219 research outputs found
Elastic instability in stratified core annular flow
We study experimentally the interfacial instability between a layer of dilute
polymer solution and water flowing in a thin capillary. The use of microfluidic
devices allows us to observe and quantify in great detail the features of the
flow. At low velocities, the flow takes the form of a straight jet, while at
high velocities, steady or advected wavy jets are produced. We demonstrate that
the transition between these flow regimes is purely elastic -- it is caused by
viscoelasticity of the polymer solution only. The linear stability analysis of
the flow in the short-wave approximation captures quantitatively the flow
diagram. Surprisingly, unstable flows are observed for strong velocities,
whereas convected flows are observed for low velocities. We demonstrate that
this instability can be used to measure rheological properties of dilute
polymer solutions that are difficult to assess otherwise.Comment: 4 pages, 4 figure
Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration
Background & Aims:
Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail.
Methods:
We performed detailed characterisation of the labelled population in the Axin2CreERT2 model. We lineage traced this cell population, quantifying the labelled population over 1 year and performed in-depth phenotypic comparisons, including transcriptomics, metabolomics and analysis of proteins through immunohistochemistry, of Axin2CreERT2 mice to WT counterparts.
Results:
We found that after careful definition of a baseline population, there are marked differences in labelling between male and female mice. Upon induced lineage tracing there was no expansion of the labelled hepatocyte population in Axin2CreERT2 mice. We found substantial evidence of disrupted homeostasis in Axin2CreERT2 mice. Offspring are born with sub-Mendelian ratios and adult mice have perturbations of hepatic Wnt/β-catenin signalling and related metabolomic disturbance.
Conclusions:
We find no evidence of predominant expansion of the pericentral hepatocyte population during liver homeostatic regeneration. Our data highlight the importance of detailed preclinical model characterisation and the pitfalls which may occur when comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci.
Impact and implications:
Understanding the source of cells which regenerate the liver is crucial to harness their potential to regrow injured livers. Herein, we show that cells which were previously thought to repopulate the liver play only a limited role in physiological regeneration. Our data helps to reconcile differing conclusions drawn from results from a number of prior studies and highlights methodological challenges which are relevant to preclinical models more generally
The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase
Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Cosmic Rays from the Knee to the Highest Energies
This review summarizes recent developments in the understanding of
high-energy cosmic rays. It focuses on galactic and presumably extragalactic
particles in the energy range from the knee (10^15 eV) up to the highest
energies observed (>10^20 eV). Emphasis is put on observational results, their
interpretation, and the global picture of cosmic rays that has emerged during
the last decade.Comment: Invited review, submitted to Progress in Particle and Nuclear Physic
The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies
We performed a 4.5-month multi-instrument campaign (from radio to VHE gamma
rays) on Mrk421 between January 2009 and June 2009, which included VLBA,
F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other
instruments and collaborations. Mrk421 was found in its typical (non-flaring)
activity state, with a VHE flux of about half that of the Crab Nebula, yet the
light curves show significant variability at all wavelengths, the highest
variability being in the X-rays. We determined the power spectral densities
(PSD) at most wavelengths and found that all PSDs can be described by
power-laws without a break, and with indices consistent with pink/red-noise
behavior. We observed a harder-when-brighter behavior in the X-ray spectra and
measured a positive correlation between VHE and X-ray fluxes with zero time
lag. Such characteristics have been reported many times during flaring
activity, but here they are reported for the first time in the non-flaring
state. We also observed an overall anti-correlation between optical/UV and
X-rays extending over the duration of the campaign.
The harder-when-brighter behavior in the X-ray spectra and the measured
positive X-ray/VHE correlation during the 2009 multi-wavelength campaign
suggests that the physical processes dominating the emission during non-flaring
states have similarities with those occurring during flaring activity. In
particular, this observation supports leptonic scenarios as being responsible
for the emission of Mrk421 during non-flaring activity. Such a temporally
extended X-ray/VHE correlation is not driven by any single flaring event, and
hence is difficult to explain within the standard hadronic scenarios. The
highest variability is observed in the X-ray band, which, within the one-zone
synchrotron self-Compton scenario, indicates that the electron energy
distribution is most variable at the highest energies.Comment: Accepted for publication in A&A, 18 pages, 14 figures (v2 has a small
modification in the acknowledgments, and also corrects a typo in the field
"author" in the metadata
A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421
Blazars are variable emitters across all wavelengths over a wide range of
timescales, from months down to minutes. It is therefore essential to observe
blazars simultaneously at different wavelengths, especially in the X-ray and
gamma-ray bands, where the broadband spectral energy distributions usually
peak.
In this work, we report on three "target-of-opportunity" (ToO) observations
of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring
event at TeV energies in 2014. These observations feature long, continuous, and
simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet
bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous
observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number
of radio and optical facilities. Although neither rapid flares nor significant
X-ray/TeV correlation are detected, these observations reveal subtle changes in
the X-ray spectrum of the source over the course of a few days. We search the
simultaneous X-ray and TeV data for spectral hysteresis patterns and time
delays, which could provide insight into the emission mechanisms and the source
properties (e.g. the radius of the emitting region, the strength of the
magnetic field, and related timescales). The observed broadband spectra are
consistent with a one-zone synchrotron self-Compton model. We find that the
power spectral density distribution at Hz from the
X-ray data can be described by a power-law model with an index value between
1.2 and 1.8, and do not find evidence for a steepening of the power spectral
index (often associated with a characteristic length scale) compared to the
previously reported values at lower frequencies.Comment: 45 pages, 15 figure
Correction: International Society of Sports Nutrition position stand: Nutrient timing
Position Statement: The position of the Society regarding nutrient timing and the intake of carbohydrates, proteins, and fats in reference to healthy, exercising individuals is summarized by the following eight points: 1.) Maximal endogenous glycogen stores are best promoted by following a high-glycemic, high-carbohydrate (CHO) diet (600 – 1000 grams CHO or ~8 – 10 g CHO/kg/d), and ingestion of free amino acids and protein (PRO) alone or in combination with CHO before resistance exercise can maximally stimulate protein synthesis. 2.) During exercise, CHO should be consumed at a rate of 30 – 60 grams of CHO/hour in a 6 – 8% CHO solution (8 – 16 fluid ounces) every 10 – 15 minutes. Adding PRO to create a CHO:PRO ratio of 3 – 4:1 may increase endurance performance and maximally promotes glycogen re-synthesis during acute and subsequent bouts of endurance exercise. 3.) Ingesting CHO alone or in combination with PRO during resistance exercise increases muscle glycogen, offsets muscle damage, and facilitates greater training adaptations after either acute or prolonged periods of supplementation with resistance training. 4.) Post-exercise (within 30 minutes) consumption of CHO at high dosages (8 – 10 g CHO/kg/day) have been shown to stimulate muscle glycogen re-synthesis, while adding PRO (0.2 g – 0.5 g PRO/kg/day) to CHO at a ratio of 3 – 4:1 (CHO: PRO) may further enhance glycogen re-synthesis. 5.) Post-exercise ingestion (immediately to 3 h post) of amino acids, primarily essential amino acids, has been shown to stimulate robust increases in muscle protein synthesis, while the addition of CHO may stimulate even greater levels of protein synthesis. Additionally, pre-exercise consumption of a CHO + PRO supplement may result in peak levels of protein synthesis. 6.) During consistent, prolonged resistance training, post-exercise consumption of varying doses of CHO + PRO supplements in varying dosages have been shown to stimulate improvements in strength and body composition when compared to control or placebo conditions. 7.) The addition of creatine (Cr) (0.1 g Cr/kg/day) to a CHO + PRO supplement may facilitate even greater adaptations to resistance training. 8.) Nutrient timing incorporates the use of methodical planning and eating of whole foods, nutrients extracted from food, and other sources. The timing of the energy intake and the ratio of certain ingested macronutrients are likely the attributes which allow for enhanced recovery and tissue repair following high-volume exercise, augmented muscle protein synthesis, and improved mood states when compared with unplanned or traditional strategies of nutrient intake
Orphan CpG Islands Identify Numerous Conserved Promoters in the Mammalian Genome
CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are “orphans” that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development
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