The role of anthropogenic NOx emissions in secondary organic aerosol (SOA) production is not fully understood but is important for understanding the contribution of emissions to air quality. Here, we ...examine the role of organic nitrates (RONO2) in SOA formation over the Korean Peninsula during the Korea–United States Air Quality field study in Spring 2016 as a model for RONO2 aerosol in cities worldwide. We use aircraft-based measurements of the particle phase and total (gas + particle) RONO2 to explore RONO2 phase partitioning. These measurements show that, on average, one-fourth of RONO2 are in the condensed phase, and we estimate that ≈15% of the organic aerosol (OA) mass can be attributed to RONO2. Furthermore, we observe that the fraction of RONO2 in the condensed phase increases with OA concentration, evidencing that equilibrium absorptive partitioning controls the RONO2 phase distribution. Lastly, we model RONO2 chemistry and phase partitioning in the Community Multiscale Air Quality modeling system. We find that known chemistry can account for one-third of the observed RONO2, but there is a large missing source of semivolatile, anthropogenically derived RONO2. We propose that this missing source may result from the oxidation of semi- and intermediate-volatility organic compounds and/or from anthropogenic molecules that undergo autoxidation or multiple generations of OH-initiated oxidation.
The concept of port sustainability has gained increasing attention and become one of the most important focus areas for improving port competitiveness. This research aims to identify crucial criteria ...for assessing sustainability of the ports in South Korea using the importance-performance analysis (IPA) technique. A total of 27 sustainability assessment items encompassing all three pillars of sustainability-environmental, economic, and social aspects-were established from previous research and interviews. A survey was conducted with the port managers to evaluate the importance of the identified assessment measures and their perceived performances. The findings indicate that the economic issue associated with offering employment opportunities was deemed the most important measure, followed by environmental concerns and social factors. They also provide useful managerial insights for the ports to understand port sustainability issues so as to discover areas for improvements and direct their resources to the appropriate areas to enhance port competitiveness.
•The port sustainability is examined by using IPA in South Korea.•It identifies crucial criteria for assessing sustainability of the ports.•The economic issue associated with offering employment opportunities was deemed the most important measure.•Environmental concern was the second important issue in port sustainability.
Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the ...therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase.
After screening tumor samples from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy.
Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects.
The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.).
The three most important commercial bacterial insecticides are all derived from subspecies of
(
). Specifically,
subsp.
(Btk) and
subsp.
(Bta) are used to control larval lepidopteran pests. The ...third,
subsp.
(Bti), is primarily used to control mosquito and blackfly larvae. All three subspecies produce a parasporal body (PB) during sporulation. The PB is composed of insecticidal proteins that damage the midgut epithelium, initiating a complex process that results in the death of the insect. Among these three subspecies of
, Bti is unique as it produces the most complex PB consisting of three compartments. Each compartment is bound by a multilaminar fibrous matrix (MFM). Two compartments contain one protein each, Cry11Aa1 and Cyt1Aa1, while the third contains two, Cry4Aa1/Cry4Ba1. Each compartment is packaged independently before coalescing into the mature spherical PB held together by additional layers of the MFM. This distinctive packaging process is unparalleled among known bacterial organelles, although the underlying molecular biology is yet to be determined. Here, we present structural and molecular evidence that the MFM has a hexagonal pattern to which Bti proteins Bt152 and Bt075 bind. Bt152 binds to a defined spot on the MFM during the development of each compartment, yet its function remains unknown. Bt075 appears to be derived from a bacteriophage major capsid protein (MCP), and though its sequence has markedly diverged, it shares striking 3-D structural similarity to the
phage HK97 Head 1 capsid protein. Both proteins are encoded on Bti's pBtoxis plasmid. Additionally, we have also identified a six-amino acid motif that appears to be part of a novel molecular process responsible for targeting the Cry and Cyt proteins to their cytoplasmic compartments. This paper describes several previously unknown features of the Bti organelle, representing a first step to understanding the biology of a unique process of sorting and packaging of proteins into PBs. The insights from this research suggest a potential for future applications in nanotechnology.
Over application of phosphate fertilizers in modern agriculture contaminates waterways and disrupts natural ecosystems. Nevertheless, this is a common practice among farmers, especially in developing ...countries as abundant fertilizers are believed to boost crop yields. The study of plant phosphate metabolism and its underlying genetic pathways is key to discovering methods of efficient fertilizer usage. The work presented here describes a genome-wide resource on the molecular dynamics underpinning the response and recovery in roots and shoots of Arabidopsis thaliana to phosphate-starvation.
Genome-wide profiling by micro- and tiling-arrays (accessible from GEO: GSE34004) revealed minimal overlap between root and shoot transcriptomes suggesting two independent phosphate-starvation regulons. Novel gene expression patterns were detected for over 1000 candidates and were classified as either initial, persistent, or latent responders. Comparative analysis to AtGenExpress identified cohorts of genes co-regulated across multiple stimuli. The hormone ABA displayed a dominant role in regulating many phosphate-responsive candidates. Analysis of co-regulation enabled the determination of specific versus generic members of closely related gene families with respect to phosphate-starvation. Thus, among others, we showed that PHR1-regulated members of closely related phosphate-responsive families (PHT1;1, PHT1;7-9, SPX1-3, and PHO1;H1) display greater specificity to phosphate-starvation than their more generic counterparts.
Our results uncover much larger, staged responses to phosphate-starvation than previously described. To our knowledge, this work describes the most complete genome-wide data on plant nutrient stress to-date.
Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes.
To evaluate the efficacy and ...safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy.
The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included.
Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients).
The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12.
Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% 200 patients for the ferric carboxymaltose group vs 54.0% 115 patients for the placebo group; absolute difference, 38.2% 95% CI, 33.6%-42.8%; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL 95% CI, 150.2-209.5; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% 95% CI, 13.1%-18.3%; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% 95% CI, 3.3%-7.6%; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients 6.8%, including injection site reactions 5 patients and urticaria 5 patients) than the placebo group (1 patient 0.4%), but no severe adverse events were reported in either group.
Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks.
clinicaltrials.gov Identifier: NCT01725789.
Selective diagnostic laparoscopy in gastric cancer patients at high risk of peritoneal metastasis is essential for optimal treatment planning.
In this study available clinicopathologic factors ...predictive of peritoneal seeding in advanced gastric cancer (AGC) were identified, and this information was translated into a clinically useful tool.
Totally 2833 patients underwent surgery for AGC between 2003 and 2013. The study identified clinicopathologic factors associated with the risk of peritoneal seeding for constructing nomograms using a multivariate logistic regression model with backward elimination. A nomogram was constructed to generate a numerical value indicating risk. Accuracy was validated using bootstrapping and cross-validation.
The proportion of seeding positive was 12.7% in females and 9.6% in males. Of 2833 patients who underwent surgery for AGC, 300 (10.6%) were intraoperatively identified with peritoneal seeding. Multivariate analysis revealed the following factors associated with peritoneal seeding: high American Society of Anesthesiologists score, fibrinogen, Borrmann type 3 or 4 tumors, the involvement of the middle, anterior, and greater curvature, cT3 or cT4cN1 or cN2 or cN3, cM1, and the presence of ascites or peritoneal thickening or plaque or a nodule on the peritoneal wall on computed tomography. The bootstrap analysis revealed a robust concordance between mean and final parameter estimates. The area under the ROC curve for the final model was 0.856 (95% CI, 0.835–0.877), which implies good performance.
This nomogram provides effective risk estimates of peritoneal seeding from gastric cancer and can facilitate individualized decision-making regarding the selective use of diagnostic laparoscopy.
Sophisticated segmentation of the craniomaxillofacial bones (the mandible and maxilla) in computed tomography (CT) is essential for diagnosis and treatment planning for craniomaxillofacial surgeries. ...Conventional manual segmentation is time-consuming and challenging due to intrinsic properties of craniomaxillofacial bones and head CT such as the variance in the anatomical structures, low contrast of soft tissue, and artifacts caused by metal implants. However, data-driven segmentation methods, including deep learning, require a large consistent dataset, which creates a bottleneck in their clinical applications due to limited datasets. In this study, we propose a deep learning approach for the automatic segmentation of the mandible and maxilla in CT images and enhanced the compatibility for multi-center datasets. Four multi-center datasets acquired by various conditions were applied to create a scenario where the model was trained with one dataset and evaluated with the other datasets. For the neural network, we designed a hierarchical, parallel and multi-scale residual block to the U-Net (HPMR-U-Net). To evaluate the performance, segmentation with in-house dataset and with external datasets from multi-center were conducted in comparison to three other neural networks: U-Net, Res-U-Net and mU-Net. The results suggest that the segmentation performance of HPMR-U-Net is comparable to that of other models, with superior data compatibility.
Disturbed blood flow (d-flow) causes endothelial cell (EC) dysfunction, leading to atherosclerotic plaque formation. We have previously shown that d-flow increases SUMOylation of p53 and ERK5 through ...downregulation of sentrin/SUMO-specific protease 2 (SENP2) function; however, it is not known how SENP2 itself is regulated by d-flow. Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis. In an LDLR-deficient murine model of atherosclerosis, EC-specific overexpression of p90RSK increased EC dysfunction and lipid accumulation in the aorta compared with control animals; however, these pathologic changes were not observed in atherosclerotic mice overexpressing dominant negative p90RSK (DN-p90RSK). Moreover, depletion of SENP2 in these mice abolished the protective effect of DN-p90RSK overexpression. We propose that p90RSK-mediated SENP2-T368 phosphorylation is a master switch in d-flow-induced signaling, leading to EC dysfunction and atherosclerosis.
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