DEB-FAPy-dG Adducts of 1,3-Butadiene: Synthesis, Structural Characterization, and Formation in 1,2,3,4-Diepoxybutane Treated DNA.

Metabolic activation of the human carcinogen 1,3-butadiene (BD) by cytochrome 450 monooxygenases gives rise to a genotoxic diepoxide, 1,2,3,4-diepoxybutane (DEB). This reactive electrophile alkylates guanine bases in DNA to produce N7-(2-hydroxy-3,4-epoxy-1-yl)-dG (N7-DE-dG) adducts. Because of the positive charge at the N7 position of the purine heterocycle, N7-DEB-dG adducts are inherently unstable and can undergo spontaneous depurination or base-catalyzed imidazole ring opening to give N6 -[2-deoxy-D-erythro-pentofuranosyl]-2,6-diamino-3,4-dihydro-4-oxo-5-N-1-(oxiran-2-yl)propan-1-ol-formamidopyrimidine (DEB-FAPy-dG) adducts. Here we report the first synthesis and structural characterization of DEB-FAPy-dG adducts. Authentic standards of DEB-FAPy-dG and its 15 N3 -labeled analogue were used for the development of a quantitative nanoLC-ESI+ -HRMS/MS method, allowing for adduct detection in DEB-treated calf thymus DNA. DEB-FAPy-dG formation in DNA was dependent on DEB concentration and pH, with higher numbers observed under alkaline conditions.

The effect of head orientation and personalized ventilation on bioaerosol deposition from a cough.

Head orientations directly determine movement directions of exhaled pathogen-laden droplets, while there is a lack of research about the effect of the infected person's head orientations on respiratory disease transmission during close contact. This work experimentally investigated the effect of different head orientations of an infected person (IP) on the bioaerosol deposition on a healthy person (HP) during close contact. Also, the effectiveness of PV flow in reducing bioaerosol deposition on the HP under the IP's different head orientations was investigated. Bacteriophage T3 was employed to represent viruses inside the cough-generated aerosols. The bioaerosol depositions on different locations of the HP's upper body (chest, shoulder, and neck) and face (chin, mucous membranes, cheek, and forehead) were characterized by a cultivation method. Results showed that the IP's different head orientations resulted in significantly different deposition density on the HP. PV flow could reduce the bioaerosol deposition remarkably for most cases investigated. The effectiveness of PV flow in reducing deposition on the HP was significantly affected by the IP's head orientations. Findings suggest that changing head orientations can be a control measure to reduce the bioaerosol deposition. Personalized ventilation can be a potential method to reduce the bioaerosol deposition on the HP.

Infection control measures for public transportation derived from the flow dynamics of obstructed cough jet.

During the COVID-19 pandemic, WHO and CDC suggest people stay 1 m and 1.8 m away from others, respectively. Keeping social distance can avoid close contact and mitigate infection spread. Many researchers suspect that suggested distances are not enough because aerosols can spread up to 7-8 m away. Despite the debate on social distance, these social distances rely on unobstructed respiratory activities such as coughing and sneezing. Differently, in this work, we focused on the most common but less studied aerosol spread from an obstructed cough. The flow dynamics of a cough jet blocked by the backrest and gasper jet in a cabin environment was characterized by the particle image velocimetry (PIV) technique. It was proved that the backrest and the gasper jet can prevent the front passenger from droplet spray in public transportation where maintaining social distance was difficult. A model was developed to describe the cough jet trajectory due to the gasper jet, which matched well with PIV results. It was found that buoyancy and inside droplets almost do not affect the short-range cough jet trajectory. Infection control measures were suggested for public transportation, including using backrest/gasper jet, installing localized exhaust, and surface cleaning of the backrest.

Effects of GSTT1 Genotype on the Detoxification of 1,3-Butadiene Derived Diepoxide and Formation of Promutagenic DNA-DNA Cross-Links in Human Hapmap Cell Lines.

Smoking is a leading cause of lung cancer, accounting for 81% of lung cancer cases. Tobacco smoke contains over 5000 compounds, of which more than 70 have been classified as human carcinogens. Of the many tobacco smoke constituents, 1,3-butadiene (BD) has a high cancer risk index due to its tumorigenic potency and its abundance in cigarette smoke. The carcinogenicity of BD has been attributed to the formation of several epoxide metabolites, of which 1,2,3,4-diepoxybutane (DEB) is the most toxic and mutagenic. DEB is formed by two oxidation reactions carried out by cytochrome P450 monooxygenases, mainly CYP2E1. Glutathione-S-transferase theta 1 (GSTT1) facilitates the conjugation of DEB to glutathione as the first step of its detoxification and subsequent elimination via the mercapturic acid pathway. Human biomonitoring studies have revealed a strong association between GSTT1 copy number and urinary concentrations of BD-mercapturic acids, suggesting that it plays an important role in the metabolism of BD. To determine the extent that GSTT1 genotype affects the susceptibility of individuals to the toxic and genotoxic properties of DEB, GSTT1 negative and GSTT1 positive HapMap lymphoblastoid cell lines were treated with DEB, and the extent of apoptosis and micronuclei (MN) formation was assessed. These toxicological end points were compared to the formation of DEB-GSH conjugates and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) DNA-DNA cross-links. GSTT1 negative cell lines were more sensitive to DEB-induced apoptosis as compared to GSTT1 positive cell lines. Consistent with the protective effect of GSH conjugation against DEB-derived apoptosis, GSTT1 positive cell lines formed significantly more DEB-GSH conjugate than GSTT1 negative cell lines. However, GSTT1 genotype did not affect formation of MN or bis-N7G-BD cross-links. These results indicate that GSTT1 genotype significantly influences BD metabolism and acute toxicity.

Respiratory bioaerosol deposition from a cough and recovery of viable viruses on nearby seats in a cabin environment.

Respiratory bioaerosol deposition in public transport cabins is critical for risk analysis and control of contact transmission. In this work, we built a two-row four-seat setup and an air duct system to simulate a cabin environment. A thermal manikin on the rear left-hand seat was taken as the infected passenger (IP) and "coughed" three times through a cough generator. The deposited viruses and droplets on nearby seats were measured by a cultivation method and microscope, respectively. The effects of seat backrest and overhead gasper jet were studied. Results showed that the number of deposited virus on the front seat was one order of magnitude higher than that on other seats which only contained droplets smaller than 10 µm in diameter. When the backrest was 15 cm higher than the cough, the deposited number of viruses was reduced to 5% of that with the backrest at the same height with the cough. The gasper jet above the IP with a velocity of 1.5 m/s can reduce the deposited viruses to 4% of that with gasper off. It indicates that both the gasper jet and backrest can work as mitigation measures to block the cough jet and protect the nearby passengers.

Site-Specific 5-Formyl Cytosine Mediated DNA-Histone Cross-Links: Synthesis and Polymerase Bypass by Human DNA Polymerase η.

DNA-protein cross-links (DPCs) between DNA epigenetic mark 5-formylC and lysine residues of histone proteins spontaneously form in human cells. Such conjugates are likely to influence chromatin structure and mediate DNA replication, transcription, and repair, but are challenging to study due to their reversible nature. Here we report the construction of site specific, hydrolytically stable DPCs between 5fdC in DNA and K4 of histone H3 and an investigation of their effects on DNA replication. Our approach employs oxime ligation, allowing for site-specific conjugation of histones to DNA under physiological conditions. Primer extension experiments revealed that histone H3-DNA crosslinks blocked DNA synthesis by hPol η polymerase, but were bypassed following proteolytic processing.

Interindividual Differences in DNA Adduct Formation and Detoxification of 1,3-Butadiene-Derived Epoxide in Human HapMap Cell Lines.

Smoking-induced lung cancer is a major cause of cancer mortality in the US and worldwide. While 11-24% of smokers will develop lung cancer, risk varies among individuals and ethnic/racial groups. Specifically, African American and Native Hawaiian cigarette smokers are more likely to get lung cancer as compared to Caucasians, Japanese Americans, and Latinos. It is important to identify smokers who are at the greatest risk of developing lung cancer as they should be candidates for smoking cessation and chemopreventive intervention programs. Among 60+ tobacco smoke carcinogens, 1,3-butadiene (BD) is one of the most potent and abundant (20-75 µg per cigarette in mainstream smoke and 205-361 µg per cigarette in side stream smoke). BD is metabolically activated to 3,4-epoxy-1-butene (EB), which can be detoxified by glutathione S-transferase theta 1 (GSTT1)-mediated conjugation with glutathione, or can react with DNA to form 7-(1-hydroxy-3-buten-2-yl)guanine (EB-GII) adducts. In the present study, we employed EBV-transformed human lymphoblastoid cell lines (HapMap cells) with known GSTT1 genotypes to examine the influence of the GSTT1 gene on interindividual variability in butadiene metabolism, DNA adduct formation/repair, and biological outcomes (apoptosis). We found that GSTT1- HapMap cells treated with EB in culture produced lower levels of glutathione conjugates and were more susceptible to apoptosis but had similar numbers of EB-GII adducts as GSTT1+ cells. Our results suggest that GSTT1 can influence an individual's susceptibility to butadiene-derived epoxides.

Study of particle resuspension from dusty surfaces using a centrifugal method.

Particle resuspension has been recognized as a secondary source of indoor air pollution by many field studies. However, some laboratory studies showed that the air velocities or force fields required to resuspend aerosol particles are very high that rarely occurred in indoor environments. In fact, the surfaces used in these studies were treated to ensure cleanliness, but in reality, dusty surfaces are ubiquitous in our daily life. This work aims to investigate the effect of dust on a surface on resuspension of a coarse particle (polyethylene) by a centrifugal method. Dusty surfaces with different loadings were made by gravitational settling of Arizona test dust on a clean poly(methyl methacrylate) substrate inside a deposition chamber. The resuspension of dust particles was first investigated, and it was found that dust particles were resuspended by two stages with different rates of resuspension. For the resuspension of the particles on the dusty surface, the remaining fraction of the polyethylene particles decreased with increasing force field and dust loading. Dust could greatly reduce the adhesion of the particles from one to two orders of magnitude depending on loadings. This gives an explanation to the discrepancy between the field and the laboratory studies.

Differential gene expression in Escherichia coli during aerosolization from liquid suspension.

Comparative transcriptome analysis was used to determine the differentially expressed genes in Escherichia coli during aerosolization from liquid suspension. Isogenic mutant studies were then used to examine the potential part played by some of these genes in bacterial survival in the air. Bioaerosols were sampled after 3 min of nebulization, which aerosolized the bacteria from the liquid suspension to an aerosol chamber (A0), and after further 30 min of airborne suspension in the chamber (A30). Bacteria at A0 showed 65 differentially expressed genes (30 downregulated and 35 upregulated) as compared to the original bacteria in the nebulizer. Droplet evaporation models predicted a drop in temperature in the bioaerosols, which coincides with the change in the expression of cold shock protein genes-cspB and cspG in the bacteria. The most notable group of differentially expressed genes was sorbitol transport and metabolism genes (srlABDEMR). Other genes associated with osmotic stress, nutrient limitation, DNA damage, and other stresses were differentially expressed in the bacteria at A0. After further airborne suspension, one gene (ypfM, which encodes a hypothetical protein with unknown function) was downregulated in the bacteria at A30 as compared to those at A0. Finally, isogenic mutants with either the dps or srlA gene deleted (both genes were upregulated at A0) had lower survival than the parental strain, which is a sign of their potential ability to protect the bacteria in the air.

Effect of human movement on airborne disease transmission in an airplane cabin: study using numerical modeling and quantitative risk analysis.

BACKGROUND: Airborne transmission of respiratory infectious disease in indoor environment (e.g. airplane cabin, conference room, hospital, isolated room and inpatient ward) may cause outbreaks of infectious diseases, which may lead to many infection cases and significantly influences on the public health. This issue has received more and more attentions from academics. This work investigates the influence of human movement on the airborne transmission of respiratory infectious diseases in an airplane cabin by using an accurate human model in numerical simulation and comparing the influences of different human movement behaviors on disease transmission. METHODS: The Eulerian-Lagrangian approach is adopted to simulate the dispersion and deposition of the expiratory aerosols. The dose-response model is used to assess the infection risks of the occupants. The likelihood analysis is performed as a hypothesis test on the input parameters and different human movement pattern assumptions. An in-flight SARS outbreak case is used for investigation. A moving person with different moving speeds is simulated to represent the movement behaviors. A digital human model was used to represent the detailed profile of the occupants, which was obtained by scanning a real thermal manikin using the 3D laser scanning system. RESULTS: The analysis results indicate that human movement can strengthen the downward transport of the aerosols, significantly reduce the overall deposition and removal rate of the suspended aerosols and increase the average infection risk in the cabin. The likelihood estimation result shows that the risk assessment results better fit the outcome of the outbreak case when the movements of the seated passengers are considered. The intake fraction of the moving person is significantly higher than most of the seated passengers. CONCLUSIONS: The infection risk distribution in the airplane cabin highly depends on the movement behaviors of the passengers and the index patient. The walking activities of the crew members and the seated passengers can significantly increase their personal infection risks. Taking the influence of the movement of the seated passengers and the index patient into consideration is necessary and important. For future studies, investigations on the behaviors characteristics of the passengers during flight will be useful and helpful for infection control.

Effects of surface material, ventilation, and human behavior on indirect contact transmission risk of respiratory infection.

Infectious particles can be deposited on surfaces. Susceptible persons who contacted these contaminated surfaces may transfer the pathogens to their mucous membranes via hands, leading to a risk of respiratory infection. The exposure and infection risk contributed by this transmission route depend on indoor surface material, ventilation, and human behavior. In this study, quantitative infection risk assessments were used to compare the significances of these factors. The risks of three pathogens, influenza A virus, respiratory syncytial virus (RSV), and rhinovirus, in an aircraft cabin and in a hospital ward were assessed. Results showed that reducing the contact rate is relatively more effective than increasing the ventilation rate to lower the infection risk. Nonfabric surface materials were found to be much more favorable in the indirect contact transmission for RSV and rhinovirus than fabric surface materials. In the cases considered in this study, halving the ventilation rate and doubling the hand contact rate to surfaces and the hand contact rate to mucous membranes would increase the risk by 3.7-16.2%, 34.4-94.2%, and 24.1-117.7%, respectively. Contacting contaminated nonfabric surfaces may pose an indirect contact risk up to three orders of magnitude higher than that of contacting contaminated fabric surfaces. These findings provide more consideration for infection control and building environmental design.

Wavelet analysis of the atmospheric flows over real urban morphology.

Winds are the basic forces for atmospheric transport such as pollutant removal and pedestrian thermal comfort. The transport capability is commonly measured in terms of length and velocity scales. In this connection, the flows in the atmospheric surface layer (ASL) over the Kowloon Peninsula, Hong Kong (HK) are scrutinized by the large-eddy simulation (LES) to characterize the motion scales over real urban morphology. Apart from statistical analysis, the streamwise fluctuating velocity u' is examined by both wavelet and energy spectrum in which a primary peak is consistently shown at streamwise wavelength 70 m ≤ λx ≤ 300 m. A secondary peak at a longer wavelength 800 m ≤ λx ≤ 3000 m, however, is unveiled by wavelet only. It denotes the existence of intermittent turbulence structures whose sizes are much larger than those of buildings. Further wavelet analysis reveals that majority energy-carrying eddies are enlarging (tens to hundreds of meters) from the roughness sublayer (RSL) to the inertial sublayer (ISL). Analogous to its smooth-wall and schematic rough-wall counterparts, the turbulence kinetic energy (TKE) over urban areas is peaked in the ISL which is carried by eddies of size 50 m ≤ λx ≤ 1000 m. The (horizontal) spatial distribution of energy-carrying eddies is further visualized to compare the crucial motion scales in the RSL and ISL. Finally, conditional sampling is used to demystify the contribution to vertical momentum flux u'w' in terms of streamwise wavelength and quadrants. The results advance our fundamental understanding of ASL transport processes, fostering sustainable environmental policy.

Empirical mode decomposition of the atmospheric flows and pollutant transport over real urban morphology.

The momentum transport and pollutant dispersion in the atmospheric surface layer (ASL) are governed by a broad spectrum of turbulence structures. Whereas, their contributions have not been explicitly investigated in the context of real urban morphology. This paper aims to elucidate the contributions from different types of eddies in the ASL over a dense city to provide the reference of urban planning, realizing more favorable ventilation and pollutant dispersion. The building-resolved large-eddy simulation dataset of winds and pollutants over the Kowloon downtown, Hong Kong, is decomposed into a few intrinsic mode functions (IMFs) via empirical mode decomposition (EMD). EMD is a data-driven algorithm that has been successfully implemented in many research fields. The results show that four IMFs are generally enough to capture most of the turbulence structures in real urban ASL. In particular, the first two IMFs, which are initiated by individual buildings, capture the small-scale vortex packets that populate within the irregular building clusters. On the other hand, the third and fourth IMFs capture the large-scale motions (LSMs) detached to the ground surface that are highly efficient in transport. They collectively contribute to nearly 40% of vertical momentum transport even with relatively low vertical turbulence kinetic energy (TKE). LSMs are long, streaky structures that mainly consist of streamwise TKE components. It is found that the open areas and regular streets promote the portion of streamwise TKE in LSMs, improving the vertical momentum transport and pollutant dispersion. In addition, these streaky LSMs are found to play a crucial role in pollutant dilution in the near field after the pollutant source, while the small-scale vortex packets are more efficient in transport in the mid-field and far-field.

Hierarchically structured passive radiative cooling ceramic with high solar reflectivity.

Passive radiative cooling using nanophotonic structures is limited by its high cost and poor compatibility with existing end uses, whereas polymeric photonic alternatives lack weather resistance and effective solar reflection. We developed a cellular ceramic that can achieve highly efficient light scattering and a near-perfect solar reflectivity of 99.6%. These qualities, coupled with high thermal emissivity, allow the ceramic to provide continuous subambient cooling in an outdoor setting with a cooling power of >130 watts per square meter at noon, demonstrating energy-saving potential on a worldwide scale. The color, weather resistance, mechanical robustness, and ability to depress the Leidenfrost effect are key features ensuring the durable and versatile nature of the cooling ceramic, thereby facilitating its commercialization in various applications, particularly building construction.

Evaluation of the drag force on single-walled carbon nanotubes in rarefied gases.

The drag force on carbon nanotubes (CNTs) in dilute gases has been previously derived. However, the drag force formulae involve collision integrals, which are complex functions of the gas-CNT interaction potential. The unavailability of the collision integrals and interaction potential makes the application of the theoretical drag force laws impossible. In this work, we develop a potential model for the interaction between a gas and single-walled CNT. The collision integrals are then calculated based on the potential and empirical expressions are proposed. Finally, the drag force is computed directly through molecular dynamics simulations and compared with the theoretical predictions.

All-weather thermochromic windows for synchronous solar and thermal radiation regulation.

Adaptive control of solar and thermal radiation through windows is of pivotal importance for building energy saving. However, such synchronous passive regulations are challenging to be integrated into one thermochromic window. Here, we develop a solar and thermal regulatory (STR) window by integrating poly(N-isopropylacrylamide) (pNIPAm) and silver nanowires (AgNWs) into pNIPAm/AgNW composites. A hitherto unexplored mechanism, originating from the temperature-triggered water capture and release due to pNIPAm phase transition, is exploited to achieve simultaneous regulations of solar transmission and thermal emission. The STR window shows excellent solar modulation (58.4%) and thermal modulation (57.1%) and demonstrates effective regulation of indoor temperatures during both daytime and nighttime. Compared to other thermochromic technologies, the STR window reduces heat loss in cold environment while promotes heat dissipation in hot conditions, achieving efficient energy saving in all weathers. This dual solar and thermal regulation mechanism may provide unidentified insights into the advancement of smart window technology.

Airborne infection risk of nearby passengers in a cabin environment and implications for infection control.

BACKGROUND: Expiratory droplets cause high infection risk to nearby passengers via airborne route. METHODS: We built a two-row four-seat setup to simulate a public transport cabin. A cough generator and a nebulizer were used to simulate the cough and talk processes respectively. Exposure and infection risk of nearby passengers was studied. The effect of gasper jet and backrest on risk mitigation was investigated. RESULTS: For the activity of coughing, the front passenger has much higher infection risk, which was around four times of that of other passengers, because of the concentration surge in the inhalation zone. For talking, the nearby passengers have similar infection risk because nearby passengers were all exposed to concentration surges with similar peak value. Gasper jet of the infected passenger and higher backrest can extinguish or reduce the concentration surge of front passengers and reduce the infection risk due to coughing and talking droplets. CONCLUSION: The passengers near the infected passenger have very high infection risk. The overhead gasper and a higher backrest can reduce the exposure and mitigate the risk of infection. It is believed that the control measures to protect nearby passengers are urgently needed in public transport cabins.

Localized Characteristics of the First Three Typical Condensation Frosting Stages in the Edge Region of a Horizontal Cold Plate.

Condensation frosting usually causes a negative influence on heat exchangers employed in engineering fields. As the relationships among the first three typical condensation frosting stages in the edge regions of cold plates are still unclear, an experimental study on the localized condensation frosting characteristics in the edge region of a cold plate was conducted. The edge effects on the water droplet condensation (WDC), water droplet frozen (WDF) and frost layer growth characteristics were quantitatively investigated. The results showed that the number of droplets coalescing in the edge-affected regions was around 50% greater than in the unaffected regions. At the end of the WDC stages, the area-average equivalent contact diameter and coverage area ratio of water droplets in the edge-affected regions were 2.69 times and 11.6% greater than those in the unaffected regions under natural convection, and the corresponding values were 2.24 times and 9.9% under forced convection. Compared with the unaffected regions, the WDF stage duration in the edge-affected regions decreased by 63.6% and 95.3% under natural and forced convection, respectively. Additionally, plate-type and feather-type frost crystals were, respectively, observed in natural and forced convection. The results of this study can help in the better understanding of the condensation frosting mechanism on a cold plate, which provides guidelines for optimizing the design of heat exchanger structures and system control strategies facing frosting problems.

Small Molecule Inhibitors of TET Dioxygenases: Bobcat339 Activity Is Mediated by Contaminating Copper(II).

Ten eleven translocation (TET) dioxygenases 1-3 are non-heme Fe(II) and α-ketoglutarate dependent enzymes that catalyze oxidation of 5-methylcytosine (5mC) in DNA to hydroxymethyl-C, formyl-C, and carboxy-C. This typically leads to gene activation and epigenetic remodeling. Most known inhibitors of TET are α-ketoglutarate mimics that may interfere with other α-ketoglutarate dependent enzymes. Recently, a novel cytosine-based inhibitor of TET, Bobcat339, was reported to have mid-µM inhibitory activity against TET1 and TET2. The molecule is now sold as a TET inhibitor by several vendors. We independently prepared Bobcat339 in our laboratory and observed that it had minimal inhibitory activity against human TET1 and TET2 via a quantitative LC-ESI-MS/MS assay. Furthermore, the inhibitory activity of commercial Bobcat339 preparations was directly correlated with Cu(II) content. We therefore conclude that Bobcat339 alone is not capable of inhibiting TET enzymes at the reported concentrations, and that its activity is enhanced by contaminating Cu(II).

A Solution-Processed Inorganic Emitter with High Spectral Selectivity for Efficient Subambient Radiative Cooling in Hot Humid Climates.

Daytime radiative cooling provides an eco-friendly solution to space cooling with zero energy consumption. Despite significant advances, most state-of-the-art radiative coolers show broadband infrared emission with low spectral selectivity, which limits their cooling temperatures, especially in hot humid regions. Here, an all-inorganic narrowband emitter comprising a solution-derived SiOx Ny layer sandwiched between a reflective substrate and a self-assembly monolayer of SiO2 microspheres is reported. It shows a high and diffusive solar reflectance (96.4%) and strong infrared-selective emittance (94.6%) with superior spectral selectivity (1.46). Remarkable subambient cooling of up to 5 °C in autumn and 2.5 °C in summer are achieved under high humidity without any solar shading or convection cover at noontime in a subtropical coastal city, Hong Kong. Owing to the all-inorganic hydrophobic structure, the emitter shows outstanding resistance to ultraviolet and water in long-term durability tests. The scalable-solution-based fabrication renders this stable high-performance emitter promising for large-scale deployment in various climates.