Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: potential impact on angiogenesis and tumor growth

In the context of radiotherapy, collateral effects of ablative ionizing radiation (AIR) on stromal components of tumors remains understudied. In this work, cancer-associated fibroblasts (CAFs) isolated from freshly resected human lung tumors were exposed to AIR (1x18Gy) and analyzed for their release of paracrine factors. Inflammatory mediators and regulators of angiogenesis and tumor growth were analyzed by multiplex protein assays in conditioned medium (CM) from irradiated and non-irradiated CAFs. Additionally, the profile of secreted proteins was examined by proteomics. In functional assays, effects of CAF-CM on proliferative and migratory capacity of lung tumor cells (H-520/H-522) and endothelial cells (HUVECs), and on the tube-forming capacity of endothelial cells was assessed. Our data show that exposure of CAFs to ablative doses of ionizing radiation results in a) down-regulated release of angiogenic factors SDF-1, angiopoietin and thrombospondin-2; b) up-regulated release of growth factor bFGF from most donors, and c) unaffected expression-levels of HGF and inflammatory mediators IL-6, IL-8, IL-1ƒÒ and TNF-£. Conditioned medium from irradiated and control CAFs did not affect differently the proliferative or migratory capacity of tumor cells (H-520/H-522), whereas migratory capacity of endothelial HUVEC cells was partially reduced in the presence of irradiated CAF conditioned medium. Overall we conclude that AIR mediates a transformation on the secretory profile of CAFs that could influence the behavior of other cells in the tumor tissue and hence guide to some extent therapeutic outcomes. The downstream consequences of the changes observed in this study merits further investigations

The Patterns of High-Level Magnetic Activity Occurring on the Surface of V1285 Aql: The OPEA Model of Flares and DFT Models of Stellar Spots

Statistically analyzing Johnson UBVR observations of V1285 Aql during the three observing seasons, both activity level and behavior of the star are discussed in respect to obtained results. We also discuss the out-of-flare variation due to rotational modulation. Eighty-three flares were detected in the U-band observations of season 2006 . First, depending on statistical analyses using the independent samples t-test, the flares were divided into two classes as the fast and the slow flares. According to the results of the test, there is a difference of about 73 s between the flare-equivalent durations of slow and fast flares. The difference should be the difference mentioned in the theoretical models. Second, using the one-phase exponential association function, the distribution of the flare-equivalent durations versus the flare total durations was modeled. Analyzing the model, some parameters such as plateau, half-life values, mean average of the flare-equivalent durations, maximum flare rise, and total duration times are derived. The plateau value, which is an indicator of the saturation level of white-light flares, was derived as 2.421{\pm}0.058 s in this model, while half-life is computed as 201 s. Analyses showed that observed maximum value of flare total duration is 4641 s, while observed maximum flare rise time is 1817 s. According to these results, although computed energies of the flares occurring on the surface of V1285 Aql are generally lower than those of other stars, the length of its flaring loop can be higher than those of more active stars.Comment: 44 pages, 10 figures, 5 tables, 2011PASP..123..659

The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel

<p>Abstract</p> <p>Background</p> <p>Different platelet function tests can be used to evaluate the degree of achieved platelet inhibition in patients treated with clopidogrel. The presence of CYP 2C19*2 polymorphism can reduce the formation of the active metabolite of clopidogrel, resulting in less platelet inhibition.</p> <p>Patients and Methods</p> <p>Patients with symptomatic coronary artery disease, all on chronic single aspirin treatment were randomized to continue on aspirin or change to clopidogrel. In 219 randomly selected clopidogrel treated patients, platelet reactivity was evaluated by VASP-PRI determination and by use of VerifyNow P2Y12-PRU. The CYP 2C19*2 G/A polymorphism was further determined.</p> <p>Results</p> <p>The total frequency of clopidogrel resistance was 29.0% by VASP-PRI and 31.6% by VerifyNow-PRU. The number of patients being hetero- and homozygous combined for the CYP 2C19*2 polymorphism (GA/AA) was 64 (29%). Platelet reactivity was significantly higher in patients with the polymorphism compared to wild-type patients (GG). VASP-PRI was 50.9% (SD19) in patients having the polymorphism compared to 38.3% (SD21) in patients with the GG genotype (p = 0.001). Correspondingly, the mean PRU was 165 (SD67) compared to 124 (SD69) (p < 0.001). The frequency of clopidogrel resistance in patients with the polymorphism was 32% compared to 16% in wild-type patients when defined by VASP-PRI (p = 0.006). When defined by PRU (VerifyNow), the corresponding frequencies were 53% and 22% (p < 0.001).</p> <p>Conclusions</p> <p>Clopidogrel treated patients with the CYP 2C19*2 polymorphism have significantly increased platelet reactivity compared to patients with the wild-type, evaluated with the VASP determination, and even more pronounced with the VerifyNow P2Y12 method.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00222261">NCT00222261</a></p

Stability Analysis for Set-based Control within the Singularity-robust Multiple Task-priority Inverse Kinematics Framework

Inverse kinematics algorithms are commonly used in robotic systems to accomplish desired behavior, and several methods exist to ensure the achievement of several tasks simultaneously. The multiple task-priority inverse kinematics framework allows tasks to be considered in a prioritized order by projecting task velocities through the nullspaces of higher priority tasks. This paper extends this framework to handle set-based tasks, i.e. tasks with a range of valid values, in addition to equality tasks, which have a specific desired value. Examples of such tasks are joint limit and obstacle avoidance. The proposed method is proven to ensure asymptotic convergence of the equality task errors and the satisfaction of all high-priority set-based tasks. Simulations results confirm the effectiveness of the proposed approach.(c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works

Bound states of 3He at the edge of a 4He drop on a cesium surface

We show that small amounts of 3He atoms, added to a 4He drop deposited on a flat cesium surface at zero temperature, populate bound states localized at the contact line. These edge states show up for drops large enough to develop well defined surface and bulk regions together with a contact line, and they are structurally different from the well-known Andreev states that appear at the free surface and at the liquid-solid interface of films. We illustrate the one-body density of 3He in a drop with 1000 4He atoms, and show that for sufficiently large number of impurities, the density profiles spread beyond the edge, coating both the curved drop surface and its flat base and eventually isolating it from the substrate.Comment: 10 pages and 7 figures. Submitted to PR

Fe XIII coronal line emission in cool M dwarfs

We report on a search for the Fe xiii forbidden coronal line at 3388.1 \AA in a sample of 15 M-type dwarf stars covering the whole spectral class as well as different levels of activity. A clear detection was achieved for LHS 2076 during a major flare and for CN Leo, where the line had been discovered before. For some other stars the situation is not quite clear. For CN Leo we investigated the timing behaviour of the Fe xiii line and report a high level of variability on a timescale of hours which we ascribe to microflare heating.Comment: 13 pages, 10 figure

Photometric Variability in the Ultracool Dwarf BRI 0021-0214: Possible Evidence for Dust Clouds

We report CCD photometric monitoring of the nonemission ultracool dwarf BRI 0021-0214 (M9.5) obtained during 10 nights in 1995 November and 4 nights in 1996 August, with CCD cameras at 1 m class telescopes on the observatories of the Canary Islands. We present differential photometry of BRI 0021-0214, and we report significant variability in the I-band light curve obtained in 1995. A periodogram analysis finds a strong peak at a period of 0.84 day. This modulation appears to be transient because it is present in the 1995 data but not in the 1996 data. We also find a possible period of 0.20 day, which appears to be present in both the 1995 and 1996 datasets. However, we do not find any periodicity close to the rotation period expected from the spectroscopic rotational broadening (< 0.14 day). BRI 0021-0214 is a very inactive object, with extremely low levels of Halpha and X-ray emission. Thus, it is unlikely that magnetically induced cool spots can account for the photometric variability. The photometric variability of BRI 0021-0214 could be explained by the presence of an active meteorology that leads to inhomogeneous clouds on the surface. The lack of photometric modulation at the expected rotational period suggests that the pattern of surface features may be more complicated than previously anticipated.Comment: Accepted for publication in ApJ. 26 pages, 13 figures include

Microwave signatures of ice hydrometeors from ground-based observations above Summit, Greenland

Multi-instrument, ground-based measurements provide unique and comprehensive data sets of the atmosphere for a specific location over long periods of time and resulting data compliment past and existing global satellite observations. This paper explores the effect of ice hydrometeors on ground-based, high-frequency passive microwave measurements and attempts to isolate an ice signature for summer seasons at Summit, Greenland, from 2010 to 2013. Data from a combination of passive microwave, cloud radar, radiosonde, and ceilometer were examined to isolate the ice signature at microwave wavelengths. By limiting the study to a cloud liquid water path of 40 g m−2 or less, the cloud radar can identify cases where the precipitation was dominated by ice. These cases were examined using liquid water and gas microwave absorption models, and brightness temperatures were calculated for the high-frequency microwave channels: 90, 150, and 225 GHz. By comparing the measured brightness temperatures from the microwave radiometers and the calculated brightness temperature using only gas and liquid contributions, any residual brightness temperature difference is due to emission and scattering of microwave radiation from the ice hydrometeors in the column. The ice signature in the 90, 150, and 225 GHz channels for the Summit Station summer months was isolated. This measured ice signature was then compared to an equivalent brightness temperature difference calculated with a radiative transfer model including microwave single-scattering properties for several ice habits. Initial model results compare well against the 4 years of summer season isolated ice signature in the high-frequency microwave channels