A method for the identification of COVID-19 biomarkers in human breath using Proton Transfer Reaction Time-of-Flight Mass Spectrometry

Background: COVID-19 has caused a worldwide pandemic, making the early detection of the virus crucial. We present an approach for the determination of COVID-19 infection based on breath analysis. Methods: A high sensitivity mass spectrometer was combined with artificial intelligence and used to develop a method for the identification of COVID-19 in human breath within seconds. A set of 1137 positive and negative subjects from different age groups, collected in two periods from two hospitals in the USA, from 26 August, 2020 until 15 September, 2020 and from 11 September, 2020 until 11 November, 2020, was used for the method development. The subjects exhaled in a Tedlar bag, and the exhaled breath samples were subsequently analyzed using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS). The produced mass spectra were introduced to a series of machine learning models. 70% of the data was used for these sub-models\u27 training and 30% was used for testing. Findings: A set of 340 samples, 95 positives and 245 negatives, was used for the testing. The combined models successfully predicted 77 out of the 95 samples as positives and 199 out of the 245 samples as negatives. The overall accuracy of the model was 81.2%. Since over 50% of the total positive samples belonged to the age group of over 55 years old, the performance of the model in this category was also separately evaluated on 339 subjects (170 negative and 169 positive). The model correctly identified 166 out of the 170 negatives and 164 out of the 169 positives. The model accuracy in this case was 97.3%. Interpretation: The results showed that this method for the identification of COVID-19 infection is a promising tool, which can give fast and accurate results

Formation and Chemical Aging of Atmospheric Carbonaceous Aerosol

<p>Atmospheric aerosols can cause serious human health problems and are also affecting the energy balance of our planet contributing to climate change. Organic aerosol (OA) is the most diverse and least understood component of submicron aerosols, in part because of a wide variety of biogenic and anthropogenic sources as well as contributions from both direct emission and secondary formation in the atmosphere. Air quality models often seriously under-predict the concentration of OA in the atmosphere due mainly to our lack of understanding of the atmospheric chemical and physical processing of the emitted organic compounds. A series of experimental studies were performed to address some of the major questions regarding atmospheric OA. In the first phase of the work, the secondary organic aerosol (SOA) production during the oxidation of β-caryophyllene by ozone (O3) and hydroxyl radicals (OH) and the subsequent chemical aging of the products during reactions with OH were investigated. Experiments were conducted with ozone, hydroxyl radicals at low NOx (zero added NOx) and at high NOx (100s of ppb). The SOA mass yield at 10 μg m-3 of organic aerosol was 27% for the ozonolysis, 20% for the reaction with OH at low NOx and 38% at high NOx under dry conditions, 20oC, and ozone excess. Parameterizations of the fresh SOA yields have been developed. The average fresh SOA atomic O:C ratio varied from 0.24 to 0.34 depending on the oxidant and the NOx level, while the H:C ratio was close to 1.5 for all systems examined. An average density of 1.06±0.1 μg m-3 of the β-caryophyllene SOA was estimated. The exposure to UV-light had no effect on the β-caryophyllene SOA concentration and Aerosol Mass Spectrometer (AMS) mass spectrum. The chemical aging of the produced β-caryophyllene SOA was studied by exposing the fresh SOA to high concentrations (107 molecules cm-3) of OH for several hours. These additional reactions ii increased the SOA concentration by 15-40% and the O:C by approximately 25%. A limited number of experiments suggested that there was a significant impact of the relative humidity on the chemical aging of the SOA. The evaporation rates of β-caryophyllene SOA were quantified by using a thermodenuder allowing us to estimate the corresponding volatility distributions and effective vaporization enthalpies. In the second step the accuracy of continuous black carbon measurements of a series of commercially available instruments was assessed for biomass burning particulate matter. Black carbon-containing particles are the most strongly light absorbing aerosols in the atmosphere. They are emitted during the combustion of fossil fuels, biofuels, and biomass. Measurements of black carbon are challenging because of its semi-empirical definition based on physical properties and not chemical structure, the complex and continuously changing morphology of the corresponding particles, and the effects of other particulate components on its absorption. In this study we compare six available commercial continuous BC instruments using biomass burning aerosol. The comparison involves a Soot Particle Aerosol Mass Spectrometer (SP-AMS), a Single Particle Soot Photometer (SP2), an aethalometer, a Multiangle Absorption Photometer (MAAP), and a blue and a green photoacoustic extinctiometer (PAX). An SP-AMS collection efficiency equal to 0.35 was measured for this aerosol system. The SP-AMS was then compared to all the other commercial instruments. Two regimes of behavior were identified corresponding to high and low organic/black carbon ratio. New mass absorption cross sections (MAC) were calculated for the optical instruments for the two regimes. The new MAC values varied from 30% to 2.3 times the instrument default values depending on the instrument and the regime. This comparison of the optical instruments suggests a stronger discrepancy among the BC measurements as the organic carbon content of the BC-containing particles increases. In the next step we focused on the chemical aging of combustion emissions. Smog chamber experiments were conducted to study the changes of the physical properties and chemical composition of biomass burning particles as they evolve in the atmosphere. A Soot Particle Aerosol Mass Spectrometer (SP-AMS) and a Single Particle Soot Photometer (SP2) were used for the chemical characterization of the particles. An Aethalometer as well as a green and a blue photoacoustic extinctiometer (PAX) were used for the study of the aerosol optical properties. As the biomass burning smoke aged, exposed to UV light, ozone, or OH radicals, organic material condensed on the preexisting particles. This coating led to an increase of the absorption of the black carbon-containing particles by as much as a factor of two. The absorption enhancement of biomass burning particles due to their coating with aromatic secondary organic aerosol (SOA) was also studied. The resulting absorption enhancement was determined mainly by the changes in the SOA mass concentration and not the changes of its oxidation state. The enhancement of the absorption of the aging biomass burning particles was consistent with the predictions of a core-shell Mie theory model assuming spherical particles and non-absorbing coating. In the last phase of the work emissions from cooking activities were studied. Cooking organic aerosol (COA) is a significant fraction of the total fine aerosol in urban areas around the world. COA chemical aging experiments took place in a smog chamber in the presence of UV light or in excess of ozone. Positive matrix factorization was used to characterize the changes in the chemical composition of the COA during the chemical aging. The chemical composition of the produced aged COA was similar for both aging methods The chemical aging processes cause an increase of the organic mass and its oxidation state. The fresh COA particles have a low CCN activity but their activity increases significantly as they chemically age.</p

An approach to the automatic synthesis of controllers with mixed qualitative/quantitative specifications.

The world of systems and control guides more of our lives than most of us realize. Most of the products we rely on today are actually systems comprised of mechanical, electrical or electronic components. Engineering these complex systems is a challenge, as their ever growing complexity has made the analysis and the design of such systems an ambitious task. This urged the need to explore new methods to mitigate the complexity and to create simplified models. The answer to these new challenges? \textit{Abstractions}. An abstraction of the the continuous dynamics is a \textit{symbolic model}, where each ``symbol'' corresponds to an ``aggregate'' of states in the continuous model. Symbolic models enable the \textit{correct-by-design} synthesis of controllers and the synthesis of controllers for classes of specifications that traditionally have not been considered in the context of continuous control systems. These include \textit{qualitative} specifications formalized using temporal logics, such as \acf{LTL}. Besides addressing qualitative specifications, we are also interested in synthesizing controllers with \textit{quantitative} specifications, in order to solve optimal control problems. To date, the use of symbolic models for solving optimal control problems, is not well explored. This MSc Thesis presents a new approach towards solving problems of optimal control. Without loss of generality, such control problems are considered as path-planning problems on finite graphs, for which we provide two shortest path algorithms; one deterministic \acf{SDSP} algorithm and one non-deterministic \acs{SDSP} algorithm, in order to solve problems with quantitative specifications in both deterministic and non-deterministic systems. The fact that certain classes of qualitative specifications result in the synthesis of (maximally-permissive) controllers, enables us to use the \acs{SDSP} algorithms to also enforce quantitative specifications. This, however, is not the only path towards our goal of synthesizing controllers with mixed qualitative-quantitative specifications; it is possible to use the \acs{SDSP} algorithms directly to synthesize controllers for the same classes of specifications. Finally, we implement the algorithms as an extension to the \texttt{MATLAB} toolbox \texttt{Pessoa}, using Binary Decision Diagrams (BDDs) as our main data structure.Embedded SystemsDelft Center for Systems and ControlMechanical, Maritime and Materials Engineerin

Formation and chemical aging of secondary organic aerosol during the β-caryophyllene oxidation

The secondary organic aerosol (SOA) production during the oxidation of &beta;-caryophyllene by ozone (O₃) and hydroxyl radicals (OH) and the subsequent chemical aging of the products during reactions with OH were investigated. Experiments were conducted with ozone and with hydroxyl radicals at low NO_<i>x</i> (zero added NO_<i>x</i>) and at high NO_<i>x</i> (hundreds of parts per billion). The SOA mass yield at 10 μg m⁻³ of organic aerosol was 27% for the ozonolysis, 20% for the reaction with OH at low NO_<i>x</i>, and 38% at high NO_<i>x</i> under dry conditions, 20 °C, and ozone excess. Parameterizations of the fresh SOA yields have been developed. The average fresh SOA atomic O : C ratio varied from 0.24 to 0.34 depending on the oxidant and the NO_<i>x</i> level, while the H : C ratio was close to 1.5 for all systems examined. An average density of 1.06 ± 0.1 μg m⁻³ of the β-caryophyllene SOA was estimated. The exposure to UV light had no effect on the &beta;-caryophyllene SOA concentration and aerosol mass spectrometer (AMS) measurements. The chemical aging of the β-caryophyllene SOA produced was studied by exposing the fresh SOA to high concentrations (10⁷ molecules cm^&minus;3) of OH for several hours. These additional reactions increased the SOA concentration by 15–40% and O : C by approximately 25%. A limited number of experiments suggested that there was a significant impact of the relative humidity on the chemical aging of the SOA. The evaporation rates of β-caryophyllene SOA were quantified by using a thermodenuder allowing us to estimate the corresponding volatility distributions and effective vaporization enthalpies

Urban Oxidation Flow Reactor Measurements Reveal Significant Secondary Organic Aerosol Contributions from Volatile Emissions of Emerging Importance

Mobile sampling studies have revealed enhanced levels of secondary organic aerosol (SOA) in source-rich urban environments. While these enhancements can be from rapidly reacting vehicular emissions, it was recently hypothesized that nontraditional emissions (volatile chemical products and upstream emissions) are emerging as important sources of urban SOA. We tested this hypothesis by using gas and aerosol mass spectrometry coupled with an oxidation flow reactor (OFR) to characterize pollution levels and SOA potentials in environments influenced by traditional emissions (vehicular, biogenic), and nontraditional emissions (e.g., paint fumes). We used two SOA models to assess contributions of vehicular and biogenic emissions to our observed SOA. The largest gap between observed and modeled SOA potential occurs in the morning-time urban street canyon environment, for which our model can only explain half of our observation. Contributions from VCP emissions (e.g., personal care products) are highest in this environment, suggesting that VCPs are an important missing source of precursors that would close the gap between modeled and observed SOA potential. Targeted OFR oxidation of nontraditional emissions shows that these emissions have SOA potentials that are similar, if not larger, compared to vehicular emissions. Laboratory experiments reveal large differences in SOA potentials of VCPs, implying the need for further characterization of these nontraditional emissions

Optical properties of black carbon in cookstove emissions coated with secondary organic aerosols: Measurements and modeling

© 2016 American Association for Aerosol Research. Cookstoves are a major source of black carbon (BC) particles and associated organic compounds, which influence the atmospheric radiative balance. We present results from experiments that characterize BC emissions from a rocket stove coated with secondary organic aerosol. Optical properties, namely, BC mass absorption cross-section (MACBC) and mass scattering cross-section (MSC), as a function of the organic-to-black carbon ratio (OA:BC) of fresh and aged cookstove emissions were compared with Mie and Rayleigh–Debye–Gans (RDG) calculations. Mie theory reproduced the measured MACBC across the entire OA:BC range. However, Mie theory failed to capture the MSC at low OA:BC, where the data agreed better with RDG, consistent with a fractal morphology of fresh BC aggregates. As the OA:BC increased, the MSC approached Mie predictions indicating that BC-containing particles approach a core–shell structure as BC cores become heavily coated. To gain insight into the implications of our findings, we calculated the spectral simple forcing efficiency (dSFE) using measured and modeled optical properties as inputs. Good agreement between dSFE estimates calculated from measurements and Mie-modeled dSFE across the entire OA:BC range suggests that Mie theory can be used to simulate the optical properties of aged cookstove emissions. Copyright © 2016 American Association for Aerosol Researc

Chemical characterization and sources of background aerosols in the eastern Mediterranean

Measurements of the composition of the gas and particulate phases were conducted from May 9 to June 4 of 2016 at the Finokalia (Greece) remote coastal site in the eastern Mediterranean, continuing the effort to track long term changes of the atmospheric chemical composition in the area. Finokalia is influenced by air masses arriving in the site from regional sources in Europe, Africa, and other locations. In this study, a series of instruments and analysis techniques were used for the first time at the Finokalia site to characterize the composition of the organic aerosol (OA). The PM 1 was composed of ammonium sulfate/bisulfate (60%), followed by organics (35%) and black carbon (BC) (4%). The OA was highly oxidized with an average oxygen-to-carbon (O:C) ratio of 0.81. Source apportionment of high-resolution organic aerosol mass spectra via positive matrix factorization (PMF) identified four factors: less oxidized oxygenated organic aerosol (LO-OOA), more oxidized oxygenated organic aerosol (MO-OOA), marine-related oxygenated organic aerosol (marine-OOA) and hydrocarbon-like organic aerosol (HOA). The LO-OOA (O:C = 0.92) was the dominant factor for most of the campaign (51% of the PM 1 OA), while the MO-OOA (O:C = 1.1) was responsible for 11% of the OA. The marine-OOA factor was also highly oxidized (O:C = 1.03), contributing on average 24% to the total OA and was found to be well correlated with sulfate (R 2 = 0.83). The anthropogenic HOA factor (O:C = 0.36) was related to activities in the island of Crete. Its mass spectrum was quite similar (R 2 = 0.86–0.95) to those of other HOA factors in the literature and its average concentration was 0.2 μg m −3 (14% of OA). High molecular weight compounds were found, suggesting the presence of oligomers in agreement with the presence of a highly oxidized quenching agent. Aromatic VOCs, like benzene, toluene, and xylenes were on average 0.17, 0.66 and 0.36 ppb, respectively with toluene concentrations indicating the presence of a local source despite the remote nature of the site. New particle formation (NPF) was observed during 26% of the days. The air masses during NPF events passed over the island of Crete and the Balkans and were characterized by a low condensation sink (5.9 ± 2.2 10 −3 s −1). Nucleation mode particle concentrations during NPF days had an additional evening peak between 17:00 and 22:00, which was accompanied by an HOA peak implying the influence of a source of sub-25 nm particles in the extended area. These findings show that even a relatively remote site like Finokalia is occasionally affected by sources located tens of kilometers away, something that should be taken into account in the interpretation of past and future measurements in this location.</p