The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference

The response characteristics of the 6 minute walk test (6MWT) in studies of idiopathic pulmonary fibrosis (IPF) are only poorly understood, and the change in walk distance that constitutes the minimum important difference (MID) over time is unknown

The great ideas of biology: Exploration through experimentation in an undergraduate lab course

We developed an introductory laboratory course to provide a visceral experience that aims at getting students truly excited about scientific study of the living world. Our vehicle to do that was to focus on what Paul Nurse dubbed “the great ideas of biology” rather than an approach to biology that celebrates specific factual knowledge. To that end, we developed eight diverse experimental modules, each of which highlights a key biological concept and gives an opportunity to use theory to generate testable hypotheses, to perform high quality measurements to test those hypotheses (some of which are clearly wrong), and to perform sophisticated computational data analysis. Some modules incorporate modern microscopy and computational techniques in classic experiments, such as bacterial growth and the Luria‐Delbrück experiment, while others address current research questions using methods like optogenetics and single molecule measurements. We have offered the course eight times, and in the most recent edition of the course, we conducted pre/post‐course interviews and attitude surveys. The students, both bio and non‐bio majors alike, reported being captivated by seeing life occur across the broad range of experiments and model organisms. We observed demonstrable development of their curiosity and enthusiasm for biology. Additionally, we found that prior to the course, students had only vague notions about what it means to make quantitative biological measurements and interpret them. They completed the course with a clearer understanding of scientific inquiry in biology and the skills and confidence to actually perform and interpret measurements in living systems

Automatic mode tracking for flight dynamic analysis using a spanning algorithm

Identifying and tracking dynamic modes in a multi-dimensional parameter space is a problem that presents itself in many engineering disciplines. In a flight dynamics context, the dynamic modes refer to the modes of motion obtained from a linearisation of the aircraft system about a known operating point. Typically dynamic results derived from these linear models are unsorted, where mode indices are unrelated from one operating point to the next. When varying the parameters, or in this case operating point, difficulties in automating the process of relating modes from a linear system derived at one parameter set to the next exists. This paper builds on the work in tracking modes in a structural context, using the Modal Assurance Criterion (MAC) to numerically relate modes from two comparable linear systems. The (MAC) is deployed within a spanning algorithm to discover and identify all modes within all conditions, with their relationship to adjacent/neighbouring conditions. This is tested on a 1-, 2- and 3-dimensional parameter space, twelve state system

Investigation on gas-liquid two-phase flow centrifugal pump performances for different rotational speeds

International audiencePerformance characteristics of a centrifugal pump under gas-liquid mixture are presented, using a direct coupled single-stage, single-suction centrifugal pump. Both experimental and numerical simulations comparison are carried out, for three different rotational speeds and different inlet gas volume fractions, the results of which are presented, based on dimensionless coefficients from similarity laws. The numerical results show that good agreement is obtained with experimental data at nominal rotational speed for several flow coefficients. It is found that the running of the pump is near the sudden break down of the present pump when the inlet void fraction is below 7%. However, numerical results are less sensitive to rotational speed effects compared with experiment ones; the influence of decreasing rotational speed on pump performances is more and more pronounced when inlet gas void fraction increases and flow coefficient decreases. Froude number effects are taken into account in order to explain part of these differences

Differential Forms on Log Canonical Spaces

The present paper is concerned with differential forms on log canonical varieties. It is shown that any p-form defined on the smooth locus of a variety with canonical or klt singularities extends regularly to any resolution of singularities. In fact, a much more general theorem for log canonical pairs is established. The proof relies on vanishing theorems for log canonical varieties and on methods of the minimal model program. In addition, a theory of differential forms on dlt pairs is developed. It is shown that many of the fundamental theorems and techniques known for sheaves of logarithmic differentials on smooth varieties also hold in the dlt setting. Immediate applications include the existence of a pull-back map for reflexive differentials, generalisations of Bogomolov-Sommese type vanishing results, and a positive answer to the Lipman-Zariski conjecture for klt spaces.Comment: 72 pages, 6 figures. A shortened version of this paper has appeared in Publications math\'ematiques de l'IH\'ES. The final publication is available at http://www.springerlink.co

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

Topological constraints in nucleic acid hybridization kinetics

A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of ‘helix-driven wrapping’. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary ‘kissing hairpins’ demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex

The Case for a Low Extragalactic Gamma-ray Background

Measurements of the diffuse extragalactic gamma-ray background (EGRB) are complicated by a strong Galactic foreground. Estimates of the EGRB flux and spectrum, obtained by modeling the Galactic emission, have produced a variety of (sometimes conflicting) results. The latest analysis of the EGRET data found an isotropic flux I_x=1.45+-0.05 above 100 MeV, in units of 10^-5 s^-1 cm^-2 sr^-1. We analyze the EGRET data in search for robust constraints on the EGRB flux, finding the gamma-ray sky strongly dominated by Galactic foreground even at high latitudes, with no conclusive evidence for an additional isotropic component. The gamma-ray intensity measured towards the Galactic poles is similar to or lower than previous estimates of I_x. The high latitude profile of the gamma-ray data is disk-like for 40<|b[deg]|<70, and even steeper for |b|>70; overall it exhibits strong Galactic features and is well fit by a simple Galactic model. Based on the |b|>40 data we find that I_x<0.5 at a 99% confidence level, with evidence for a much lower flux. We show that correlations with Galactic tracers, previously used to identify the Galactic foreground and estimate I_x, are not satisfactory; the results depend on the tracers used and on the part of the sky examined, because the Galactic emission is not linear in the Galactic tracers and exhibits spectral variations across the sky. The low EGRB flux favored by our analysis places stringent limits on extragalactic scenarios involving gamma-ray emission, such as radiation from blazars, intergalactic shocks and production of ultra-high energy cosmic rays and neutrinos. We suggest methods by which future gamma-ray missions such as GLAST and AGILE could indirectly identify the EGRB.Comment: Accepted for publication in JCAP. Increased sizes of polar regions examined, and added discussion of spectral data. Results unchange