503 research outputs found

    Signal recognition particle binds to translating ribosomes before emergence of a signal anchor sequence.

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    The bacterial signal recognition particle (SRP) is part of the machinery that targets ribosomes synthesizing membrane proteins to membrane-embedded translocons co-translationally. Recognition of nascent membrane proteins occurs by virtue of a hydrophobic signal-anchor sequence (SAS) contained in the nascent chain, usually at the N terminus. Here we use fluorescence-based stopped-flow to monitor SRP-ribosome interactions with actively translating ribosomes while an SRP substrate is synthesized and emerges from the peptide exit tunnel. The kinetic analysis reveals that, at cellular concentrations of ribosomes and SRP, SRP rapidly binds to translating ribosomes prior to the emergence of an SAS and forms an initial complex that rapidly rearranges to a more stable engaged complex. When the growing peptide reaches a length of ∼50 amino acids and the SAS is partially exposed, SRP undergoes another conformational change which further stabilizes the complex and initiates targeting of the translating ribosome to the translocon. These results provide a reconciled view on the timing of high-affinity targeting complex formation, while emphasizing the existence of preceding SRP recruitment steps under conditions of ongoing translation

    Explanation for Anomalous Shock Temperatures Measured by Neutron Resonance Spectroscopy

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    Neutron resonance spectrometry (NRS) has been used to measure the temperature inside Mo samples during shock loading. The temperatures obtained were significantly higher than predicted assuming ideal hydrodynamic loading. The effect of plastic flow and non-ideal projectile behavior were assessed. Plastic flow was calculated self-consistently with the shock jump conditions: this is necessary for a rigorous estimate of the locus of shock states accessible. Plastic flow was estimated to contribute a temperature rise of 53K compared with hydrodynamic flow. Simulations were performed of the operation of the explosively-driven projectile system used to induce the shock in the Mo sample. The simulations predicted that the projectile was significantly curved on impact, and still accelerating. The resulting spatial variations in load, including radial components of velocity, were predicted to increase the apparent temperature that would be deduced from the width of the neutron resonance by 160K. These corrections are sufficient to reconcile the apparent temperatures deduced using NRS with the accepted properties of Mo, in particular its equation of state.Comment: near-final version, waiting for final consent from an autho

    Flexible Power Modeling of LTE Base Stations

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    With the explosion of wireless communications in number of users and data rates, the reduction of network power consumption becomes more and more critical. This is especially true for base stations which represent a dominant share of the total power in cellular networks. In order to study power reduction techniques, a convenient power model is required, providing estimates of the power consumption in different scenarios. This paper proposes such a model, accurate but simple to use. It evaluates the base station power consumption for different types of cells supporting the 3GPP LTE standard. It is flexible enough to enable comparisons between state-of-the-art and advanced configurations, and an easy adaptation to various scenarios. The model is based on a combination of base station components and sub-components as well as power scaling rules as functions of the main system parameters

    Atrazine and Water Quality: An Evaluation of Restricting Atrazine Use on Corn and Sorghum to Postemergent Applications

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    Atrazine is the most widely used herbicide for corn and sorghum and the most commonly encountered in ground and surface water. In addition to water quality problems, atrazine poses hazards through atmospheric transport, food residues, and exposure of applications and wildlife. If atrazine use is restricted, substitute herbicides will come into wider use, increasing the likelihood of occurrence of their own sets of potentially undesirable side effects and imposing cost or efficacy penalties

    Superbeams versus Neutrino Factories

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    We compare the physics potential of planned superbeams with the one of neutrino factories. Therefore, the experimental setups as well as the most relevant uncertainties and errors are considered on the same footing as much as possible. We use an improved analysis including the full parameter correlations, as well as statistical, systematical, and degeneracy errors. Especially, degeneracies have so far not been taken into account in a numerical analysis. We furthermore include external input, such as improved knowledge of the solar oscillation parameters from the KamLAND experiment. This allows us to determine the limiting uncertainties in all cases. For a specific comparison, we choose two representatives of each class: For the superbeam, we take the first conceivable setup, namely the JHF to SuperKamiokande experiment, as well as, on a longer time scale, the JHF to HyperKamiokande experiment. For the neutrino factory, we choose an initially conceivable setup and an advanced machine. We determine the potential to measure the small mixing angle sin^2 2 theta_{13}, the sign of Delta m^2_{31}, and the leptonic CP phase \deltacp, which also implies that we compare the limitations of the different setups. We find interesting results, such as the complete loss of the sensitivity to the sign of Delta m^2_{31} due to degeneracies in many cases.Comment: Revised version with JHF energy resolution corrected, discussion of detector issues added (App. B), and references added. Summary and conclusions unchanged. 51 pages, 28 figures, 4 table

    High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach.

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    In 29 chemotherapy-naive patients with stage II-III breast cancer, peripheral blood stem cells (PBSCs) were mobilised following fluorouracil 500 mg m-2, epirubicin 90-120 mg m-2 and cyclophosphamide 500 mg m-2 (FEC) and granulocyte colony-stimulating factor (G-CSF; Filgrastim) 300 microgram s.c. daily. In all but one patient, mobilisation was successful, requiring three or fewer leucocytopheresis sessions in 26 patients; 28 patients subsequently underwent high-dose chemotherapy consisting of carboplatin 1600 mg m-2, thiotepa 480 mg m-2 and cyclophosphamide 6 g m-2 (CTC) followed by PBSC transplantation. Haemopoietic engraftment was rapid with a median time to neutrophils of 500 x 10(6) l(-1) of 9 days (range 8-10) in patients who received G-CSF after PBSC-transplantation; platelet transfusion independence was reached within a median of 10 days (range 7-16). Neutropenic fever occurred in 96% of patients. Gastrointestinal toxicity was substantial but reversible. Renal, neural or ototoxicity was not observed. Complications related to the central venous catheter were encountered in 64% of patients, with major vein thrombosis occurring in 18%. High-dose CTC-chemotherapy with PBSC-transplantation, harvested after mobilisation with FEC and G-CSF, is reasonably well tolerated without life-threatening toxicity and is a suitable high-dose strategy for the adjuvant treatment of breast cancer

    Quantitative Gadolinium-Free Cardiac Fibrosis Imaging in End Stage Renal Disease Patients Reveals a Longitudinal Correlation with Structural and Functional Decline

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    Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to a healthy age matched control cohort. Ventricular mechanics, including circumferential strain and diastolic strain rate were unchanged in patients with ESRD. No correlation was observed between fibrotic burden and concomitant measures of either circumferential or longitudinal strains or strain rates. However, among patients who returned for follow up examination a strong correlation existed between initial fibrotic burden and subsequent loss of contractile function. Gadolinium-free myocardial fibrosis imaging in patients with ESRD revealed a complex and longitudinal, not contemporary, association between fibrosis and ventricular contractile function
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