3,389 research outputs found

    HAPTEN-SANDWICH LABELING : I. A GENERAL PROCEDURE FOR SIMULTANEOUS LABELING OF MULTIPLE CELL SURFACE ANTIGENS FOR FLUORESCENCE AND ELECTRON MICROSCOPY

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    A hapten-sandwich procedure has been developed for specific labeling of cell surface antigens for fluorescence or electron microscopy. Haptens are azo-coupled to immunoglobulins specific for a cell surface antigen; the hapten-modified cell-bound antibodies can then be visualized by adding fluorescent antihapten antibody, or by adding antihapten antibody followed by hapten-modified markers for electron microscopy. Virus or high molecular weight protein markers are lightly cross-linked before conjugation with hapten to prevent their disruption. Such stable hapten-modified markers, and the accessibility of many different purified anti-azophenyl-hapten antibodies, make it feasible to distinguish more than one membrane antigen in a given labeling experiment. When mouse lymphoid cell populations are labeled with separate markers for Ig and for thymus-associated antigens, many cells exhibit the Ig marker exclusively or the thymic marker predominantly, and some cells are completely free of label

    Exploring Model Complexity in Machine Learned Potentials for Simulated Properties

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    Machine learning (ML) enables the development of interatomic potentials that promise the accuracy of first principles methods while retaining the low cost and parallel efficiency of empirical potentials. While ML potentials traditionally use atom-centered descriptors as inputs, different models such as linear regression and neural networks can map these descriptors to atomic energies and forces. This begs the question: what is the improvement in accuracy due to model complexity irrespective of choice of descriptors? We curate three datasets to investigate this question in terms of ab initio energy and force errors: (1) solid and liquid silicon, (2) gallium nitride, and (3) the superionic conductor LGPS. We further investigate how these errors affect simulated properties with these models and verify if the improvement in fitting errors corresponds to measurable improvement in property prediction. Since linear and nonlinear regression models have different advantages and disadvantages, the results presented herein help researchers choose models for their particular application. By assessing different models, we observe correlations between fitting quantity (e.g. atomic force) error and simulated property error with respect to ab initio values. Such observations can be repeated by other researchers to determine the level of accuracy, and hence model complexity, needed for their particular systems of interest

    Key Residues Defining the Μ-Opioid Receptor Binding Pocket: A Site-Directed Mutagenesis Study

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    Structural elements of the rat Μ-opioid receptor important in ligand receptor binding and selectivity were examined using a site-directed mutagenesis approach. Five single amino acid mutations were made, three that altered conserved residues in the Μ, Δ, and Κ receptors (Asn 150 to Ala, His 297 to Ala, and Tyr 326 to Phe) and two designed to test for Μ/Δ selectivity (Ile 198 to Val and Val 202 to Ile). Mutation of His 297 in transmembrane domain 6 (TM6) resulted in no detectable binding with [ 3 H]DAMGO ( 3 H-labeled d-Ala 2 , N -Me-Phe 4 ,Gly-ol 5 -enkephalin), [ 3 H]bremazocine, or [ 3 H]ethylketocyclazocine. Mutation of Asn 150 in TM3 produces a three- to 20-fold increase in affinity for the opioid agonists morphine, DAMGO, fentanyl, Β-endorphin 1–31 , JOM-13, deltorphin II, dynorphin 1–13 , and U50,488, with no change in the binding of antagonists such as naloxone, naltrexone, naltrindole, and nor-binaltorphamine. In contrast, the Tyr 326 mutation in TM7 resulted in a decreased affinity for a wide spectrum of Μ, Δ, and Κ agonists and antagonists. Altering Val 202 to Ile in TM4 produced no change on ligand affinity, but Ile 198 to Val resulted in a four- to fivefold decreased affinity for the Μ agonists morphine and DAMGO, with no change in the binding affinities of Κ and Δ ligands.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65474/1/j.1471-4159.1997.68010344.x.pd

    Local models of stellar convection: Reynolds stresses and turbulent heat transport

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    We study stellar convection using a local three-dimensional MHD model, with which we investigate the influence of rotation and large-scale magnetic fields on the turbulent momentum and heat transport. The former is studied by computing the Reynolds stresses, the latter by calculating the correlation of velocity and temperature fluctuations, both as functions of rotation and latitude. We find that the horisontal correlation, Q_(theta phi), capable of generating horisontal differential rotation, is mostly negative in the southern hemisphere for Coriolis numbers exceeding unity, corresponding to equatorward flux of angular momentum in accordance with solar observations. The radial component Q_(r phi) is negative for slow and intermediate rotation indicating inward transport of angular momentum, while for rapid rotation, the transport occurs outwards. Parametrisation in terms of the mean-field Lambda-effect shows qualitative agreement with the turbulence model of Kichatinov & R\"udiger (1993) for the horisontal part H \propto Q_(theta phi)/cos(theta), whereas for the vertical part, V \propto Q_(r phi)/sin(theta), agreement only for intermediate rotation exists. The Lambda-coefficients become suppressed in the limit of rapid rotation, this rotational quenching being stronger for the V component than for H. We find that the stresses are enhanced by the presence of the magnetic field for field strengths up to and above the equipartition value, without significant quenching. Concerning the turbulent heat transport, our calculations show that the transport in the radial direction is most efficient at the equatorial regions, obtains a minimum at midlatitudes, and shows a slight increase towards the poles. The latitudinal heat transport does not show a systematic trend as function of latitude or rotation.Comment: 26 pages, 20 figures, final published version. For a version with higher resolution figures, see http://cc.oulu.fi/~pkapyla/publ.htm

    Lower bounds on the complexity of simulating quantum gates

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    We give a simple proof of a formula for the minimal time required to simulate a two-qubit unitary operation using a fixed two-qubit Hamiltonian together with fast local unitaries. We also note that a related lower bound holds for arbitrary n-qubit gates.Comment: 6 page

    Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery : a cohort study

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    Background: In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods: A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results: Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion: In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery

    Spectroscopy of luminous z>7 galaxy candidates and sources of contamination in z>7 galaxy searches

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    We present three bright z+ dropout candidates selected from deep Near-Infrared (NIR) imaging of the COSMOS 2 square degree field. All three objects match the 0.8-8um colors of other published z>7 candidates but are three magnitudes brighter, facilitating further study. Deep spectroscopy of two of the candidates covering 0.64-1.02um with Keck-DEIMOS and all three covering 0.94-1.10um and 1.52-1.80um with Keck-NIRSPEC detects weak spectral features tentatively identified as Ly-alpha at z=6.95 and z=7.69 in two of the objects. The third object is placed at z~1.6 based on a 24um and weak optical detection. A comparison with the spectral energy distributions of known z<7 galaxies, including objects with strong spectral lines, large extinction, and large systematic uncertainties in the photometry yields no objects with similar colors. However, the lambda>1um properties of all three objects can be matched to optically detected sources with photometric redshifts at z~1.8, so the non-detection in the i+ and z+ bands are the primary factors which favors a z>7 solution. If any of these objects are at z~7 the bright end of the luminosity function is significantly higher at z>7 than suggested by previous studies, but consistent within the statistical uncertainty and the dark matter halo distribution. If these objects are at low redshift, the Lyman-Break selection must be contaminated by a previously unknown population of low redshift objects with very strong breaks in their broad band spectral energy distributions and blue NIR colors. The implications of this result on luminosity function evolution at high redshift is discussed. We show that the primary limitation of z>7 galaxy searches with broad filters is the depth of the available optical data.Comment: 15 Pages, 15 figures, accepted to Ap

    Surprising variations in the rotation of the chemically peculiar stars CU Virginis and V901 Orionis

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    CU Vir and V901 Ori belong among these few magnetic chemically peculiar stars whose rotation periods vary on timescales of decades. We aim to study the stability of the periods in CU Vir and V901 Ori using all accessible observational data containing phase information. We collected all available relevant archived observations supplemented with our new measurements of these stars and analysed the period variations of the stars using a novel method that allows for the combination of data of diverse sorts. We found that the shapes of their phase curves were constant, while the periods were changing. Both stars exhibit alternating intervals of rotational braking and acceleration. The rotation period of CU Vir was gradually shortening until the year 1968, when it reached its local minimum of 0.52067198 d. The period then started increasing, reaching its local maximum of 0.5207163 d in the year 2005. Since that time the rotation has begun to accelerate again. We also found much smaller period changes in CU Vir on a timescale of several years. The rotation period of V901 Ori was increasing for the past quarter-century, reaching a maximum of 1.538771 d in the year 2003, when the rotation period began to decrease. A theoretically unexpected alternating variability of rotation periods in these stars would remove the spin-down time paradox and brings a new insight into structure and evolution of magnetic upper-main-sequence stars.Comment: 5 pages, 3 figure

    Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

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    LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window
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