The role of initial geometry in experimental models of wound closing

Wound healing assays are commonly used to study how populations of cells, initialised on a two-dimensional surface, act to close an artificial wound space. While real wounds have different shapes, standard wound healing assays often deal with just one simple wound shape, and it is unclear whether varying the wound shape might impact how we interpret results from these experiments. In this work, we describe a new kind of wound healing assay, called a sticker assay, that allows us to examine the role of wound shape in a series of wound healing assays performed with fibroblast cells. In particular, we show how to use the sticker assay to examine wound healing with square, circular and triangular shaped wounds. We take a standard approach and report measurements of the size of the wound as a function of time. This shows that the rate of wound closure depends on the initial wound shape. This result is interesting because the only aspect of the assay that we change is the initial wound shape, and the reason for the different rate of wound closure is unclear. To provide more insight into the experimental observations we describe our results quantitatively by calibrating a mathematical model, describing the relevant transport phenomena, to match our experimental data. Overall, our results suggest that the rates of cell motility and cell proliferation from different initial wound shapes are approximately the same, implying that the differences we observe in the wound closure rate are consistent with a fairly typical mathematical model of wound healing. Our results imply that parameter estimates obtained from an experiment performed with one particular wound shape could be used to describe an experiment performed with a different shape. This fundamental result is important because this assumption is often invoked, but never tested

Gas distribution, kinematics and star formation in faint dwarf galaxies

We compare the gas distribution, kinematics and the current star formation in a sample of 10 very faint (-13.37 < M_B < -9.55) dwarf galaxies. For 5 of these galaxies we present fresh, high sensitivity, GMRT HI 21cm observations. For all our galaxies we construct maps of the HI column density at a constant linear resolution of ~300 pc; this forms an excellent data set to check for the presence of a threshold column density for star formation. We find that while current star formation (as traced by Halpha emission) is confined to regions with relatively large (N_HI > (0.4 -1.7) X 10^{21} atoms cm^{-2}) HI column density, the morphology of the Halpha emission is in general not correlated with that of the high HI column density gas. Thus, while high column density gas may be necessary for star formation, in this sample at least, it is not sufficient to ensure that star formation does in fact occur. We examine the line profiles of the HI emission, but do not find a simple relation between regions with complex line profiles and those with on-going star formation. Finally, we examine the very fine scale (~20-100 pc) distribution of the HI gas, and find that at these scales the emission exhibits a variety of shell like, clumpy and filamentary features. The Halpha emission is sometimes associated with high density HI clumps, sometimes the Halpha emission lies inside a high density shell, and sometimes there is no correspondence between the Halpha emission and the HI clumps. In summary, the interplay between star formation and gas density in these galaxy does not seem to show the simple large scale patterns observed in brighter galaxies (abridged).Comment: 15 pages, 6 tables, 13 figures. Accepted for publication in MNRA

The active and passive populations of Extremely Red Objects

[abridged] The properties of galaxies with the reddest observed R-K colors (Extremely Red Objects, EROs), including their apparent division into passive and obscured active objects with roughly similar number densities, are a known challenge for models of galaxy formation. We produce mock catalogues generated by interfacing the predictions of the semi-analytical MORGANA model for the evolution of galaxies in a Lambda-CDM cosmology with the spectro-photometric + radiative transfer code GRASIL and Infrared (IR) template library to show that the model correctly reproduces number counts, redshift distributions and active fractions of R-K>5 sources. We test the robustness of our results against different dust attenuations and, most importantly, against the inclusion of TP-AGB stars in Simple Stellar Populations used to generate galaxy spectra, and find that the inclusion of TP-AGBs has a relevant effect, in that it allows to increase by a large factor the number of very red active objects at all color cuts. We find that though the most passive and the most obscured active galaxies have a higher probability of being selected as EROs, many EROs have intermediate properties and the population does not show bimodality in specific star formation rate (SSFR). We predict that deep observations in the Far-IR, from 100 to 500 micron, are the most efficient way to constrain the SSFR of these objects; we give predictions for future Herschel observations. Finally, we test whether a simple evolutionary sequence for the formation of z=0 massive galaxies, going through a sub-mm-bright phase and then a ERO phase, are typical in this galaxy formation model. We find that this sequence holds for ~25 per cent of z=0 massive galaxies, while the model typically shows a more complex connection between sub-mm, ERO and massive galaxies. [abridged]Comment: 14 pages, 12 figures, MNRAS in pres

The Spiral Structure of the Milky Way, Cosmic Rays, and Ice Age Epochs on Earth

The short term variability of the Galactic cosmic ray flux (CRF) reaching Earth has been previously associated with variations in the global low altitude cloud cover. This CRF variability arises from changes in the solar wind strength. However, cosmic ray variability also arises intrinsically from variable activity of and motion through the Milky Way. Thus, if indeed the CRF climate connection is real, the increased CRF witnessed while crossing the spiral arms could be responsible for a larger global cloud cover and a reduced temperature, thereby facilitating the occurrences of ice ages. This picture has been recently shown to be supported by various data (Shaviv, 2001). In particular, the variable CRF recorded in Iron meteorites appears to vary synchronously with the appearance ice ages. Here we expand upon the original treatment with a more thorough analysis and more supporting evidence. In particular, we discuss the cosmic ray diffusion model which considers the motion of the Galactic spiral arms. We also elaborate on the structure and dynamics of the Milky Way's spiral arms. In particular, we bring forth new argumentation using HI observations which imply that the galactic spiral arm pattern speed appears to be that which fits the glaciation period and the cosmic-ray flux record extracted from Iron meteorites. In addition, we show that apparent peaks in the star formation rate history, as deduced by several authors, coincides with particularly icy epochs, while the long period of 1 to 2 Gyr before present, during which no glaciations are known to have occurred, coincides with a significant paucity in the past star formation rate.Comment: 33 pages, 11 figures. To Appear in New Astronom

Will the US Economy Recover in 2010? A Minimal Spanning Tree Study

We calculated the cross correlations between the half-hourly times series of the ten Dow Jones US economic sectors over the period February 2000 to August 2008, the two-year intervals 2002--2003, 2004--2005, 2008--2009, and also over 11 segments within the present financial crisis, to construct minimal spanning trees (MSTs) of the US economy at the sector level. In all MSTs, a core-fringe structure is found, with consumer goods, consumer services, and the industrials consistently making up the core, and basic materials, oil and gas, healthcare, telecommunications, and utilities residing predominantly on the fringe. More importantly, we find that the MSTs can be classified into two distinct, statistically robust, topologies: (i) star-like, with the industrials at the center, associated with low-volatility economic growth; and (ii) chain-like, associated with high-volatility economic crisis. Finally, we present statistical evidence, based on the emergence of a star-like MST in Sep 2009, and the MST staying robustly star-like throughout the Greek Debt Crisis, that the US economy is on track to a recovery.Comment: elsarticle class, includes amsmath.sty, graphicx.sty and url.sty. 68 pages, 16 figures, 8 tables. Abridged version of the manuscript presented at the Econophysics Colloquim 2010, incorporating reviewer comment

Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope.

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission. OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB). DESIGN: Prospective, multicenter, comparative study. SETTING: Six academic hospitals. PATIENTS: A total of 105 patients with OGIB. INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion. MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination. RESULTS: Data analysis resulted in 43 (48%) abnormal cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P \u3c .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10). LIMITATIONS: Readers were not blinded to the particular capsule they were reading. CONCLUSION: A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. (Clinical trial registration number: NCT00878982.)

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Extended investigation of superdeformed bands in 151,152^{151,152}Tb nuclei

A detailed study of known and new SD bands in Tb isotopes has been performed with the use of the EUROBALL IV -ray array. The high-statistics data set has allowed for the extension of known SD bands at low and high spins by new -ray transitions. These transitions, as it turns out, correspond to the rotational frequencies where the principal superdeformed gaps (Z=66,N=86) close giving rise to up- or down-bending mechanisms. This enables to attribute the underlying theoretical configurations with much higher confidence as compared to the previous identifications. Five new SD bands have been discovered, three of them assigned to the 152Tb and the two others to the 151Tb nuclei. Nuclear mean-field calculations have been used to interpret the structure of known SD bands as well as of the new ones in terms of nucleonic configurations