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

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

Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males

Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this ‘glucose memory facilitation effect’ are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual’s sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic–pituitary–adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14–17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic–pituitary–adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety

Output feedback tracking of ships

Abstract-In this brief, we consider output feedback tracking of ships with position and orientation measurements only. Ship dynamics are highly nonlinear, and for tracking control, as opposed to dynamic positioning, these nonlinearities have to be taken into account in the control design. We propose an observer-controller scheme which takes into account the complete ship dynamics, including Coriolis and centripetal forces and nonlinear damping, and results in a semi-globally uniformly stable closed-loop system. Furthermore, a gain tuning procedure for the observer-controller scheme is developed. Experimental results are presented where the observer-controller scheme is implemented onboard a Froude scaled 1:70 model supply ship. The experimentally obtained results are compared with simulation results under ideal conditions and both support the theoretical results on semi-global exponential stability of the closed-loop system

Selvopplevd oral helse hos eldre i Troms i alderen 67 til 79 år

Mål med studien: Målet med oppgaven var å kartlegge den selvopplevde orale helsen hos et utvalg eldre i aldersgruppen 67 til 79 år i Troms fylke. Vi ville også undersøke hvordan den selvopplevde tannhelsen påvirkes av tannstatus, munntørrhet og selvopplevd generell helse. Material og metode: Oppgaven baserer seg på materiale innhentet fra prosjektet «Tromstannen – munnhelse i Troms fylkeskommune» fra 2013. Våre analyser er basert på 264 respondenter i aldersgruppen 67-79år. Svar fra spørreskjema ble koblet mot data fra kliniske undersøkelser (røntgenbilder og kliniske foto). I tillegg gjennomførte vi litteratursøk på blant annet Pubmed.gov. Resultater: Resultatene viser at få har proteser, og at andelen med egne tenner er høy. Vi fikk bekreftet hypotesene «Eldre med 20 eller flere tenner har bedre selvopplevd tannhelse», «Pasienter med protese har dårlig selvopplevd tannhelse» og «Mennesker med nedsatt generell helse har dårlig selvopplevd tannhelse». Mens hypotesen «Munntørrhet gir dårligere selvopplevd tannhelse» ble avkreftet. Konklusjon: Tannstatusen i Nord-Norge synes å ha bedret seg betraktelig i løpet av de siste 20 årene, og er nå på samme nivå som resten av landet. Antall tenner spiller en viktig rolle både for egenvurdering av tannhelse og den generelle helse

Does the information in the phase of low frequency LFP reflect the low frequency envelope of local spike rates?

Recently, it has been shown that when the timing of spikes is measured relative to the phase of the cortical local field potentials (LFP), spikes can carry substantial more information about an external stimulus [1]. Experimental studies in sensory cortices of macaque have shown that the extra information obtained with such phase-of-firing codes above that in the firing rate alone ranges from 55 in primary visual cortex [1] to more than 100 in primary auditory cortex [2]. Here, we use a mathematical model that relates local spike trains and the resulting LFP, to explain the emergence of the phase-of-firing codes in cortex. The model is based on the one proposed in [3] and incorporates two types of integration over the spiking activity: i) a time convolution that results from the filtering properties of neural structures [4], which embeds history effects in LFP from past spiking activity, and ii) an integration step over the activity of neurons in the neighbourhood of the measuring electrode. When the spikes recorded from macaque primary visual cortex were used to synthesize the LFP, the model could reproduce the phase-of-firing information found using the real LFP, as shown in Figure 1. This suggests that an important component of phase-of-firing information originates from the surrounding neural population and past spiking activity. The next question that arises is what is the relative contribution of the neuron population size and the length of the firing rate history embedded in the LFP. We are currently investigating this question by parametrically varying both the population size and time integration ranges in generating the synthetic LFP

The Density of Coronal Plasma in Active Stellar Coronae

We have analyzed high-resolution X-ray spectra of a sample of 22 active stars observed with the High Energy Transmission Grating Spectrometer on {\em Chandra} in order to investigate their coronal plasma density. Densities where investigated using the lines of the He-like ions O VII, Mg XI, and Si XIII. While Si XIII lines in all stars of the sample are compatible with the low-density limit, Mg XI lines betray the presence of high plasma densities ($> 10^{12}$ cm$^{-3}$) for most of the sources with higher X-ray luminosity ($> 10^{30}$ erg/s); stars with higher $L_X$ and $L_X/L_{bol}$ tend to have higher densities at high temperatures. Ratios of O VII lines yield much lower densities of a few $10^{10}$ cm$^{-3}$, indicating that the ``hot'' and ``cool'' plasma resides in physically different structures. Our findings imply remarkably compact coronal structures, especially for the hotter plasma emitting the Mg XI lines characterized by coronal surface filling factor, $f_{MgXI}$, ranging from $10^{-4}$ to $10^{-1}$, while we find $f_{OVII}$ values from a few $10^{-3}$ up to $\sim 1$ for the cooler plasma emitting the O VII lines. We find that $f_{OVII}$ approaches unity at the same stellar surface X-ray flux level as solar active regions, suggesting that these stars become completely covered by active regions. At the same surface flux level, $f_{MgXI}$ is seen to increase more sharply with increasing surface flux. These results appear to support earlier suggestions that hot $10^7$ K plasma in active coronae arises from flaring activity, and that this flaring activity increases markedly once the stellar surface becomes covered with active regions.Comment: 53 pages, 19 figures, accepted for publication in Astrophysical Journal. A version of the paper with higher quality figures is available from http://www.astropa.unipa.it/Library/preprint.htm

Microtubules in Bacteria: Ancient Tubulins Build a Five-Protofilament Homolog of the Eukaryotic Cytoskeleton

Microtubules play crucial roles in cytokinesis, transport, and motility, and are therefore superb targets for anti-cancer drugs. All tubulins evolved from a common ancestor they share with the distantly related bacterial cell division protein FtsZ, but while eukaryotic tubulins evolved into highly conserved microtubule-forming heterodimers, bacterial FtsZ presumably continued to function as single homopolymeric protofilaments as it does today. Microtubules have not previously been found in bacteria, and we lack insight into their evolution from the tubulin/FtsZ ancestor. Using electron cryomicroscopy, here we show that the tubulin homologs BtubA and BtubB form microtubules in bacteria and suggest these be referred to as “bacterial microtubules” (bMTs). bMTs share important features with their eukaryotic counterparts, such as straight protofilaments and similar protofilament interactions. bMTs are composed of only five protofilaments, however, instead of the 13 typical in eukaryotes. These and other results suggest that rather than being derived from modern eukaryotic tubulin, BtubA and BtubB arose from early tubulin intermediates that formed small microtubules. Since we show that bacterial microtubules can be produced in abundance in vitro without chaperones, they should be useful tools for tubulin research and drug screening