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

CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis

Objective: To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Methods: Case report with neuroimaging and pathologic data. Results: A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. Conclusions: The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.Comment: 21 pages, 8 figure

Visual orbit for the low-mass binary Gliese 22 AC from speckle interferometry

Based on 14 data points obtained with near-infrared speckle interferometry and covering an almost entire revolution, we present a first visual orbit for the low-mass binary system Gliese 22 AC. The quality of the orbit is largely improved with respect to previous astrometric solutions. The dynamical system mass is 0.592 +- 0.065 solar masses, where the largest part of the error is due to the Hipparcos parallax. A comparison of this dynamical mass with mass-luminosity relations on the lower main sequence and theoretical evolutionary models for low-mass objects shows that both probably underestimate the masses of M dwarfs. A mass estimate for the companion Gliese 22 C indicates that this object is a very low-mass star with a mass close to the hydrogen burning mass limit.Comment: Accepted by Astronomy and Astrophysics, 6 pages, 2 figure

The Chromospheric Activity and Ages of M Dwarf Stars in Wide Binary Systems

We investigate the relationship between age and chromospheric activity for 139 M dwarf stars in wide binary systems with white dwarf companions. The age of each system is determined from the cooling age of its white dwarf component. The current limit for activity-age relations found for M dwarfs in open clusters is 4 Gyr. Our unique approach to finding ages for M stars allows for the exploration of this relationship at ages older than 4 Gyr. The general trend of stars remaining active for a longer time at later spectral type is confirmed. However, our larger sample and greater age range reveals additional complexity in assigning age based on activity alone. We find that M dwarfs in wide binaries older than 4 Gyr depart from the log-linear relation for clusters and are found to have activity at magnitudes, colors and masses which are brighter, bluer and more massive than predicted by the cluster relation. In addition to our activity-age results, we present the measured radial velocities and complete space motions for 161 white dwarf stars in wide binaries.Comment: 22 pages including 9 figures and 5 tables. Accepted for publication in The Astronomical Journa

Atmospheric Ice Accretion on Railway Overhead Powerline Conductors- A Numerical Case Study

Ice accretion on railway overhead contact wires/conductors can cause various critical operational and safety issues such as overloading, arc formation, mass imbalance, and wire galloping. The focus of this multiphase numerical study is to understand and analyze the ice accretion physics on railway overhead powerline conductors at various operating conditions. In this regard, two different geometric shape conductors of 12 mm diameter, 1) a grooved shape contact wire (like an actual railway conductor); 2) a standard circular shape contact wire are used. Computational Fluid Dynamics (CFD) based numerical simulations are carried out for both geometric configurations at different operating parameters such as wind speed, Liquid Water Content (LWC), cloud droplet size distribution, Median Volume Diameter (MVD), and atmospheric temperature. Analysis shows that variation in the operating weather parameters for both geometric configurations considerably affects the ice accretion, both in terms of accreted ice thickness and mass

The X-ray spectra of the flaring and quiescent states of AT Microscopii observed by XMM-Newton

The X-ray spectrum of the late-type M-dwarf binary AT Mic (dM4.5e+dM4.5e) is observed in the wavelength range 1 - 40 Angstrom by means of rgs and epic-mos on board XMM-Newton. During the exposure a flare occured. We have performed a 3-temperature fit and a DEM-modeling to the flaring and quiescent part of the spectrum. We report the coronal temperature distribution, emission measures, and abundances of the flaring and quiescent state of this bright X-ray source. The temperature range stretches from about 1 to 60 MK. The total volume emission measure in this temperature interval is ~12.2*10^51 cm^-3 for the quiescent state and ~19.5*10^51 cm^-3 for the flare state. This difference is due to the contribution of the hot temperature component. The high-resolution spectrum of AT Mic, obtained by rgs, is dominated by the H- and He-like transitions of C, N, O, and Ne and by Fe XVII lines, produced by the plasma with temperatures from 1 to 10 MK. The epic-mos spectrum below 10 Angstrom shows H- and He-like Ne, Si and the iron K-shell transitions. They are produced by the hot component (30 MK). The iron K-shell is more prominent in the flare state. The abundance pattern in the quiescent state of AT Mic shows the depletion of low-FIP elements relative to high-FIP elements, indicating the presence of an I(nverse)FIP effect in this active star. In the flare state, however, some flattening of this IFIP effect is present.Comment: 7 pages, 11 figures ordered as: 1, 2ab, 3, 4abc, 5ab, 6a