this chemistry are key for air quality and climate studies due to the large contribution of organic aerosols to submicron aerosol mass. Currently, only explicit models, such as the Generator for Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A), can fully represent the chemical processing of thousands of organic species. However, their extreme computational cost prohibits their use in current chemistry-climate models, which rely on simplified empirical parameterizations to predict SOA concentrations. This study demonstrates that machine learning can accurately emulate SOA formation from an explicit chemistry model with an approximate error of 2%&ndash;8%, up to five days for several precursors and for potentially up to one month for recurrent neural network models, and with 100 to 100,000 times speedup over GECKO-A, making it computationally useable in a chemistry-climate model. We generated the training data using thousands of GECKO-A box simulations sampled from a broad range of initial environmental conditions, and focused on three representative SOA precursors: the oxidation by OH of two anthropogenic (toluene, dodecane), and the oxidation by O3 of one biogenic VOC (&alpha;-pinene). We compare several neural models and quantify their underlying uncertainty and robustness. These are promising results, suggesting that neural network models could be applied to predict SOA in chemistry-climate models, limited however to the range of environmental conditions that were considered in the training datasets. &nbsp;</p

Global impact of nitrate photolysis in sea-salt aerosol on NOx, OH, and O3 in the marine boundary layer

Recent field studies have suggested that sea-salt particulate nitrate (NITs) photolysis may act as a significant local source of nitrogen oxides (NOx) over oceans. We present a study of the global impact of this process on oxidant concentrations in the marine boundary layer (MBL) using the GEOS-Chem model, after first updating the model to better simulate observed gas-particle phase partitioning of nitrate in the marine boundary layer. Model comparisons with long-term measurements of NOx from the Cape Verde Atmospheric Observatory (CVAO) in the eastern tropical North Atlantic provide support for an in situ source of NOx from NITs photolysis, with NITs photolysis coefficients about 25-50 times larger than corresponding HNO3 photolysis coefficients. Short-term measurements of nitrous acid (HONO) at this location show a clear daytime peak, with average peak mixing ratios ranging from 3 to 6 pptv. The model reproduces the general shape of the diurnal HONO profile only when NITs photolysis is included, but the magnitude of the daytime peak mixing ratio is under-predicted. This under-prediction is somewhat reduced if HONO yields from NITs photolysis are assumed to be close to unity. The combined NOx and HONO analysis suggests that the upper limit of the ratio of NITs : HNO3 photolysis coefficients is about 100. The largest simulated relative impact of NITs photolysis is in the tropical and subtropical marine boundary layer, with peak local enhancements ranging from factors of 5 to 20 for NOx, 1.2 to 1.6 for OH, and 1.1 to 1.3 for ozone. Since the spatial extent of the sea-salt aerosol (SSA) impact is limited, global impacts on NOx, ozone, and OH mass burdens are small ( ∼ 1-3 %). We also present preliminary analysis showing that particulate nitrate photolysis in accumulation-mode aerosols (predominantly over continental regions) could lead to ppbv-level increases in ozone in the continental boundary layer. Our results highlight the need for more comprehensive long-term measurements of NOx, and related species like HONO and sea-salt particulate nitrate, to better constrain the impact of particulate nitrate photolysis on marine boundary layer oxidant chemistry. Further field and laboratory studies on particulate nitrate photolysis in other aerosol types are also needed to better understand the impact of this process on continental boundary layer oxidant chemistry