A conserved role for Snail as a potentiator of active transcription

The transcription factors of the Snail family are key regulators of epithelial-mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ~25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of "Snail-activated" genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development

Self-selected Foot Strike Patterns in Runners when Transitioning from the Shod to Barefoot Condition: A Systematic Review of the Literature

Purpose and Background: Recent research has begun to focus on foot strike patterns as they relate to injuries in runners. Runners who employ a rear-foot strike (RFS) pattern (in which the heel lands before the ball of the foot) are more likely to experience repetitive stress injuries such as tibial stress fractures, patellofemoral pain syndrome (PFPS), and plantar fasciitis. Conversely, runners demonstrating a forefoot strike (FFS) pattern (defined as the ball of the foot-usually the 4th and 5th metatarsal heads-landing before the heel) are more susceptible to Achilles tendon, plantarflexor, and metatarsal injuries. Several systematic studies have concluded that barefoot runners employed a FFS pattern while shod runners used a RFS pattern. The purpose of this systematic review was to determine the effects of transitioning from traditionally shod running to barefoot running on self-selected initial contact patterns in long distance runners.https://jdc.jefferson.edu/dptcapstones/1010/thumbnail.jp

The SARAF-LINAC Project for SARAF-PHASE 2

THPF005International audienceSNRC and CEA collaborate to the upgrade of theSARAF accelerator to 5 mA CW 40 MeV deuteron andproton beams (Phase 2). This paper presents the referencedesign of the SARAF-LINAC Project including a fourvane176 MHz RFQ, a MEBT and a superconducting linacmade of four five-meter cryomodules housing 26superconducting HWR cavities and 20 superconductingsolenoids. The first two identical cryomodules house lowbeta($\beta$opt = 0.091), 280 mm long (flange to flange), 176MHz HWR cavities, the two identical last cryomoduleshouse high-beta ($\beta$opt = 0.181), 410 mm long, 176 MHz,HWR cavities. The beam is focused with superconductingsolenoids located between cavities housing steering coils.A BPM is placed upstream each solenoid

The probe beam linac in CTF3

JACoW web site http://accelconf.web.cern.ch/AccelConf/e06/The test facility CTF3, presently under construction at CERN within an international collaboration, is aimed at demonstrating the key feasibility issues of the multi-TeV linear collider CLIC. The objective of the probe beam linac is to "mimic" the main beam of CLIC in order to measure precisely the performances of the 30 GHz CLIC accelerating structures. In order to meet the required parameters of this 200 MeV probe beam, in terms of emittance, energy spread and bunch-length, the most advanced techniques have been considered: laser triggered photo-injector, velocity bunching, beam-loading compensation, RF pulse compression ... The final layout is described, and the selection criteria and the beam dynamics results are reviewed

Comparing open-source DEM frameworks for simulations of common bulk processes

Multiple software frameworks based on the Discrete Element Method (DEM) are available for simulating granular materials. All of them employ the same principles of explicit time integration, with each time step consisting of three main steps: contact detection, calculation of interactions, and integration of the equations of motion. However, there exist significant algorithmic differences, such as the choice of contact models, particle and wall shapes, and data analysis methods. Further differences can be observed in the practical implementation, including data structures, architecture, parallelization and domain decomposition techniques, user interaction, and the documentation of resources. This study compares, verifies, and benchmarks nine widely-used software frameworks. Only open-source packages were considered, as these are freely available and their underlying algorithms can be reviewed, edited, and tested. The benchmark consists of three common bulk processes: silo emptying, drum mixing, and particle impact. To keep it simple and comparable, only standard features were used, such as spherical particles and the Hertz-Mindlin model for dry contacts. Scripts for running the benchmarks in each software are provided as a dataset.</p

4DXpress: a database for cross-species expression pattern comparisons

In the major animal model species like mouse, fish or fly, detailed spatial information on gene expression over time can be acquired through whole mount in situ hybridization experiments. In these species, expression patterns of many genes have been studied and data has been integrated into dedicated model organism databases like ZFIN for zebrafish, MEPD for medaka, BDGP for Drosophila or GXD for mouse. However, a central repository that allows users to query and compare gene expression patterns across different species has not yet been established. Therefore, we have integrated expression patterns for zebrafish, Drosophila, medaka and mouse into a central public repository called 4DXpress (expression database in four dimensions). Users can query anatomy ontology-based expression annotations across species and quickly jump from one gene to the orthologues in other species. Genes are linked to public microarray data in ArrayExpress. We have mapped developmental stages between the species to be able to compare developmental time phases. We store the largest collection of gene expression patterns available to date in an individual resource, reflecting 16 505 annotated genes. 4DXpress will be an invaluable tool for developmental as well as for computational biologists interested in gene regulation and evolution. 4DXpress is available at http://ani.embl.de/4DXpress

A FABRY-PEROT CAVITY FOR COMPTON POLARIMETRY

A new kind of Compton polarimeter using a resonant Fabry—Pe« rot cavity as a power buildup for the photon beam is proposed. A prototype of such a cavity is described, along with the results obtained in terms of source to be used in a Compton scattering polarimeter. ( 1998 Elsevier Science B.V. All rights reserved

Ozone and PM(2.5) Exposure and Acute Pulmonary Health Effects: A Study of Hikers in the Great Smoky Mountains National Park

To address the lack of research on the pulmonary health effects of ozone and fine particulate matter (≤ 2.5 μm in aerodynamic diameter; PM(2.5)) on individuals who recreate in the Great Smoky Mountains National Park (USA) and to replicate a study performed at Mt. Washington, New Hampshire (USA), we conducted an observational study of adult (18–82 years of age) day hikers of the Charlies Bunion trail during 71 days of fall 2002 and summer 2003. Volunteer hikers performed pre- and posthike pulmonary function tests (spirometry), and we continuously monitored ambient O(3), PM(2.5), temperature, and relative humidity at the trailhead. Of the 817 hikers who participated, 354 (43%) met inclusion criteria (nonsmokers and no use of bronchodilators within 48 hr) and gave acceptable and reproducible spirometry. For these 354 hikers, we calculated the posthike percentage change in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), FVC/FEV(1), peak expiratory flow, and mean flow rate between 25 and 75% of the FVC and regressed each separately against pollutant (O(3) or PM(2.5)) concentration, adjusting for age, sex, hours hiked, smoking status (former vs. never), history of asthma or wheeze symptoms, hike load, reaching the summit, and mean daily temperature. O(3) and PM(2.5) concentrations measured during the study were below the current federal standards, and we found no significant associations of acute changes in pulmonary function with either pollutant. These findings are contrasted with those in the Mt. Washington study to examine the hypothesis that pulmonary health effects are associated with exposure to O(3) and PM(2.5) in healthy adults engaged in moderate exercise

Do Parents Recognize Autistic Deviant Behavior Long before Diagnosis? Taking into Account Interaction Using Computational Methods

BACKGROUND: To assess whether taking into account interaction synchrony would help to better differentiate autism (AD) from intellectual disability (ID) and typical development (TD) in family home movies of infants aged less than 18 months, we used computational methods. METHODOLOGY AND PRINCIPAL FINDINGS: First, we analyzed interactive sequences extracted from home movies of children with AD (N = 15), ID (N = 12), or TD (N = 15) through the Infant and Caregiver Behavior Scale (ICBS). Second, discrete behaviors between baby (BB) and Care Giver (CG) co-occurring in less than 3 seconds were selected as single interactive patterns (or dyadic events) for analysis of the two directions of interaction (CG→BB and BB→CG) by group and semester. To do so, we used a Markov assumption, a Generalized Linear Mixed Model, and non negative matrix factorization. Compared to TD children, BBs with AD exhibit a growing deviant development of interactive patterns whereas those with ID rather show an initial delay of development. Parents of AD and ID do not differ very much from parents of TD when responding to their child. However, when initiating interaction, parents use more touching and regulation up behaviors as early as the first semester. CONCLUSION: When studying interactive patterns, deviant autistic behaviors appear before 18 months. Parents seem to feel the lack of interactive initiative and responsiveness of their babies and try to increasingly supply soliciting behaviors. Thus we stress that credence should be given to parents' intuition as they recognize, long before diagnosis, the pathological process through the interactive pattern with their child