1,080 research outputs found

    The Deep Space Network: A Radio Communications Instrument for Deep Space Exploration

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    The primary purpose of the Deep Space Network (DSN) is to serve as a communications instrument for deep space exploration, providing communications between the spacecraft and the ground facilities. The uplink communications channel provides instructions or commands to the spacecraft. The downlink communications channel provides command verification and spacecraft engineering and science instrument payload data

    Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells

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    Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells

    Targeting Survivin with YM155 (Sepantronium Bromide): A novel therapeutic strategy for paediatric acute myeloid leukaemia

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    Despite aggressive chemotherapy, approximately one-third of children with acute myeloid leukaemia(AML) relapse. More effective treatments are urgently needed. Survivin is an inhibitor-of-apoptosis protein with key roles in regulating cell division, proliferation and apoptosis. Furthermore, high expression of Survivin has been associated with poor clinical outcome in AML. The Survivin suppressant YM155 (Sepantronium Bromide) has pre-clinical activity against a range of solid cancers and leukemias, although data in AML is limited. Therefore, we undertook a comprehensive pre-clinical evaluation of YM155 in paediatric AML. YM155 potently inhibited cell viability in a diverse panel of AML cell lines. All paediatric cell lines were particularly sensitive, with a median IC50 of 0.038 mu M. Cell cycle analyses demonstrated concentration-dependent increases in a sub-G1 population with YM155 treatment, suggestive of apoptosis that was subsequently confirmed by an increase in annexin-V positivity. YM155-mediated apoptosis was confirmed across a panel of 8 diagnostic bone marrow samples from children with AML. Consistent with the proposed mechanism of action, YM155 treatment was associated with down-regulation of Survivin mRNA and protein expression and induction of DNA damage

    Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).

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    OBJECTIVES: Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. METHODS: Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. RESULTS: Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. CONCLUSIONS: miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS

    Observation of Scaling Violations in Scaled Momentum Distributions at HERA

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    Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of xx and Q2Q^2 using the ZEUS detector. The evolution of the scaled momentum, xpx_p, with Q2,Q^2, in the range 10 to 1280 GeV2GeV^2, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of Q2Q^2.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

    D* Production in Deep Inelastic Scattering at HERA

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    This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel D+(D0Kπ+)π+D^{*+}\to (D^0 \to K^- \pi^+) \pi^+ (+ c.c.) has been used in the study. The e+pe^+p cross section for inclusive D^{*\pm} production with 5<Q2<100GeV25<Q^2<100 GeV^2 and y<0.7y<0.7 is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {1.3<pT(D±)<9.01.3<p_T(D^{*\pm})<9.0 GeV and η(D±)<1.5| \eta(D^{*\pm}) |<1.5}. Differential cross sections as functions of p_T(D^{*\pm}), η(D±),W\eta(D^{*\pm}), W and Q2Q^2 are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and η\eta(D^{*\pm}), the charm contribution F2ccˉ(x,Q2)F_2^{c\bar{c}}(x,Q^2) to the proton structure function is determined for Bjorken xx between 2 \cdot 104^{-4} and 5 \cdot 103^{-3}.Comment: 17 pages including 4 figure

    Escherichia coli induces apoptosis and proliferation of mammary cells

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    Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

    Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

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    Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

    Measurement of Jet Shapes in Photoproduction at HERA

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    The shape of jets produced in quasi-real photon-proton collisions at centre-of-mass energies in the range 134277134-277 GeV has been measured using the hadronic energy flow. The measurement was done with the ZEUS detector at HERA. Jets are identified using a cone algorithm in the ηϕ\eta - \phi plane with a cone radius of one unit. Measured jet shapes both in inclusive jet and dijet production with transverse energies ETjet>14E^{jet}_T>14 GeV are presented. The jet shape broadens as the jet pseudorapidity (ηjet\eta^{jet}) increases and narrows as ETjetE^{jet}_T increases. In dijet photoproduction, the jet shapes have been measured separately for samples dominated by resolved and by direct processes. Leading-logarithm parton-shower Monte Carlo calculations of resolved and direct processes describe well the measured jet shapes except for the inclusive production of jets with high ηjet\eta^{jet} and low ETjetE^{jet}_T. The observed broadening of the jet shape as ηjet\eta^{jet} increases is consistent with the predicted increase in the fraction of final state gluon jets.Comment: 29 pages including 9 figure

    Pooled retrospective analysis of 70 mg erenumab in episodic and chronic migraine: a two tertiary headache centers experience during clinical practice

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    Erenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients ( N  = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days ( p  < 0.001). There was also a significant reduction in reported headache intensity ( p  = 0.004) and average duration of headache attacks ( p  = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy ( p  = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group
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