Introduction Neutrophils can generate extracellular net-like structures by releasing their DNA–histone complexes and antimicrobial peptides, which is called neutrophil extracellular traps (NETs). Various stimuli can induce NET formation. In particular, neutrophils and NET formation are abundant in tumor tissue. This study investigated how cancer cells induce NET formation and whether this NET formation promotes plasma thrombin generation and cancer progression. Methods Induction of NET formation by a pancreatic cancer cell line (AsPC-1) was assessed by measuring the histone–DNA complex level. The endogenous thrombin potential (ETP) was measured by thrombin generation assay. In vitro migration, invasion, and tubule formation assays were performed. The circulating levels of NET markers and hypercoagulability markers were assessed in 62 patients with pancreatobiliary malignancy and 30 healthy controls. Results AsPC-1 significantly induced NET formation in a dose-dependent manner. Conditioned medium (CM) from AsPC-1 also induced NETs. Interestingly, NET-formation was abolished by heat-inactivated CM, but not by lipid-extracted CM, suggesting an important role of protein components. A reactive oxygen species inhibitor did not inhibit cancer cell–induced NET formation, but prostaglandin E1 (PGE1, cyclic adenosine monophosphate inducer) and antithrombin did. NETs significantly increased ETP of normal plasma. Of note, NETs promoted cancer cell migration and invasion as well as angiogenesis, which were inhibited by histone-binding agents (heparin, polysialic acid), a DNA-degrading enzyme, and Toll-like receptor neutralizing antibodies. In patients with pancreatobiliary malignancy, elevated NET markers correlated well with hypercoagulability makers. Conclusion Our findings indicate that cancer cell–induced NET formation enhances both hypercoagulability and cancer progression and suggest that inhibitors of NET formation such as PGE1 and antithrombin can be potential therapeutics to reduce both hypercoagulability and cancer progression.

Temperature and precipitation changes over South Korea have been studied since 1954, both in terms of means and extreme events, using observational station data. Recurrence intervals are defined to examine trends in extreme events at each station. Generally, it is possible to describe trends in temperature and precipitation over South Korea as follows. The annual mean temperature shows an upward trend at a rate of 0.23°C decade −1 in the past four to five decades. There are some indications that climatic extremes have increased during recent decades. The diurnal temperature range increased in the later part of the time series (except for summer) as a result of a faster increase in maximum temperature than in minimum temperature. This is not consistent with the results reported elsewhere in the world. A wavelet analysis of wintertime temperatures indicates that the rapid warming in the recent decade may be associated with the warm phase of a decadal-interdecadal variation. The frequency of occurrence of extreme maximum temperature events shows an increasing trend, with higher values in the 1980s and 1990s. The frequency of occurrence of extreme minimum temperature events shows the opposite, with a statistically significant decreasing trend.

Fluid supported lipid bilayers provide an excellent platform for studying multivalent protein-ligand interactions because the two-dimensional fluidity of the membrane allows for lateral rearrangement of ligands in order to optimize binding. Our laboratory has combined supported lipid bilayer-coated microfluidic platforms with total internal reflection fluorescence microscopy (TIRFM) to obtain equilibrium dissociation constant (K D ) data for these systems. This high throughput, on-chip approach provides highly accurate thermodynamic information about multivalent binding events while requiring only very small sample volumes. Herein, we review some of the most salient findings from these studies. In particular, increasing ligand density on the membrane surface can provide a modest enhancement or attenuation of ligand-receptor binding depending upon whether the surface ligands interact strongly with each other. Such effects, however, lead to little more than one order of magnitude change in the apparent K D values. On the other hand, the lipophilicity and presentation of lipid bilayer-conjugated ligands can have a much greater impact. Indeed, changing the way a particular ligand is conjugated to the membrane can alter the apparent K D value by at least three orders of magnitude. Such a result speaks strongly to the role of ligand availability for multivalent ligand-receptor binding.

Herein, we describe a highly sensitive technique for detecting protein-ligand binding at the liquid/solid interface. The method is based upon modulation of the interfacial pH when the protein binds. This change is detected by ortho-Texas Red DHPE, which is doped into supported phospholipid bilayers and used as a pH sensitive dye. The dye molecule fluoresces strongly at acidic pH values, but not basic ones and has an apparent pKA of 7.8 in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes containing 0.5 mol% biotin-cap-PE. This method was used to detect anti-biotin/biotin binding interactions as well as the binding of cholera toxin B subunits to GM1. Since these proteins are negatively charged under the conditions of the experiment, the interface became slightly more acidic upon binding. In each case, the equilibrium dissociation constant was determined by following the rise in fluorescence as protein was introduced. This change is essentially linear with protein coverage under the conditions employed. For the biotin/anti-biotin system, it was determined that KD = 24 ± 5 nM, which is in excellent agreement with classical measurements made by total internal reflection fluorescence microscopy involving fluorophore-conjugated antibody molecules. Moreover, the limit of detection was ~350 fM at the 99% confidence level. This corresponds to 1 part in 69,000 of the KD value. Such a finding compares favorably with surface plasmon resonance studies of similar systems and conditions. The assay could be run in imaging mode to obtain multiple simultaneous measurements by using a CCD camera.

Nano-size TiO2 photocatalysts were prepared by sol-gel and ultrasonic-assisted sol-gel methods using two different sources of ultrasonicator, i.e., a bath type and tip type. The physicochemical characteristics of the catalysts were investigated by BET, XRD and TEM analyses and the photocatalytic properties of the TiO2 catalysts prepared by three different methods were compared. The intrinsic and extrinsic properties of TiO2, such as the particle size, surface area, pore-volume, pore-diameter, crystallinity as well as anatase, rutile and brookite phase ratios, could be controlled by the ultrasonic-assisted sol-gel method. During this preparation method, the effect of such important operating variables as the ultrasonic irradiation time, power density, the ultrasonic sources (bath-type and tip-type), magnetic stirring during synthesis, initial temperatures and size of the reactors are discussed here. It was found that each of the parameters played a significant role in controlling the properties of the TiO2 nano-particles. Among the three different methods, TiO2 photocatalysts prepared by ultrasonic (tip-US) assisted sol-gel possessed the smallest particle size, highest surface area and highest pore-volume than the catalysts prepared by the other two methods. 4-Chlorophenol was used as a pollutant to observe the photocatalytic degradation ability of the prepared photocatalysts and the TiO2 catalysts prepared by the bath-US ultrasonic-assisted sol-gel method were shown to be the most highly active. This is due to their high surface area and high pore-diameter. This study clearly demonstrates the importance and advantages of ultrasonication in the modification and improvement of the photocatalytic properties of mesoporous nano-size TiO2 particles.