OH and HO₂ radicals chemistry at a suburban site during the EXPLORE-YRD campaign in 2018

The first OH and HO2 radical observation in Yangtze River Delta, one of the four major urban agglomerations in China, was carried out at a suburban site Taizhou in summer 2018 from May to June, aiming to elucidate the atmospheric oxidation capacity in this region. The maximum diurnal averaged OH and HO2 concentrations were 1.0 × 107 cm−3 and 1.1 × 109 cm−3, respectively, which were the second highest HOx (sum of OH and HO2) radical concentrations observed in China. HONO photolysis was the dominant radical primary source, accounting for 42 % of the total radical initiation rate. Other contributions were from carbonyl photolysis (including HCHO, 24 %), O3 photolysis (17 %), alkenes ozonolysis (14 %), and NO3 oxidation (3 %). A chemical box model based on RACM2-LIM1 mechanism could generally reproduce the observed HOx radicals, but systematic discrepancy remained in the afternoon for OH radical, when NO mixing ratio was less than 0.3 ppb. Additional recycling mechanism equivalent to 100 ppt NO was capable to fill the gap. The sum of monoterpenes was on average up to 0.4 ppb during daytime, which was allocated all to α-pinene in the base model. Sensitivity test without monoterpene input showed the modelled OH and HO2 concentrations would increase by 7 % and 4 %, respectively, but modelled RO2 concentration would significantly decrease by 23 %, indicating that monoterpene was an important precursor of RO2 radicals in this study. Consequently, the daily integrated net ozone production would reduce by 6.3 ppb if without monoterpene input, proving the significant role of monoterpene on the photochemical O3 production in this study. Besides, the generally good agreement between observed and modelled HOx concentrations suggested no significant HO2 heterogeneous uptake process during this campaign. Incorporation of HO2 heterogeneous uptake process would worsen the agreement between HOx radical observation and simulation, and the discrepancy would be beyond the measurement-model combined uncertainties using an effective uptake coefficient of 0.2. Finally, the ozone production efficiency (OPE) was only 1.7 in this study, a few folds lower than other studies in (sub)urban environments. The low OPE indicated slow radical propagation rate and short chain length. As a consequence, ozone formation was suppressed by the low NO concentration in this study.

Robustness of DNA Looping Across Multiple Divisions in Individual Bacteria

DNA looping has emerged as a central paradigm of transcriptional regulation as it is shared across many living systems. One core property of DNA looping-based regulation is its ability to greatly enhance repression or activation of genes with only a few copies of transcriptional regulators. However, this property based on small number of proteins raises the question of the robustness of such a mechanism with respect to the large intracellular perturbations taking place during growth and division of the cell. Here we address the issue of sensitivity to variations of intracellular parameters of gene regulation by DNA looping. We use the lac system as a prototype to experimentally identify the key features of the robustness of DNA looping in growing E. coli cells. Surprisingly, we observe time intervals of tight repression spanning across division events, which can sometimes exceed ten generations. Remarkably, the distribution of such long time intervals exhibits memoryless statistics that is mostly insensitive to repressor concentration, cell division events, and the number of distinct loops accessible to the system. By contrast, gene regulation becomes highly sensitive to these perturbations when DNA looping is absent. Using stochastic simulations, we propose that the robustness to division events of memoryless distributions emerges from the competition between fast, multiple re-binding events of repressors and slow initiation rate of the RNA-polymerase. We argue that fast re-binding events are a direct consequence of DNA looping that ensures robust gene repression across a range of intracellular perturbations.

Estimating the Public Health Impact from Introducing Tobacco-Free Nicotine Pouches Into the US

BackgroundFor smokers not intending to quit, switching to a reduced-risk nicotine product should be healthier than continuing smoking. We estimate the health impact, over the period 2000-2050, of introducing into the US the nicotine pouch ZYN. ZYN’s toxicant profile and method of use is like that for Swedish snus, a product with known health effects much less than smoking. MethodsOur modelling approach is similar to others developed for estimating potential effects of new tobacco products. It starts with a simulated cohort of 100,000 individuals in the year 2000 subdivided by age, sex, and smoking status (including years since quitting). They are followed annually accounting for births, net immigrations, deaths and product use changes, with follow-up carried out in the Base Case (ZYN not introduced) and Modified Case (ZYN introduced). Using informed assumptions about initiation, quitting and switching rates, distributions of the population over time are then constructed for each Case, which are used to estimate product-related mortality based on assumptions about the relative risk according to product use. ResultsWhereas in both Base and Modified Cases, the prevalence of any current product use is predicted to decline from about 22% to 10% during follow-up, in the Modified Case about 25% of current users use ZYN by 2050, about a quarter being dual users and the rest ZYN-only users. Over the 50 years, deaths at ages 35-84 from product use among the 100,000 are estimated as 249 less in the Modified than the Base Case, equivalent to about 700,000 less deaths in the whole US. Sensitivity analyses varying individual parameter values confirm the benefits of switching to ZYN, which increase as either the switching rate to ZYN increases or the initiation rate of ZYN relative to smoking increases. Even assuming the reduction in excess mortality risk using ZYN use is 20% of that from smoking rather than the 3.5% assumed in the main analyses, the reduction in product-related deaths would still be 213, or about 600,000 in the US. ConclusionsAlthough such model-based estimates are subject to uncertainties, the results suggest that introducing ZYN could substantially reduce smoking-attributable deaths.

Children’s Health Capital Investment: Effects of U.S. Infant Breastfeeding on Teenage Obesity

Obesity, as a health and social problem with rising prevalence and soaring economic cost, is increasingly drawing scholarly and public policy attention. While many studies have suggested that infant breastfeeding protects against childhood obesity, empirical evidence on this causal relationship is fragile. Using the health capital development theory, this study exploited multiple data sources from the U.S. and a three-way error components model (ECM) with a jackknife resampling plan to estimate the effect of in-hospital breastfeeding initiation and breastfeeding for durations of 3, 6, and 12 months on the prevalence of obesity during teenage years. The main finding was that a 1% rise in the in-hospital breastfeeding initiation rate reduces the teenage obesity prevalence rate by 1.7% (9.6% of a standard deviation). The magnitude of this effect declines as the infant breastfeeding duration lengthens—e.g., the 12-month infant breastfeeding duration rate is associated with a 0.53% (3.7% of a standard deviation) reduction in obesity prevalence in the teenage years (9th to 12th grades). The study findings agree with both the behavioral and physiological theories on the long-term effects of breastfeeding, and have timely implications for public policies promoting infant breastfeeding to reduce the economic burden of teenage and later adult-stage obesity prevalence rates.

Eligibility, Utilization, and Effectiveness of 17-Alpha Hydroxyprogesterone Caproate (17OHPC) in a Statewide Population-Based Cohort of Medicaid Enrollees

Objectives The primary objective was to estimate the initiation and adherence rates of 17 α-hydroxyprogesterone caproate (17OHPC) among eligible mothers in a statewide population-based cohort of Medicaid enrollees. The secondary objectives were to (1) determine the association of maternal sociodemographic and clinical characteristics with 17OHPC utilization and (2) assess the real-world effectiveness of 17OHPC on recurrent preterm birth prevention and admission to neonatal intensive care unit (NICU). Study Design This is a retrospective cohort study using a linked, longitudinal administrative dataset of birth certificates and medical assistance claims. Medicaid-enrolled mothers in Pennsylvania were included in this study if they had at least one singleton live birth from 2014 to 2016 following at least one spontaneous preterm birth. Maternal Medicaid claims were used to ascertain the use of 17OHPC from various manufacturers, including compounded formulations. Propensity score matching was used to create a covariate balance between 17OHPC treatment and comparison groups. Results We identified 4,781 Medicaid-covered 17OHPC-eligible pregnancies from 2014 to 2016 in Pennsylvania, 3.4% of all Medicaid-covered singleton live births. The population-based initiation rate was 28.5% among eligible pregnancies. Among initiators, 50% received ≥16 doses as recommended, while 10% received a single dose only. The severity of previous spontaneous preterm birth was the strongest predictor for the initiation and adherence of 17OHPC. In the matched treatment (n = 1,210) and comparison groups (n = 1,210), we found no evidence of 17OHPC effectiveness. The risks of recurrent preterm birth (relative risk [RR] 1.10, 95% confidence interval [CI] 0.97–1.24) and births admitted to NICU (RR 1.00, 95% CI 0.84–1.18) were similar in treated and comparison mothers. Conclusion The 17OHPC-eligible population represented 3.4% of singleton live births. Less than one-third of eligible mothers initiated treatment. Among initiators, 50% were treatment adherent. We found no difference in the risk of recurrent preterm birth or admission to NICU between treatment and comparison groups. Key Points

Estimating the reduction in US mortality if cigarettes were largely replaced by e-cigarettes

Background Recent estimates indicated substantially replacing cigarettes by e-cigarettes would, during 2016–2100, reduce US deaths and life-years lost (millions) by 6.6 and 86.7 (Optimistic Scenario) and 1.6 and 20.8 (Pessimistic). To provide additional insight we use alternative modelling based on a shorter period (1991–2040), four main smoking-associated diseases, deaths aged 30–79 years, and a full product history. We consider variations in: assumed effective dose of e-cigarettes versus cigarettes (F); their relative quitting rate (Q); proportions smoking after 10 years (X); and initiation rate (I) of vaping, relative to smoking. Methods We set F = 0.05, X = 5%, Q = 1.0 and I = 1.0 (Main Scenario) and F = 0.4, X = 10%, Q = 0.5 and I = 1.5 (Pessimistic Scenario). Sensitivity Analyses varied Main Scenario parameters singly; F from 0 to 0.4, X 0.01% to 15%, and Q and I 0.5 to 1.5. To allow comparison with prior work, individuals cannot be dual users, re-initiate, or switch except from cigarettes to e-cigarettes. Results Main Scenario reductions were 2.52 and 26.23 million deaths and life-years lost; Pessimistic Scenario reductions were 0.76 and 8.31 million. These were less than previously, due to the more limited age-range and follow-up, and restriction to four diseases. Reductions in deaths (millions) varied most for X, from 3.22 (X = 0.01%) to 1.31 (X = 15%), and F, 2.74 (F = 0) to 1.35 (F = 0.4). Varying Q or I had little effect. Conclusions Substantial reductions in deaths and life-years lost were observed even under pessimistic assumptions. Estimates varied most for X and F. These findings supplement literature indicating e-cigarettes can importantly impact health challenges from smoking.

Enhanced Production of a Thermostable Carbonic Anhydrase in Escherichia coli by Using a Modified NEXT Tag

Carbonic anhydrase (CA) is an ultrafast enzyme that catalyzes the reversible conversion of carbon dioxide (CO2) to bicarbonate. CA is considered to be a green catalyst for enzyme-based CO2 capture and utilization. In particular, the CA of Thermovibrio ammonificans (taCA) has attracted increasing attention as a highly stable enzyme. However, the poor solubility and the low expression level in Escherichia coli have hampered further utilization of taCA. In a recent study, these limitations were partly resolved by using a small solubility-enhancing fusion tag named NEXT, which originates from the N-terminal extension of Hydrogenovibrio marinus CA. In this study, the NEXT tag was engineered by adding small peptides to the N terminus to further increase the production yield of NEXT-tagged taCA. The addition of ng3 peptide (His-Gly-Asn) originating from the N-terminal sequence of Neisseria gonorrhoeae CA improved the expression of NEXT-taCA, while the previously developed translation-enhancing element (TEE) and Ser-Lys-Ile-Lys (SKIK) tag were not effective. The expression test with all 16 codon combinations for the ng3 sequence revealed that the change in translation initiation rate brought about by the change in nucleotide sequence was not the primary determinant for the change in expression level. The modified ng3-NEXT tag may be applied to increase the production yields of various recombinant proteins.

Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes

We present a new theoretical framework for large-scale mRNA translation using a network of models called the ribosome flow model with Langmuir kinetics (RFMLK), interconnected via a pool of free ribosomes. The input to each RFMLK depends on the pool density, and it affects the initiation rate and the internal ribosome entry rates at each site along each RFMLK. Ribosomes that detach from an RFMLK due to termination or premature drop-off are fed back into the pool. We prove that the network always converges to a steady-state, and study its sensitivity to variations in the parameters. For example, we show that if the drop-off rate at some site in some RFMLK is increased then the pool density increases and consequently the steady-state production rate in all the other RFMLKs increases. Surprisingly, we also show that modifying a parameter of a certain RFMLK can lead to arbitrary effects on the densities along the modified RFMLK, depending on the parameters in the entire network. We conclude that the competition for shared resources generates an indirect and intricate web of mutual effects between the mRNA molecules, that must be accounted for in any analysis of translation.

HIV diagnosis period influences ART initiation: findings from a prospective cohort study in China

Background We estimated the predictive effects of ART-related perceptions on the actual ART uptake behavior among ART naïve PLWH stratified by different time of HIV diagnosis under the new strategy. Methods A prospective cohort study was conducted among ART naïve PLWH in Guangzhou, China from June 2016 to June 2017. Cox regression model was used to evaluate the predictive effects of ART-related perceptions on ART initiation among PLWH stratified by different timepoint of HIV diagnosis (i.e., before or after the update of the new treatment policy). Results Among 411 participants, 150 and 261 were diagnosed before (pre-scaleup group) and after (post-scaleup group) the implementation of the new strategy, respectively. The ART initiation rate in the post-scaleup group (88.9%) was higher than that in the pre-scaleup group (73.3%) (p < 0.001). A significant difference of mean score was detected in each HBM construct between pre- and post-scaleup groups (p < 0.05). After adjusting for significant background variables, among all participants, only the self-efficacy [adjusted HR (HRa) = 1.23, 95% CI 1.06 to 1.43, p = 0.006], has a predictive effect on ART initiation; in pre-scaleup group, all constructs of HBM-related ART perceptions were predictors of ART initiation (HRa = 0.71 to 1.83, p < 0.05), while in post-scaleup group, no significant difference was found in each construct (p > 0.05). Conclusions The ART initiation rate was high particularly among participants who diagnosed after the new treatment strategy. The important role of the time of HIV diagnosis on ART initiation identified in this study suggested that future implementation interventions may consider to modify the ART-related perceptions for HIV patients who diagnosed before the implementation of the new ART strategy, while expand the accessibility of ART service for those who diagnosed after the implementation of the new strategy.