The chemokine (C-X-C motif) ligand 1 (CXCL1) and its receptor CXCR2 are associated with metastasis potential. Our studies were designed to clarify the CXCL1 and CXCR2 expression patterns and to ...explore their potential role in gastric cancer
The expression of CXCL1 was determined in primary gastric cancer specimens using quantitative PCR, immunohistochemistry, and western blotting. To investigate the functional significance of CXCL1 expression, a CXCL1 expression vector and short hairpin RNA targeting the CXCL1 or CXCR2 were transfected into gastric cancer cell lines to examine the biological outcomes of these cells.
The expression of CXCL1 and CXCR2 was higher in gastric cancer tissues compared with adjacent noncancerous tissues. The upregulation of CXCL1 correlated significantly with tumor progression, advanced stage of gastric cancer patients, and was one of the independent prognostic factors for patient's survival. Furthermore, cancer cells expressing CXCL1 stably exhibited an increase in their migration and invasion ability, whereas CXCL1 or CXCR2 depletion significantly reduced the migration and invasion ability of each cell line.
These results provide strong evidence that CXCL1 plays an important role in gastric cancer progression and migration and suggest that CXCL1 is a promising marker for the detection and prognosis of gastric cancer.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The possible effect of directional larval swimming on the recruitment success of the Japanese eel, Anguilla japonica, was examined with a three-dimensional particle-tracking ocean circulation model ...using horizontal northwestward swimming and diel vertical migration (DVM). Four separate experiments included virtual larvae (v-larvae) movement from the spawning area over 290 days (total migration) and 160 days (stage A), from the STCC eddy region in 70 days (stage B), and from the origin of the Kuroshio in 60 days (stage C) to evaluate the effect of directional swimming and DVM compared to simple drifting. Passive or random swimming were not the most effective strategies for larvae dispersing from the spawning area because most v-larvae remained south of 20°N without entering the Kuroshio. Northwestward swimming resulted in wider dispersion and a better chance of successful recruitment, with v-larvae becoming widely distributed in the STCC eddy zone, arriving at the east coast of the Philippines (stage A), escaping the STCC eddy area and reaching the Kuroshio (stage B), and crossing the Kuroshio into the East China Sea shelf (stage C). DVM slightly shortened the migration period due to faster shallow layer ocean currents during nighttime. The NEC transported non-swimming v-larvae westward to the Kuroshio and occasionally northward into the Subtropical Countercurrent (STCC) area where eddies transported v-larvae westward into the Kuroshio, but less than with swimming. Directional swimming increased recruitment success, northwestward swimming was more effective than other directions, and a slower swimming speed was still better than no/random swimming in sensitivity tests. The present study demonstrated a first view of the possibility that Japanese eel larvae might be able to use a strategy of single-direction swimming to increase arrival at their recruitment areas.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health insurance claims and electronic health records (EHR) databases have been considered the preferred data sources with which to study drug safety and effectiveness in routine care. Linking claims ...data to EHR allows researchers to leverage the complementary advantages of each data source to enhance study validity. We propose a framework to evaluate the need for supplementing claims data with EHR and vice versa to optimize outcome ascertainment, exposure assessment, and confounding adjustment.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Japanese eel (Anguilla japonica) recruitment to Japan was very low during the early 2017-2018 recruitment season when most glass eels are usually caught, but catches increased in the late recruitment ...season when recruitment usually decreases. Concurrently, the Kuroshio meander south of Japan had formed again after the previous event ended in 2005. The role of the large meander and ocean circulation features such as the North Equatorial Current (NEC) in the unusual 2017-2018 Japanese eel recruitment timing-pattern was investigated using a three-dimensional particle tracking model that simulated swimming behaviors of virtual larvae (v-larvae) in addition to their drift in ocean currents. Four recruitment seasons were selected for when the Kuroshio large meander was present (2004-2005, 2017-2018) or absent (2009-2010, 2015-2016), and when NEC was shifted north (2004-2005, 2015-2016) or south (2009-2010, 2017-2018). The simulated recruitment timing-patterns were similar to the actual recent-year recruitment, with no early recruitment period v-larvae arrival to southern Japan and increased late period recruitment occurring. Rather than being related to the presence of the Kuroshio large meander, the late arrival appeared to be caused by a southward shifted, weak North Equatorial Current near the spawning area, a longer Subtropical Countercurrent eddy region retention time, and a weak Kuroshio during the early migration and recruitment period of those years. In the late recruitment period, the Kuroshio was stronger than other selected years near the East China Sea and south of Japan and v-larvae were transported more rapidly. The Kuroshio large meander may influence local eel recruitment in Japan, and the recirculation formed by the large meander could potentially enhance recruitment to the Tokai region. Oriented (northwestward) swimming v-larvae were less affected by the large meander, and showed higher recruitment success than those using along-current swimming. Although the Kuroshio large meander did not seem to be responsible for the unusual recruitment pattern in 2018, how Japanese eel larvae and glass eels actually cross out of the Kuroshio and reach coastal waters in Japan remains to be explored.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Activating mutations in FLT3 occur in ~30% of adult acute myeloid leukemia, primarily consisting of internal tandem duplication (ITD) mutations (~25%) and point mutations in the tyrosine kinase ...domain (~5%), commonly at the activation loop residue D835. Secondary kinase domain mutations in FLT3-ITD, particularly at the D835 residue are frequently associated with acquired clinical resistance to effective FLT3 tyrosine kinase inhibitors (TKIs). Molecular docking studies have suggested that D835 mutations primarily confer resistance by stabilizing an active Asp-Phe-Gly in ('DFG-in') kinase conformation unfavorable to the binding of type II FLT3 TKIs, which target a 'DFG-out' inactive conformation. We profiled the activity of active type II FLT3 TKIs against D835 kinase domain mutants that have been clinically detected to date. We found that type II inhibitors (quizartinib, sorafenib, ponatinib and PLX3397) retain activity against specific D835 substitutions. Modeling studies suggest that bulky hydrophobic substitutions (D835Y/V/I/F) at this residue are particularly resistant, whereas mutations that preserve interactions between D835 and S838 are relatively sensitive (D835E/N). All mutants retain sensitivity to the type I inhibitor crenolanib. These results suggest that patients with relatively sensitive D835 mutations should be included in clinical trials of type II FLT3 TKIs.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT We present scaling relations between the integrated Sunyaev-Zel'dovich effect (SZE) signal, , its X-ray analogue, , and total mass, , for the 45 galaxy clusters in the Bolocam X-ray SZ ...(BOXSZ) sample. All parameters are integrated within . values are measured using SZE data collected with Bolocam, operating at 140 GHz at the Caltech Submillimeter Observatory. The temperature, , and mass, , of the intracluster medium are determined using X-ray data collected with Chandra, and is derived from assuming a constant gas mass fraction. Our analysis accounts for several potential sources of bias, including selection effects, contamination from radio point sources, and the loss of SZE signal due to noise filtering and beam-smoothing effects. We measure the - scaling to have a power-law index of 0.84 0.07, and a fractional intrinsic scatter in of at fixed , both of which are consistent with previous analyses. We also measure the scaling between and , finding a power-law index of 1.06 0.12 and a fractional intrinsic scatter in at fixed mass of . While recent SZE scaling relations using X-ray mass proxies have found power-law indices consistent with the self-similar prediction of 5/3, our measurement stands apart by differing from the self-similar prediction by approximately 5 . Given the good agreement between the measured - scalings, much of this discrepancy appears to be caused by differences in the calibration of the X-ray mass proxies adopted for each particular analysis.
Marine hazards often occur unexpectedly. Long-term (> few weeks) projections are sometimes needed to predict the potential route of drifting targets (e.g. pumice, oil, shipwreck) in order to prevent ...further disaster, yet reliable long-term forecast data may be unavailable. The present study examined the long-term projection of pumice dispersion originating from the 2021 submarine eruption of Fukutoku-Oka-no-Ba volcano, Japan, based on hindcast reanalysis of the past 28 years of wind and ocean currents using the particle tracking method. The ensemble distribution showed a wide dispersion, which was dominated by the ocean currents. By contrast, wind provided a relatively uniform transport. Apart from the prevailing wind, typhoons also play a role in affecting pumice dispersion. The multi-year simulation provides a general view of pumice dispersion accounting for different uncertainty, which could be used for deducing the potential dispersion under different wind and ocean conditions.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Marine piracy has traditionally been a serious threat to marine security, highlighting the great significance of piracy risk assessment and prevention to the marine industry and global economy. This ...study uses data on piracy attacks between 1994 and 2017 to estimate the probability of a vessel being attacked by pirates and the success rate of piracy attacks. The results of the employed binary logistic regression model show that small vessels and open registry vessels are more likely to be targeted by pirates. Further, the probability of successful boarding by pirates is higher for a vessel at berth or anchor, at night, in territorial waters and port areas, and in South America, the South China Sea, and the Strait of Malacca. Moreover, the rate of successful boarding will decreases from 99.42% to 86.71% if crews take passive measures and decreases further to 9.39% if crews take active measures. These results can not only be used by stakeholders to estimate the likelihood of piracy incidents, but can also provide information on how and the extent to which the identified factors influence piracy, helping marine stakeholders take appropriate anti-piracy measures. Moreover, these results can also be used for crew training and education to counter pirates as well as to help insurance companies set a premium rate for the different risk levels calculated by the model.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We describe Sunyaev-Zel'dovich (SZ) effect measurements and analysis of the intracluster medium (ICM) pressure profiles of a set of 45 massive galaxy clusters imaged using Bolocam at the Caltech ...Submillimeter Observatory. We deproject the average pressure profile of our sample into 13 logarithmically spaced radial bins between 0.07R sub(500) and 3.5R sub(500), and we find that a generalized Navarro, Frenk, and White (gNFW) profile describes our data with sufficient goodness-of-fit and best-fit parameters (C sub(500), alpha , beta , gamma , P sub(0) = 1.18, 0.86, 3.67, 0.67, 4.29). We use X-ray data to define cool-core and disturbed subsamples of clusters, and we constrain the average pressure profiles of each of these subsamples. We find that, given the precision of our data, the average pressure profiles of disturbed and cool-core clusters are consistent with one another at R > 0.15/Goo, with cool-core systems showing indications of higher pressure at R <, ~ 0.15R sub(500). In addition, for the first time, we place simultaneous constraints on the mass scaling of cluster pressure profiles, their ensemble mean profile, and their radius-dependent intrinsic scatter between 0.1R sub(500) and 2.0R sub(500). The scatter among profiles is minimized at radii between Asymptotically = to0.2R sub(500) and Asymptotically = to0.5R sub(500), with a value of Asymptotically = to20%. These results for the intrinsic scatter are largely consistent with previous analyses, most of which have relied heavily on X-ray derived pressures of clusters at significantly lower masses and redshifts compared to our sample. Therefore, our data provide further evidence that cluster pressure profiles are largely universal with scatter of Asymptotically = to20%-40% about the universal profile over a wide range of masses and redshifts.
PDF
