548 research outputs found
LINC complex-Lisl interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration
Cancer cells' ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter
Data collected by the Pierre Auger Observatory through 31 August 2007 showed
evidence for anisotropy in the arrival directions of cosmic rays above the
Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{eV}. The
anisotropy was measured by the fraction of arrival directions that are less
than from the position of an active galactic nucleus within 75 Mpc
(using the V\'eron-Cetty and V\'eron catalog). An updated
measurement of this fraction is reported here using the arrival directions of
cosmic rays recorded above the same energy threshold through 31 December 2009.
The number of arrival directions has increased from 27 to 69, allowing a more
precise measurement. The correlating fraction is , compared
with expected for isotropic cosmic rays. This is down from the early
estimate of . The enlarged set of arrival directions is
examined also in relation to other populations of nearby extragalactic objects:
galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in
hard X-rays by the Swift Burst Alert Telescope. A celestial region around the
position of the radiogalaxy Cen A has the largest excess of arrival directions
relative to isotropic expectations. The 2-point autocorrelation function is
shown for the enlarged set of arrival directions and compared to the isotropic
expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression
Background and Objectives: Research in Multiple Sclerosis (MS) has recently focused on extracting knowledge from real-world clinical data sources. This type of data is more abundant than data produced during clinical trials and potentially more informative about real-world clinical practice. However, this comes at the cost of less curated and controlled data sets. In this work we aim to predict disability progression by optimally extracting information from longitudinal patient data in the real-world setting, with a special focus on the sporadic sampling problem. Methods: We use machine learning methods suited for patient trajectories modeling, such as recurrent neural networks and tensor factorization. A subset of 6682 patients from the MSBase registry is used. Results: We can predict disability progression of patients in a two-year horizon with an ROC-AUC of 0.85, which represents a 32% decrease in the ranking pair error (1-AUC) compared to reference methods using static clinical features. Conclusions: Compared to the models available in the literature, this work uses the most complete patient history for MS disease progression prediction and represents a step forward towards AI-assisted precision medicine in MS
Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory
The advent of the Auger Engineering Radio Array (AERA) necessitates the
development of a powerful framework for the analysis of radio measurements of
cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air
shower radio emission in coincidence with the surface particle detectors and
fluorescence telescopes of the Pierre Auger Observatory, the radio analysis
functionality had to be incorporated in the existing hybrid analysis solutions
for fluoresence and surface detector data. This goal has been achieved in a
natural way by extending the existing Auger Offline software framework with
radio functionality. In this article, we lay out the design, highlights and
features of the radio extension implemented in the Auger Offline framework. Its
functionality has achieved a high degree of sophistication and offers advanced
features such as vectorial reconstruction of the electric field, advanced
signal processing algorithms, a transparent and efficient handling of FFTs, a
very detailed simulation of detector effects, and the read-in of multiple data
formats including data from various radio simulation codes. The source code of
this radio functionality can be made available to interested parties on
request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to
author list and references in v
Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory
We present the results of searches for dipolar-type anisotropies in different
energy ranges above eV with the surface detector array of
the Pierre Auger Observatory, reporting on both the phase and the amplitude
measurements of the first harmonic modulation in the right-ascension
distribution. Upper limits on the amplitudes are obtained, which provide the
most stringent bounds at present, being below 2% at 99% for EeV
energies. We also compare our results to those of previous experiments as well
as with some theoretical expectations.Comment: 28 pages, 11 figure
A global multinational survey of cefotaxime-resistant coliforms in urban wastewater treatment plants
The World Health Organization Global Action Plan recommends integrated surveillance programs as crucial strategies for monitoring antibiotic resistance. Although several national surveillance programs are in place for clinical and veterinary settings, no such schemes exist for monitoring antibiotic-resistant bacteria in the environment. In this transnational study, we developed, validated, and tested a low-cost surveillance and easy to implement approach to evaluate antibiotic resistance in wastewater treatment plants (WWTPs) by targeting cefotaxime-resistant (CTX-R) coliforms as indicators. The rationale for this approach was: i) coliform quantification methods are internationally accepted as indicators of fecal contamination in recreational waters and are therefore routinely applied in analytical labs; ii) CTX-R coliforms are clinically relevant, associated with extended-spectrum β-lactamases (ESBLs), and are rare in pristine environments. We analyzed 57 WWTPs in 22 countries across Europe, Asia, Africa, Australia, and North America. CTX-R coliforms were ubiquitous in raw sewage and their relative abundance varied significantly (<0.1% to 38.3%), being positively correlated (p < 0.001) with regional atmospheric temperatures. Although most WWTPs removed large proportions of CTX-R coliforms, loads over 103 colony-forming units per mL were occasionally observed in final effluents. We demonstrate that CTX-R coliform monitoring is a feasible and affordable approach to assess wastewater antibiotic resistance status
DIRAC Experiment and Test of Low-Energy QCD
The low-energy QCD predictions to be tested by the DIRAC experiment are revised. The experimental method, the setup characteristics and capabilities, along with first experimental results are reported. Preliminary analysis shows good detector performance: alignment error via mass measurement with , relative momentum resolution , and evidence for $\pi^
Representation of Dynamical Stimuli in Populations of Threshold Neurons
Many sensory or cognitive events are associated with dynamic current modulations in cortical neurons. This raises an urgent demand for tractable model approaches addressing the merits and limits of potential encoding strategies. Yet, current theoretical approaches addressing the response to mean- and variance-encoded stimuli rarely provide complete response functions for both modes of encoding in the presence of correlated noise. Here, we investigate the neuronal population response to dynamical modifications of the mean or variance of the synaptic bombardment using an alternative threshold model framework. In the variance and mean channel, we provide explicit expressions for the linear and non-linear frequency response functions in the presence of correlated noise and use them to derive population rate response to step-like stimuli. For mean-encoded signals, we find that the complete response function depends only on the temporal width of the input correlation function, but not on other functional specifics. Furthermore, we show that both mean- and variance-encoded signals can relay high-frequency inputs, and in both schemes step-like changes can be detected instantaneously. Finally, we obtain the pairwise spike correlation function and the spike triggered average from the linear mean-evoked response function. These results provide a maximally tractable limiting case that complements and extends previous results obtained in the integrate and fire framework
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