4,829 research outputs found

    MDM2 negatively regulates the human telomerase RNA gene promoter

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    <b>Background:</b> We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the hTR promoter, but the mechanism of pRb directed activation is unknown. It has recently been reported that pRB induces Sp1 activity by relieving inhibition mediated by mdm2. The aim was to investigate possible roles for mdm2 in hTR promoter regulation. <b>Methods:</b> Chromatin immunoprecipitation was used to determine binding of mdm2 to the hTR promoter. Transfection and luciferase assays were used to investigate mdm2 repression of the promoter activity and interaction with known transcriptional modulators. <b>Results:</b> Here we show using chromatin immunoprecipitation that mdm2 specifically binds the hTR promoter in vivo. Transient co-transfection experiments using an hTR promoter luciferase reporter construct show that hTR promoter activity is inhibited by over-expression of mdm2 in 5637 bladder carcinoma cells (p53 and pRB negative, low mdm2). Titration of mdm2 was able to antagonise activation of hTR promoter activity mediated by pRB or Sp1 over-expression, although in the presence of pRB, mdm2 could not repress promoter activity below basal levels. Using an Sp1 binding site mutation construct we showed that mdm2 repression did not absolutely require Sp1 binding sites in the hTR promoter, suggesting the possibility of pRB/Sp1 independent mechanisms of repression. Finally, we show that NF-Y mediated transactivation of the hTR promoter was also suppressed by mdm2 in a dose-dependent manner. <b>Conclusions:</b> These studies suggest that mdm2 may inhibit the hTR promoter by multiple mechanisms. Mdm2 may directly repress activation by both pRB and Sp1, or activation by NF-Y. Furthermore, the ability of mdm2 to interact and interfere with components of the general transcription machinery might partly explain the general repressive effect seen here. Elucidation of new regulators affecting hTR basal promoter activity in cancer cells provides a basis for future studies aimed at improving our understanding of the differential hTR expression between normal and cancer cells

    Self-compression of 4.9 µm pulses to sub-40 fs with 2 mJ energy in Zinc Sulfide

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    Nonlinear self-compression of few-cycle multi-mJ pulses at 4.9 µm in ZnS is presented. 80 fs input pulses are compressed to 37 fs with 2.1 mJ energy at a 1 kHz repetition rate. © 2024 The Author(s

    Differences between European birthweight standards: Impact on classification of \u27small for gestational age\u27

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    We describe a quantitative and comparative review of a selection of European birthweight standards for gestational age for singletons, to enable appropriate choices to be made for clinical and research use. Differences between median values at term across standards in 10 regions and misclassification of \u27small for gestational age\u27 (SGA), were studied. Sex and parity differences, exclusion criteria, and methods of construction were considered. There was wide variation between countries in exclusion criteria, methods of calculating standards, and median birthweight at term. The lightest standards (e.g. France\u27s medians are 255g lower than Norway\u27s medians) were associated with fewer exclusion criteria. Up to 20% of the population used in the construction of the Scottish standard would be classified as SGA using the Norwegian standard. Substantial misclassification of SGA is possible. Assumptions about variation used in the construction of some standards were not justified. It is not possible to conclude that there are real differences in birthweight standards between European countries. Country-based standards control for some population features but add misclassification due to the differing ways in which standards are derived. Standards should be chosen to reflect clinical or research need. If standards stratified by sex or parity are not available, adjustments should be made. In multinational studies, comparisons should be made between results using both a common standard and country-based standards. \ua9 2006 Mac Keith Press

    Correction to: Chamoun et al., Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection

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    Chamoun MN, Blumenthal A, Sullivan MJ, Schembri MA, Ulett GC. 2018. Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection. Critical Reviews in Microbiology. https://doi.org/10.1080/1040841X.2018.1426556. When the above article was first published online, the below three corrections were missed. The author ‘Antje Blumenthal’ was wrongly affiliated to the affiliation “cSchool of Chemistry and Molecular Biosciences, and Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Australia”. Now this affiliation has been removed for this author. The affiliation ‘bTranslational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, Australia’ of the author ‘Antje Blumenthal’ should read ‘bThe University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia’. In Table 3, the sentence ‘Benefit of manipulating IL-17 levels to improve immunization strategies M. tuberculosis’ should read “Benefit of manipulating IL-17 levels to improve immunization strategies against M. tuberculosis”.No Full Tex

    Generation of 22-mJ, 2.0-ps Pulses from a 1-kHz Ho:YLF Regenerative Chirped Pulse Amplifier

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    We report a CW-pumped Ho:YLF regenerative amplifier (RA) delivering pulses with 22.5-mJ energy and 2.0-ps duration at 1 kHz. The RA emitting at 2051 nm is broadband-seeded and implemented in a chirped pulse amplification system. © 2024 The Author(s

    Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein

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    The regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function

    Pure-rotational 1D-CARS spatiotemporal thermometry with a single regenerative amplifier system

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    We report spatiotemporal pure-rotational coherent anti-Stokes Raman spectroscopy (CARS) in a one-dimensional imaging arrangement obtained with a single ultrafast regenerative amplifier system. The femtosecond pump/Stokes photon pairs, used for impulsive excitation, are delivered by an external compressor operating on a ∼35% beam split of the uncompressed amplifier output (2.5 mJ/pulse). The picosecond 1.2 mJ probe pulse is produced via the second-harmonic bandwidth compression (SHBC) of the ∼65% remainder of the amplifier output (4.5 mJ/pulse), which originates from the internal compressor. The two pump/Stokes and probe pulses are spatially, temporally, and repetition-wise correlated at the measurement, and the signal generation plane is relayed by a wide-field coherent imaging spectrometer onto the detector plane, which is refreshed at the same repetition rate as the ultrafast regenerative amplifier system. We demonstrate 1 kHz cinematographic 1D-CARS gas-phase thermometry across an unstable premixed methane/air flame-front, achieved with a single-shot precision <1% and accuracy <3%, 1.4 mm field of view, and an excellent <20 µm line-spread function.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Flight Performance and Propulsio

    Some opertaing characteristics of novel ignition devices for hydrocarbon/air mixtures

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    An introduction to the problems of ignition in the petrol and gas turbine engine is given. Two new ignition devices are considered for their suitability to overcome these problems and a series of experiments were performed to evaluate their relative merits. The use of a laser spark and the development of a plasma plug igniter were compared with sparks of variable energy produced between two electrodes. A simple combustion chamber was used for the experiments and ionisation probes were used to follow the propagation of the flame from the ignition source and through the gaseous mixtures. The conditions of the experiments were as follows: Pre-mixed methane/air of 1.0, 0.8 and 0.6 stoichiometry Pressures101 kN/m2 - 1067 kN/m2 Laser spark energies30 mJ - 400 mJ Plasma plug energies50 mJ - 1500 mJ Electrode spark energies10 mJ - 2500 mJ Samples of the combustion products were taken and the results for the three mixture ratios are presented. The performances of the three ignition methods are presented by plotting the flame speeds observed from the ignition sources as functions of energy. Practical considerations eliminate the use of the laser as an ignition method but the plasma plug could be used for automotive applications if some control of the energy was exercised. The gas turbine engine appears to be the roost likely application of the plasma plug as it offers greater penetration into the combustion chamber than current surface discharge igniters

    Project: Establishing an accounting outsourcing company "MJ Grāmatvedība" Ltd

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    Projekta ideja ir izveidot grāmatvedības ārpakalpojumu uzņēmumu SIA „MJ Grāmatvedība”, kurš sniegtu pilna vai daļēja cikla grāmatvedības pakalpojumus, sākot ar pirmreizējo dokumentu apstrādi un beidzot ar visu nepieciešamo atskaišu sagatavošanu, kā arī konsultāciju sniegšanu. Projekta mērķis ir ne tikai sniegt grāmatvedības pakalpojumus, bet arī analizēt uzņēmumu darbību un izstrādāt ieteikumus darbības uzlabošanai. Darba autore uzskata, ka nozares pārstāvjiem ir būtiski jāpierāda sava nozīme un to kādam jābūt mūsdienu grāmatvedim. Grāmatvedis nav tikai persona, kura izdara konkrētus darbus, nodos atskaites, tas ir cilvēks, kuram labi jāpārzina nodokļu sistēma, finanšu vadīšana, jāspēj sniegt padomus uzņēmuma finanšu vadības uzlabošanai, kā arī jāspēj pielāgoties tehnoloģiju radītajām izmaiņām. Maģistra darbs apjoms ir uz 105 lappusēm, kas sastāv no 7 nodaļām, 17 pielikumiem, 22 tabulām un 7 attēliem. Darba izstrādē izmantoti 70 informācijas avoti.The general project idea is to establish the accountancy firm MJ Accountancy Ltd., which would provide full or half-cycle accountancy services including the processing of primary documentation, reports’ preparation, and providing of the accountancy consultations. The aim of the project is not only to provide accountancy consultations but also to deal with firms activity analysis and developing suggestions on their activity improvement. The author of the project supports the idea that the field representatives must constantly sustain the status of the accountant’s profession in current times. The accountant is not only the person who executes one’s regular duties and submits reports, but also the person who is competent in the field of taxes, financial management, able to advise on improvements in financial management, and above all able to adapt to the technological changes. The volume of the project is 105 pages, which includes 7 chapters, 17 appendices, 22 tables, 7 figures. 70 sources of information were used in master’s thesis

    Initial state and transition-state solvation effects in the cobaltotungstate oxidation of iodide in binary aqueous solvent mixtures

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