Flight rescheduling of an airline underground delay program considering delay propagation in multiple airports

The purpose of this study is to reschedule flights for an airline's profit to correspond to the airport’s changed capacity. In the event of a ground delay program (GDP), the number of flights the airport can accommodate is reduced. We formulated a mixed-integer linear programming (MILP) model to reschedule flights. The MILP models were divided into two versions to handle the uncertainty of the future. In scenarios in which the GDP is changed again, an optimal model obtains solutions for each scenario. The stochastic model solution obtains a minimizing expectation cost of all scenarios. All flights are connected to both the origin and destination airports, and one aircraft may be used for more than one flight. Therefore, we considered delay propagation not only within the same airport but from other airports by extending the setup to include several airports at once. Because the objective of this study is to minimize the operation cost of airline, we also considered costs associated with airline resources such as aircrafts and crews. Related experiments were conducted including comparison between two suggested versions.</p

stationarity initial n=100 lambda=5

Mathematica code used to generate Figure

sj-pdf-1-pus-10.1177_09636625231217080 – Supplemental material for Communicating uncertainties regarding COVID-19 vaccination: Moderating roles of trust in science, government, and society

Supplemental material, sj-pdf-1-pus-10.1177_09636625231217080 for Communicating uncertainties regarding COVID-19 vaccination: Moderating roles of trust in science, government, and society by Jarim Kim, Jiyeon Lee, Jinha Baek and Jiyeon Ju in Public Understanding of Science</p

Integration of Automated Static Analysis Alert Classification and Prioritization with Auditing Tools: Special Focus on SCALe

This report summarizes technical progress and plans as of late September 2018 for developing a system to perform automated classification and advanced prioritization of static analysis alerts. Many features and fields have been added to the Source Code Analysis Laboratory (SCALe) static analysis alert auditing tool to support this functionality. This report describes the new features and fields, and how to use them. It also describes the plan to connect this enhanced version of SCALe to an architecture that will provide classification and prioritization via API calls, and provides the API definition that has been developed. A prototype that instantiates the architecture is being developed; future work will complete the prototype and integrate the latest version of SCALe with it

Insulin-Like Growth Factor 2 Silencing Restores Taxol Sensitivity in Drug Resistant Ovarian Cancer

<div><p>Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 <i>in vivo</i>. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated <i>in vitro</i> and <i>in vivo</i>. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone.</p></div

High IGF2 expression is associated with early recurrence, poor survival, and drug resistance.

<p>IGF2 expression and ovarian cancer survival. Using the cBioPortal for Cancer Genomics to analyze the data from the Cancer Genome Atlas study of ovarian serous cystadenocarcinoma, we compared the progression-free survival and overall survival in patients with high tumor levels of IGF2 mRNA (greater than 1.6 standard deviations above the mean; gray line) and those with normal tumor levels of IGF2 mRNA (all other patients; black line). Patients with high IGF2 mRNA levels had significantly shortened progression-free survival (A) and overall survival (B). (C) IGF2 expression in sensitive and resistant cell lines. By RT-qPCR, we measured the IGF2 mRNA level in six drug resistant ovarian carcinoma cell lines and their three cell lines of origin. All drug resistant cell lines have significantly higher IGF2 mRNA expression compared to their sensitive cell line of origin. Bars show the mean±SEM of IGF2 mRNA expression score for at least two independent experiments for each cell line, each done in triplicate, and the symbol above the bar indicates the statistical significance comparing that resistant cell line with its parental counterpart; *p<0.05, ***p<0.001, ****p<0.0001 by One-way ANOVA with Bonferroni posttest. (D) ABCB1 expression. ABCB1 mRNA expression levels were measured by RT-qPCR in HEY, HEY-T30, A2780 and A2780-T15. HEY-T30 has higher ABCB1 mRNA expression compared to the other cell lines. Bars show the mean±SEM of ABCB1 mRNA expression score for at least four independent experiments for each cell line, each done in triplicate, (E) ABCB1 DNA copy number. By qPCR performed on genomic DNA, HEY-T30 has a six-fold increase in ABCB1 DNA copy number indicating gene amplification. Bars show the mean±SEM of two independent experiments, each done in triplicate.</p

Trapping Alkali Halide Cluster Ions Inside the Cucurbit[7]uril Cavity

In this study, the distinctive behavior of cucurbit[n]uril (CB[n]), which captures a variety of alkali halide clusters inside the cavity during the droplet evaporation, has been investigated by using ion mobility spectrometry–mass spectrometry. Complexes of CB[7] with various alkali chloride cluster cations or anions generated during the electrospray ionization were studied, and their collision cross-section (CCS) values were obtained to determine whether these clusters were trapped inside the cavity or not. It was found that the clusters smaller than a specific critical size were trapped inside the CB[7] cavity in the gas phase, although trapping of alkali halide clusters at the given concentration is supposed to be unfavorable in solution. We suggest that the rapid solvent evaporation rapidly increases ion concentrations and subsequently forms alkali-chloride contact ion pairs; therefore, it may provide a specific environment to enable the formation of the inclusion complexes

Characterization of the drug resistance phenotype.

<p>Proliferation kinetics of cell lines. Cells were grown in complete media with the indicated concentration of Taxol in 6-well dishes, and cells from duplicate wells counted every 24 hours. (A) HEY-T30 cells in the presence or absence of 30 nM Taxol proliferate more slowly than HEY cells (p<0.05, Repeated Measures Two-way ANOVA, Bonferroni posttest). (B) A2780-T15 in the presence of 2 nM and 15 nM Taxol grow similarly to A2780. However, in the absence of Taxol, A2780-T15 proliferates more slowly, suggesting Taxol dependence (p<0.01, Two-way ANOVA, Bonferroni posttest). Each growth curve represents the mean of at least two independent experiments each done in duplicates, each point is represented as the mean±SEM. (C) IC₅₀’s of chemotherapeutic drugs in sensitive and resistant cell lines. In 96-well plates, cells were treated with serial dilutions of the indicated drugs and the concentration of 50% proliferation inhibition (IC₅₀) determined using the SRB cytotoxicity assay. HEY-T30 are cross-resistant to ixabepilone and to vinblastine. There is modest cross-resistance to doxorubicin but not to CDDP. A2780-T15 are cross-resistant to ixabepilone, and modestly cross-resistant to doxorubicin and CDDP, but more sensitive to vinblastine. Data are presented as the mean±SEM of at least three independent experiments performed with six replicates. P-values calculated by unpaired t-test. (D, E) Comparison of HEY-T30 and HEY xenograft response to Taxol. Following subcutaneous injection of HEY-T30 or HEY cells, mice were divided into treatment groups of 6 animals each. When the average xenograft volume reached 120 mm³, Taxol treatment was administered at the maximal tolerated dose (MTD) of 20 mg/kg intraperitoneally every three days for five treatments (treatment days: 0, 3, 6, 9, 12), resulting in a cumulative dose of 100 mg/kg. Control animals received intraperitoneal injections of the diluent (5% dextrose in water; D5W) according to the same schedule. Tumors were measured every three days, and mean tumor volumes±SEM for each group shown at each time point. HEY xenografts responded to Taxol treatment, which potently suppressed tumor growth (Fig. 2D; dashed blue line). HEY-T30 xenografts did not respond to Taxol treatment (Fig. 2E; dashed orange line) and grew at a similar rate as vehicle-treated HEY-T30 xenografts. HEY Taxol vs HEY D5W on day 19, p<0.001; unpaired t-test.</p

IGF2 knockdown alters the cellular response to Taxol.

<p>Taxol-induced G2/M arrest. (A) HEY-T30 cells were treated for 16 hours with the indicated concentrations of Taxol, and DNA content analyzed by flow cytometry. In HEY-T30 cells, G2/M arrest occurred after Taxol treatment at 375 nM but not lower concentrations. (B) shows HEY-T30 shIGF2-p (gray shaded) and HEY-T30 shScrambled (black dotted line) treated with DMSO or with Taxol (50 nM) for 16 hours. The HEY-T30 shIGF2-p cells showed G2/M arrest in response to Taxol while HEY-T30 shScrambled cells did not, at this Taxol concentration. Data from one representative experiment, of two independent experiments, are shown. (C) Apoptosis analysis. Similar to (B), cells were treated with Taxol (50 nM) for 16 hours, harvested and stained with F2N12S (membrane asymmetry marker) and Sytox (dead cell marker), and analyzed by flow cytometry. Cell populations were gated in quadrants for quantitation, where the early apoptotic cell population is delineated by their decreased 585 nm/530 nm ratio due to loss of membrane asymmetry compared to non-apoptotic cells, and are Sytox-negative. Taxol treatment of HEY-T30 shIGF2-p cells resulted in a higher percentage of apoptotic cells compared to treatment with vehicle (DMSO), and Taxol-induced apoptosis was significantly enhanced in HEY-T30 shIGF2 cells compared to HEY-T30 shScrambled, at this time point. **p<0.01; One-way ANOVA with Bonferroni posttest. The bars show the mean±SEM of two independent experiments.</p

Trapping Alkali Halide Cluster Ions Inside the Cucurbit[7]uril Cavity

In this study, the distinctive behavior of cucurbit[n]uril (CB[n]), which captures a variety of alkali halide clusters inside the cavity during the droplet evaporation, has been investigated by using ion mobility spectrometry–mass spectrometry. Complexes of CB[7] with various alkali chloride cluster cations or anions generated during the electrospray ionization were studied, and their collision cross-section (CCS) values were obtained to determine whether these clusters were trapped inside the cavity or not. It was found that the clusters smaller than a specific critical size were trapped inside the CB[7] cavity in the gas phase, although trapping of alkali halide clusters at the given concentration is supposed to be unfavorable in solution. We suggest that the rapid solvent evaporation rapidly increases ion concentrations and subsequently forms alkali-chloride contact ion pairs; therefore, it may provide a specific environment to enable the formation of the inclusion complexes