Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro

In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in an extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc. Although various computational models have been proposed to explain the role of each of these biochemical and biomechanical effects, the understanding of the mechanisms underlying in vitro angiogenesis is still incomplete. Most explanations focus on predicting the whole vascular network or sprout from the underlying cell behavior, and do not check if the same model also correctly captures the intermediate scale: the pairwise cell-cell interactions or single cell responses to ECM mechanics. Here we show, using a hybrid cellular Potts and finite element computational model, that a single set of biologically plausible rules describing (a) the contractile forces that endothelial cells exert on the ECM, (b) the resulting strains in the extracellular matrix, and (c) the cellular response to the strains, suffices for reproducing the behavior of individual endothelial cells and the interactions of endothelial cell pairs in compliant matrices. With the same set of rules, the model also reproduces network formation from scattered cells, and sprouting from endothelial spheroids. Combining the present mechanical model with aspects of previously proposed mechanical and chemical models may lead to a more complete understanding of in vitro angiogenesis.Comment: 25 pages, 6 figures, accepted for publication in PLoS Computational Biolog

Randomized clinical trials to identify optimal antibiotic treatment duration

Background Antibiotic resistance is a major barrier to the continued success of antibiotic treatment. Such resistance is often generated by overly long durations of antibiotic treatment. A barrier to identifying the shortest effective treatment duration is the cost of the sequence of clinical trials needed to determine shortest optimal duration. We propose a new method to identify the optimal treatment duration of an antibiotic treatment regimen. Methods Subjects are randomized to varying treatment durations and the cure proportions of these durations are linked using a logistic regression model, making effective use of information across all treatment duration groups. In this paper, Monte Carlo simulation is used to evaluate performance of such a model. Results Using a hypothetical dataset, the logistic regression model is seen to provide increased precision in defining the point estimate and confidence interval (CI) of the cure proportion at each treatment duration. When applied to the determination of non-inferiority, the regression model allows identification of the shortest duration meeting the predefined non-inferiority margin. Conclusions This analytic strategy represents a practical way to develop shortened regimens for tuberculosis and other infectious diseases. Application of this strategy to clinical trials of antibiotic therapy could facilitate decreased antibiotic usage, reduce cost, minimize toxicity, and decrease the emergence of antibiotic resistance

An X-ray Survey of Galaxies in Pairs

Results are reported from the first survey of X-ray emission from galaxies in pairs. The sample consists of fifty-two pairs of galaxies from the Catalog of Paired Galaxies Karachentsev (1972) whose coordinates overlap ROSAT Position Sensitive Proportional Counter pointed observations. The mean observed log l_x for early-type pairs is 41.35 +/-0.21 while the mean log l_x predicted using the l_x-l_b relationship for isolated early-type galaxies is 42.10 +/-0.19. With 95% confidence, the galaxies in pairs are underluminous in the X-ray, compared to isolated galaxies, for the same l_b. A significant fraction of the mixed pair sample also appear similarly underluminous. A spatial analysis shows that the X-ray emission from pairs of both types typically has an extent of ~10 - 50 kpc, much smaller than group intergalactic medium and thus likely originates from the galaxies. CPG 564, the most X-ray luminous early-type pair, 4.7x10^42 ergs/sec, is an exception. The extent of it's X-ray emission, >169 kpc, and HWHM, ~80 kpc, is comparable to that expected from an intergalactic medium. The sample shows only a weak correlation, ~81% confidence, between l_x and l_b, presumably due to variations in gas content within the galaxies. No correlation between l_x and the pair velocity difference, separation, or far-infrared luminosity is found though the detection rate is low, 22%.Comment: 40 pages, 6 jpg figures, ApJ (in press

HST NICMOS Images of the HH 7/11 Outflow in NGC1333

We present near infrared images in H2 at 2.12um of the HH 7/11 outflow and its driving source SVS 13 taken with HST NICMOS 2 camera, as well as archival Ha and [SII] optical images obtained with the WFPC2 camera. The NICMOS high angular resolution observations confirm the nature of a small scale jet arising from SVS 13, and resolve a structure in the HH 7 working surface that could correspond to Mach disk H2 emission. The H2 jet has a length of 430 AU (at a distance of 350 pc), an aspect ratio of 2.2 and morphologically resembles the well known DG Tau optical micro-jet. The kinematical age of the jet (approx. 10 yr) coincides with the time since the last outburst from SVS 13. If we interpret the observed H2 flux density with molecular shock models of 20-30 km/s, then the jet has a density as high as 1.e+5 cc. The presence of this small jet warns that contamination by H2 emission from an outflow in studies searching for H2 in circumstellar disks is possible. At the working surface, the smooth H2 morphology of the HH 7 bowshock indicates that the magnetic field is strong, playing a major role in stabilizing this structure. The H2 flux density of the Mach disk, when compared with that of the bowshock, suggests that its emission is produced by molecular shocks of less than 20 km/s. The WFPC2 optical images display several of the global features already inferred from groundbased observations, like the filamentary structure in HH 8 and HH 10, which suggests a strong interaction of the outflow with its cavity. The H2 jet is not detected in {SII] or Ha, however, there is a small clump at approx. 5'' NE of SVS 13 that could be depicting the presence either of a different outburst event or the north edge of the outflow cavity.Comment: 13 pages, 5 figures (JPEGs

The Relation between Radio Polarization and Gamma-ray Emission in AGN Jets

We have compared the parsec-scale jet linear polarization properties of the Fermi LAT-detected and non-detected sources in the complete flux-density-limited (MOJAVE-1) sample of highly beamed AGN. Of the 123 MOJAVE sources, 30 were detected by the LAT during its first three months of operation. We find that during the era since the launch of Fermi, the unresolved core components of the LAT-detected jets have significantly higher median fractional polarization at 15 GHz. This complements our previous findings that these LAT sources have higher apparent jet speeds, brightness temperatures and Doppler factors, and are preferentially found in higher activity states.Comment: 6 pages, 3 figures, to appear in the proceedings of "High Energy Phenomena In Relativistic Outflows II" (Buenos Aires, Argentina, October 26-30, 2009) International Journal of Modern Physics

The RASSCALS: An X-ray and Optical Study of 260 Galaxy Groups

We describe the ROSAT All-Sky Survey-Center for Astrophysics Loose Systems (RASSCALS), the largest X-ray and optical survey of low mass galaxy groups to date. We draw 260 groups from the combined Center for Astrophysics and Southern Sky Redshift Surveys, covering one quarter of the sky to a limiting Zwicky magnitude of 15.5. We detect 61 groups (23%) as extended X-ray sources. The statistical completeness of the sample allows us to make the first measurement of the X-ray selection function of groups, along with a clean determination of their fundamental scaling laws. We find robust evidence of similarity breaking in the relationship between the X-ray luminosity and velocity dispersion. Groups with sigma < 340 km/s are overluminous by several orders of magnitude compared to the familiar LX ~ sigma^4 law for higher velocity dispersion systems. An understanding of this break depends on the detailed structure of groups with small velocity dispersions sigma < 150 km/s.Comment: 16 pages, including 6 figures. To appear in The Astrophysical Journa

Laser Guide Star Adaptive Optics Integral Field Spectroscopy of a Tightly Collimated Bipolar Jet from the Herbig Ae star LkHa 233

We have used the integral field spectrograph OSIRIS and laser guide star adaptive optics at Keck Observatory to obtain high angular resolution (0.06"), moderate spectral resolution (R ~ 3800) images of the bipolar jet from the Herbig Ae star LkHa 233, seen in near-IR [Fe II] emission at 1.600 & 1.644 microns. This jet is narrow and tightly collimated, with an opening angle of only 9 degrees, and has an average radial velocity of ~ 100 km/s. The jet and counterjet are asymmetric, with the red-shifted jet much clumpier than its counterpart at the angular resolution of our observations. The observed properties are in general similar to jets seen around T Tauri stars, though it has a relatively large mass flux of (1.2e-7 +- 0.3e-7) M_sun/year, near the high end of the observed mass flux range around T Tauri stars. We also spatially resolve an inclined circumstellar disk around LkHa 233, which obscures the star from direct view. By comparison with numerical radiative transfer disk models, we estimate the disk midplane to be inclined i = 65 +- 5 degrees relative to the plane of the sky. Since the star is seen only in scattered light at near-infrared wavelengths, we detect only a small fraction of its intrinsic flux. Because previous estimates of its stellar properties did not account for this, either LkHa 233 must be located closer than the previously believed, or its true luminosity must be greater than previously supposed, consistent with its being a ~4 M_sun star near the stellar birthline.Comment: Accepted for publication in the Ap

HeI 1.083 micron emission and absorption in DG Tau: line excitation in jet, hot wind, and accretion flow

We present long-slit spectroscopy and spectro-astrometry of HeI 1.083 micron emission in the T Tauri star, DG Tau. We identify three components in the HeI feature: (1) a blueshifted emission component atv -200 km s^-1, (2) a bright emission component at zero-velocity with a FWZI of ~500 km s^-1, and (3) a blueshifted absorption feature at velocities between -250 and -500 km s^-1. The position and velocity of the blueshifted HeI emission coincide with a high-velocity component (HVC) of the [FeII] 1.257 micron emission, which arises from a jet within an arcsecond of the star. The presence of such a high excitation line (excitation energy ~ 20 eV) within the jet supports the scenario of shock heating. The bright HeI component does not show any spatial extension, and it is likely to arise from magnetospheric accretion columns. The blueshifted absorption shows greater velocities than that in H-alpha, suggesting that these absorption features arise from the accelerating wind close to the star.Comment: 10 pages including 2 figures, accepted for publication in the Astrophysical Journal Letter

Do HIV treatment eligibility expansions crowd out the sickest? Evidence from rural South Africa

OBJECTIVE: The 2015 WHO recommendation to initiate all HIV patients on antiretroviral therapy (ART) at diagnosis could potentially overextend health systems and crowd out sicker patients, mitigating the policy's impact. We evaluate whether South Africa's prior eligibility expansion from CD4 ≤200 to CD4 ≤350 cells/μL reduced ART uptake in the sickest patients. METHODS: Using data on all patients presenting to the Hlabisa HIV Treatment and Care Program in KwaZulu-Natal from April 2010 - June 2012 (n=13,809), we assessed the impact of the August 2011 eligibility expansion on the number of patients seeking care, number initiating ART, and time from HIV diagnosis to ART initiation among patients always eligible (CD4 0-200), newly eligible (CD4 201-350), and not yet eligible by CD4 count (>350). We used interrupted time series methods to control for long-run trends and isolate the effect of the policy. RESULTS: Expanding ART eligibility led to an increased number of patients initiating ART per month [+95.5; 95% CI (-1.3; 192.3)]. Newly eligible patients (CD4 201-350) initiated treatment 47% faster than before (95% CI 19%; 82%), while the sickest patients (CD4 ≤200) saw no decline in the monthly number of patients initiating treatment or the rate of treatment uptake. CONCLUSION: The Hlabisa program successfully extended ART to patients with CD4 ≤350 cells/μL, while ensuring that the sickest patients did not experience delays in ART initiation. Treatment programs must be vigilant to maintain quality of care for the sickest as countries move to treat all patients irrespective of CD4 count. This article is protected by copyright. All rights reserved

Modelling full waveform Lidar data on forest structures at plot level : a sensitivity analysis of forest and sensor main characteristics on full-waveform simulated data

[Departement_IRSTEA]Territoires [TR1_IRSTEA]SYNERGIE [Axe_IRSTEA]TETIS-ATTOSSilviLaser, La Grande Motte, FRA, 28-/09/2015 - 30/09/2015International audienceA new approach for LIDAR altimetry mission for biomass applications (tree height measurement) is explored based on low emitted laser energy at high repetition frequency. Low energy approach drastical ly reduces the laser induced risks. Altimetry performances meet preliminary science requirements . The proposed instrument design is compatible with a space mission