406 research outputs found

    Temperature compensation of NdFeB permanent magnets

    Get PDF
    Permanent magnet blocks of NdFeB have a relatively high maximum energy product. Because of its relatively low Curie temperature, however, NdFeB has a large temperature coefficient for its residual induction. The temperature coefficients of the relative magnetic fields ({Delta}B/B)/{Delta}T in the air gap of NdFeB dipole magnets were reduced from {minus}1.1 {times} 10{sup {minus}3}/c to less than 2 {times} 10{sup {minus}5}/{degree}C under operating temperatures of {+-} 6 C. This was achieved passively by using 1.25-mm-thick strips of 30%-Ni-Fe alloy as flux shunts for the NdFeB blocks. The magnets with soft-steel poles and flux-return yokes were assembled and measured in a temperature-controlled environment

    Dynamical fingerprints for probing individual relaxation processes in biomolecular dynamics with simulations and kinetic experiments

    Get PDF
    There is a gap between kinetic experiment and simulation in their views of the dynamics of complex biomolecular systems. Whereas experiments typically reveal only a few readily discernible exponential relaxations, simulations often indicate complex multistate behavior. Here, a theoretical framework is presented that reconciles these two approaches. The central concept is “dynamical fingerprints” which contain peaks at the time scales of the dynamical processes involved with amplitudes determined by the experimental observable. Fingerprints can be generated from both experimental and simulation data, and their comparison by matching peaks permits assignment of structural changes present in the simulation to experimentally observed relaxation processes. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation

    The initial step of DNA hairpin folding: a kinetic analysis using fluorescence correlation spectroscopy

    Get PDF
    Conformational fluctuations of single-stranded DNA (ssDNA) oligonucleotides were studied in aqueous solution by monitoring contact-induced fluorescence quenching of the oxazine fluorophore MR121 by intrinsic guanosine residues (dG). We applied fluorescence correlation spectroscopy as well as steady-state and time-resolved fluorescence spectroscopy to analyze kinetics of DNA hairpin folding. We first characterized the reporter system by investigating bimolecular quenching interactions between MR121 and guanosine monophosphate in aqueous solution estimating rate constants, efficiency and stability for formation of quenched complexes. We then studied the kinetics of complex formation between MR121 and dG residues site-specifically incorporated in DNA hairpins. To uncover the initial steps of DNA hairpin folding we investigated complex formation in ssDNA carrying one or two complementary base pairs (dC–dG pairs) that could hybridize to form a short stem. Our data show that incorporation of a single dC–dG pair leads to non-exponential decays for opening and closing kinetics and reduces rate constants by one to two orders of magnitude. We found positive activation enthalpies independent of the number of dC–dG pairs. These results imply that the rate limiting step of DNA hairpin folding is not determined by loop dynamics, or by mismatches in the stem, but rather by interactions between stem and loop nucleotides

    Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples

    Get PDF
    Atherosclerosis can occur throughout the arterial vascular system and lead to various diseases. Early diagnosis of atherosclerotic processes and of individual disease patterns would be more likely to be successful if targeted therapies were available. For this, it is important to find reliable biomarkers that are easily accessible and with little inconvenience for patients. There are many cell culture, animal model or tissue studies that found biomarkers at the microRNA (miRNA) and mRNA level describing atherosclerotic processes. However, little is known about their potential as circulating and liquid biopsy markers in patients. In this study, we examined serum-derived miRNA – profiles from 129 patients and 28 volunteers to identify potential biomarkers. The patients had four different atherosclerotic manifestations: abdominal aneurysm (n = 35), coronary heart disease (n = 34), carotid artery stenosis (n = 24) and peripheral arterial disease (n = 36). The samples were processed with an extracellular vesicle enrichment protocol, total-RNA extraction and small RNA-sequencing were performed. A differential expression analysis was performed bioinformatically to find potentially regulated miRNA biomarkers. Resulting miRNA candidates served as a starting point for an overrepresentation analysis in which relevant target mRNAs were identified. The Gene Ontology database revealed relevant biological functions in relation to atherosclerotic processes. In patients, expression of specific miRNAs changed significantly compared to healthy volunteers; 27 differentially expressed miRNAs were identified. We were able to detect a group-specific miRNA fingerprint: miR-122-5p, miR-2110 and miR-483-5p for abdominal aortic aneurysm, miR-370-3p and miR-409-3p for coronary heart disease, miR-335-3p, miR-381-3p, miR493-5p and miR654-3p for carotid artery stenosis, miR-199a-5p, miR-215-5p, miR-3168, miR-582-3p and miR-769-5p for peripheral arterial disease. The results of the study show that some of the identified miRNAs have already been associated with atherosclerosis in previous studies. Overrepresentation analysis on this data detected biological processes that are clearly relevant for atherosclerosis, its development and progression showing the potential of these miRNAs as biomarker candidates. In a next step, the relevance of these findings on the mRNA level is to be investigated and substantiated

    Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

    Get PDF
    Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient β-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events

    Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

    Get PDF
    It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.This is the final published version. It's also available from ACS in Analytical Chemistry: http://pubs.acs.org/doi/pdf/10.1021/ac501188r

    Reconstruction of sea surface temperature variations in the Arabian Sea over the last 23 kyr using organic proxies (TEX86 and U37K')

    Get PDF
    Two sediment cores from the western Arabian Sea, NIOP905 and 74KL, were analyzed to determine sea surface temperature (SST) variations over the last 23 kyr. Two organic molecular SST proxies were used, the well-established U37K' based on long-chain unsaturated ketones synthesized by haptophyte algae and the newly proposed TEX86 derived from the membrane lipids of Crenarchaeota. Comparison of NIOP905 and 74KL core top data with present-day SST (0-10 m) values indicates that both proxies yield temperatures similar to local annual mean SSTs. However, TEX86 and U37K' SST down-core records derived from the same cores differ in magnitude and phasing. The alkenone SST record of NIOP905 shows small changes in SST (∼0.5°C) over the last 23 kyr, while that of core 74KL shows a ∼2°C increase from the Last Glacial Maximum (LGM) (23-19 calendar (cal) kyr B.P.) through the Holocene (the last 11.5 cal kyr B.P.) synchronous with changes in the Northern Hemisphere. In contrast, the TEX86 records of both cores show a large increase in SST from 22°-23°C in the LGM to 28°-30°C during Termination I (19-11.5 cal kyr B.P.), decreasing to present-day annual means of ∼26°C. A cold phase between 14.5 and 12 cal kyr B.P. that may correspond to the Antarctic cold reversal is also observed. This implies a Southern Hemisphere control on tropical SST reconstructed by the TEX86, possibly related to SW monsoon. Our results suggest that the application of both TEX86 and U37K' give different but complementary information on SST developments in past marine environments
    corecore