153 research outputs found
Empire of Liberty
M. Michaela Hampf analyzes American history from the end of the Civil War to the epochal year 1898. She argues that the rise of the United States to become an imperial power had already begun in the years following 1865. The study takes new methodical approaches to explain America’s special path, drawing upon the theory of path-dependency
The HiSCORE Project
A central question of Astroparticle Physics, the origin of cosmic rays, still remains unsolved. HiSCORE (Hundred*i Square-km Cosmic ORigin Explorer) is a concept for a large-area wide-angle non-imaging air shower detector, addressing this question by searching for cosmic ray pevatrons in the energy range from 10TeV to few PeV and cosmic rays in the energy range above 100TeV. In the framework of the Tunka-HiSCORE project, first prototypes have been deployed on the site of the Tunka-133 experiment, where we plan to install an engineering array covering an area of the order of 1km2. On the same site, also imaging and particle detectors are planned, potentially allowing a future hybrid detector system. Here we present the HiSCORE detector principle, its potential for cosmic ray origin search and the status of ongoing activities in the framework of the Tunka-HiSCORE experiment
Somatic Mutation Profiles of MSI and MSS Colorectal Cancer Identified by Whole Exome Next Generation Sequencing and Bioinformatics Analysis
BACKGROUND: Colorectal cancer (CRC) is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS) and microsatellite instable (MSI) colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations
Subtle motor disturbances in PREDICT-PD participants
PREDICT-PD has been funded by Parkinson’'s UK (reference F1201)
The 2010 very high energy gamma-ray flare & 10 years of multi-wavelength observations of M 87
Abridged: The giant radio galaxy M 87 with its proximity, famous jet, and
very massive black hole provides a unique opportunity to investigate the origin
of very high energy (VHE; E>100 GeV) gamma-ray emission generated in
relativistic outflows and the surroundings of super-massive black holes. M 87
has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray
emission displays strong variability on timescales as short as a day. In this
paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and
VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE
was detected triggering further observations at VHE (H.E.S.S.), X-rays
(Chandra), and radio (43 GHz VLBA). The excellent sampling of the VHE gamma-ray
light curve enables one to derive a precise temporal characterization of the
flare: the single, isolated flare is well described by a two-sided exponential
function with significantly different flux rise and decay times. While the
overall variability pattern of the 2010 flare appears somewhat different from
that of previous VHE flares in 2005 and 2008, they share very similar
timescales (~day), peak fluxes (Phi(>0.35 TeV) ~= (1-3) x 10^-11 ph cm^-2
s^-1), and VHE spectra. 43 GHz VLBA radio observations of the inner jet regions
indicate no enhanced flux in 2010 in contrast to observations in 2008, where an
increase of the radio flux of the innermost core regions coincided with a VHE
flare. On the other hand, Chandra X-ray observations taken ~3 days after the
peak of the VHE gamma-ray emission reveal an enhanced flux from the core. The
long-term (2001-2010) multi-wavelength light curve of M 87, spanning from radio
to VHE and including data from HST, LT, VLA and EVN, is used to further
investigate the origin of the VHE gamma-ray emission. No unique, common MWL
signature of the three VHE flares has been identified.Comment: 19 pages, 5 figures; Corresponding authors: M. Raue, L. Stawarz, D.
Mazin, P. Colin, C. M. Hui, M. Beilicke; Fig. 1 lightcurve data available
online: http://www.desy.de/~mraue/m87
Sleep, vigilance, and thermosensitivity
The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs
Crosstalk between different family members: IL27 recapitulates IFNγ responses in HCC cells, but is inhibited by IL6-type cytokines
Interleukin-27 (IL27) is a type-I-cytokine of the IL6/IL12 family predominantly secreted by activated macrophages and dendritic cells. In the liver, IL27 expression was observed to be upregulated in patients with hepatitis B, and sera of hepatocellular carcinoma (HCC) patients contain significantly elevated levels of IL27 compared to healthy controls or patients with hepatitis and/or liver cirrhosis. In this study, we show that IL27 induces STAT1 and STAT3 phosphorylation in 5 HCC lines and 3 different types of non-transformed liver cells. We were especially interested in the relevance of the IL27-induced STAT3 activation in liver cells. Thus, we compared the IL27 responses with those induced by IFNγ (STAT1-dominated response) or IL6-type cytokines (IL6, hyper-IL6 (hy-IL6) or OSM) (STAT3-dominated response) by microarray analysis and find that in HCC cells, IL27 induces an IFNγ-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. Validation experiments corroborate the finding from the microarray evaluation. Interestingly, the availability of STAT1 seems critical in the shaping of the IL27 response, as the siRNA knock-down of STAT1 revealed the ability of IL27 to induce the acute-phase protein γ-fibrinogen, a typical IL6 family characteristic. Moreover, we describe a crosstalk between the signaling of IL6-type cytokines and IL27: responses to the gp130-engaging cytokine IL27 (but not those to IFNs) can be inhibited by IL6-type cytokine pre-stimulation, likely by a SOCS3-mediated mechanism. Thus, IL27 recapitulates IFNγ responses in liver cells, but differs from IFNγ by its sensitivity to SOCS3 inhibition
Pluto's lower atmosphere and pressure evolution from ground-based stellar occultations, 1988-2016
Context. The tenuous nitrogen (N2) atmosphere on Pluto undergoes strong seasonal effects due to high obliquity and orbital eccentricity, and has recently (July 2015) been observed by the New Horizons spacecraft.
Aims. The main goals of this study are (i) to construct a well calibrated record of the seasonal evolution of surface pressure on Pluto and (ii) to constrain the structure of the lower atmosphere using a central flash observed in 2015.
Methods. Eleven stellar occultations by Pluto observed between 2002 and 2016 are used to retrieve atmospheric profiles (density, pressure, temperature) between altitude levels of ~5 and ~380 km (i.e. pressures from ~ 10 μbar to 10 nbar).
Results. (i) Pressure has suffered a monotonic increase from 1988 to 2016, that is compared to a seasonal volatile transport model, from which tight constraints on a combination of albedo and emissivity of N2 ice are derived. (ii) A central flash observed on 2015 June 29 is consistent with New Horizons REX profiles, provided that (a) large diurnal temperature variations (not expected by current models) occur over Sputnik Planitia; and/or (b) hazes with tangential optical depth of ~0.3 are present at 4–7 km altitude levels; and/or (c) the nominal REX density values are overestimated by an implausibly large factor of ~20%; and/or (d) higher terrains block part of the flash in the Charon facing hemisphere
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Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation
Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)
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