Transition state search is at the center of multiple types of computational chemical predictions related to mechanistic investigations, reactivity and regioselectivity predictions, and catalyst ...design. The process of finding transition states in practice is, however, a laborious multistep operation that requires significant user involvement. Here, we report a highly automated workflow designed to locate transition states for a given elementary reaction with minimal setup overhead. The only essential inputs required from the user are the structures of the separated reactants and products. The seamless workflow combining computational technologies from the fields of cheminformatics, molecular mechanics, and quantum chemistry automatically finds the most probable correspondence between the atoms in the reactants and the products, generates a transition state guess, launches a transition state search through a combined approach involving the relaxing string method and the quadratic synchronous transit, and finally validates the transition state via the analysis of the reactive chemical bonds and imaginary vibrational frequencies as well as by the intrinsic reaction coordinate method. Our approach does not target any specific reaction type, nor does it depend on training data; instead, it is meant to be of general applicability for a wide variety of reaction types. The workflow is highly flexible, permitting modifications such as a choice of accuracy, level of theory, basis set, or solvation treatment. Successfully located transition states can be used for setting up transition state guesses in related reactions, saving computational time and increasing the probability of success. The utility and performance of the method are demonstrated in applications to transition state searches in reactions typical for organic chemistry, medicinal chemistry, and homogeneous catalysis research. In particular, applications of our code to Michael additions, hydrogen abstractions, Diels–Alder cycloadditions, carbene insertions, and an enzyme reaction model involving a molybdenum complex are shown and discussed.
As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.
Zircon and rutile are common accessory minerals whose essential structural constituents, Zr, Ti, and Si can replace one another to a limited extent. Here we present the combined results of high ...pressure-temperature experiments and analyses of natural zircons and rutile crystals that reveal systematic changes with temperature in the uptake of Ti in zircon and Zr in rutile. Detailed calibrations of the temperature dependencies are presented as two geothermometers--Ti content of zircon and Zr content of rutile--that may find wide application in crustal petrology. Synthetic zircons were crystallized in the presence of rutile at 1-2 GPa and 1,025-1,450 degrees C from both silicate melts and hydrothermal solutions, and the resulting crystals were analyzed for Ti by electron microprobe (EMP). To augment and extend the experimental results, zircons hosted by five natural rocks of well-constrained but diverse origin (0.7-3 GPa; 580-1,070 degrees C) were analyzed for Ti, in most cases by ion microprobe (IMP). The combined experimental and natural results define a log-linear dependence of equilibrium Ti content (expressed in ppm by weight) upon reciprocal temperature: (formula omitted)In a strategy similar to that used for zircon, rutile crystals were grown in the presence of zircon and quartz (or hydrous silicic melt) at 1-1.4 GPa and 67-1,450 degrees C and analyzed for Zr by EMP. The experimental results were complemented by EMP analyses of rutile grains from six natural rocks of diverse origin spanning 0.35-3 GPa and 470-1,070 degrees C. The concentration of Zr (ppm by weight) in the synthetic and natural rutiles also varies in log-linear fashion with T -1: (formula omitted) The zircon and rutile calibrations are consistent with one another across both the synthetic and natural samples, and are relatively insensitive to changes in pressure, particularly in the case of Ti in zircon. Applied to natural zircons and rutiles of unknown provenance and/or growth conditions, the thermometers have the potential to return temperatures with an estimated uncertainty of +/- 10 degrees or better in the case of zircon and +/- 20 degrees or better in the case of rutile over most of the temperature range of interest (approximately 400-1,000 degrees C). Estimates of relative temperature or changes in temperature (e.g., from zoning profiles in a single mineral grain) made with these thermometers are subject to analytical uncertainty only, which can be better than +/- 5 degrees depending on Ti or Zr concentration (i.e., temperature), and also upon the analytical instrument (e.g., IMP or EMP) and operating conditions.PUBLICATION ABSTRACT
Quartz and rutile were synthesized from silica-saturated aqueous fluids between 5 and 20 kbar and from 700 to 940°C in a piston-cylinder apparatus to explore the potential pressure effect on Ti ...solubility in quartz. A systematic decrease in Ti-in-quartz solubility occurs between 5 and 20 kbar. Titanium K-edge X-ray absorption near-edge structure (XANES) measurements demonstrate that Ti
4+
substitutes for Si
4+
on fourfold tetrahedral sites in quartz at all conditions studied. Molecular dynamic simulations support XANES measurements and demonstrate that Ti incorporation onto fourfold sites is favored over interstitial solubility mechanisms. To account for the
P
–
T
dependence of Ti-in-quartz solubility, a least-squares method was used to fit Ti concentrations in quartz from all experiments to the simple expression
where
R
is the gas constant 8.3145 J/K,
T
is temperature in Kelvin,
is the mole fraction of TiO
2
in quartz and
is the activity of TiO
2
in the system. The
P
–
T
dependencies of Ti-in-quartz solubility can be used as a thermobarometer when used in combination with another thermobarometer in a coexisting mineral, an independent
P
or
T
estimate of quartz crystallization, or well-constrained phase equilibria. If temperature can be constrained within ±25°C, pressure can be constrained to approximately ±1.2 kbar. Alternatively, if pressure can be constrained to within ±1 kbar, then temperature can be constrained to approximately ±20°C.
•Well-aged Canadian wildfire aerosols observed in marine boundary layer over the Azores.•Dry intrusions accelerate the descent of wildfire aerosols into marine boundary layer.•Optical properties of ...aged wildfire aerosols suggest nearly complete loss of brown carbon.•Aged wildfire aerosols contribute efficiently to CCN population for marine low clouds.
Wildfire is a major source of biomass burning aerosols, which greatly impact Earth climate. Tree species in North America (NA) boreal forests can support high-intensity crown fires, resulting in elevated injection height and longer lifetime (on the order of months) of the wildfire aerosols. Given the long lifetime, the properties of aged NA wildfire aerosols are required to understand and quantify their effects on radiation and climate. Here we present comprehensive characterization of climatically relevant properties, including optical properties and cloud condensation nuclei (CCN) activities of aged NA wildfire aerosols, emitted from the record-breaking Canadian wildfires in August 2017. Despite the extreme injection height of ~12 km, some of the wildfire plumes descended into the marine boundary layer in the eastern North Atlantic over a period of ~2 weeks, owing to the dry intrusions behind mid-latitude cyclones. The aged wildfire aerosols have high single scattering albedos at 529 nm (ω529; 0.92–0.95) while low absorption Ångström exponents (Åabs) at 464 nm/648 nm (0.7–0.9). In comparison, Åabs of fresh/slightly aged ones are typically 1.4–3.5. This low Åabs indicates a nearly complete loss of brown carbon, likely due to bleaching and/or evaporation, during the long-range transport. The nearly complete loss suggests that on global average, direct radiative forcing of BrC may be minor. Combining Mie calculations and the measured aerosol hygroscopicity, volatility and size distributions, we show that the high ω529 and low Åabs values are best explained by an external mixture of non-absorbing organic particles and absorbing particles of large BC cores (>~110 nm diameter) with thick non-absorbing coatings. The accelerated descent of the wildfire plume also led to strong increase of CCN concentration at the supersaturation levels representative of marine low clouds. The hygroscopicity parameter, κCCN, of the aged wildfire aerosols varies from 0.2 to 0.4, substantially lower than that of background marine boundary layer aerosols. However, the high fraction of particles with large diameter (i.e., within accumulation size ranges, ~100–250 nm) compensates for the low values of κ, and as a result, the aged NA wildfire aerosols contribute more efficiently to CCN population. These results provide direct evidence that the long-range transported NA wildfires can strongly influence CCN concentration in remote marine boundary layer, therefore the radiative properties of marine low clouds. Given the expected increases of NA wildfire intensity and frequency and regular occurrence of dry intrusion following mid-latitude cyclones, the influence of NA wildfire aerosols on CCN and clouds in remote marine environment need to be further examined.
Several studies have reported the
P
–
T
dependencies of Ti-in-quartz solubility, and there is close agreement among three of the four experimental calibrations. New experiments were conducted in the ...present study to identify potential experimental disequilibrium, and to determine which Ti-in-quartz solubility calibration is most accurate. Crystals of quartz, rutile and zircon were grown from SiO
2
-, TiO
2
-, and ZrSiO
4
-saturated aqueous fluids in an initial synthesis experiment at 925 °C and 10 kbar in a piston-cylinder apparatus. A range of quartz crystal sizes was produced in this experiment; both large and small examples were analyzed by electron microprobe to determine whether Ti concentrations are correlated with crystal size. Cathodoluminescence images and EPMA measurements show that intercrystalline and intracrystalline variations in Ti concentrations are remarkably small regardless of crystal size. The average Ti-in-quartz concentration from the synthesis experiment is 392 ± 1 ppmw Ti, which is within 95 % confidence interval of data from the 10 kbar isobar of Wark and Watson (Contrib Mineral Petrol 152:743–754,
2006
) and Thomas et al. (Contrib Mineral Petrol 160:743–759,
2010
). As a cross-check on the Ti-in-quartz calibration, we also measured the concentration of Zr in rutile from the synthesis experiment. The average Zr-in-rutile concentration is 4337 ± 32 ppmw Zr, which is also within the 95 % confidence interval of the Zr-in-rutile solubility calibration of Ferry and Watson (Contrib Mineral Petrol 154:429–437,
2007
). The
P
–
T
dependencies of Ti solubility in quartz and Zr solubility in rutile were applied as a thermobarometer to the experimental sample. The average Ti-in-quartz isopleth calculated from the calibration of Thomas et al. (Contrib Mineral Petrol 160:743–759,
2010
) and the average Zr-in-rutile isopleth calculated from the calibration of Tomkins et al. (J Metamorph Geol 25:703–713,
2007
) cross at 9.5 kbar and 920 °C, which is in excellent agreement with the
P
–
T
conditions of the synthesis experiment. Separates of the high-Ti quartz from the initial synthesis experiment described above were used as starting material in subsequent experiments at 20 kbar, at which pressure the solubility of Ti in quartz is expected to be significantly lower in the recrystallized quartz. These recrystallization experiments were conducted under wet and dry conditions at 925 °C, and under wet conditions at 850 °C. Both wet and dry recrystallization experiments produced polycrystalline quartzites. Rutile occurs as inclusions in quartz, and as individual crystals dispersed along quartz grain boundaries. Quartz that grew during the recrystallization experiments has dark cathodoluminescence indicating substantially lower Ti concentrations. The average Ti concentrations in quartz from the recrystallization experiments are within the 95 % confidence interval of a linear fit to the 20 kbar data of Thomas et al. (Contrib Mineral Petrol 160:743–759,
2010
). Collectively, the results from the synthesis and recrystallization experiments confirm that the Ti-in-quartz concentrations used to calibrate the
P
–
T
dependencies of Ti-in-quartz solubility in Thomas et al.’s (Contrib Mineral Petrol 160:743–759,
2010
) calibration represent the equilibrium concentrations of Ti in quartz.
Isoprene photochemistry over the Amazon rainforest Liu, Yingjun; Brito, Joel; Dorris, Matthew R. ...
Proceedings of the National Academy of Sciences - PNAS,
05/2016, Letnik:
113, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Isoprene photooxidation is a major driver of atmospheric chemistry over forested regions. Isoprene reacts with hydroxyl radicals (OH) and molecular oxygen to produce isoprene peroxy radicals ...(ISOPOO). These radicals can react with hydroperoxyl radicals (HO₂) to dominantly produce hydroxyhydroperoxides (ISOPOOH). They can also react with nitric oxide (NO) to largely produce methyl vinyl ketone (MVK) and methacrolein (MACR). Unimolecular isomerization and bimolecular reactions with organic peroxy radicals are also possible. There is uncertainty about the relative importance of each of these pathways in the atmosphere and possible changes because of anthropogenic pollution. Herein, measurements of ISOPOOH and MVK + MACR concentrations are reported over the central region of the Amazon basin during the wet season. The research site, downwind of an urban region, intercepted both background and polluted air masses during the GoAmazon2014/5 Experiment. Under background conditions, the confidence interval for the ratio of the ISOPOOH concentration to that of MVK + MACR spanned 0.4–0.6. This result implies a ratio of the reaction rate of ISOPOO with HO₂ to that with NO of approximately unity. A value of unity is significantly smaller than simulated at present by global chemical transport models for this important, nominally low-NO, forested region of Earth. Under polluted conditions, when the concentrations of reactive nitrogen compounds were high (>1 ppb), ISOPOOH concentrations dropped below the instrumental detection limit (<60 ppt). This abrupt shift in isoprene photooxidation, sparked by human activities, speaks to ongoing and possible future changes in the photochemistry active over the Amazon rainforest.
The radiative impact of organic aerosols (OA) is a large source of uncertainty in estimating the global direct radiative effect (DRE) of aerosols. This radiative impact includes not only light ...scattering but also light absorption from a subclass of OA referred to as brown carbon (BrC). However, the absorption properties of BrC are poorly understood, leading to large uncertainties in modeling studies. To obtain observational constraints from measurements, a simple absorption Ångström exponent (AAE) method is often used to separate the contribution of BrC absorption from that of black carbon (BC). However, this attribution method is based on assumptions regarding the spectral dependence of BC that are often violated in the ambient atmosphere. Here we develop a new AAE method which improves upon previous approaches by using the information from the wavelength-dependent measurements themselves and by allowing for an atmospherically relevant range of BC properties, rather than fixing these at a single assumed value. We note that constraints on BC optical properties and mixing state would help further improve this method. We apply this method to multiwavelength absorption aerosol optical depth (AAOD) measurements at AERONET sites worldwide and surface aerosol absorption measurements at multiple ambient sites. We estimate that BrC globally contributes up to 40 % of the seasonally averaged absorption at 440 nm. We find that the mass absorption coefficient of OA (OA-MAC) is positively correlated with the BC ∕ OA mass ratio. Based on the variability in BC properties and BC ∕ OA emission ratio, we estimate a range of 0.05–1.5 m2 g−1 for OA-MAC at 440 nm. Using the combination of AERONET and OMI UV absorption observations we estimate that the AAE388∕440 nm for BrC is generally ∼ 4 worldwide, with a smaller value in Europe (< 2). Our analyses of observations at two surface sites (Cape Cod, to the southeast of Boston, and the GoAmazon2014/5 T3 site, to the west of Manaus, Brazil) reveal no significant relationship between BrC absorptivity and photochemical aging in urban-influenced conditions. However, the absorption of BrC measured during the biomass burning season near Manaus is found to decrease with photochemical aging with a lifetime of ∼ 1 day. This lifetime is comparable to previous observations within a biomass burning plume but much slower than estimated from laboratory studies. Given the large uncertainties associated with AERONET retrievals of AAOD, the most challenging aspect of our analysis is that an accurate, globally distributed, multiple-wavelength aerosol absorption measurement dataset is unavailable at present. Thus, achieving a better understanding of the properties, evolution, and impacts of global BrC will rely on the future deployment of accurate multiple-wavelength absorption measurements to which AAE methods, such as the approach developed here, can be applied.
Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The ...underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.
An understanding of the effects of climate on fuel is required to predict future changes to fire. We explored the climatic determinants of variations in surface fine fuel parameters across forests ...(dry and wet sclerophyll plus rainforest) and grassy woodlands of south‐eastern Australia. Influences of vegetation type and climate on fuel were examined through statistical modelling for estimates of litterfall, decomposition and steady state fine litter fuel load obtained from published studies. Strong relationships were found between climate, vegetation type and all three litter parameters. Litterfall was positively related to mean annual rainfall and mean annual temperature across all vegetation types. Decomposition was both negatively and positively related to mean annual temperature at low and high levels of warm‐season rainfall respectively. Steady state surface fine fuel load was generally, negatively related to mean annual temperature but mean annual rainfall had divergent effects dependent on vegetation type: i.e. positive effect in low productivity dry sclerophyll forests and grassy woodlands versus negative effect in high productivity wet sclerophyll forests and rainforests. The species composition of the vegetation types may have influenced decomposition and steady state fuel load responses in interaction with climate: e.g. lower decomposition rates in the low productivity vegetation types that occupied drier environments may be partially due to the predominance of species with sclerophyllous leaves. The results indicate that uncertain and highly variable future trends in precipitation may have a crucial role in determining the magnitude and direction of change in surface fine fuel load across south‐eastern Australia.
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