There are widespread policy assumptions that the phase-out of gasoline and diesel internal combustion engines will over time lead to much reduced emissions of Volatile Organic Compounds (VOCs) from ...road transport and related fuels. However, the use of real-world emissions measurements from a new mobile air quality monitoring station demonstrated a large underestimation of alcohol-based species in road transport emissions inventories. Scaling of industry sales statistics enabled the discrepancy to be attributed to the use of ancillary solvent products such as screenwash and deicer which are not included in internationally applied vehicle emission methodologies. A fleet average nonfuel nonexhaust VOC emission factor of 58 ± 39 mg veh–1 km–1 was calculated for the missing source, which is greater than the total of all VOCs emitted from vehicle exhausts and their associated evaporative fuel losses. These emissions are independent of the vehicle energy/propulsion system and therefore applicable to all road vehicle types including those with battery-electric powertrains. In contrast to predictions, vehicle VOC emissions may actually increase given a predicted growth in total vehicle kilometers driven in a future electrified fleet and will undergo a complete VOC respeciation due to the source change.
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IJS, KILJ, NUK, PNG, UL, UM
The impact of biogenic emissions on ozone and secondary organic aerosol (SOA) has been widely acknowledged; nevertheless, biogenic emissions emitted from urban landscapes have been largely ignored. ...We find that including urban isoprene in megacities like Beijing improves not only the modeled isoprene concentrations but also its diurnal cycle. Specifically, the mean bias of the simulated isoprene concentrations is reduced from 87% to 39% by adding urban isoprene emissions while keeping the diurnal cycle the same as that in non-urban or rural areas. Further adjusting the diurnal cycle of isoprene emissions to the urban profile steers the original early morning peak of the isoprene concentration to a double quasi-peak, i.e., bell shape, consistent with observations. The efficiency of ozone generation caused by isoprene emissions in urban Beijing is found to be twice as large as those in rural areas, indicative of vital roles of urban BVOC emissions in modulating the ozone formation. Our study also shows that in the future along with NOx emission reduction, isoprene emissions from urban landscapes will become more important for the formation of ozone in urban area, and their contributions may exceed that of isoprene caused by transport from rural areas. Finally, the impact of biogenic emissions on SOA is examined, revealing that biogenic induced SOA accounts for 16% of the total SOA in urban Beijing. The effect of isoprene on SOA (iSOA) is modulated through two pathways associated with the abundance of NOx emissions, and the effect can be amplified in future when NOx emissions are reduced. The findings of our study are not limited to Beijing but also apply to other megacities or densely populated regions, suggesting an urgent need to construct an accurate emission inventory for urban landscapes and evaluate their impact on ozone and SOA in air quality planning and management.
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•Urban isoprene emissions improve the modeled isoprene concentration and diurnal cycle.•Urban isoprene may trigger ozone formation twice as efficiently as that in rural area.•The impact of biogenic emissions on secondary organic aerosol (SOA) is examined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
3.
The first board examination in pediatric surgery Hopkins, James W.; Hopkins, Nancy J.; Nakayama, Don K.
Journal of pediatric surgery,
January 2022, 2022-Jan, 2022-01-00, 20220101, Volume:
57, Issue:
1
Journal Article
Peer reviewed
The inaugural certifying examination for special competence in pediatric surgery in North America was given by the American Board of Surgery (ABS) in April 1975, the day before the sixth meeting of ...the American Pediatric Surgical Association at a resort near San Juan, PR. The event came after failed applications before the ABS and the Advisory Board for Medical Specialties in 1957, 1961, and 1967. The specialty had matured with a scholarly publication devoted to the field (Journal of Pediatric Surgery, 1965), the establishment of standards for training and training programs (1966), and a society independent of pediatrics and devoted solely to pediatric surgery (American Pediatric Surgical Association, first meeting 1970). Harvey Beardmore had guided the successful campaign for a certificate for pediatric surgery under the aegis of the ABS that was approved in June 1972. Pediatric surgery had thus gained full recognition as a specialty of surgery.
A group photograph of its participants became one of the iconic images in our specialty. Thanks to Jim and Nancy Hopkins of Windsor Heights, IA, and to their many friends and colleagues, nearly half (71 of 151) of the pediatric surgeons in the photo were identified, marking their places in the history of pediatric surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Volatile organic compounds (VOCs) and oxygenated VOCs (OVOCs) were measured in Ho Chi Minh City (HCMC) and Hanoi, the two largest and most populous cities in Vietnam. The purpose of this study is to ...better understand the VOC atmospheric composition and their role in ground-level ozone formation. Online measurements of a wide range of VOCs and other pollutants were conducted using numerous instruments during different seasons (dry and rainy) in HCMC and Hanoi (spring). Our results show that the mean mixing ratio of total measured VOCs in Hanoi was 80.8 ± 40.7 ppb (mean ± standard deviation), and was similar to that observed during the rainy season (75.2 ± 44.8 ppb) in HCMC. During the dry season campaign in HCMC, which was coincident with the Hanoi campaign, total VOC was around 50% lower (40.7 ± 19.5 ppb), largely a result of increased planetary boundary layer (PBL) height and the direction of the prevailing wind. VOC profiles in both cities were dominated by alkanes (31–35%) and OVOCs (27–33%) and the proportion of alkenes (13–17%) and aromatics (12–19%) were comparable. Similarities in diurnal variation for most VOC species (except for isoprene) are seen in both cities with two clear peaks during the morning (7:00–8:00 a.m.) and evening (18:00 p.m.) rush hours, as observed for vehicular-combustion tracers (acetylene and CO). Comparisons of the ambient ratios of paired VOCs, namely i/n-pentane, and toluene/benzene, with those reported in motorcycle exhaust, roadside and gasoline samples indicate that motorcycle-related emission is likely a major contributor to VOC pollution. According to the propylene-equivalent concentration (PE conc.) and maximum incremental reactivity (MIR) methods, alkenes and aromatics were determined to be the main contributors to reactivity and ozone potential formation. Furthermore, the initial mixing ratio of VOC species was estimated based on the photochemical age method. The consumed VOCs (initial VOCs minus measured VOCs) has a similar variation trend to ground-level ozone, and a good correlation is observed in HCMC. In contrast, this result was not seen in Hanoi despite relatively high levels of PE conc. and MIR.
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•Extensive VOC evaluation including composition, spatio-temporal variability and their role in surface ozone formation are investigated for the first time in Vietnam•Ambient VOC levels are strongly impacted by motorcycle-related emissions•Variability in VOC levels are ruled by wind pattern and planetary boundary layer height•Alkenes and aromatics dominated the potential ozone formation.•Higher levels of ethane were observed from air masses passing over China mainland
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Wintertime in situ measurements of OH, HO2 and
RO2 radicals and OH reactivity were made in central Beijing
during November and December 2016. Exceptionally elevated NO was
observed on occasions, up ...to ∼250 ppbv. The daily
maximum mixing ratios for radical species varied significantly
day-to-day over the ranges 1–8×106 cm−3 (OH),
0.2–1.5×108 cm−3 (HO2) and
0.3–2.5×108 cm−3 (RO2). Averaged over
the full observation period, the mean daytime peak in radicals was
2.7×106, 0.39×108 and 0.88×108 cm−3 for OH, HO2 and total RO2,
respectively. The main daytime source of new radicals via
initiation processes (primary production) was the photolysis of HONO
(∼83 %), and the dominant termination pathways were the
reactions of OH with NO and NO2, particularly under
polluted haze conditions. The Master Chemical Mechanism (MCM) v3.3.1
operating within a box model was used to simulate the concentrations
of OH, HO2 and RO2. The model underpredicted OH,
HO2 and RO2, especially when NO mixing ratios were
high (above 6 ppbv). The observation-to-model ratio of OH,
HO2 and RO2 increased from ∼1 (for all
radicals) at 3 ppbv of NO to a factor of ∼3, ∼20
and ∼91 for OH, HO2 and RO2, respectively,
at ∼200 ppbv of NO. The significant underprediction of
radical concentrations by the MCM suggests a deficiency in the
representation of gas-phase chemistry at high NOx. The OH
concentrations were surprisingly similar (within 20 % during the
day) in and outside of haze events, despite j(O1D)
decreasing by 50 % during haze periods. These observations provide
strong evidence that gas-phase oxidation by OH can continue to
generate secondary pollutants even under high-pollution episodes,
despite the reduction in photolysis rates within haze.
Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and ...biological variation in primary solid tumor tissues and patient-derived mouse xenografts for scRNA-seq are not well understood.
We use low temperature (6 °C) protease and collagenase (37 °C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNA-seq dataset comprising 155,165 cells from patient cancer tissues, patient-derived breast cancer xenografts, and cancer cell lines. We observe substantial variation in standard quality control metrics of cell viability across conditions and tissues. From the contrast between tissue protease dissociation at 37 °C or 6 °C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37 °C), which are minimized by dissociation with a cold active protease (6 °C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues.
The method and conditions of tumor dissociation influence cell yield and transcriptome state and are both tissue- and cell-type dependent. Interpretation of stress pathway expression differences in cancer single-cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with the identification of such effects in dissociated scRNA-seq experiments.
Measurements of OH, HO2, complex RO2 (alkene- and aromatic-related RO2) and total RO2 radicals taken during the integrated Study of AIR Pollution PROcesses in Beijing (AIRPRO) campaign in central ...Beijing in the summer of 2017, alongside observations of OH reactivity, are presented. The concentrations of radicals were elevated, with OH reaching up to 2.8×107moleculecm-3, HO2 peaking at 1×109moleculecm-3 and the total RO2 concentration reaching 5.5×109moleculecm-3. OH reactivity (k(OH)) peaked at 89 s-1 during the night, with a minimum during the afternoon of ≈22s-1 on average. An experimental budget analysis, in which the rates of production and destruction of the radicals are compared, highlighted that although the sources and sinks of OH were balanced under high NO concentrations, the OH sinks exceeded the known sources (by 15 ppbvh-1) under the very low NO conditions (<0.5ppbv) experienced in the afternoons, demonstrating a missing OH source consistent with previous studies under high volatile organic compound (VOC) emissions and low NO loadings. Under the highest NO mixing ratios (104 ppbv), the HO2 production rate exceeded the rate of destruction by ≈50ppbvh-1, whilst the rate of destruction of total RO2 exceeded the production by the same rate, indicating that the net propagation rate of RO2 to HO2 may be substantially slower than assumed. If just 10 % of the RO2 radicals propagate to HO2 upon reaction with NO, the HO2 and RO2 budgets could be closed at high NO, but at low NO this lower RO2 to HO2 propagation rate revealed a missing RO2 sink that was similar in magnitude to the missing OH source. A detailed box model that incorporated the latest Master Chemical Mechanism (MCM3.3.1) reproduced the observed OH concentrations well but over-predicted the observed HO2 under low concentrations of NO (<1ppbv) and under-predicted RO2 (both the complex RO2 fraction and other RO2 types which we classify as simple RO2) most significantly at the highest NO concentrations. The model also under-predicted the observed k(OH) consistently by ≈10s-1 across all NOx levels, highlighting that the good agreement for OH was fortuitous due to a cancellation of missing OH source and sink terms in its budget. Including heterogeneous loss of HO2 to aerosol surfaces did reduce the modelled HO2 concentrations in line with the observations but only at NO mixing ratios <0.3ppbv. The inclusion of Cl atoms, formed from the photolysis of nitryl chloride, enhanced the modelled RO2 concentration on several mornings when the Cl atom concentration was calculated to exceed 1×104atomscm-3 and could reconcile the modelled and measured RO2 concentrations at these times. However, on other mornings, when the Cl atom concentration was lower, large under-predictions in total RO2 remained. Furthermore, the inclusion of Cl atom chemistry did not enhance the modelled RO2 beyond the first few hours after sunrise and so was unable to resolve the modelled under-prediction in RO2 observed at other times of the day. Model scenarios, in which missing VOC reactivity was included as an additional reaction that converted OH to RO2, highlighted that the modelled OH, HO2 and RO2 concentrations were sensitive to the choice of RO2 product. The level of modelled to measured agreement for HO2 and RO2 (both complex and simple) could be improved if the missing OH reactivity formed a larger RO2 species that was able to undergo reaction with NO, followed by isomerisation reactions reforming other RO2 species, before eventually generating HO2. In this work an α-pinene-derived RO2 species was used as an example. In this simulation, consistent with the experimental budget analysis, the model underestimated the observed OH, indicating a missing OH source. The model uncertainty, with regards to the types of RO2 species present and the radicals they form upon reaction with NO (HO2 directly or another RO2 species), leads to over an order of magnitude less O3 production calculated from the predicted peroxy radicals than calculated from the observed peroxy radicals at the highest NO concentrations. This demonstrates the rate at which the larger RO2 species propagate to HO2, to another RO2 or indeed to OH needs to be understood to accurately simulate the rate of ozone production in environments such as Beijing, where large multifunctional VOCs are likely present.
Measurements of OH, HO2, RO2i (alkene
and aromatic-related RO2) and total RO2 radicals taken during the
ClearfLo campaign in central London in the summer of 2012 are presented. A
photostationary ...steady-state calculation of OH which considered measured OH
reactivity as the OH sink term and the measured OH sources (of which
HO2+ NO reaction and HONO photolysis dominated) compared well with the
observed levels of OH. Comparison with calculations from a detailed box model
utilising the Master Chemical Mechanism v3.2, however, highlighted a
substantial discrepancy between radical observations under lower NOx
conditions (NO < 1 ppbv), typically experienced during the
afternoon hours, and indicated that the model was missing a significant
peroxy radical sink; the model overpredicted HO2 by up to a factor of
10 at these times. Known radical termination steps, such as HO2 uptake
on aerosols, were not sufficient to reconcile the model–measurement
discrepancies alone, suggesting other missing termination processes. This
missing sink was most evident when the air reaching the site had previously
passed over central London to the east and when elevated temperatures were
experienced and, hence, contained higher concentrations of VOCs. Uncertainties
in the degradation mechanism at low NOx of complex biogenic and diesel
related VOC species, which were particularly elevated and dominated OH
reactivity under these easterly flows, may account for some of the model–measurement disagreement. Under higher NO (> 3 ppbv) the box
model increasingly underpredicted total RO2. The modelled and
observed HO2 were in agreement, however, under elevated NO
concentrations ranging from 7 to 15 ppbv. The model uncertainty under low NO conditions leads to more ozone production
predicted using modelled peroxy radical concentrations
(∼ 3 ppbv h−1) versus ozone production from peroxy radicals
measured (∼ 1 ppbv h−1). Conversely, ozone production derived
from the predicted peroxy radicals is up to an order of magnitude lower than
from the observed peroxy radicals as NO increases beyond 7 ppbv due to the
model underprediction of RO2 under these conditions.
Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid ...development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial protein catalyzed capture agent (PCC) technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant
Klebsiella pneumoniae
, an opportunistic Gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of
K. pneumoniae
for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC
50
∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing
K. pneumoniae
, but not to other pathogenic bacterial species. AR-PCCs that bear a hapten moiety promoted antibody recruitment to
K. pneumoniae
, leading to enhanced phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria.
Antibody-recruiting protein-catalyzed capture agent (AR-PCCs) are a new class of all-synthetic and highly targeted antibiotics that recruit endogenous immune responses to eliminate drug-resistant microbes.
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IJS, KILJ, NUK, UL, UM, UPUK
Fast-replicating neurotropic herpesviruses exemplified by herpes simplex virus-1 (HSV-1) naturally infect the central nervous system (CNS). However, most individuals intrinsically suppress the virus ...during a primary infection and preclude it from significantly damaging the CNS. Optineurin (OPTN) is a conserved autophagy receptor with little understanding of its role in neurotropic viral infections. We show that OPTN selectively targets HSV-1 tegument protein, VP16, and the fusion glycoprotein, gB, to degradation by autophagy. OPTN-deficient mice challenged with HSV-1 show significant cognitive decline and susceptibility to lethal CNS infection. OPTN deficiency unveils severe consequences for recruitment of adaptive immunity and suppression of neuronal necroptosis. Ocular HSV-1 infection is lethal without OPTN and is rescued using a necroptosis inhibitor. These results place OPTN at the crux of neuronal survival from potentially lethal CNS viral infections.
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