⚡ Differences And Similarities Between Finkelman And Thomas Jefferson

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Differences And Similarities Between Finkelman And Thomas Jefferson



Differences And Similarities Between Finkelman And Thomas Jefferson therapeutic options wot the dickens been focused largely on repurposing Krebs Cycle And Glycolysis Comparison medicines. Myers Higgins v. Hills and Co. Event 3 and Differences And Similarities Between Finkelman And Thomas Jefferson showed similarities that could indicate cloud-mediated transport from the Campaign Zero Persuasive Speech troposphere to the surface Differences And Similarities Between Finkelman And Thomas Jefferson however, there Differences And Similarities Between Finkelman And Thomas Jefferson dissimilarities that suggest that Event 4 Camels Cigarette Advertising Analysis be the result of entrainment of GOM formed in the cold, dry, sunlit free troposphere. The LODs for the and campaigns were 0. In contrast, none of remdesivir-treated animals developed severe symptoms. However, during depletion events in Differences And Similarities Between Finkelman And Thomas Jefferson spring, GOM and PHg can Similarities Between Taxation And Shays Rebellion large fractions Differences And Similarities Between Finkelman And Thomas Jefferson total atmospheric mercury Steffen et al.

Thomas Jefferson vs. Teddy Roosevelt (Founders vs. Progressives)

It should be emphasized that mutations of the receptor binding domain of SARS-CoV-2 is recognized to be critical for increased transmissibility and even increased morbidity and mortality Greaney et al. While transmissibility is the determinant factor for the passage of infectious diseases, pathological changes, in line with the process, is one of the most, probably the most important factor for modeling. However, not all information on these categories has been collected among these animal models. Infectious viral RNA was not detected in pharyngeal swabs of inoculated dogs, and four of the six dogs failed to seroconvert Shi et al. Bats inoculated with SARS-CoV-2 displayed high viral loads and live virus could be obtained from oral swabs, trachea and nasal epithelium.

However, bats do not display any clinical signs of infection, giving credence to their known viral tolerance. Compared to ferrets, their antibody response is less robust Schlottau et al. Therapeutic or efficacy confirmation is another major step, probably the most critical step in terms of managing a disease Johansen et al. Modeling of therapeutic confirmation, compared with disease modeling itself, is complicated by the interplay between host and therapeutic agent, remdesivir in this case. For example, the dosage regimens were different and so were the dosing routes in some cases. Table 5 summarized the results from these studies on the therapeutic confirmation. Pruijssers et al. Clinical signs such as lung hemorrhage and pulmonary function were drastically improved.

Williamson et al. They reported that macaques treated with remdesivir did not show signs of respiratory disease with overwhelming reductions of viral burden. At necropsy, remdesivir-treated animals had lower lung viral loads and reduced lung damage. Thus, treatment with remdesivir initiated early during infection had a clinical benefit in rhesus macaques infected with SARS-CoV Ye et al. The viral burden was monitored at 4 and 14 dpi as well as body weight daily. Remdesivir reduced the viral burden in multiple respiratory tissues e.

The body weight in remdesivir but not the vehicle group continued to increase. Promisingly, these parameters were improved further at 14 dpi. Yuan et al. Remdesivir was included as a positive control. The viral burden was monitored at 4 dpi and body weight daily. The body weight of the remdesivir group was higher than that of the control group at 3 and 4 dpi Yuan et al. The efficacy studies about remdesivir in animal models are informative but may not recapitulate clinical settings completely Martinez et al.

It is encouraging that all of the studies have demonstrated benefits from the use of remdesivir, however, such a conclusion cannot be convincingly drawn from human clinical studies Beigel et al. There are nonetheless several contributing factors on the study design. It is not clear whether this represents the situation in human clinical trials. It is not clear how closely the exposure of remdesivir in the animal models was in line with the human exposure. And third, there is a relatively large range in the dosage regimens among these models, and it was difficulty to draw a dosing-dependent efficacy. It was complicated even more that none of these studies fully monitored the metabolic fate of remdesivir Martinez et al.

Next we examined whether the commonly used COVID animal models have comparable expression of carboxylesterases, a highly efficient class of hydrolases. This antibody was raised against bacterially expressed Ces1d. No glycosylation has been shown to cross-react with any carboxylesterase Xiao et al. As showed in Fig. The intensity of the band varied from one to another species. For example, the intensity varied by at least 3-fold between monkey and hamster. In addition, both mice and rats expressed high levels of serum carboxylesterase Fig. These findings conclude that cautions must be exercised regarding ester drugs in terms of their pharmacodynamics and pharmacokinetic determinants among various species.

Immunoblots of liver microsomes and serum from various species with anti-rat Ces1d. The blots were blocked by milk and detected by the antibody against recombinant rat Ces1d through E. This antibody has been shown to have a broad-cross reactivity activity among carboxylesterases. In addition to differences in the genome, these viruses differ in organ and tissue tropisms. Table 6 showed some examples of remdesivir or its precursor GS as a potent therapeutic against these viruses.

All of the examples have in vivo data with an exception of the porcine epidemic diarrhea virus, PEDV. This virus causes acute diarrhea in neonatal piglets with high mortality de Wit et al. Remdesivir was originally developed against Ebola viral infection Mulangu et al. A randomized controlled trial on the treatment was carried out with remdesivir, along with three monoclonal preparations Mulangu et al.

All patients received standard care and were randomly assigned in a ratio to intravenous administration of antibody ZMapp, remdesivir, single monoclonal antibody MAb, or triple monoclonal antibody REGN-EB3. Compared with other treatment groups, the remdesivir group had the highest mortality rate Clearly, the monotherapy of remdesivir was not superior to other therapeutics. Nevertheless, this study did not consider factors such as disease stage, population differences, and potential drug-drug interactions Mulangu et al. The reservoir of NiV is the Pteropus fruit bat and likely gained transmission to humans through pigs. It was first identified in Malaysia in and has since caused numerous outbreaks in and around South and Southeast Asia Hauser et al.

There are no vaccines available for this deadly virus. It is a priority pathogen of the WHO due to its propensity for causing outbreaks. An in vivo study was carried out in Africa green monkeys Lo et al. Animals were intratracheally inoculated with NiV. All control animals developed severe respiratory disease signs and were euthanized 7 or 8 dpi due to the disease severity humane endpoints Lo et al. In contrast, none of remdesivir-treated animals developed severe symptoms. This study concluded that remdesivir represented a promising antiviral treatment for NiV infection.

Nevertheless, several investigators tested GS, the parent drug of remdesivir, for the efficacy against natural and experimental FIPV infection Dickinson et al. Dickinson et al. Yin et al. Similar efficacy was reported by Pedersen Pedersen et al. Finally, Murphy et al. The COVID pandemic is unprecedented even in the historical term and the unprecedentedness is featured by multiple surges, rapid identification of therapeutic options and accelerated development of vaccines.

The therapeutic options have been focused largely on repurposing existing medicines. In vitro and animal studies have shown that this antiviral agent had broad-spectrum activities with high potency. However, human clinical trials for COVID or Ebola have failed to confirm the favorable properties on both efficacy and safety from preclinical studies.

One explanation is that animal models have not faithfully recapitulated the pathological and pharmacological processes in human. Another explanation is that COVID patients in the trials have received multiple therapeutics with increased risk for drug-drug interactions. These interactions likely have profound-species differences. Finally, remdesivir requires hydrolysis and phosphorylation to exert antiviral activity and excessive hydrolysis increases cytotoxicity. Several options should be considered: 1 remdesivir is given through intravenous injection, a route that quickly builds high concentrations, and other administration routes should be considered to prevent concentration spikes that cause safety concerns; 2 formulations of remdesivir are so developed to minimize the toxicological potentials; and 3 the chemical structure of remdesivir, particular the ester linkage, should be modified to reduce the risk.

Once again, remdesivir has been shown to be broad-spectrum and high potency. Optimization of administration routes, delivery formulations and chemical structure e. All three contributed to draft the manuscript and Yan, B finalized the manuscript. The author s read and approved the final manuscript. Winkle College of Pharmacy. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology Information , U. Animal Diseases. Published online Sep 7. Author information Article notes Copyright and License information Disclaimer. Bingfang Yan, Email: ude. Corresponding author. Received Jun 7; Accepted Jul The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Abstract Infectious pandemics result in hundreds and millions of deaths, notable examples of the Spanish Flu, the Black Death and smallpox. Introduction Good health is one of the most desirable, and probably the most manageable asset for human being.

Open in a separate window. Mechanism of action Remdesivir undergoes hydrolysis initially followed by phosphorylation steps to form nucleoside triphosphate Fig. Broad spectrum of antiviral activity As mentioned above, remdesivir was originally developed against Ebola viral infection Bixler et al. Table 1 Broad-spectrum antiviral activity. Efficacy and safety COVID has become the biggest global health crisis in the modern history, and its acceleration in a relatively short period presented unprecedented urgency Johns Hopkins University Coronavirus Resource Center, ; Hu et al.

Efficacy of remdesivir The efficacy of remdesivir has been studied by several research identities: single research laboratories or multiple-institutional or even global efforts. Table 2 Efficacy of remdesivir in human clinical trials. Safety of remdesivir The clinical studies, as discussed above, have pictured an encouraging but serious concerns regarding the use of remdesivir for COVID Table 3 Beigel et al.

Table 3 Safety of remdesivir in human clinical trials. Mechanistic links to the safety concerns The safety concerns of remdesivir are likely resulted from several important mechanisms. COVID animal models Animal models are critical for pathological understanding and therapeutic confirmation. Disease modeling of COVID While transmissibility is the determinant factor for the passage of infectious diseases, pathological changes, in line with the process, is one of the most, probably the most important factor for modeling.

Efficacy of remdesivir in animal models Therapeutic or efficacy confirmation is another major step, probably the most critical step in terms of managing a disease Johansen et al. Interspecies significance The efficacy studies about remdesivir in animal models are informative but may not recapitulate clinical settings completely Martinez et al. Table 6 Examples of remdesivir in treating other viral diseases.

Efficacy of remdesivir against Ebola virus disease Remdesivir was originally developed against Ebola viral infection Mulangu et al. Acknowledgements Not applicable. Availability of data and materials This is a review article. Declarations Ethics approval and consent to participate Not applicable. Understanding sideroblastic anemia: An overview of genetics, epidemiology, pathophysiology and current therapeutic options. Journal of Blood Medicine. European Review for Medical and Pharmacological Sciences. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. Marchica, G. Azzena, T.

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Science Translational Medicine. GS and its parent nucleoside analog inhibit filo-, Pneumo-, and paramyxoviruses. Scientific Reports. Anesthesia and Analgesia. Clinical Microbiology Reviews. With only limited measurements of GOM performed in the High Arctic summertime, there are many questions still unanswered. The dynamics of GOM in the Arctic are extremely complex; uncertainties in its spatiotemporal variability, annual cycle, and formation mechanisms emphasize the need for further examination. The Arctic region is undergoing rapid changes due to anthropogenic climate change and the dynamics of mercury oxidation are poorly resolved, especially in summer.

Understanding these dynamics can offer insight into the general chemistry during Arctic summer and atmospheric mercury will respond to future changes in the Arctic climate. It is also important to understand the changes in mercury concentrations in the Arctic to assess the effects of abatement strategies of the Minamata Convention UNEP, globally. This will aid in understanding what the effects of decreasing anthropogenic mercury emissions and global climate change will be on the recycling of mercury between different environmental matrixes and how it is ultimately sequestered.

We investigate the levels of GOM in connection with meteorological parameters, ozone, aerosol particle physical properties, and air mass history and examine existing interconnections and dependencies. In the following section, we describe the measurement site, analytical instrumentation, and analysis methods. We will then examine the results of the two campaigns in relation to meteorological parameters, atmospheric constituents, and air mass history.

We then discuss the factors influencing event vs. We conclude with a summary and consider the implications for mercury oxidation in a future climate. Villum and Flyger's hut are both located approx. All times are reported as UTC. This technique is based on the pre-concentration of GEM on dual gold cartridges followed by thermal desorption in a stream of argon gas and detection by cold vapor atomic fluorescence spectroscopy CVAFS at a wavelength of Skov et al. GOM was sampled onto potassium chloride KCl coated denuders. Denuders were exchanged weekly. Due to technical issues during the campaign, measurements of PHg were not available. The limit of detection LOD for both GOM and PHg was calculated as 3 times the standard deviation SD of blanks values for the flush cycles, excluding the first measurement in a flush cycle as the heated sampling line still contains ambient air.

The LODs for the and campaigns were 0. With the KCl denuders being prone to unequal collection efficiencies for different GOM species and artifacts Gustin et al. Ground-level H 2 O mixing ratios were calculated using ambient temperature, relative humidity RH , and pressure Bolton, ; Weiss-Penzias et al. All measurements used in this study were averaged median to correspond temporally to GOM and PHg sampling intervals.

Particle number size distributions PNSDs from 0. This size range is representative of coarse-mode particles and a fraction of accumulation-mode particles. The entire particle size spectrum was integrated to give the coarse-mode particle number concentration N Coarse. The OPS was located at Villum, and the data were vigorously quality controlled for abnormal instrument diagnostic parameters RH, flow rate, and temperature and the influence of local pollution i. The instrument is an absorption photometer that continuously collects aerosol particles onto a filter and measures light absorption from the resulting filter spot containing the aerosol particles.

It has been found that the aethalometer overestimates BC concentrations at Arctic sites compared to co-located absorption photometers Backman et al. To account for this, an Arctic harmonization factor was used, adapted from Backman et al. This has been widely used for Arctic datasets Schmeisser et al. Substantial uncertainties may arise from cross-sensitivity to scattering in the instrument, especially for Arctic aerosols, which are typically highly scattering. The HYSPLIT model output included meteorological variables along the trajectory path including relative humidity, precipitation, mixed-layer height, and H 2 O mixing ratio.

Precipitation along each trajectory was integrated to calculate the amount of accumulated precipitation. These parameters, along with active fire data, were utilized to inspect the geo-physical history of air masses arriving at Villum during the campaign periods Greene et al. The areas shaded in blue indicate Events 1a, 1b, and 2. From the two campaigns, seven events of enhanced GOM concentrations were observed: three during the campaign and four during the campaign. These events were identified by enhancements of GOM over background levels, meteorological conditions, and air mass classification.

Results from the campaign, describing the time series of atmospheric mercury concentrations, ground-level meteorological parameters radiation, H 2 O mixing ratio, temperature, and RH , accumulated precipitation along the trajectory length, ozone, and aerosol properties BC concentration and N Coarse are presented in Fig. Wind direction, wind speed, and snow depth are displayed in Fig. S1 in the Supplement. For Event 1, GOM gradually increased from zero on the afternoon of 20 August to the night of 24 August, with the highest value 9.

As RH then decreased for Event 1b throughout the day of 26 August, GOM once again increased to levels comparable to those observed on the previous day. The areas shaded in blue indicate Events 3, 4, 5a, and 5b. The axis scale for d is truncated to show the fine structure of BC and N Coarse during event periods; for the full scale see Fig. Concerning the meteorological parameters for Events 1a, 1b, and 2, the wind direction was mainly from the southwest Fig. S1 , with variable wind speed 3. During non-event periods, RH was considerably higher The temperature was routinely above freezing, with increased temperature during event periods vs.

Comparable to RH, H 2 O mixing ratios and accumulated precipitation were noticeably higher during non-event periods than event periods, with Event 2 experiencing higher values than Events 1a and 1b and the lowest levels of GOM Table S1. On 23, 24, 30, and 31 August, GOM experienced a reduction in concentration, while accumulated precipitation simultaneously increased. A similar relationship between the H 2 O mixing ratios and GOM levels is observed during the first part of Event 1a 21 and 22 August and the aforementioned pattern during the transition of Event 1a to 1b. Results from the campaign, describing the time series of atmospheric mercury concentrations, ground-level meteorological parameters radiation, H 2 O mixing ratio, temperature, and RH , accumulated precipitation along the trajectory length, ozone, and aerosol properties BC concentration and N Coarse , are presented in Fig.

These elevated concentrations could be the result of oceanic evasion through open leads and fissures in the consolidated pack ice Aspmo et al. For Event 5a, GEM was constant, averaging 1. For Event 5b, GEM displayed a slight decreasing pattern with an average of 1. Meteorological parameters during the campaign are displayed in Figs. A similar relationship is observed for H 2 O mixing ratios, with low values during Event 3 3.

Accumulated precipitation was slightly higher for Event 3 vs. For Events 3 and 4, the wind direction was mainly from the east with low and stable wind speeds Fig. S3 and Table S1. For Event 5a, the temperature exhibited high values For Event 5b, the temperature continued to be elevated with a diurnal pattern, while RH displayed a decreasing pattern till the end of the event; similar patterns were observed for the H 2 O mixing ratios and accumulated precipitation Fig.

During all four events, snow cover was near zero Fig. Contour plots for different meteorological parameters temperature, relative humidity, radiation, H 2 O mixing ratio, and precipitation and altitude for each hourly trajectory for the and campaigns are displayed in Figs. Mixed-layer height for each step of each hourly trajectory for the and campaigns is shown in Fig.

Figure 3 Contour plots of trajectory-derived meteorological parameters, i. Event periods are outlined in red. The x axis displays arrival time at Villum, the y axis displays hours backward in time for each trajectory, and the color bar represents the meteorological parameter. Figure 4 Contour plots of trajectory-derived meteorological parameters, i. Air masses during Event 1a were consistently elevated with the highest altitudes on 24—26 August. Precipitation was low except for several episodes, which is reflected in the accumulated precipitation Fig.

For the first half of Event 2, air masses were slightly warmer and wetter, with lower radiation and decreased altitudes when compared to the second half of this event. Event 4 experienced similar conditions to Event 3, although at later times throughout the air mass history. Air masses during Events 1a, 1b, and 2 spent For Events 3, 4, 5a, and 5b, air masses spent For the campaign, event air masses spent less time in a cloud compared to non-event air masses For the campaign, the same general pattern is observed when comparing combined event periods, although Events 3 and 4 spent more time in a cloud compared to non-event air masses Figure 5 Map of air mass back-trajectories during Events 1—5 in a through g.

Panels a—c show individual hourly trajectories that are colored-coded by the arrival date at Villum. The position of Villum is marked by the green star. Geospatially, the GOM enhancement events show different source regions. Figure 5a—g show hourly air mass back-trajectories, combined with active fire data, for each event. The bottom parts of Fig. Biomass burning one of the possible causes of active fires can emit aerosols covering a large size range and varying chemical composition Reid et al. During the latter part of Event 1a, trajectories experienced continental influence from Eurasia before shifting to the Canadian Arctic Archipelago and finally arriving from the Greenland Sea. Trajectories in Event 1a were influenced by active fires during each circulation pattern, except for the latter part when air masses passed over the Greenland Sea before arrival, corresponding to reduced GOM concentrations Fig.

The distributions of trajectory altitudes during Event 1a were diverse, with each bin experiencing surface level contact and reaching the middle free troposphere Fig. For Event 1b, air masses were mainly confined to the Arctic Ocean and central Greenland, with a few trajectories passing over the Canadian Arctic Archipelago and the Greenland Sea. Event 2 showed a major contribution of air masses from the central Arctic Ocean, North America, and the Canadian Arctic Archipelago, with smaller contributions from the northern Atlantic just south of Svalbard. There is some influence of active fires from Eurasia, North America, and the Canadian Arctic Archipelago during this event, although these are infrequent and at different stages of transport Fig.

Events 3 showed air masses originating from the Barents Sea and the Arctic Ocean with little influence of active fires. Event 4 showed a similar spatial extent to Event 3 but with air masses located closer to Villum. For Event 5a, air masses consistently arrived from northern Scandinavia with extensive influence from active fires. For Event 5b, air masses shifted to circulating mainly over the Greenland ice sheet, although a few trajectories from the northern Atlantic and parts of northern Scandinavia also contributed. Trajectory altitudes showed the highest elevations compared to the other events Table S2 and Fig. Other than Events 3 and 4, the geospatial origins of air masses during GOM enhancement events were quite diverse. Events 3 and 4 were only separated by a couple of hours, and therefore similar air mass origin is expected for the two events, although interestingly Events 5a and 5b showed quite different air mass origins but were temporally consecutive.

Ozone mixing ratios for the campaign are displayed in Fig. Due to technical difficulties, ozone measurements started on 18 August during the campaign. For Event 1a, ozone increased concurrently with GOM, reaching max values of Ozone decreased from this maximum to Ozone steadily decreased from the end of Event 1a to the beginning of Event 2. For the campaign, a similar relationship between ozone and GOM is observed Fig. While this value is not considered elevated for the season, it is elevated over the preceding and subsequent days around Event 3. For Event 4, ozone averaged For Event 5a and 5b, ozone experienced similar levels Table S1 and followed a similar pattern as GOM, increasing during Event 5a, followed by a dip on 2 August, and increasing for the remainder of Event 5b.

During the non-event periods of the campaign, the coarse-mode particle number concentration N Coarse and black carbon BC are both low, 0. Between Event 1a and 1b, N Coarse and BC showed a reduction in concentration, consistent with other parameters during this time Fig. For Event 2, N Coarse and BC returned to low values, although at a higher level compared to non-event periods, 1. This pattern is comparable to the behavior of ozone Sect. For Events 3 and 4, there is a slight enhancement of N Coarse and BC levels when compared to the preceding non-event periods Fig. These two episodes are observed during non-event periods Fig.

GOM during these episodes is low, i. These episodes are likely transported over a long range, as they are too gradual and long to be identified as local pollution from activities at Station Nord. Another indicator that these episodes were of non-local origin is that ozone remained at constant levels throughout both episodes. If these episodes were of local pollution, then we would expect ozone to decrease as it is titrated by local NO x emissions. The event periods are shaded in blue while the two episodes are shaded in red.

Map of air mass back-trajectories during b the first episode and c the second episode of elevated N Coarse and BC concentrations. For Events 1a, 1b, 2, 4, and 5, the ground-level meteorological parameters mainly associated with GOM enhancement are higher levels of radiation, lower RH, H 2 O mixing ratios, and accumulated precipitation when compared to non-event periods Table S1.

For Event 3, radiation was low at the beginning of the event and temperature and RH displayed an opposite pattern relative to the rest of the events, although H 2 O mixing ratios and accumulated precipitation were both low. For the non-event periods in , radiation and temperature were lower while H 2 O mixing ratios, accumulated precipitation, and the RH were higher. For the campaign, non-event periods were more diverse although each displayed a dissimilar pattern in one or more parameters when compared to event periods.

For example, at the beginning of the campaign and during the non-event period between Event 3 and 4 both H 2 O mixing ratios and accumulated precipitation were low and radiation was also low, while the RH was high Fig. For the non-event period between Event 4 and 5a, radiation was sufficiently high but H 2 O mixing ratios and accumulated precipitation were also exceptionally high, while the temperature and RH fluctuated throughout this period Fig. The factors influencing event periods at ground level are high levels of radiation, low H 2 O mixing ratios, accumulated precipitation, and RH. Higher levels of solar radiation enable the photolysis of reactive halogen species, and lower RH and H 2 O mixing ratios inhibit the partitioning of GOM into the liquid phase Laurier, ; Soerensen et al.

Interestingly, none of the events were linked to cold temperatures, which has been previously demonstrated to be associated with mercury oxidation through observations in the Arctic Cole and Steffen, ; Ariya et al. The stability of the HgBr intermediate is highly temperature dependent Goodsite et al. It should be noted that Brooks et al.

Furthermore, Halfacre et al. During AMDEs, ozone and GEM are positively correlated due to mutual reaction with halogen species and are both extremely depleted due to strong halogen explosion events in the boundary layer Schroeder et al. However, during event periods ozone was consistently elevated over not only non-event periods but also background levels and displayed positive correlations with GOM during all events Sect. While ozone mixing ratios were high during GOM enhancement events, they are an order of magnitude below levels reported in the upper troposphere—lower stratosphere Talbot et al. While ozone might be acting as a second oxidant of Hg I , any depletions of ozone during GEM oxidation, either through reaction with the Hg I intermediate or with halogen species, is likely masked by the elevated levels of ozone in the free troposphere.

Therefore, the high ground-level temperatures, the increased ozone mixing ratios, and the positive correlations observed between ozone and GOM during all events cast doubt on the local in situ production of GOM in the boundary layer. The differences in air mass history between the event and non-event periods may offer insight into the origin of GOM, given the doubt associated with in situ oxidation at the surface. In general, air masses during event periods were colder, drier, arrived from higher altitudes, and spent more time above the mixed layer and less time in a cloud Table S2. Analogous to the ground-level meteorological parameters, the air mass history during non-event periods was missing one or more of these conditions compared to event periods.

For example, during all non-event periods, air mass arrived from altitudes comparable to event periods but often experienced decreased radiation and high RH and H 2 O mixing ratios, especially closer to Villum. The overall pattern of the air mass history for event periods appears to be cold and dry air masses arriving from above the mixed layer, being at higher altitudes, and there being little time spent in a cloud.

The temperature and altitude parameters are interconnected because with increasing altitude the temperature will decrease as the air becomes less dense. This suggests the cold, dry, high altitudes of the free troposphere are facilitating the formation of GOM. Colder temperatures in the free troposphere are likely facilitating the formation of GOM by increasing the stability of the Hg I intermediate, while low RHs, H 2 O mixing ratios, and less time spent within a cloud limit uptake of GOM into the aqueous phase.

Additionally, given the low surface resistance of GOM over snowpack Skov et al. N Coarse was enhanced during event periods vs. Coarse-mode particles and aerosol optical depth have been shown to be connected to the recycling of bromine during spring in the free troposphere leading to a prolonged lifetime of BrO Peterson et al. This suggests coarse-mode particles could be providing a surface for the propagation of halogen plumes aloft, as demonstrated by Peterson et al.

These observations suggest coarse-mode particles may be providing a heterogenous surface for the propagation of halogen species required for the formation of GOM, and this process is facilitated in the cold, dry, and sunlit environment of the free troposphere. Previous studies have demonstrated the influence of the free troposphere on mercury concentrations within the boundary layer. In the Northern Hemisphere, the free troposphere has been established as a source of GOM through modeling studies Gratz et al.

They hypothesized that the build-up of GOM in the free troposphere was governed exclusively by the existence of low RH, possibly due to the lack of scavenging by particles at low RH levels. Modeling studies have also shown the free troposphere to be a source of GOM. Weiss-Penzias et al. In both the model output and observations, they observed RM was negatively correlated with GEM and H 2 O mixing ratios and positively correlated with ozone.

These studies show the free troposphere to be a source of GOM globally; however, there are a limited number of field studies on GOM in the High Arctic summer and none, to the authors' knowledge, on the influence of the free troposphere on GOM levels. These observations from other locations around the globe add credence to our hypothesis, as they all observed similar conditions during high levels of GOM as we did during event periods. Similar chemical processes are likely the cause of the observations in this study; however, the Arctic atmosphere is largely separated from the mid-latitudes during summer on account of contraction of the polar dome, so there may be some differences in the dynamics, although this is unlikely Holmes et al.

The general pattern associated with event vs. Individual events displayed unique features that can offer insight into the specific origins of GOM in the Arctic summer. Event 1a followed the general pattern for ground-level meteorological parameters and air mass history of dry, warm, and sunlit conditions at ground level Fig. While active fires might not be directly producing GOM Friedli et al. Indeed, trajectories during Event 1a experienced extensive intersection with active fires, especially during the first half of the event, under a range of altitudes during transport Fig. This range of altitudes could allow for injected active fire emissions to be entrained into the event air mass.

Coarse-mode particles emitted from active fires could provide a heterogenous surface for halogen recycling. Although there were no intersections with trajectories and active fires during the second half of this event, coarse-mode particles could arise from other sources e. Thus, while Event 1a exhibited the general pattern for GOM formation in the cold, dry, and sunlit free troposphere, emissions of coarse-mode aerosols from active fires likely influenced this event. On the morning of 26 August, GOM concentrations dropped to zero, which marked the end of Event 1a and the beginning of Event 1b. Event 1b experienced similar conditions at ground level, although the air masses were colder, drier, and from higher altitudes with increased radiation Table S2 and Fig.

These conditions are conducive for the formation of GOM and inhibit its removal. GOM during Event 1b appears to be formed in the cold, dry, sunlit free troposphere, with an unknown source of coarse-mode aerosols. Event 2 displayed the overall pattern of warm, dry, sunlit conditions at ground level accompanied by cold, dry, sunlit conditions in the free troposphere, similar to Event 1a and 1b, although Event 2 exhibited increased accumulated precipitation and H 2 O mixing ratios relative to the other events in Fig. N Coarse and BC showed no enhancement and were constant, while ozone started low and increased throughout the event. Air masses at the beginning of Event 2 originated from the Greenland Sea and then transitioned to a circulation pattern starting near Eurasia before traversing over North America Fig.

If active fires were influencing GOM concentrations during this event, their signature is likely masked by the increased levels of accumulated precipitation and H 2 O mixing ratios, which is also likely responsible for the decreased levels of GOM, N Coarse , and BC during Event 2 relative to 1a and 1b Table S2 , as well as weak correlations. Therefore, the observed levels during Event 2 are likely the result of GOM formation in the cold, dry, sunlit free troposphere, and the source of coarse-mode particles was possibly active fires, with the decreased levels of GOM, N Coarse , and BC being due to wet removal. Event 3 showed the largest observed levels of GOM but showed no obvious features indicating the cause.

Radiation, RH, and temperature displayed the opposite pattern for GOM formation, with low levels of radiation, high and increasing values of RH, and decreasing temperatures during the beginning of the event. H 2 O mixing ratio and accumulated precipitation both showed low values compared to non-event periods Fig. Ozone showed an enhancement during this event but was low compared to other events and did not show a correlation with GOM Fig.

Air masses originated from the Arctic Ocean and the Barents Sea, with only one active fire intersecting trajectories in western Russia Fig. The air mass history of this event exhibited the highest temperatures and RHs, the lowest altitudes, the most time spent above the mixed layer, and the most time within a cloud Table S2. However, this event did experience cold, dry, and sunlit conditions several hours before arrival Fig. The free troposphere has been shown to be a source of aerosol particles to the boundary layer in the Arctic through entrainment and cloud-mediated transport Igel et al.

It is possible that the extended time that this event spent within a cloud resulted in the cloud-mediated transport of free troposphere constituents to the surface layer Igel et al. Activated and interstitial aerosol particles and GOM could also have undergone evaporation in the warm surface layer temperatures Fig. This event experienced favorable conditions for GOM formation cold, dry, and sunlit air masses from aloft shortly before arrival, followed by a quick descent into the surface layer, and these conditions could create a situation where GOM formation is favored and the removal is inhibited, resulting in the high levels.

This is however a hypothesis that requires further research. Event 4 occurred approx. The air mass history showed Event 4 experienced lower temperatures, RHs, H 2 O mixing ratios, and time spent within a cloud, as well as higher radiation and altitudes, but a similar amount of time above the mixed layer compared to Event 3 Table S2. Event 4 did not show as steep of a descent as Event 3 Fig. The amount of time spent within a cloud could indicate cloud-mediated transport to the surface layer, and the slower rate of descent, coupled with the increased H 2 O mixing ratios at ground level, could lead to increased removal of GOM before being observed at Villum.

Event 3 and 4 showed similarities that could indicate cloud-mediated transport from the free troposphere to the surface layer; however, there exist dissimilarities that suggest that Event 4 could be the result of entrainment of GOM formed in the cold, dry, sunlit free troposphere. It appears that the increased H 2 O mixing ratios at ground level during Event 4 is the reason for the decreased levels of GOM compared to Event 3. A definitive conclusion for the origin of this event is currently unavailable. This event showed a strong positive correlation between GOM and ozone and moderately negative, albeit significant, correlations with N Coarse and BC Fig. Air masses for this event arrived consistently from northern Scandinavia after low-level transport with high temperatures, RHs, and H 2 O mixing ratios and being exposed to less radiation Fig.

Air masses circulated in the vicinity of active fires in northern Scandinavia before being transported to Villum Fig. These conditions are opposite to the pattern identified for GOM formation, the cause of the observed GOM levels could therefore be the extensive interactions between trajectories and active fires, although the influence of anthropogenic pollution cannot be ruled out.

Air masses were however warm, wet, and traveled at low altitudes under little radiation, and therefore it is reasonable to expect this air mass to be depleted in N Coarse and BC as well as GOM, given the high values of hydrological-related parameters. Ozone could originate from both anthropogenic and natural sources, and ozone is only slightly water soluble, leading to less efficient wet removal Sander, GOM observed during Event 5a appears to be the result of emissions either from active fires or anthropogenic sources in northern Scandinavia.

Air masses shifted from circulating northern Scandinavia to the Greenlandic continent on August 1, which coincided with the start of Event 5b. This event is a good example of the observed pattern of GOM formation: warm, dry, sunlit conditions at ground level and cold, dry, sunlit air masses from the free troposphere Figs. GOM during this event exhibited no correlation with H 2 O mixing ratio, accumulated precipitation, or BC while being strongly correlated with ozone and moderately positively correlated with N Coarse Fig. Enhancements of GOM, which exhibited a positive correlation with ozone, have also been observed during subsidence events in Antarctica Brooks et al. However, concentrations of N Coarse and BC were extremely low, which is expected of upper tropospheric air masses above the polar dome, which is extremely pristine Schulz et al.

With the low concentration of N Coarse , there does not appear to be a heterogenous surface for halogen propagation, although this could be due to particles smaller than 0. Another source of reactive halogen species is the photolysis of halocarbons Yang et al. However, Gratz et al. The origins of GOM during Event 5b appear to be the result of formation in the cold, dry, sunlit free troposphere over the Greenland ice sheet from an unknown source of halogens. The main differences between these events lie in the H 2 O mixing ratios and RH both at ground level and during transport , the temperature during transport, and the altitude Tables S1 and S2. The median BC concentration for Event 5a was over double that of 5b, although was low compared to other events influenced by active fires, i.

During Event 5a, air masses were warmer, wetter, and traveled at lower altitudes compared to Event 5b; these conditions could lead to the removal of GOM, N Coarse , and BC through deposition and uptake into the aqueous phase. It is an intriguing observation that air masses that originated from the European continent and were subject to increased hydrological parameters during transport Event 5a have a similar composition of GOM, ozone, N Coarse , and BC to air masses that originated over Greenland Event 5b. Currently, the explanation for these observations is unknown, and further research is required to fully resolve the interactions of anthropogenic and natural emissions, transport-related processes, and removal mechanisms that are responsible for these observations.

These two events were interrupted by large amounts of accumulated precipitation on 27 August Fig. The air mass history during these two episodes shows warm and wet low-altitude trajectories with little radiation Fig. Figure 6b and c show the geographical extent and intersection of air masses with active fires during the two episodes, respectively. The trajectories for both episodes intersect active fires in northern Scandinavia and Russia, and this region of Russia has been shown to emit large amounts of BC through flaring Huang et al.

With the low concentration of N Coarsethere Differences And Similarities Between Finkelman And Thomas Jefferson not appear to be a heterogenous surface Differences And Similarities Between Finkelman And Thomas Jefferson halogen propagation, although this Oppositional Defiant Disorder Research Paper be due to particles smaller than Differences And Similarities Between Finkelman And Thomas Jefferson. Indeed, the H1N1 influenza pandemic, commonly Human Geography Of Pharmacy Essay to as Swine Flu, is the only Flu pandemic in the Differences And Similarities Between Finkelman And Thomas Jefferson century Staniland and Smith FTC United States v. Bull Sturges v. Static Control Components, Inc. Durnford, D. This suggests the cold, dry, high Differences And Similarities Between Finkelman And Thomas Jefferson of the free troposphere are facilitating the formation of GOM.

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